Enzyme-Like Catalysis of Vinyl Copolymer Carrying Boron Directly Connected to Backbone: Catalytic Esterification through Cooperation of Boron with Neighboring Carboxylic Anhydride.

Alternating-rich copolymer of vinylboronic acid pinacol ester (VBpin) and maleic anhydride (MAH) was found to catalyze direct dehydrative esterification of carboxylic acid and alcohol. The key to the catalytic function is the activation of the MAH unit by the neighboring Lewis acidic boron directly connected to the backbone through the formation of five-membered ring. The effects of the side-chain cooperation were clarified through comparisons with the polymers having similar structures and a conventional titanium catalyst as well as the analyses of reactions with carboxylic acid or alcohol. The catalytic activity was enhanced as the molecular weight was higher, which is owing to the structural feature that boron is directly attached to the backbone. The cooperative catalysis is of interest because of its conceptual similarity with enzyme.

Laryngospasm Treated With Intramuscular Rocuronium in a Pediatric Patient Without Intravenous Access: A Case Report.

We present a case in which intramuscular rocuronium was used successfully to treat laryngospasm in a pediatric patient. An 11-month-old infant weighing 9.7 kg was scheduled for an elective laparoscopic inguinal hernia repair surgery. Anesthesia was induced with oxygen, nitrous oxide, and sevoflurane. After loss of consciousness, mask ventilation became impossible, and laryngospasm was suspected. Intravenous access was attempted without success; as there was no immediate access to succinylcholine, rocuronium 10 mg (1.0 mg/kg) was injected intramuscularly into the vastus lateralis muscle. We were able to mask-ventilate the patient within one minute of intramuscular rocuronium, followed by successful endotracheal intubation with a video laryngoscope. The duration of hypoxia (saturation of peripheral oxygen (SpO2) < 90%) was approximately two minutes, and the patient's lowest oxygen saturation during induction was 76%. At the end of the surgery, the patient was uneventfully extubated. We conclude that intramuscular rocuronium may provide an alternative treatment for laryngospasm in pediatric patients with no intravenous access and no availability of succinylcholine.

Effects of volatile anesthetics on circadian rhythm in mice: a comparative study of sevoflurane, desflurane, and isoflurane.

PURPOSE: Volatile anesthetics affect the circadian rhythm of mammals, although the effects of different types of anesthetics are unclear. Here, we anesthetized mice using several volatile anesthetics at two different times during the day. Our objective was to compare the effects of these anesthetics on circadian rhythm. METHODS: Male adult C57BL/6 J mice were divided into eight groups (n = 8 each) based on the anesthetic (sevoflurane, desflurane, isoflurane, or no anesthesia) and anesthesia time (Zeitgeber time [ZT] 6-12 or ZT18-24). Mice were anesthetized for 6 h using a 0.5 minimum alveolar concentration (MAC) dose under constant dark conditions. The difference between the start of the active phase before and after anesthesia was measured as a phase shift. Clock genes were measured by polymerase chain reaction in suprachiasmatic nucleus (SCN) samples removed from mouse brain after anesthesia (n = 8-9 each). RESULTS: Phase shift after anesthesia at ZT6-12 using sevoflurane (- 0.49 h) was smaller compared with desflurane (- 1.1 h) and isoflurane (- 1.4 h) (p < 0.05). Clock mRNA (ZT6-12, p < 0.05) and Per2 mRNA (ZT18-24, p < 0.05) expression were different between the groups after anesthesia. CONCLUSION: 0.5 MAC sevoflurane anesthesia administered during the late inactive to early active phase has less impact on the phase shift of circadian rhythm than desflurane and isoflurane. This may be due to differences in the effects of volatile anesthetics on the expression of clock genes in the SCN, the master clock of the circadian rhythm.

Dietary Iron Restriction Protects against Aneurysm Rupture in a Mouse Model of Intracranial Aneurysm.

INTRODUCTION: Iron accumulation in vessel walls induces oxidative stress and inflammation, which can cause cerebrovascular damage, vascular wall degeneration, and intracranial aneurysmal formation, growth, and rupture. Subarachnoid hemorrhage from intracranial aneurysm rupture results in significant morbidity and mortality. This study used a mouse model of intracranial aneurysm to evaluate the effect of dietary iron restriction on aneurysm formation and rupture. METHODS: Intracranial aneurysms were induced using deoxycorticosterone acetate-salt-induced hypertension and a single injection of elastase into the cerebrospinal fluid of the basal cistern. Mice were fed an iron-restricted diet (n = 23) or a normal diet (n = 25). Aneurysm rupture was detected by neurological symptoms, while the presence of intracranial aneurysm with subarachnoid hemorrhage was confirmed by post-mortem examination. RESULTS: The aneurysmal rupture rate was significantly lower in iron-restricted diet mice (37%) compared with normal diet mice (76%; p < 0.05). Serum oxidative stress, iron accumulation, macrophage infiltration, and 8-hydroxy-2'-deoxyguanosine in the vascular wall were lower in iron-restricted diet mice (p < 0.01). The areas of iron positivity were similar to the areas of CD68 positivity and 8-hydroxy-2'-deoxyguanosine in both normal diet and iron-restricted diet mouse aneurysms. CONCLUSIONS: These findings suggest that iron is involved in intracranial aneurysm rupture via vascular inflammation and oxidative stress. Dietary iron restriction may have a promising role in preventing intracranial aneurysm rupture.

Manipulating the growth environment through co-culture to enhance stress tolerance and viability of probiotic strains in the gastrointestinal tract.

IMPORTANCE: The viability of probiotics in the human gastrointestinal tract is important, as some reports indicate that the health benefits of live bacteria are greater than those of dead ones. Therefore, the higher the viability of the probiotic strain, the better it may be. However, probiotic strains lose their viability due to gastrointestinal stress such as gastric acid and bile. This study provides an example of the use of co-culture or pH-controlled monoculture, which uses more stringent conditions (lower pH) than normal monoculture to produce probiotic strains that are more resistant to gastrointestinal stress. In addition, co-cultured beverages showed higher viability of the probiotic strain in the human gastrointestinal tract than monocultured beverages in our human study.

Emergence of cortical network motifs for short-term memory during learning.

Learning of adaptive behaviors requires the refinement of coordinated activity across multiple brain regions. However, how neural communications develop during learning remains poorly understood. Here, using two-photon calcium imaging, we simultaneously recorded the activity of layer 2/3 excitatory neurons in eight regions of the mouse dorsal cortex during learning of a delayed-response task. Across learning, while global functional connectivity became sparser, there emerged a subnetwork comprising of neurons in the anterior lateral motor cortex (ALM) and posterior parietal cortex (PPC). Neurons in this subnetwork shared a similar choice code during action preparation and formed recurrent functional connectivity across learning. Suppression of PPC activity disrupted choice selectivity in ALM and impaired task performance. Recurrent neural networks reconstructed from ALM activity revealed that PPC-ALM interactions rendered choice-related attractor dynamics more stable. Thus, learning constructs cortical network motifs by recruiting specific inter-areal communication channels to promote efficient and robust sensorimotor transformation.

The probiotic Lacticaseibacillus paracasei strain Shirota (LcS) in a fermented milk beverage survives the gastrointestinal tract of generally healthy U.S. Adults.

The probiotic strain Lacticaseibacillus paracasei (previously Lactobacillus casei) strain Shirota (LcS) has demonstrated its survivability in the gastrointestinal tract across populations in different countries. The objective of this study was to validate this survivability in the United States, where evidence is lacking. Faecal samples were collected from 26 healthy individuals (age: 32.0 ± 5.9 years) at baseline, after 7 and 14 days of daily consumption of 80 mL fermented milk containing 108 colony forming units (CFU) LcS/mL, and after a subsequent 14-days of no product consumption. Live LcS counts significantly (p < 0.001) increased after 7 and 14 days of product consumption (6.37 ± 1.18 and 5.24 ± 1.81 log10 CFU/g faeces, respectively) and returned to baseline in 87% of participants. These results indicate LcS survives passage through the gastrointestinal tract of generally healthy U.S. adults, providing support for its uniquely accumulated evidence of universal survival capacity in the gastrointestinal tract.

Identification of genes essential for bile acid resistance in the probiotic Lacticaseibacillus paracasei strain Shirota.

Bile acid resistance is crucial to allow probiotic strains to survive in the gastrointestinal tract and exert health-promoting effects on their hosts. Our aim here was to determine the mechanism of this resistance via a genetic approach by identifying the genes essential for bile acid resistance in Lacticaseibacillus paracasei strain Shirota (LcS). We generated 4649 transposon-inserted lines of L. paracasei YIT 0291, which has the same genome sequence as LcS but lacks the pLY101 plasmid, and we screened them for bile-acid-sensitive mutants. The growth of 14 mutated strains was strongly inhibited by bile acid, and we identified 10 genes that could be involved in bile acid resistance. Expression of these genes was not markedly induced by bile acid, suggesting that their homeostatic expression is important for exerting bile acid resistance. Two mutants in which the transposon was independently inserted into cardiolipin synthase (cls) genes, showed strong growth inhibition. Disruption of the cls genes in LcS caused decreased cardiolipin (CL) production and the accumulation of the precursor phosphatidylglycerol in bacterial cells. These data suggest that LcS possesses several mechanisms for exerting bile acid resistance, and that homeostatic CL production is among the factors most essential for this resistance.

Postoperative norepinephrine versus dopamine in patients undergoing noncardiac surgery: a propensity-matched analysis using a nationwide intensive care database.

BACKGROUND: Choosing catecholamines, such as norepinephrine and dopamine, for perioperative blood pressure control is essential for anesthesiologists and intensivists. However, studies specific to noncardiac surgery are limited. Therefore, we aimed to evaluate the effects of postoperative norepinephrine and dopamine on clinical outcomes in adult noncardiac surgery patients by analyzing a nationwide intensive care patient database. METHODS: The Japanese Intensive care PAtient Database (JIPAD) was used for this multicenter retrospective study. Adult patients in the JIPAD who received norepinephrine or dopamine within 24 h after noncardiac surgery in 2018-2020 were included. We compared the norepinephrine and dopamine groups using a one-to-one propensity score matching analysis. The primary outcome was in-hospital mortality. Secondary outcomes were intensive care unit (ICU) mortality, hospital length of stay, and ICU length of stay. RESULTS: A total of 6,236 eligible patients from 69 ICUs were allocated to the norepinephrine (n = 4,652) or dopamine (n = 1,584) group. Propensity score matching was used to create a matched cohort of 1,230 pairs. No differences in the in-hospital mortality was found between the two propensity score matched groups (risk difference: 0.41%, 95% CI [-1.15, 1.96], P = 0.608). Among the secondary outcomes, only the ICU length of stay was significantly shorter in the norepinephrine group than in the dopamine group (median length: 3 vs. 4 days, respectively; P < 0.001). CONCLUSIONS: In adult patients after noncardiac surgery, norepinephrine was not associated with decreased mortality but was associated with a shorter ICU length of stay than dopamine.

Comparison of postoperative nausea and vomiting between remimazolam and propofol: a propensity score-matched, retrospective, observational, single-center cohort study.

BACKGROUND: Remimazolam is a novel ultrashort-acting benzodiazepine that has recently become available for general anesthesia. However, the incidence of postoperative nausea and vomiting (PONV) associated with remimazolam remains unknown. In this propensity score-matched, retrospective, observational study, we compared the rates of PONV between remimazolam and propofol. METHODS: In this retrospective observational study, propensity score-matching was performed to minimize selection bias. Patients who received total intravenous anesthesia with remimazolam or propofol at the Hamamatsu University Hospital between August 2020 and July 2021 were enrolled in the study. Data on patient demographics, anesthetic agents, and PONV within the first 24 h were collected and analyzed. RESULTS: Of the 1,239 patients who met the study selection criteria, 585 received remimazolam and 684 received propofol. After propensity score matching, 333 matched pairs were further analyzed. Patient demographics and the anesthetic agents used were comparable between the matched cohorts. The incidence of PONV was significantly higher in the remimazolam group than in the propofol group (35% vs. 21%, P < 0.001). CONCLUSIONS: The incidence of PONV is higher with remimazolam anesthesia than with propofol anesthesia. The findings of this study require confirmation in larger prospective randomized controlled trials.

Association between remimazolam and postoperative delirium in older adults undergoing elective cardiovascular surgery: a prospective cohort study.

PURPOSE: Postoperative delirium is one of the most common complications after cardiovascular surgery in older adults. Benzodiazepines are a reported risk factor for delirium; however, there are no studies investigating remimazolam, a novel anesthetic agent. Therefore, we prospectively investigated the effect of remimazolam on postoperative delirium. METHODS: We included elective cardiovascular surgery patients aged ≥ 65 years at Hamamatsu University Hospital between August 2020 and February 2022. Patients who received general anesthesia with remimazolam were compared with those who received other anesthetics (control group). The primary outcome was delirium within 5 days after surgery. Secondary outcomes were delirium during intensive care unit stay and hospitalization, total duration of delirium, subsyndromal delirium, and differences in the Mini-Mental State Examination scores from preoperative to postoperative days 2 and 5. To adjust for differences in the groups' baseline covariates, we used stabilized inverse probability weighting as the primary analysis and propensity score matching as the sensitivity analysis. RESULTS: We enrolled 200 patients; 78 in the remimazolam group and 122 in the control group. After stabilized inverse probability weighting, 30.3% of the remimazolam group patients and 26.6% of the control group patients developed delirium within 5 days (risk difference, 3.8%; 95% confidence interval -11.5% to 19.1%; p = 0.63). The secondary outcomes did not differ significantly between the groups, and the sensitivity analysis results were similar to those for the primary analysis. CONCLUSION: Remimazolam was not significantly associated with postoperative delirium when compared with other anesthetic agents.

Arithmetic value representation for hierarchical behavior composition.

The ability to compose new skills from a preacquired behavior repertoire is a hallmark of biological intelligence. Although artificial agents extract reusable skills from past experience and recombine them in a hierarchical manner, whether the brain similarly composes a novel behavior is largely unknown. In the present study, I show that deep reinforcement learning agents learn to solve a novel composite task by additively combining representations of prelearned action values of constituent subtasks. Learning efficacy in the composite task was further augmented by the introduction of stochasticity in behavior during pretraining. These theoretical predictions were empirically tested in mice, where subtask pretraining enhanced learning of the composite task. Cortex-wide, two-photon calcium imaging revealed analogous neural representations of combined action values, with improved learning when the behavior variability was amplified. Together, these results suggest that the brain composes a novel behavior with a simple arithmetic operation of preacquired action-value representations with stochastic policies.

Anthranilamide-protected vinylboronic acid: rational monomer design for improved polymerization/transformation ability providing access to conventionally inaccessible copolymers.

We have studied several protecting groups for vinylboronic-acid derivatives as monomers in radical polymerizations with the objective to improve the polymerization ability and C-B bond-cleaving post-transformation performance. Anthranilamide (aam)-protected vinylboronic acid (VBaam) exhibited experimentally a relatively high polymerization activity, which was theoretically corroborated by density functional theory (DFT) calculations that revealed a peculiar effect of the interaction between the aam groups on the polymerization behavior. The VBaam units in the copolymers can subsequently be transformed into vinyl alcohols or into ethylene units through C-B-bond-cleaving side-chain replacement, which affords valuable copolymers such as poly(vinyl alcohol-co-styrene), poly(ethylene-co-styrene), and poly(ethylene-co-acrylate).

Two synchronous pseudoaneurysms after bile duct resection for distal cholangiocarcinoma.

Pseudoaneurysm is a potentially life-threatening complication after hepatobiliary pancreatic surgery. Although various measures have been taken to prevent the formation of postoperative pseudoaneurysms, completely avoiding complications can be difficult. An 83-year-old man underwent bile duct resection and systematic regional lymphadenectomies for distal cholangiocarcinoma. Polyethylene glycolic acid mesh with fibrin glue was applied to the pancreas around the distal stump and detached artery to prevent leakage of pancreatic juice and reinforce the arterial wall. Screening contrast-enhanced computed tomography on the 7th postoperative day indicated no pseudoaneurysm. The patient was discharged on the 20th postoperative day after an uneventful course. However, 4 days later, the patient visited the emergency outpatient department with a complaint of fever. Contrast-enhanced computed tomography revealed an abscess formation and a pseudoaneurysm around it. Emergency celiac arteriography revealed two pseudoaneurysms at the left hepatic artery and posterior superior pancreaticoduodenal artery; they were successfully treated with transcatheter arterial embolization using microcoils and covered stent placement. The patient was discharged 9 days after interventional radiology treatment. At the 14 months postoperative follow-up, the patient had no recurrence or stent obstruction. Multiple synchronous pseudoaneurysms are rare; accurately identifying the site by angiography and selecting appropriate treatment for each site is important.

Incorporation of a boryl pendant as the trigger in a methacrylate polymer for backbone degradation.

Alkenylboronate units were incorporated into poly(methyl methacrylate) as trigger sites for backbone degradation. The complexation of a fluoride anion to the boron pendant and subsequent activation by a manganese salt triggered the degradation through the generation of a main-chain carbon radical and ß-scission in an adjacent methacrylate unit. The addition of catechol was required, and presumably the chelate coordination to the Mn center was crucial for the degradation.

Representation learning in the artificial and biological neural networks underlying sensorimotor integration.

The integration of deep learning and theories of reinforcement learning (RL) is a promising avenue to explore novel hypotheses on reward-based learning and decision-making in humans and other animals. Here, we trained deep RL agents and mice in the same sensorimotor task with high-dimensional state and action space and studied representation learning in their respective neural networks. Evaluation of thousands of neural network models with extensive hyperparameter search revealed that learning-dependent enrichment of state-value and policy representations of the task-performance-optimized deep RL agent closely resembled neural activity of the posterior parietal cortex (PPC). These representations were critical for the task performance in both systems. PPC neurons also exhibited representations of the internally defined subgoal, a feature of deep RL algorithms postulated to improve sample efficiency. Such striking resemblance between the artificial and biological networks and their functional convergence in sensorimotor integration offers new opportunities to better understand respective intelligent systems.

[A Case of Advanced Gastric Cancer Successfully Treated with FOLFOX].

The Japanese gastric cancer clinical practice guideline recommends FOLFOX as one of the first-line chemotherapy for advanced gastric cancer. Since FOLFOX is administered intravenously, it is helpful for patients who have difficulty in oral intake. Herein, we report a patient in which FOLFOX was significantly effective after failure to treatment with S-1 plus CDDP. A 75-year-old gastric cancer patient with paraaortic lymph node metastasis and multiple liver metastases(Stage ⅣB)was treated. Severe stomatitis and impaired consciousness due to dehydration appeared after administration of S-1 plus CDDP. After his general condition recovered, we changed his regimen to FOLFOX. No serious adverse events were observed, and partial response was achieved after 4 courses of treatment. Partial response was maintained until the onset of oxaliplatin drug allergy in the 10th course. FOLFOX is a promising option for patients with difficulties in oral intake.