Water detection in organic solvents using a copolymer membrane immobilised with a fluorescent intramolecular charge transfer-type dye: effects of intramolecular hydrogen bonds.

Numerous fluorescent dye-based optical sensors have been developed to detect water in organic solvents. However, only a few such sensors can detect water in polar solvents such as methanol or dimethyl sulfoxide, and their detection range is generally narrow. Therefore, in this study, a copolymer membrane incorporated with a pyridinium betaine dye (denoted PB1), which exhibited intramolecular charge transfer (ICT) characteristics, was developed to realise simple water detection in organic solvents. The pyridinium betaine structure, comprising intramolecular hydrogen bonds between the oxygen in the maleimide moiety and the hydrogen in the pyridinium, was vital for achieving efficient fluorescence emission. The membrane was prepared by copolymerising PB1 with the N,N-dimethyl acrylamide/acrylamide monomer on a glass plate, and the fluorescence in water-mixed organic solvents was investigated (λabs = 490 nm, λfl = 630 nm). The fluorescence intensity of the dye-immobilised membrane decreased with increasing water content of the organic solvents. The detection ranges in tetrahydrofuran, ethanol, methanol, and dimethyl sulfoxide were approximately <40, <40, <40, and <60 vol% water, respectively. In contrast, membranes based on a quaternary pyridinium dye (without intramolecular hydrogen bonds) did not detect water in methanol and dimethyl sulfoxide, although it was more sensitive than PB1 in the narrow region of low water concentration in THF. Theoretical calculations corroborated the importance of the pyridinium betaine structure in detecting water in organic solvents, with the increase in polarity and the formation of intermolecular hydrogen bonds between PB1 and water found to induce molecular rotation and fluorescence quenching.

Impaired monoamine neural system in the mPFC of SHRSP/Ezo as an animal model of attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is the most common childhood-onset psychiatric disorder. We investigated the effects of systemic administration of monoamine reuptake inhibitors on long-term potentiation (LTP) formation and monoamine release in the medial prefrontal cortex (mPFC) of the stroke-prone spontaneously hypertensive rat (SHRSP)/Ezo, an animal model of ADHD, and its genetic control, Wistar Kyoto (WKY)/Ezo, to elucidate the functional changes in the mPFC monoamine neural system. Methylphenidate (dopamine (DA) and noradrenaline (NA) reuptake inhibitor) and desipramine (NA reuptake inhibitor) improved LTP formation defects in the mPFC of SHRSP/Ezo, suggesting that NA or both DA and NA are required for improvement of impaired LTP. Methylphenidate increased mPFC DA in both WKY/Ezo and SHRSP/Ezo, but the increase was greater in the former. GBR-12909 (DA reuptake inhibitor) increased mPFC DA in WKY/Ezo but had no effect in SHRSP/Ezo. This may be because DA transporter in SHRSP/Ezo is functionally impaired and contributes less to DA reuptake, so its inhibition did not increase DA level. Meanwhile, basal DA levels in the mPFC of SHRSP/Ezo were paradoxically decreased. These results suggest that functional changes in the DA and NA neural system in the frontal lobe are involved in the pathology of ADHD.

Photobase-Driven Excited-State Intramolecular Proton Transfer (ESIPT) in a Strapped π-Electron System.

We report a new design strategy for an excited-state intramolecular proton transfer (ESIPT) fluorophore that can be used in acidic media. A photobasic pyridine-centered donor-acceptor-donor-type fluorophore is combined with a basic trialkylamine "strap". In the presence of an acid, protonation occurs predominantly at the amine moiety in the ground state. A single-crystal X-ray diffraction analysis confirmed the formation of a pre-organized intramolecular hydrogen-bonded structure between the resulting ammonium moiety and the pyridine ring. Upon excitation, the intramolecular charge-transfer transition increases the basicity of the pyridine moiety in the excited state, resulting in proton transfer from the amine to the pyridine moiety. Consequently, the fluorophore takes on a polymethine-dye character in the ESIPT state, which gives rise to significantly red-shifted emission with an increased fluorescence quantum yield.

Related factors associated with exercise behavior in patients with peripheral arterial disease.

[Purpose] This study aimed to identify the factors associated with exercise behavior in patients with peripheral arterial disease. [Participants and Methods] The study included 43 patients with peripheral arterial disease (mean age, 75.2 ± 5.6 years) who were admitted for endovascular treatment from January 2020 to June 2021. Participants were surveyed through questionnaires to assess their physical function for determining their exercise behavior and the presence of physical, personal, and environmental factors that might have affected their stage of change regarding exercise behavior. [Results] A comparison of physical, personal, and environmental factors between the two groups classified by the presence or absence of exercise behavior showed that subjective health and exercise self-efficacy were significantly lower in the group without exercise. Furthermore, a difference was noted in the presence or absence of work. The adjusted binomial logistic regression analysis results using each of the factors differing between the groups, plus the walking impairment questionnaire total score as explanatory variables, showed a significant relationship with exercise self-efficacy only. [Conclusion] The results of this study showed that exercise self-efficacy presented a useful predictive relationship with the presence of exercise behavior in patients with peripheral arterial disease.

Combination chemoradiotherapy with temozolomide, vincristine, and interferon-ß might improve outcomes regardless of O6-methyl-guanine-DNA-methyltransferase (MGMT) promoter methylation status in newly glioblastoma.

BACKGROUND: This investigator-initiated, open-label, single-arm, single-institute study was conducted to investigate the effectiveness of induction combination chemoradiotherapy and long-term maintenance therapy with temozolomide (TMZ) plus interferon (IFN)-ß for glioblastoma. METHODS: The initial induction combination chemoradiotherapy comprised radiotherapy plus TMZ plus vincristine plus IFN-ß. Maintenance chemotherapy comprised monthly TMZ, continued for 24-50 cycles, plus weekly IFN-ß continued for as long as possible. The primary endpoint was 2-year overall survival (2y-OS). The study protocol was to be considered valid if the expected 2y-OS was over 38% and the lower limit of the 95% confidence interval (CI) was no less than 31.7% compared with historical controls, using Kaplan-Meier methods. Secondary endpoints were median progression-free survival (mPFS), median OS (mOS), 5-year OS rate (5y-OS), and mPFS and mOS classified according to MGMT promoter methylation status. RESULTS: Forty-seven patients were analyzed. The 2y-OS was 40.7% (95%CI, 27.5-55.4%). The mPFS and mOS were 11.0 months and 18.0 months, respectively, and 5y-OS was 20.3% (95%CI, 10.9-34.6%). The mPFS in groups with and without MGMT promoter methylation in the tumor was 10.0 months and 11.0 months (p = 0.59), respectively, and mOS was 24.0 months and 18.0 months (p = 0.88), respectively. The frequency of grade 3/4 neutropenia was 19.1%. CONCLUSIONS: The 2y-OS with induction multidrug combination chemoradiotherapy and long-term maintenance therapy comprising TMZ plus IFN-ß tended to exceed that of historical controls, but the lower limit of the 95%CI was below 31.7%. Although the number of cases was small, this protocol may rule out MGMT promoter methylation status as a prognostic factor. TRIAL REGISTRATION: University Hospital Medical Information Network (number UMIN000040599 ).

Etiology and mortality in severe acute pancreatitis: A multicenter study in Japan.

BACKGROUND/OBJECTIVES: Severe acute pancreatitis (SAP) has a high mortality rate despite ongoing attempts to improve prognosis through a various therapeutic modalities. This study aimed to delineate etiology-based routes that may guide clinical decisions for the treatment of SAP. METHODS: Using data from a recent retrospective multicenter study in Japan, we analyzed the association between clinical outcomes, mainly in-hospital mortality and pancreatic infection, and various etiologies while considering confounding factors. We performed additional multivariate analyses and built decision tree models. RESULTS: The 1097 participating patients were classified into the following groups by etiology: alcohol (n = 436, 39.7%); cholelithiasis (n = 230, 21.0%); idiopathic (n = 227, 20.7%); and others (n = 204, 18.6%). Mortality at hospital discharge was 8.4%, 12.2%, 16.7%, and 16.2% in the alcohol, cholelithiasis, idiopathic, and others groups, respectively. According to multivariable analysis, early enteral nutrition (EN) was significantly associated with reduced in-hospital mortality only in the cholelithiasis group. However, there was a consistent association between age and the need for mechanical ventilation and increased mortality, regardless of etiology. Our decision tree models presented different contributing factors depending on the etiology and patient background. Interaction analysis showed that EN and the use of prophylactic antibiotics may influence these results differently according to etiology. CONCLUSIONS: No study has yet used comprehensive models to investigate etiology-related prognostic factors for SAP; our results can, therefore, be used as a reference for improving clinical decisions.

Effects of intravesicular loading of a Ca2+ chelator and depolymerization of actin fibers on neurotransmitter release in frog motor nerve terminals.

Ca2+ -induced Ca2+ release (CICR) via type-3 ryanodine receptor enhances neurotransmitter release in frog motor nerve terminals. To test a possible role of synaptic vesicle in CICR, we examined the effects of loading of EGTA, a Ca2+ chelator, into synaptic vesicles and depolymerization of actin fibers. Intravesicular EGTA loading via endocytosis inhibited the ryanodine sensitive enhancement of transmitter release induced by tetanic stimulation and the associated rises in intracellular-free Ca2+ ([Ca2+ ]i : Ca2+ transients). Latrunculin A, a depolymerizer of actin fibers, enhanced both spontaneous and stimulation-induced transmitter release, but inhibited the enhancement of transmitter release elicited by successive tetanic stimulation. The results suggest a possibility that the activation of CICR from mobilized synaptic vesicles caused the enhancement of neurotransmitter release.

Verification and rectification of cell type-specific splicing of a Seckel syndrome-associated ATR mutation using iPS cell model.

Seckel syndrome (SS) is a rare spectrum of congenital severe microcephaly and dwarfism. One SS-causative gene is Ataxia Telangiectasia and Rad3-Related Protein (ATR), and ATR (c.2101 A>G) mutation causes skipping of exon 9, resulting in a hypomorphic ATR defect. This mutation is considered the cause of an impaired response to DNA replication stress, the main function of ATR, contributing to the pathogenesis of microcephaly. However, the precise behavior and impact of this splicing defect in human neural progenitor cells (NPCs) is unclear. To address this, we established induced pluripotent stem cells (iPSCs) from fibroblasts carrying the ATR mutation and an isogenic ATR-corrected counterpart iPSC clone. SS-patient-derived iPSCs (SS-iPSCs) exhibited cell type-specific splicing; exon 9 was dominantly skipped in fibroblasts and iPSC-derived NPCs, but it was included in undifferentiated iPSCs and definitive endodermal cells. SS-iPSC-derived NPCs (SS-NPCs) showed distinct expression profiles from ATR non-mutated NPCs with negative enrichment of neuronal genesis-related gene sets. In SS-NPCs, abnormal mitotic spindles occurred more frequently than in gene-corrected counterparts, and the alignment of NPCs in the surface of the neurospheres was perturbed. Finally, we tested several splicing-modifying compounds and found that TG003, a CLK1 inhibitor, could pharmacologically rescue the exon 9 skipping in SS-NPCs. Treatment with TG003 restored the ATR kinase activity in SS-NPCs and decreased the frequency of abnormal mitotic events. In conclusion, our iPSC model revealed a novel effect of the ATR mutation in mitotic processes of NPCs and NPC-specific missplicing, accompanied by the recovery of neuronal defects using a splicing rectifier.

A strap strategy for construction of an excited-state intramolecular proton transfer (ESIPT) system with dual fluorescence.

An amine-embedded flexible alkyl strap has been incorporated into an emissive boryl-substituted dithienylpyrrole skeleton as a new entity of excited-state intramolecular proton transfer (ESIPT) chromophores. The π-electron system shows a dual emission, which covers a wide range of the visible region depending on the solvent polarity. The incorporation of the aminoalkyl strap as well as the terminal boryl groups efficiently stabilize the zwitterionic excited-state species resulting from the ESIPT even in an aqueous medium.

Appropriate Endotracheal Tube Position for Percutaneous Dilatational Tracheostomy: A Single-Center Observational Study.

Aim This study aimed to investigate the appropriate endotracheal tube (ETT) position during percutaneous dilatational tracheostomy (PDT). Methods This single-center observational study included hospitalized patients who underwent surgical tracheostomy (ST) between August 2021 and October 2022. During ST, the trachea was opened, and the ETT was pulled out visually. It stopped when the ETT was no longer visible, and the tracheostomy tube was placed in the trachea. The ETT position was measured by considering the ETT position during ST to be the appropriate position during PDT. The correlation between the measured ETT position and patient characteristics was evaluated. A prediction equation for the ETT position was derived from the derivation group, and validation of the prediction equation was evaluated by the validation group. Results Forty-six and 15 patients were in the derivation and validation groups, respectively. Weight, duration of intubation, and in-hospital mortality were significantly different between the two groups. The measured ETT position correlated with body height (r=0.60, p<0.001) and sex (r=0.45, p=0.002), while the ETT position before ST showed a weak correlation (r=0.34, p=0.020). The predicted and measured values in the validation group correlated with each other (r=0.58, p=0.024). Conclusion The appropriate ETT position for PDT correlates with body height, and the equation "body height×0.112-0.323 cm" was derived. This predictive equation may be useful as a guide for ETT positioning during PDT puncture.

Unveiling a new aspect of oxocarbons: open-shell character of 4- and 5-membered oxocarbon derivatives showing near-infrared absorption.

Oxocarbon derivatives consisting of 4- and 5-membered rings, referred to as croconaine and squaraine dyes and regarded as closed-shell molecules, are found to have an intermediate open-shell character from the experimental results of 1H-NMR, ESR spectroscopy, SQUID magnetometric analysis, and X-ray crystallography. We employed two chalcogenopyrylium moieties with O and S chalcogen atoms as substitutions on oxocarbons. The singlet-triplet energy gaps (ΔE S-T) associated with the degree of diradical nature are smaller for croconaines than for squaraines and smaller for thiopyrylium than for pyrylium groups. The diradical nature impacts the electronic transition energy that decreased with a decreasing degree of diradical contribution. They exhibit substantial two-photon absorption in the region over 1000 nm. The diradical character y of the dye was determined experimentally from the observed one- and two-photon absorption peaks and the triplet energy level. The present finding provides new insight into diradicaloids with the contribution of non-Kekulé oxocarbon and also showcases the correlation between the electronic transition energy and their diradical character.

Squaraine Appended with Benzodipyrrole for Fluorescent Sensing of Methanol: Exciton Coupling Controls Photophysical Properties.

The photophysical properties of dyes composed of two squaraine chromophores fused with a benzodipyrrole central moiety (BS1 and BS2), were investigated using steady-state absorption, fluorescence, and transient absorption spectroscopy. The dyes exhibit solvent-independent split electronic absorption due to exciton-coupling. Interestingly significant solvent-dependent fluorescence properties were observed. In toluene, they emit from the lowest excited state, while in methanol, they show weak emission in the higher energy region. In the low-temperature glass matrix, emission from the lowest excited state dominates similarly to that in toluene. The transient absorption spectra exhibit similar ground-state bleaching in toluene and methanol, revealing the formation of delocalized excited states by exciton coupling independent of solvent. However, the excited state deactivates rapidly in ultrafast time scale in methanol, likely due to solvent interaction, leading to rapid non-radiative deactivation. The PEG film doped with the exciton-coupled bis-squaraine shows a distinct fluorescence response to methanol vapor.

Effect of Past Chlamydophila pneumoniae Infection on the Short-Time Mortality of COVID-19: A Retrospective Cohort Study.

BACKGROUND: Although Chlamydophila pneumoniae (CP)is known to play a role in atherosclerosis and endothelial injury, its past infection on the mortality of coronavirus disease 2019 (COVID-19), which was also reported to be a vascular disease, remains unknown. METHODS: In this retrospective cohort study, we examined 78 COVID-19 patients and 32 bacterial pneumonia patients who visited a tertiary emergency center in Japan between April 1, 2021, and April 30, 2022. CP antibody levels, including IgM, IgG, and IgA, were measured. RESULTS: Among all patients, the CP IgA-positive rate was significantly associated with age (P = 0.002). Between the COVID-19 and non-COVID-19 groups, no difference in the positive rate for both CP IgG and IgA was observed (P = 1.00 and 0.51, respectively). The mean age and proportion of males were significantly higher in the IgA-positive group than in the IgA-negative group (60.7 vs. 75.5, P = 0.001; 61.5% vs. 85.0%, P = 0.019, respectively). Smoking and dead outcomes were significantly higher both in the IgA-positive group and IgG-positive group (smoking: 26.7% vs. 62.2, P = 0.003; 34.7% vs. 73.1%, P = 0.002, dead outcome: 6.5% vs. 29.8%, P = 0.020; 13.5% vs. 34.6%, P = 0.039, respectively). Although the log-rank test revealed higher 30-day mortality in the IgG-positive group compared to the IgG-negative group (P = 0.032), Cox regression analysis demonstrated no significant difference between the IgG-positive and negative groups (hazard ratio (HR) = 4.10, 95%CI = 0.94-18.0, P = 0.061). CONCLUSION: The effect of past CP infection on 30-day mortality in COVID-19 patients was not obvious.

Comparison of contamination levels on the exterior surfaces of vials containing platinum anticancer drugs in Japan.

Contamination of the external surface of anticancer drug vials supplied to hospital pharmacies has been recognized as a potential health hazard. The aim of this study was to investigate the levels of contamination on the exterior surface of vials containing platinum anticancer drugs in Japan. Platinum contamination on the exterior surface of vials containing cisplatin or carboplatin was examined using products commercially available in Japan. Cisplatin vials from 42 batches (2 drug contents, 10 products and 5 manufacturers) and carboplatin vials from 28 batches (3 drug contents, 7 products and 3 manufacturers) were used. Five vials were randomly sampled from each batch. Exterior contamination levels of 0.070-144 ng/vial as cisplatin and 0.21-1630 ng/vial as carboplatin were detected. Significant differences in the levels of contamination among the batch numbers were observed in 6 of 10 cisplatin products and 6 of 7 carboplatin products. Significant differences in the levels of contamination were observed in 3 cisplatin products with different contents of drug within the vials and 1 carboplatin product with different contents of drug within the vials. Significant differences in the contamination levels among the cisplatin manufacturers but not carboplatin manufacturers were observed. The degree of contamination of the carboplatin products was significantly higher than that of the cisplatin products. In conclusion, external contamination was confirmed in all cisplatin and carboplatin vials tested. The degree of contamination was different among different batch numbers, drug contents, manufacturers, and platinum anticancer drug.

Synthesis and photophysical properties of photostable 1,8-naphthalimide dyes incorporating benzotriazole-based UV absorbers.

We developed a series of blue-emitting 1,8-naphthalimide dyes covalently attached to 2-(2-hydroxyphenyl)-2H-benzotriazoles that retard photodegradation of the fluorophore. The dyes displayed weaker fluorescence emissions than the parent 1.8-naphthalimide. Quantum chemical calculations suggested that the decreased fluorescence was caused by the nonradiative deactivation promoted through the excited state intramolecular proton transfer (ESIPT) in benzotriazole components. The dyes' phosphorescences in a degassed solution at 77 K were more efficient than that of the parent 1.8-naphthalimide, indicating a possible deactivation pathway through intersystem crossing. PMMA films doped with these dyes showed higher resistance against photoaging than the film doped with an equimolar mixture of constituent 1.8-naphthalimide and the benzotriazole derivatives. Thus, the covalently linked benzotriazole units slow fluorophore degradation not only by preferential absorption of harmful UV light, which is found in the film with a simple mixture of two components, but also by the nonradiative deactivation involved in benzotriazole units.

Awake intubation with videolaryngoscopy and fiberoptic bronchoscope.

By combining video laryngoscopy and fiberoptic bronchoscopy, awake intubation can be performed more safely.

Acute pancreatitis caused by duodenal bezoar and treated with endoscopic procedures.

Background: Acute pancreatitis triggered by causative agents, including alcohol consumption, gallstones, dyslipidemia, drugs, and infection, is frequently addressed. However, reports of acute pancreatitis caused by duodenal bezoars are limited. Case Presentation: A 75-year-old man experiencing abdominal pain and frequent vomiting was transferred to our hospital. His medical records presented history of diabetes, hypertension, dyslipidemia, and gastric cancer surgery. Computed tomography of the abdomen indicated duodenal dilatation, enlarged pancreas, and fluid retention, with no bile duct stones present. Minor bleeding and duodenal bezoar were endoscopically detected with esophagogastroduodenoscopy (EGD). He was diagnosed with severe acute pancreatitis caused by a bezoar and admitted to the intensive care unit. The duodenal bezoar was dissected and removed with three repetitions of EGD, and the patient was discharged without any complications. Conclusion: Herein, we report a case showing that endoscopic procedures could be effective treatment options in severe pancreatitis caused by duodenal bezoars.

Methylprednisolone pulse therapy for critically ill patients with coronavirus disease 2019: A single-center retrospective observational study.

Aim: This study compared the clinical outcomes of critically ill patients with coronavirus disease (COVID-19) pneumonia treated with high-dose methylprednisolone and other steroids. Methods: This retrospective observational study included critically ill COVID-19 pneumonia adult patients with tracheal intubation treated between April 1, 2020, and September 15, 2021. Of the 46 patients who met the inclusion criteria, 36 received steroid pulse therapy (Group P) and 10 received steroids without pulse therapy (Group NP). Subgroup analyses in Group P by methylprednisolone dose of 1000 or 500 mg for 3 days during intensive care unit stay were carried out. The primary and secondary outcomes were 28-day mortality and steroid-associated complications, respectively. Results: In the Kaplan-Meier curve analysis, there was no difference in the 28-day survival between P and NP groups (log-rank P = 0.046). Univariate Cox proportional hazard model also showed that Group P had a decreased 28-day mortality (hazard ratio 0.30; [95% confidence interval, 0.20-0.44]; P < 0.01). After adjusting for covariates (age, sex, remdesivir, baricitinib, and favipiravir), using the multivariate Cox proportional hazards model, Group P had improved 28-day mortality (0.50 [0.30-0.85], P = 0.01). Conclusion: Steroid pulse therapy might improve the 28-day and in-hospital mortality in critically ill patients with COVID-19 pneumonia.

De novo creation of a naked eye-detectable fluorescent molecule based on quantum chemical computation and machine learning.

Designing fluorescent molecules requires considering multiple interrelated molecular properties, as opposed to properties that straightforwardly correlated with molecular structure, such as light absorption of molecules. In this study, we have used a de novo molecule generator (DNMG) coupled with quantum chemical computation (QC) to develop fluorescent molecules, which are garnering significant attention in various disciplines. Using massive parallel computation (1024 cores, 5 days), the DNMG has produced 3643 candidate molecules. We have selected an unreported molecule and seven reported molecules and synthesized them. Photoluminescence spectrum measurements demonstrated that the DNMG can successfully design fluorescent molecules with 75% accuracy (n = 6/8) and create an unreported molecule that emits fluorescence detectable by the naked eye.

Chronic Pulmonary Aspergillosis During Convalescence From Severe COVID-19 Treated With Oral Itraconazole: A Report of Two Cases.

Invasive pulmonary aspergillosis (IPA) has been reported to occur secondary to coronavirus disease 2019 (COVID-19), and the condition has been termed COVID-19-associated pulmonary aspergillosis (CAPA). We diagnosed two severe COVID-19 cases with multiple cavitary lung lesions and chronic pulmonary aspergillosis (CPA) on days 58 and 48 of admission, respectively, with gradual improvement in the respiratory status. Both patients were positive for Aspergillus-precipitating antibodies (APAb). We chose oral itraconazole (ITCZ) for both patients because of its convenience in terms of long-term treatment. Cavitary lesions diminished after ITCZ administration. The risk factors for pulmonary aspergillosis in both patients were determined to be steroid pulse therapy, use of baricitinib, diabetes mellitus (DM), ICU admission, long hospital stay, and the use of broad-spectrum antibiotics. Pulmonary aspergillosis must be suspected in patients with severe COVID-19, even if they are asymptomatic, because not only IPA but also CPA can occur following COVID-19. Therefore, oral ITCZ may be a treatment option for CPA following COVID-19.