Deep learning-based correction for time truncation in cerebral computed tomography perfusion.

Cerebral computed tomography perfusion (CTP) imaging requires complete acquisition of contrast bolus inflow and washout in the brain parenchyma; however, time truncation undoubtedly occurs in clinical practice. To overcome this issue, we proposed a three-dimensional (two-dimensional + time) convolutional neural network (CNN)-based approach to predict missing CTP image frames at the end of the series from earlier acquired image frames. Moreover, we evaluated three strategies for predicting multiple time points. Seventy-two CTP scans with 89 frames and eight slices from a publicly available dataset were used to train and test the CNN models capable of predicting the last 10 image frames. The prediction strategies were single-shot prediction, recursive multi-step prediction, and direct-recursive hybrid prediction.Single-shot prediction predicted all frames simultaneously, while recursive multi-step prediction used prior predictions as input for subsequent steps, and direct-recursive hybrid prediction employed separate models for each step with prior predictions as input for the next step. The accuracies of the predicted image frames were evaluated in terms of image quality, bolus shape, and clinical perfusion parameters. We found that the image quality metrics were superior when multiple CTP images were predicted simultaneously rather than recursively. The bolus shape also showed the highest correlation (r = 0.990, p < 0.001) and the lowest variance (95% confidence interval, -453.26-445.53) in the single-shot prediction. For all perfusion parameters, the single-shot prediction had the smallest absolute differences from ground truth. Our proposed approach can potentially minimize time truncation errors and support the accurate quantification of ischemic stroke.

Separation and purification of short-, medium-, and long-stranded RNAs by RP-HPLC using different mobile phases and C18 columns with various pore sizes.

Nucleic acids, which have been employed in medicines for various diseases, are attracting attention as a new pharmaceutical model. Depending on the target substances, nucleic acid medicines with various nucleic acid chain lengths (several tens of nucleotides [nt] to several thousands of nt) exist. The purification of synthesized nucleic acids is crucial as various impurities remain in the crude product after synthesis. Presently, reversed-phase high-performance liquid chromatography (RP-HPLC) represents an effective purification method for nucleic acids. However, the information regarding the HPLC conditions for separating and purifying nucleic acids of various chain lengths is insufficient. Thus, this technical note describes the separation and purification of short-, medium-, and long-stranded nucleic acids (several tens of nt to thousands of nt) by RP-HPLC with various mobile phases and octadecyl-based columns with various pore sizes, such as normal (9-12 nm), wide (30 nm), and super wide (>30 nm) pores.

Cerebral regional oxygen saturation as a predictive parameter for preoperative heart failure and delayed hemodynamic recovery in transcutaneous aortic valve implantation: a retrospective cohort study.

This study aimed to investigate the relationship of perioperative cerebral regional oxygen saturation (rSO2) with various preoperative clinical variables and hemodynamic changes during transfemoral transcatheter aortic valve implantation (TAVI) under general anesthesia. We retrospectively analyzed cerebral rSO2 values from left-hemisphere measurements obtained using near-infrared spectroscopy (O3™ regional oximetry) at five time points: pre-induction, the start of the procedure, the start of valve deployment, time of lowest cerebral rSO2 value during valve deployment, and the end of the procedure. This study included 91 patients (60 with balloon-expandable valves and 31 with self-expandable valves). The baseline cerebral rSO2 values were correlated with B-type natriuretic peptide, hemoglobin, fractional shortening, ejection fraction, left ventricular mass index, left ventricular end-systolic diameter, STS risk of mortality, and STS morbidity or mortality. The patients who took longer to recover their systolic blood pressure to 90 mmHg after valve deployment with a balloon-expandable valve (group B) had lower cerebral rSO2 values during deployment compared to patients with faster recovery with balloon-expandable valve (group A) and with self-expandable valve (group C). Baseline cerebral rSO2 is associated with preoperative variables related to cardiac failure and function, and a significant decline during valve deployment may indicate a risk of prolonged hypotension during TAVI.

Improving the depiction of small intracranial vessels in head computed tomography angiography: a comparative analysis of deep learning reconstruction and hybrid iterative reconstruction.

This study aimed to evaluate the ability of deep learning reconstruction (DLR) compared to that of hybrid iterative reconstruction (IR) to depict small vessels on computed tomography (CT). DLR and two types of hybrid IRs were used for image reconstruction. The target vessels were the basilar artery (BA), superior cerebellar artery (SCA), anterior inferior cerebellar artery (AICA), and posterior inferior cerebellar artery (PICA). The peak value, ΔCT values defined as the difference between the peak value and background, and full width at half maximum (FWHM), were obtained from the profile curves. In all target vessels, the peak and ΔCT values of DLR were significantly higher than those of the two types of hybrid IR (p < 0.001). Compared to that associated with hybrid IR, the FWHM of DLR was significantly lower in the SCA (p < 0.001), AICA (p < 0.001), and PICA (p < 0.001). In conclusion, DLR has the potential to improve visualization of small vessels.

Simultaneous separation and identification of all structural isomers and enantiomers of aminobutyric acid using a highly sensitive chiral resolution labeling reagent.

Aminobutyric acid has structural isomers (α-, ß-, and γ-aminobutyric acids) and enantiomers (D/L-forms) with various unique functions. Therefore, a quantitative method for determining the content of each aminobutyric acid must be developed. In general, quantitative simultaneous analysis of multiple compounds is conducted via high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS). However, simultaneous separation and highly sensitive detection of all aminobutyric acids are complicated, so highly sensitive analytical methods for the separation and identification of each compound have not yet been established. We previously developed highly sensitive chiral resolution labeling reagents. Herein, we propose a highly sensitive analytical method for the simultaneous separation and identification of all aminobutyric acids via LC-MS and labeling with our original highly sensitive chiral resolution labeling reagent, 1-fluoro-2,4-dinitrophenyl-5-L-valine-N,N-dimethylethylenediamine amide (L-FDVDA). The labeling reagent was completely bound to all aminobutyric acids through incubation overnight (>15 h) at 50 °C. Additionally, the labeled aminobutyric acids could be stored for at least 1 week at 4 °C. Furthermore, we demonstrated simultaneous separation and identification of aminobutyric acids in biological samples and foods through LC-MS using a C18 column after labeling with L-FDVDA. Our method is expected to be adopted for the analysis of the contents of all aminobutyric acids in biological and clinical samples as well as various foods.

Separation and Identification of Isoleucine Enantiomers and Diastereomers Using an Original Chiral Resolution Labeling Reagent.

D-Amino acids, which are present in small amounts in living organisms, are responsible for a variety of physiological functions. Some bioactive/biomolecular peptides also contain D-amino acids in their sequences; such peptides express different functions than peptides composed only of L-form amino acids. Among the 20 amino acids that make up proteins, threonine (Thr) and isoleucine (Ile) have two chiral carbons and thus have two enantiomers and diastereomers. These stereoisomers have been previously analyzed through HPLC using chiral columns or chiral resolution labeling reagents. However, the separation and identification of these stereoisomers are highly laborious and complicated. Herein, we propose an analytical method for the separation and identification of Ile stereoisomers through LC-MS using our original chiral resolution labeling reagent, 1-fluoro-2,4-dinitrophenyl-5-L-valine-N,N-dimethylethylenediamine-amide (L-FDVDA) and a PBr column packed with pentabromobenzyl-modified silica gel. Twenty DL-amino acids including Thr stereoisomers (41 amino acids including glycine) were separated and identified using C18 column. Ile stereoisomers could be separated using not a C18 column but a PBr column. Additionally, we showed that peptides containing Thr and Ile stereoisomers can be accurately detected through labeling with L-FDVDA.

Effect of linearly polarized microwaves on nanomorphology of calcium carbonate mineralization using peptides.

Microwaves are used for diverse applications such as mobile phones, ovens, and therapy devices. However, there are few reports on the effects of microwaves on diseases other than cancer, and on physiological processes. Here, we focused on CaCO3 mineralization as a model of biomineralization and attempted to elucidate the effect of microwaves on CaCO3 mineralization using peptides. We conducted AFM, ζ potential, HPLC, ICP-AES, and relative permittivity measurements. Our findings show that microwaves alter the nanomorphology of the CaCO3 precipitate, from sphere-like particles to string-like structures. Furthermore, microwaves have little effect on the mineralization when the mineralization ability of a peptide is high, but a large effect when the precipitation ability is low. Our findings may be applicable to not only the treatment of teeth and bones but also the development of organic-inorganic nanobiomaterials. This methodology can be expanded to other molecular/atomic reactions under various microwave conditions to alter reaction activity parameters.

Separation of highly hydrophilic nicotinamide metabolites using a COSMOSIL PBr column.

Highly hydrophilic compounds such as nicotinamide metabolites are very difficult to separate via high-performance liquid chromatography (HPLC) using octadecyl (C18) columns. In general, for the separation of hydrophilic compounds, hydrophilic interaction liquid chromatography (HILIC) columns are used instead of reversed phase chromatography using C18 columns. However, HILIC columns generally obey complex separation mechanisms because ionic interactions are involved in the retention process, which hinders the optimization of the separation conditions. Additionally, the resulting peak shapes are disturbed when large amounts of aqueous samples are injected. This study demonstrates that COSMOSIL PBr columns, in which both hydrophobic and dispersive interactions occur, show high retention for various hydrophilic compounds under similar separation conditions as those used with C18 columns. Specifically, using a COSMOSIL PBr column, 11 nicotinamide metabolites could be separated under simpler conditions than those used previously with C18 columns, affording better peak shape for each compound. The applicability of the method was evaluated using a tomato sample, from which the nicotinamide metabolites were successfully separated. The results show that the COSMOSIL PBr column is a good alternative to the C18 column for a good separation of all the peaks, including impurity peaks.

Separation of amyloid ß fragment peptides with racemised and isomerised aspartic acid residues using an original chiral resolution labeling reagent.

We developed a system to separate and identify racemised and isomerised aspartic acid (Asp) residues in amyloid ß (Aß) by labeling with an original chiral resolution labeling reagent, 1-fluoro-2,4-dinitrophenyl-5-D-leucine-N,N-dimethylethylenediamine-amide (D-FDLDA). The racemised and isomerised Asp residues labeled with D-FDLDA in Aß fragments generated by digesting with trypsin and endoproteinase Glu-C were separated and identified by liquid chromatography-mass spectrometry (LC-MS) under simple gradient conditions. Furthermore, the labeled Aß fragments did not aggregate and remained stable at least for 1 week at 4 °C.

Separation of long-stranded RNAs by RP-HPLC using an octadecyl-based column with super-wide pores.

Messenger ribonucleic acids (mRNAs) have been used in vaccines for various diseases and are attracting attention as a new pharmaceutical paradigm. The purification of mRNAs is necessary because various impurities, such as template DNAs and transcription enzymes, remain in the crude product after mRNA synthesis. Among the various purification methods, reversed-phase high-performance liquid chromatography (RP-HPLC) is currently attracting attention. Herein, we optimized the pore size of the packing materials, the mobile phase composition, and the temperature of the process; we also evaluated changes in the separation patterns of RNA strands of various lengths via RP-HPLC. Additionally, single-stranded (50-1000 nucleotides in length) and double-stranded (80-500 base pairs in length) RNAs were separated while their non-denatured states were maintained by performing the analysis at 60 °C using triethylammonium acetate as the mobile phase and octadecyl-based RNA-RP1 with super-wide pores (> 30 nm) as the column. Furthermore, impurities in a long-stranded RNA of several thousand nucleotides synthesized by in vitro transcription were successfully separated using an RNA-RP1 column. The columns used in this study are expected to separate various RNA strands and the impurities contained in them.

Separation of nicotinamide metabolites using a PBr column packed with pentabromobenzyl group modified silica gel.

Nicotinamide adenine dinucleotide, a coenzyme involved in the activation of sirtuins, contributes to various regulations in vivo. However, highly hydrophilic nicotinamide metabolites are difficult to separate by high-performance liquid chromatography (HPLC) using octadecyl (C18) columns, which operate via hydrophobic interaction. PBr columns packed with silica gel modified with the pentabromobenzyl group having strong dispersion forces show good retention ability for various highly hydrophilic compounds. Additionally, the peak shape obtained with the PBr column did not collapse like that of the HILIC column, even when a large amount of water was injected. Separation of 11 highly hydrophilic nicotinamide metabolites using a PBr column under simple conditions resulted in baseline separation, but separation on a C18 column was not complete. The peak shape for each compound was better than that in previous studies. Furthermore, the separation of nicotinamide metabolites in tomato using a PBr column enable a more sensitive detection than that using a C18 column. SUBJECT CATEGORY: Chromatographic Technique.

Separation and identification of the DL-forms of short-chain peptides using a new chiral resolution labeling reagent.

There are several reports of D-amino acids being the causative molecules of serious diseases, resulting in the formation of, for example, prion protein and amyloid ß. D-Amino acids in peptides and proteins are typically identified by sequencing each residue by Edman degradation or by hydrolysis with hydrochloric acid for amino acid analysis. However, these approaches can result in racemization of the L-form to the D-form by hydrolysis and long pre-treatment for hydrolysis. To address these problems, we aimed to identify the DL-forms of amino acids in peptides without hydrolysis. Here, we showed that the DL-forms in peptides which are difficult to separate on a chiral column can be precisely separated by labeling with 1-fluoro-2,4-dinitrophenyl-5-D-leucine-N,N-dimethylethylenediamine-amide (D-FDLDA). Additionally, the peptides could be quantitatively analyzed using the same labeling method as for amino acids. Furthermore, the detection sensitivity of a sample labeled with D-FDLDA was higher than that of the conventional reagents Nα-(5-fluoro-2,4-dinitrophenyl)-L-alaninamide (L-FDAA) and Nα-(5-fluoro-2,4-dinitrophenyl)-L-leucinamide (L-FDLA) used in Marfey's method. The proposed method for identifying DL-forms of amino acids in peptides is a powerful tool for use in organic chemistry, biochemistry, and medical science.

The Efficacy and Safety of Dexmedetomidine for Procedural Sedation in Patients Receiving Local Anesthesia Outside the Intensive Care Unit: A Prospective, Double-Blind, Randomized Clinical Phase III Trial in Japan.

BACKGROUND: Few studies (in other countries than the US) have reported on the efficacy and safety of dexmedetomidine for sedation of patients undergoing surgical or medical procedures under local anesthesia without intubation outside the intensive care unit. We performed a randomized, double-blind study in Japan. METHODS: Adult patients were randomly allocated to receive placebo, dexmedetomidine 0.5 µg/kg (DEX 0.5 group), or dexmedetomidine 1.0 µg/kg (DEX 1.0 group) over 10 min. Then, both dexmedetomidine groups received dexmedetomidine 0.2-0.7 µg/kg/h for maintaining an Observer's Assessment of Alertness/Sedation Scale (OAA/S) score of ≤ 4; however, propofol was administered to rescue patients whose score exceeded this value. The primary endpoint was the percentage of patients who did not require rescue propofol to achieve and maintain an OAA/S score of ≤ 4. RESULTS: In total, 162 patients were included in the placebo (n = 53), DEX 0.5 (n = 53), and DEX 1.0 (n = 56) groups. Propofol was not required in significantly more patients in the dexmedetomidine 0.5 and 1.0 µg/kg groups (52.8% and 57.1%, respectively) compared with the placebo group (1.9%) (P < 0.001 for both). Common adverse events were protocol-defined hypotension, respiratory depression and bradycardia. The incidence of bradycardia was significantly higher in the DEX 0.5 (26.4%) and DEX 1.0 (30.4%) groups than in the placebo group (9.4%) (P = 0.041 and P = 0.008, respectively). CONCLUSION: We concluded that a loading dose of 0.5 or 1.0 µg/kg dexmedetomidine followed by infusion at a rate of 0.2-0.7 µg/kg/h provided effective and well-tolerated sedation in patients undergoing surgical or medical procedures under local anesthesia without intubation.Clinical trials.gov identifier: NCT01438931.

Comparisons of the efficiency of respiratory rate monitoring devices and acoustic respiratory sound during endoscopic submucosal dissection.

During moderate sedation for gastrointestinal endoscopic submucosal dissection (ESD), monitoring of ventilatory function is recommended. We compared the following techniques of respiratory rate (RR) measurement with respiratory sound (RRa): capnography (RRc), thoracic impedance (RRi), and plethysmograph (RRp). This study enrolled patients aged ≥ 20 years who underwent esophageal (n = 19) and colorectal (n = 5) ESDs. RRc, RRi, RRp, and RRa were measured by Capnostream™ 20P, BSM-2300, Nellcor™ PM1000N, and Radical-7®, respectively. In total, 413 RR data were collected from the esophageal ESD group and 114 RR data were collected from the colorectal ESD group. Compared with RRa during colorectal ESD, that during esophageal ESD had larger bias [95% limit of agreement (LOA)] with RRc [1.9 (- 11.0-14.8) vs. - 0.4 (- 2.9-2.2)], RRi [9.4 (- 16.8-9.4) vs. - 1.5 (- 12.0-8.9)], and RRp [0.3 (- 5.7-6.4) vs. 0.2 (- 3.2-3.6)]. Of the correct RR values displayed during esophageal ESD, > 90% were measured as RRa and RRp. Moreover, RRc was a useful parameter during colorectal ESD. To maximize patient safety during ESD under sedation, endoscopists and medical staff should know the feature and principle of the devices used for RR measurement. During esophageal ESD, RRa and RRp may be a good parameter to detect bradypnea or apnea. RRc, RRa and RRp are useful for reliable during colorectal ESD.Trial registration UMIN-CTR (UMIN000025421).

Right ventricular perforation, pneumothorax, and a pneumatocele by a pacemaker lead: a case report.

BACKGROUND: Perforation of the right ventricle by a pacemaker lead is a rare and potentially life-threatening complication. We present a patient who developed right ventricular perforation, pneumothorax, and a cyst and underwent partial lung resection. CASE PRESENTATION: A 94-year-old woman was diagnosed with sick sinus syndrome and underwent a dual-chamber permanent pacemaker implantation. The next day, pacing failed and chest radiography showed that the right ventricular lead was outside the cardiac silhouette. Computed tomography revealed that the lead had perforated the right ventricular apex, causing a left-sided pneumothorax and a cystic lesion at the site of pulmonary injury by the pacemaker lead. The patient underwent lung resection and a right ventricular lead extraction. Pathological analysis revealed the cystic lesion to be an acute pneumatocele. CONCLUSIONS: Pneumothorax and pneumatocele associated with right ventricular pacemaker lead perforation is extremely rare. In our case, a radical surgical intervention provided an excellent outcome.

Intraoperative panic attack in patients undergoing awake craniotomy: a retrospective analysis of risk factors.

PURPOSE: Intraoperative anxiety is the most common psychological response of the patient during awake craniotomy. Psychological stress can trigger patient decline, resulting in failed awake craniotomy and significantly poor outcomes. This study aimed to identify the risk factors for panic attack (PA) during awake craniotomies. METHODS: With the local ethics committee approval, we conducted a manual chart review of the medical record of patients who underwent consecutive awake craniotomies between November 1999 and October 2016 at Tokyo Women's Medical University. A total of 405 patients were identified and assigned to 2 groups based on the Diagnostic and Statistical Manual of Mental Disorders-V criteria: those that met the PA criteria (Group PA) and those that did not (Group non-PA). Patient characteristics and the incidence of the PA specifier were collected. The features of the two groups were statistically compared, and risk factors for PA occurrence were determined by regression analysis. RESULTS: Sixteen of 405 patients met the diagnostic criteria of PA. Patients' characteristics were not statistically different between the groups. Multivariate logistic regression showed that intraoperative anxiety (p = 0.0002) and age younger than 39 years (as opposed to age > = 39 years; p = 0.0328) were significantly associated with the occurrence of PA during awake craniotomy. CONCLUSIONS: For patients undergoing awake craniotomy, intraoperative anxiety and age younger than 39 years were considered risk factors of PA. As PA often necessitates conversion to general anesthesia, intensive perioperative psychological support and pain management are required to achieve patient satisfaction and the surgical goal of awake craniotomy.

Forehead Regional Oxygen Saturation (rSO2)-Related Ear-Level Arterial Pressure and Lower Thigh rSO2 in the Steep Trendelenburg Position with CO2 Pneumoperitoneum and the Beach Chair Position.

Introduction Regional oxygen saturation (rSO2) reflects tissue perfusion. This observational study aimed to examine the change in the forehead and lower thigh rSO2 associated with intraoperative posture, anesthesia regimen, or mean arterial pressure (mAP) at heart and external auditory meatus (ear) levels. Methods Patients undergoing robot-assisted laparoscopic radical prostatectomy in the Trendelenburg position at 30° with pneumoperitoneum (TPP) or arthroscopic shoulder surgery in the beach chair position at 70° (BCP) under desflurane-remifentanil (D/R) or propofol-remifentanil (P/R) anesthesia were examined. Bilateral forehead and lower thigh rSO2 values and mean radial artery pressure were measured simultaneously at heart and ear levels. Results In TPP, there were no differences under anesthesia regimens in the forehead or lower thigh rSO2change, although one patient with an absolute lower thigh rSO2 of ≤50% in the lithotomy position complained of transient limb pain. No correlation was observed between rSO2 and mAP. In BCP, forehead rSO2 decreased and lower thigh rSO2 increased under either of the anesthesia regimens. The coefficient of correlation between forehead rSO2 andheart-level and ear-level mAP was 0.341 and 0.236, respectively. Conclusions There were no differences under anesthesia regimens in the changes of forehead rSO2 and lower thigh rSO2. In TPP, significant changes in forehead rSO2 and lower thigh rSO2 were not observed. Monitoring lower thigh rSO2 might be useful for preventing lower extremity pain. In BCP, forehead rSO2 decreased and lower thigh rSO2 increased from the supine position to the BCP. To prevent brain damage, anesthesiologists should pay attention to heart- and ear-level mAP.

Unrecognized Postoperative Opioid-Induced Movement Disorder: A Case Report.

A 22-year-old man, with a medical history significant for posttraumatic stress disorder and chronic pain, underwent ankle surgery at the United States Naval Hospital, Yokosuka, Japan. His immediate postoperative course was complicated by episodic muscle rigidity, necessitating admission for diagnostic evaluation. The differential was necessarily broad and included local anesthetic toxicity, medication mediated effect, seizures, serotonin syndrome, and malignant hyperthermia. Cultural and systemic differences in patient care delivery at a Japanese hospital helped to elucidate the mechanism. This case highlights cultural differences in pain management and navigates the differential of an acute onset movement disorder in the immediate postoperative period.

Intracellular mineralization of gold nanoparticles using gold ion-binding peptides with cell-penetrating ability.

We developed a system to directly produce gold nanoparticles in cells by intracellular mineralization in lower concentration than conventional methods using a peptide consisting of a cell-penetrating sequence and a gold ion-binding sequence. Furthermore, we could control the uniquely shaped gold nanostructures that were produced by changing peptide structures.