Perturbations of Telmisartan Alone and in Combination with Ranolazineor Dapagliflozin on the Amplitude and Gating of Voltage-gated Na + Current in Neuroblastoma Neuronal Cells.

A recent study investigated the correlation between telmisartan (TEL) exposure and Alzheimer's disease (AD) risk among African Americans (AAs) and European Americans. Their findings indicated that moderate-to-high TEL exposure was linked to a decreased incidence of AD among AAs. These results suggest a potential association between TEL and a reduced risk of AD specifically within the AA population. Here, we investigated the effects of TEL, either alone or in combination with ranolazine (Ran) or dapagliflozin (Dapa), on voltage-gated Na + currents ( INa ) in Neuro-2a cells. TEL, primarily used for treating hypertension and cardiovascular disorders, showed a stimulatory effect on INa , while Ran and Dapa reversed this stimulation. In Neuro-2a cells, we demonstrated that with exposure to TEL, the transient ( INa(T) ) and late ( INa(L) ) components of INa were differentially stimulated with effective EC 50 's of 16.9 and 3.1 µM, respectively. The research implies that TEL's impact on INa might be associated with enhanced neuronal excitability. This study highlights the complex interplay between TEL, Ran, and Dapa on INa and their potential implications for AD, emphasizing the need for further investigation to understand the mechanisms involved.

A Cross-Stage Partial Network and a Cross-Attention-Based Transformer for an Electrocardiogram-Based Cardiovascular Disease Decision System.

Cardiovascular disease (CVD) is one of the leading causes of death globally. Currently, clinical diagnosis of CVD primarily relies on electrocardiograms (ECG), which are relatively easier to identify compared to other diagnostic methods. However, ensuring the accuracy of ECG readings requires specialized training for healthcare professionals. Therefore, developing a CVD diagnostic system based on ECGs can provide preliminary diagnostic results, effectively reducing the workload of healthcare staff and enhancing the accuracy of CVD diagnosis. In this study, a deep neural network with a cross-stage partial network and a cross-attention-based transformer is used to develop an ECG-based CVD decision system. To accurately represent the characteristics of ECG, the cross-stage partial network is employed to extract embedding features. This network can effectively capture and leverage partial information from different stages, enhancing the feature extraction process. To effectively distill the embedding features, a cross-attention-based transformer model, known for its robust scalability that enables it to process data sequences with different lengths and complexities, is employed to extract meaningful embedding features, resulting in more accurate outcomes. The experimental results showed that the challenge scoring metric of the proposed approach is 0.6112, which outperforms others. Therefore, the proposed ECG-based CVD decision system is useful for clinical diagnosis.

In vitro and in vivo studies on exogenous polyamines and α-difluoromethylornithine to enhance bone formation and suppress osteoclast differentiation.

Exogenous polyamines, including putrescine (PUT), spermidine (SPD), and spermine (SPM), and the irreversible inhibitor of the rate-limiting enzyme ornithine decarboxylase (ODC) of polyamine biosynthesis, α-difluoromethylornithine (DFMO), are implicated as stimulants for bone formation. We demonstrate in this study the osteogenic potential of exogenous polyamines and DFMO in human osteoblasts (hOBs), murine monocyte cell line RAW 264.7, and an ovariectomized rat model. The effect of polyamines and DFMO on hOBs and RAW 264.7 cells was studied by analyzing gene expression, alkaline phosphatase (ALP) activity, tartrate-resistant acid phosphatase (TRAP) activity, and matrix mineralization. Ovariectomized rats were treated with polyamines and DFMO and analyzed by micro computed tomography (micro CT). The mRNA level of the early onset genes of osteogenic differentiation, Runt-related transcription factor 2 (Runx2) and ALP, was significantly elevated in hOBs under osteogenic conditions, while both ALP activity and matrix mineralization were enhanced by exogenous polyamines and DFMO. Under osteoclastogenic conditions, the gene expression of both receptor activator of nuclear factor-κB (RANK) and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) was reduced, and TRAP activity was suppressed by exogenous polyamines and DFMO in RAW 264.7 cells. In an osteoporotic animal model of ovariectomized rats, SPM and DFMO were found to improve bone volume in rat femurs, while trabecular thickness was increased in all treatment groups. Results from this study provide in vitro and in vivo evidence indicating that polyamines and DFMO act as stimulants for bone formation, and their osteogenic effect may be associated with the suppression of osteoclastogenesis.

Minimally Invasive Resection of a Foraminal Lumbar Root Schwannoma.

Background and Importance: This video article reports a rare case of a right L5/S1 foraminal root schwannoma that presents the natural course of the disease, imaging findings, treatment protocol, operative procedure, and highlights some of the possible surgical complications. Clinical Presentation: Magnetic resonance imaging (MRI) revealed an intradural, extramedullary, well-enhanced mass at the right L5/S1 level. The operative procedure involved a right minimal L5/S1 laminotomy/foraminotomy posteriorly to open the right L5 root. The facet joints were preserved to prevent spinal instability. The tumor was located along the root after opening the right L5/S1 foramen. Intraoperative electromyography (IOM) was conducted to detect any nerve injury in the patient. After opening the dura, the tumor was carefully separated from the normal root nerve under IOM monitoring. The mass was removed piece-by-piece using mini-forceps. Conclusion: Histopathological examination confirmed the diagnosis of a schwannoma. The patient recovered without incident after surgery with minimal soreness and numbness in the right leg.

Multi-Task Learning-Based Deep Neural Network for Steady-State Visual Evoked Potential-Based Brain-Computer Interfaces.

Amyotrophic lateral sclerosis (ALS) causes people to have difficulty communicating with others or devices. In this paper, multi-task learning with denoising and classification tasks is used to develop a robust steady-state visual evoked potential-based brain-computer interface (SSVEP-based BCI), which can help people communicate with others. To ease the operation of the input interface, a single channel-based SSVEP-based BCI is selected. To increase the practicality of SSVEP-based BCI, multi-task learning is adopted to develop the neural network-based intelligent system, which can suppress the noise components and obtain a high level of accuracy of classification. Thus, denoising and classification tasks are selected in multi-task learning. The experimental results show that the proposed multi-task learning can effectively integrate the advantages of denoising and discriminative characteristics and outperform other approaches. Therefore, multi-task learning with denoising and classification tasks is very suitable for developing an SSVEP-based BCI for practical applications. In the future, an augmentative and alternative communication interface can be implemented and examined for helping people with ALS communicate with others in their daily lives.

Novel Aptamer-Based Small-Molecule Drug Screening Assay to Identify Potential Sclerostin Inhibitors against Osteoporosis.

A novel aptamer-based competitive drug screening platform for osteoporosis was devised in which fluorescence-labeled, sclerostin-specific aptamers compete with compounds from selected chemical libraries for the binding of immobilized recombinant human sclerostin to achieve high-throughput screening for potential small-molecule sclerostin inhibitors and to facilitate drug repurposing and drug discovery. Of the 96 selected inhibitors and FDA-approved drugs, six were shown to result in a significant decrease in the fluorescence intensity of the aptamer, suggesting a higher affinity toward sclerostin compared with that of the aptamer. The targets of these potential sclerostin inhibitors were correlated to lipid or bone metabolism, and several of the compounds have already been shown to be potential osteogenic activators, indicating that the aptamer-based competitive drug screening assay offered a potentially reliable strategy for the discovery of target-specific new drugs. The six potential sclerostin inhibitors suppressed the level of both intracellular and/or extracellular sclerostin in mouse osteocyte IDG-SW3 and increased alkaline phosphatase activity in IDG-SW3 cells, human bone marrow-derived mesenchymal stem cells and human fetal osteoblasts hFOB1.19. Potential small-molecule drug candidates obtained in this study are expected to provide new therapeutics for osteoporosis as well as insights into the structure-activity relationship of sclerostin inhibitors for rational drug design.

A novel optical technology based on 690 nm and 850 nm wavelengths to assist needle thoracostomy.

The sensitivity of pneumothorax diagnosis via handheld ultrasound is low, and there is no equipment suitable for use with life-threatening tension pneumothorax in a prehospital setting. This study proposes a novel technology involving optical fibers and near-infrared spectroscopy to assist in needle thoracostomy decompression. The proposed system via the optical fibers emitted dual wavelengths of 690 and 850 nm, allowing distinction among different layers of tissue in vivo. The fundamental principle is the modified Beer-Lambert law (MBLL) which is the basis of near-infrared tissue spectroscopy. Changes in optical density corresponding to different wavelengths (690 and 850 nm) and hemoglobin parameters (levels of Hb and HbO2) were examined. The Kruskal-Wallis H test was used to compare the differences in parameter estimates among tissue layers; all p-values were < 0.001 relevant to 690 nm and 850 nm. In comparisons of Hb and HbO2 levels relative to those observed in the vein and artery, all p-values were also < 0.001. This study proposes a new optical probe to assist needle thoracostomy in a swine model. Different types of tissue can be identified by changes in optical density and hemoglobin parameters. The aid of the proposed system may yield fewer complications and a higher success rate in needle thoracostomy procedures.

Dual-wavelength fiber-optic technique to assist needle cricothyroidotomy.

The traditional needle cricothyroidotomy procedure is performed blindly without any medical equipment. Complications including posterior tracheal wall perforation, accidental vessel puncture, and missed tracheal puncture are reported. Therefore, we proposed a dual-wavelength fiber-optic technique based on the technique of near-infrared spectroscopy to assist operators performing needle cricothyroidotomy in a swine model. We embedded optical fibers in a 16-gauge intravenous needle catheter. Real-time data were displayed on an oscilloscope, and we used the program to analyze the data immediately. The change of optical density corresponding to 690-nm and 850-nm wavelengths and hemoglobin parameters (HbO2 and Hb concentrations) was analyzed immediately using the program in the laptop. Unique and significant optical differences were presented in this experiment. We could easily identify every different tissue by the change of optical density corresponding to 690-nm and 850-nm wavelengths and hemoglobin parameters (HbO2 and Hb concentrations). Statistical method (Kruskal-Wallis H test) was used to compare differences in tissues at each time-point, respectively. The p values in every tissue in optical density change corresponding to 690 nm and 850 nm were all < 0.001. Furthermore, the p values in every tissue in Hb and HbO2 were also all < 0.001. The results were statistically significant. This is the first and novel study to introduce a dual-wavelength embedded fibers into a standard cricothyroidotomy needle. This proposed system might be helpful to provide us real-time information of the advanced needle tip to decrease possible complications.

A Novel Smart Assistance System for Blood Vessel Approaching: A Technical Report Based on Oximetry.

In clinical practice, the catheter has to be placed at an accurate position during anesthesia administration. However, effectively guiding the catheter to the accurate position in deeper tissues can be difficult for an inexperienced practitioner. We aimed to address the current issues associated with catheter placement using a novel smart assistance system for blood vessel catheter placement. We used a hollow introducer needle embedded with dual wavelength (690 and 850 nm) optical fibers to advance the tip into the subclavian vessels in anesthetized piglets. The results showed average optical density changes, and the difference between the absorption spectra and hemoglobin concentrations of different tissue components effectively identified different tissues (p < 0.05). The radial basis function neural network (RBFNN) technique was applied to distinguish tissue components (the F-measure value and accuracy were 93.02% and 94%, respectively). Finally, animal experiments were designed to validate the performance of the proposed system. Using this system based on oximetry, we easily navigated the needle tip to the target vessel. Based on the experimental results, the proposed system could effectively distinguish different tissue layers of the animals.

High Effectiveness in Actions of Carfilzomib on Delayed-Rectifier K+ Current and on Spontaneous Action Potentials.

Carfilzomib (CFZ, Kyprolis®) is widely recognized as an irreversible inhibitor of proteasome activity; however, its actions on ion currents in electrically excitable cells are largely unresolved. The possible actions of CFZ on ionic currents and membrane potential in pituitary GH3, A7r5 vascular smooth muscle, and heart-derived H9c2 cells were extensively investigated in this study. The presence of CFZ suppressed the amplitude of delayed-rectifier K+ current (I K(DR)) in a time-, state-, and concentration-dependent manner in pituitary GH3 cells. Based on minimal reaction scheme, the value of dissociation constant for CFZ-induced open-channel block of I K(DR) in these cells was 0.33 µM, which is similar to the IC50 value (0.32 µM) used for its efficacy on inhibition of I K(DR) amplitude. Recovery from I K(DR) block by CFZ (0.3 µM and 1 µM) could be well fitted by single exponential with 447 and 645 ms, respectively. The M-type K+ current, another type of K+ current elicited by low-threshold potential, was slightly suppressed by CFZ (1 µM). Under current-clamp condition, addition of CFZ depolarized GH3 cells, broadened the duration of action potentials as well as raised the firing frequency. In A7r5 vascular smooth muscle cells or H9c2 cardiac cells, the CFZ-induced inhibition of I K(DR) remained efficacious. Therefore, our study led us to reflect that CFZ or other structurally similar compounds should somehow act on the activity of membrane KV channels through which they influence the functional activities in different types of electrically excitable cells such as endocrine, neuroendocrine cells, smooth muscle cells, or heart cells, if similar in vivo findings occur.

Anesthesia for a patient with unexpected giant tracheobronchomegaly.

Tracheobronchomegaly (also called Mounier-Kuhn syndrome) is a rare disease characterized by flaccid and markedly dilated trachea and main bronchi on inspiration with narrowing or collapse on expiration or cough. It is associated with recurrent lower respiratory tract infection. A 75-year-old man with unexpected giant tracheomegaly had a significant peritubal air leak which impeded an operation. Lumbar epidural anesthesia was performed for a subsequent operation without any sequela. Careful evaluation with chest radiography is basic to exclude a large airway. Chest computed tomography and fiber-optic bronchoscopy provided the diagnosis of a large airway. If a large airway is suspected, these examinations help to evaluate and manage the airway.

An innovative nonpharmacological intervention combined with intravenous patient-controlled analgesia increased patient global improvement in pain and satisfaction after major surgery.

PURPOSE: This study aimed to evaluate whether a nonpharmacological approach through implementation of a communication improvement program (named CICARE for Connect, Introduce, Communicate, Ask, Respond and Exit) into standard operating procedure (SOP) in acute pain service (APS) improved satisfaction in patients receiving intravenous patient-controlled analgesia (IV-PCA). PATIENTS AND METHODS: This was a nonrandomized before-after study. Adult patients (aged between 20 and 80 years) who received IV-PCA after major surgery were included. Implementing CICARE into SOP was conducted in APS. Anonymous questionnaires were used to measure outcomes in this prospective two-part survey. The first part completed by APS nurses contained patients' characteristics, morphine dosage, delivery/demand ratios, IV-PCA side effects and pain at rest measured with an 11-point numeric rating scale (NRS, 0-10). A score of NRS ≥4 was defined as inadequately treated pain. The ten-question second part was completed by patients voluntarily after IV-PCA was discontinued. Each question was assessed with a 5-point Likert scale (1: extremely poor; 5: excellent). Patients were separated into "before" and "after" CICARE groups. Primary outcomes were patient global impression of improvement in pain (PGI-Improvement) and patient satisfaction. Secondary outcomes included quality of communication skills, instrument proficiency and accessibility/availability of IV-PCA. RESULTS: The response rate was 55.3%, with 187 usable questionnaires. CICARE effectively improved patient global impression of improvement in pain, patient satisfaction, communication skills and accessibility/availability of IV-PCA. No significant differences were noted in instrument proficiency, morphine dosage, delivery/demand ratios, rates of inadequately treated pain at rest and side effects of IV-PCA between groups. Paradoxical findings were noted between the rates of inadequately treated pain/side effects and PGI-Improvement in pain/patient satisfaction, which were affected by psychological factors. CONCLUSION: Nonpharmacological interventions carried out by implementing CICARE into SOP for APS effectively improved patient satisfaction and postoperative pain management quality, but this did not affect actual pain.

Evaluating the influence of perceived organizational learning capability on user acceptance of information technology among operating room nurse staff.

OBJECTIVES: Medical institutions are eager to introduce new information technology to improve patient safety and clinical efficiency. However, the acceptance of new information technology by medical personnel plays a key role in its adoption and application. This study aims to investigate whether perceived organizational learning capability (OLC) is associated with user acceptance of information technology among operating room nurse staff. MATERIALS AND METHODS: Nurse anesthetists and operating room nurses were recruited in this questionnaire survey. A pilot study was performed to ensure the reliability and validity of the translated questionnaire, which consisted of 14 items from the four dimensions of OLC, and 16 items from the four constructs of user acceptance of information technology, including performance expectancy, effort expectancy, social influence, and behavioral intention. Confirmatory factor analysis was applied in the main survey to evaluate the construct validity of the questionnaire. Structural equation modeling was used to test the hypothetical relationships between the four dimensions of user acceptance of information technology and the second-ordered OLC. Goodness of fit of the hypothetic model was also assessed. RESULTS: Performance expectancy, effort expectancy, and social influence positively influenced behavioral intention of users of the clinical information system (all p < 0.001) and accounted for 75% of its variation. The second-ordered OLC was positively associated with performance expectancy, effort expectancy, and social influence (all p < 0.001). However, the hypothetic relationship between perceived OLC and behavioral intention was not significant (p = 0.87). The fit statistical analysis indicated reasonable model fit to data (root mean square error of approximation = 0.07 and comparative fit index = 0.91). CONCLUSION: Perceived OLC indirectly affects user behavioral intention through the mediation of performance expectancy, effort expectancy, and social influence in the operating room setting.

Successful removal of a potentially lethal left atrial thrombus detected by transesophageal echocardiography following the removal of a left ventricular assist device inflow cannula.

The left ventricular assist device (LVAD) is a battery-operated, mechanical pump-type device that helps in maintaining the pumping ability of a failing heart. Thromboembolism poses a significant risk during and after LVAD implantation. It occurs in up to 35% of patients with adverse sequelae. We present the case of a 75-year-old man who underwent coronary artery bypass graft surgery and LVAD implantation for acute myocardial ischemia and severe left ventricular dysfunction. However, subsequent transthoracic echocardiographic examination revealed an LVAD thrombus, and LVAD removal was suggested following the failure of thrombolytic therapy. After the LVAD cannula was removed, transesophageal echocardiography (TEE) revealed a residual thrombus in the left atrium. Thrombectomy was successfully performed by opening the left atrium with cardiopulmonary bypass. We believe that TEE monitoring aided the implantation and removal of the LVAD device. In this case, we found that TEE not only helped in monitoring the ventricular function but also in detecting other problems such as the residual thrombus. We strongly recommend TEE monitoring during the entire LVAD-removal procedure, particularly for patients who need to undergo LVAD removal because of thrombosis formation.

Successful management of contrast medium extravasation injury through stellate ganglion block and intra-arterial nitroglycerin.

We describe the successful management of extravasation injury to the left hand by contrast medium with stellate ganglion block and intra-arterial nitroglycerin in a patient which befell during contrast-enhanced imaging. The incidence of contrast-medium extravasation injury is increasing because of the convenience and availability of contrast-enhanced imaging and ease of injection access. Extravasation of contrast medium may results in severe pain, erythema, cyanosis, and edema or even skin necrosis, which is largely related to the ionization, osmolarity, and volume of the contrast medium. The conservative treatment is often adequate in small amount extravasation, but if the extravasation is overwhelming further energetic management is mandatory. A 29-year-old man was brought to our emergency because of diffuse abdominal pain and he was arranged to receive intravenous contrast media enhanced abdominal computed tomography for diagnosis. Ruptured appendicitis with abscess formation was suspected; then the patient underwent emergent appendectomy and drainage of the abscess. However, severe swelling and cyanotic change that radiated from the intravenous catheter insertion site in every direction over the entire dorsum of the left hand were noted after the surgery. Contrast-medium extravasation injury was highly contemplated and a left stellate ganglion block was performed immediately for relief of symptoms. The consulting surgeon ruled out compartment syndrome, but advised emergent left upper limb arteriography, which revealed signs of vasospasm with high intravascular pressure of the left distal ulnar and radial arteries; thus nitroglycerin was injected into left distal ulnar and radial arteries for relief of vasospasm. The clinical symptoms were improved after the above managements and the patient was discharged 7 days later without any sequela.