Assessment of Preoperative Anxiety and Influencing Factors in Patients Undergoing Elective Surgery: An Observational Cross-Sectional Study.

Background and Objectives: Preoperative anxiety is a common emotional response before elective surgery that influences postoperative outcomes and can increase analgesic requirements. However, clinicians frequently overlook these concerns. This study aimed to quantify preoperative anxiety and evaluate its association with patient-related factors. Materials and Methods: Anxiety levels were evaluated in adult patients awaiting elective surgery using the Korean-translated version of the Amsterdam Preoperative Anxiety and Information Scale (APAIS) and the State-Trait Anxiety Inventory-Korean YZ form (STAI-KYZ). The patients were also surveyed regarding the subjective causes of preoperative anxiety. Results: The study found that a total of 55 adult patients had a well-balanced subject distribution. Both questionnaires showed high internal consistency (Cronbach's alpha values of 0.85 and 0.93). Significant correlations were observed in situational anxiety scores from the questionnaires, indicating differences between groups with high trait anxiety and those with normal anxiety levels (p < 0.05). Notably, female sex was the only patient-related factor that significantly affected the anxiety scores (p < 0.05). Furthermore, when considering additional patient factors stratified by sex, it became evident that younger females and females with prior general anesthesia experience displayed higher anxiety levels than their male counterparts. The most commonly reported subjective concern related to anesthesia was the fear of not regaining consciousness, followed by concerns about postoperative pain, intraoperative emergence, and other issues. Conclusions: This study confirms that being female is a significant risk factor for preoperative anxiety. Therefore, it is necessary to provide enhanced preoperative anxiolytic therapies, including preoperative patient education and other interventions, to individuals undergoing surgical procedures.

Enhancing Reliability and Safety in Industrial Applications: Assessing the Applicability of Energy b-Value to Composites.

This study investigates the fracture behavior of glass fiber-reinforced plastic (GFRP) under various loading conditions using acoustic emission (AE) testing. Using fracture tests and time series analysis of AE signals, parameters such as b-value, improved b-value (Ib-value), and energy b-value (be-value) were examined to understand crack initiation, growth, and structural failure. The stress-strain curve revealed distinct responses during tensile and step loading, and time series analysis highlighted variations in amplitude, AE energy, and Kaiser and Felicity effects. Under tensile loading, the Ib-value exhibited a linear decrease, while step loading introduced complexities, including the Felicity effect. The be-value, incorporating energy considerations, fluctuated, providing insights into micro-cracks and macro-cracks. Statistical analysis demonstrated a consistent decrease in the be-value, emphasizing its potential for long-term monitoring. This study provides a comprehensive technique for assessing composite material fracture behavior, enhancing understanding for critical applications in hydrogen storage vessels and pressure pipes as well as advancing reliability and safety in industrial sectors.

Enhancing Structural Health Monitoring with Acoustic Emission Sensors: A Case Study on Composites under Cyclic Loading.

This study conducts an in-depth analysis of the failure behavior of woven GFRP under cyclic loading, leveraging AE sensors for monitoring damage progression. Utilizing destructive testing and AE methods, we observed the GFRP's response to varied stress conditions. Key findings include identifying distinct failure modes of GFRP and the effectiveness of AE sensors in detecting broadband frequency signals indicative of crack initiation and growth. Notably, the Felicity effect was observed in AE signal patterns, marking a significant characteristic of composite materials. This study introduces the Ibe-value, based on statistical parameters, to effectively track crack development from inception to growth. The Ibe-values potential for assessing structural integrity in composite materials is highlighted, with a particular focus on its variation with propagation distance and frequency-dependent attenuation. Our research reveals challenges in measuring different damage modes across frequency ranges and distances. The effectiveness of Ibe-values, combined with the challenges of propagation distance, underscores the need for further investigation. Future research aims to refine assessment metrics and improve crack evaluation methods in composite materials, contributing to the field's advancement.

Smooth Emergence from General Anesthesia after Deep Extubation in a Pediatric Patient Diagnosed with Catecholaminergic Polymorphic Ventricular Tachycardia: A Case Report.

Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare genetic disorder where catecholamine causes bidirectional ventricular tachycardia, potentially leading to cardiac arrest. In patients undergoing surgery, sympathetic responses can be triggered in situations associated with surgical stimulations as well as high anxiety before the surgery, anesthetic maneuvers such as endotracheal intubation and extubation, and postoperative pain. Therefore, planning for surgery demands meticulous attention to anesthesia during the perioperative period in order to prevent potentially life-threatening arrhythmias. Case: We discuss a case of an 11-year-old male pediatric patient with known CPVT who required elective strabismus surgery for exotropia involving both eyes. After thorough planning of general anesthesia to minimize catecholamine response, sufficient anesthesia and analgesia were achieved to blunt the stressful response during intubation and maintained throughout the surgical procedure. Complete emergence was achieved after deep extubation, and the patient did not complain of pain or postoperative nausea and vomiting. Conclusions: Anesthesiologists should not only be able to plan and manage the catecholamine response during surgery but also anticipate and be prepared for situations that may lead to arrhythmias before and after the procedure. In certain cases, deep extubation can be beneficial as it reduces hemodynamic changes during the extubation process.

Guidewire insertion into the vertebral vein during right internal jugular vein central venous catheterization -A rare case report.

BACKGROUND: Internal jugular veins are the most frequently accessed site for central venous catheterization in patient management, whereas complications involving vertebral veins are a rare occurrence. CASE: A 73-year-old male suspected to have a urothelial carcinoma was scheduled for elective left nephroureterectomy. During central venous catheterization using the anatomic landmark technique to target the internal jugular vein, a guidewire is inadvertently inserted into the suspected vertebral vein. Following the correction of the catheterization, a radiologist reviewed the preoperative enhanced computed tomography and confirmed that the initially punctured vessel was the vertebral vein. On the third day after surgery, the central venous catheter was removed, and the patient did not exhibit any complications, such as bleeding, swelling, and neurological symptoms. CONCLUSIONS: The use of ultrasonography during central venous catheterization is recommended to evaluate the anatomy of the puncture site and prevent misinsertion of the catheter, which can lead to several complications.

Unexpected Tension Pneumothorax Developed during Anesthetic Induction Aggravated by Positive Pressure Ventilation: A Case Report.

Background and Objectives: Tension pneumothorax is a life-threatening emergency condition that requires immediate diagnosis and intervention. However, due to the non-specific symptoms and the rarity of its occurrence during surgery, anesthesiologists encounter difficulties in promptly diagnosing tension pneumothorax when it arises intraoperatively. Diagnosing tension pneumothorax can become even more challenging in unexpected situations in patients with normal preoperative evaluation for general anesthesia. Materials and Methods, Results: We report the case of a 66-year-old woman who underwent general anesthesia for oblique lateral interbody fusion surgery of her lumbar spine. Though she did not have any respiratory symptoms prior to the induction of anesthesia, auscultation following endotracheal intubation indicated decreased breathing sound in the left hemithorax of the chest. Subsequently, her vital signs showed tachycardia, hypotension, and hypoxemia, and the ventilator indicated a gradual increase in the airway pressure. We verified the proper depth of the endotracheal tube to exclude one-lung ventilation, and, in the meantime, learned that there had been unsuccessful attempts at left subclavian venous catheterization by the surgical department on the previous day. Tension pneumothorax was diagnosed through portable chest radiography in the operating room, and needle thoracostomy and chest tube insertion were performed immediately, which in turn stabilized her vital signs and airway pressure. The surgery was uneventful, and the chest tube was removed one week later after evaluation by the cardiothoracic department. The patient was discharged from hospital on postoperative day 14 without known complications. Conclusions: Anesthesiologists should be aware of the conditions and risk factors that may cause tension pneumothorax and remain vigilant for signs of its development throughout surgery, even for patients who show normal preoperative assessments. An undetected small pneumothorax without any symptoms can progress to tension pneumothorax through positive pressure ventilation during general anesthesia, posing a life-threatening situation. If a tension pneumothorax is highly suspected through clinical assessments, its prompt differentiation and timely diagnosis are crucial, allowing for rapid intervention to stabilize vital signs.

Predictive factors for conversion from conservatively to surgically treatment osteoporotic thoracolumbar compression fractures based on sagittal parameters and magnetic resonance imaging features.

PURPOSE: To investigate the relationship between sagittal plane characteristics of the spinal column and conservative treatment failure in acute osteoporotic spinal fractures (OSFs). METHODS: As a retrospective study of single-institute data, thoracolumbar OSF patients with similar propensities in terms of location of fractures and results of bone mineral density were analyzed. Among them, 43 patients (group I) who needed reconstructive surgical interventions and 39 patients (group II) who obtained successful treatment through conservative care were included. General demographic data, radiographic features of fractures, and magnetic resonance imaging (MRI) features of fractures were analyzed. To investigate the relationship between global sagittal alignment of the spine and occurrence of delayed complication following OSFs, radiological sagittal parameters were analyzed. RESULTS: The number of cases requiring reconstructive surgery was significantly higher when the index vertebra showed diffuse or mid-portion bone marrow changes in MRI. In terms of sagittal parameters, pelvic incidence (group I 59.1° ± 11.9°, group II 54.6° ± 9.8°) and thoracolumbar angle (group I 26.5° ± 14.1°, group II 17.4° ± 11.2°) were significantly higher in group I. Logistic regression analysis showed that higher pelvic incidence (OR 1.09, 95% CI 1.01-1.18, p value < 0.05) and higher thoracolumbar angle (OR 1.09, 95% CI 1.02-1.17, p value < 0.05) were significant risk factors for delayed complications requiring reconstructive surgery following OSFs. CONCLUSION: Delayed complications requiring reconstructive surgery following OSFs are related to sagittal plane parameters of the spine such as high pelvic incidences, in addition to previously known radiographic characteristics of fractures.

Asymptomatic Type 2 Perioperative Myocardial Infarction Detected before Anesthetic Induction in a Patient Undergoing Non-Cardiac Surgery-A Case Report.

Background: Perioperative myocardial infarction (PMI) is a life-threatening complication in major non-cardiac surgeries (NCS) and constitutes the most common cause of postoperative morbidity and mortality. A PMI that is associated with prolonged oxygen supply-demand imbalance and its etiology is defined as a type 2 MI. Asymptomatic myocardial ischemia can occur in patients with stable coronary artery disease (CAD), especially those with comorbidities such as diabetes mellitus (DM), hypertension, or, in some cases, without any risk factors. Case: We report a case of asymptomatic PMI in a 76-year-old patient with underlying hypertension and DM without a previous history of CAD. During the induction of anesthesia, abnormal electrocardiography was discovered, and the surgery was postponed after further studies revealed almost completely occluded three-vessel CAD and type 2 PMI. Conclusions: Anesthesiologists should closely monitor and evaluate the associated cardiovascular risk, including cardiac biomarkers of each patient before surgery, to minimize the possibility of PMI.

Management of unanticipated difficult airway in a patient with well-visualized vocal cords using video laryngoscopy - A case report.

BACKGROUND: Difficult airway occurs due to anatomical abnormalities of the airway that can be predicted through airway assessments; however, abnormalities beyond the vocal cord can be clinically asymptomatic and undetected until intubation failure to advance the endotracheal tube. CASE: We present a case of an unanticipated difficult airway in a stuporous 80-year-old female with a recent history of intracerebral hemorrhage and prolonged intubation. She required emergency ventriculo-peritoneal shunt surgery due to the progression of her hydrocephalus. Under anesthesia, facemask ventilation was easy and video laryngoscopy provided a full view of the glottis; however, endotracheal tube (ETT) entry failed. We suspected stenosis beyond the vocal cord, and a smaller diameter ETT was inserted and maintained for airway management during emergency surgery. Postoperative neck computed tomography findings revealed laryngotracheal stenosis (LTS). CONCLUSIONS: Anesthesiologists should be aware that LTS may be asymptomatic and consider difficult airway guidelines in patients with history of prolonged endotracheal intubation.

Detection of Prosthetic Loosening in Hip and Knee Arthroplasty Using Machine Learning: A Systematic Review and Meta-Analysis.

Background: prosthetic loosening after hip and knee arthroplasty is one of the most common causes of joint arthroplasty failure and revision surgery. Diagnosis of prosthetic loosening is a difficult problem and, in many cases, loosening is not clearly diagnosed until accurately confirmed during surgery. The purpose of this study is to conduct a systematic review and meta-analysis to demonstrate the analysis and performance of machine learning in diagnosing prosthetic loosening after total hip arthroplasty (THA) and total knee arthroplasty (TKA). Materials and Methods: three comprehensive databases, including MEDLINE, EMBASE, and the Cochrane Library, were searched for studies that evaluated the detection accuracy of loosening around arthroplasty implants using machine learning. Data extraction, risk of bias assessment, and meta-analysis were performed. Results: five studies were included in the meta-analysis. All studies were retrospective studies. In total, data from 2013 patients with 3236 images were assessed; these data involved 2442 cases (75.5%) with THAs and 794 cases (24.5%) with TKAs. The most common and best-performing machine learning algorithm was DenseNet. In one study, a novel stacking approach using a random forest showed similar performance to DenseNet. The pooled sensitivity across studies was 0.92 (95% CI 0.84-0.97), the pooled specificity was 0.95 (95% CI 0.93-0.96), and the pooled diagnostic odds ratio was 194.09 (95% CI 61.60-611.57). The I2 statistics for sensitivity and specificity were 96% and 62%, respectively, showing that there was significant heterogeneity. The summary receiver operating characteristics curve indicated the sensitivity and specificity, as did the prediction regions, with an AUC of 0.9853. Conclusions: the performance of machine learning using plain radiography showed promising results with good accuracy, sensitivity, and specificity in the detection of loosening around THAs and TKAs. Machine learning can be incorporated into prosthetic loosening screening programs.

Effect of neoadjuvant chemotherapy on effect-site concentration of propofol for sedation in patients with breast cancer.

BACKGROUND: Some studies have demonstrated that chemotherapy drugs enhance sensitivity to anesthetics owing to its systemic toxicity, while others have demonstrated that chemotherapy drugs have no effect. This study aimed to determine whether neoadjuvant chemotherapy influences the effect-site concentration (Ce) of propofol for sedation in patients withbreast cancer. METHODS: This study included patients aged 19-75 years who were scheduled to undergobreast cancer surgery under general anesthesia. Patients who received neoadjuvant chemotherapy were assigned to group C, whereas those who never received chemotherapy wereassigned to group N. Propofol was administered through an effect-site target-controlled infusion, and the Modified Observer's Assessment of Alertness/Sedation scale (MOAA/S) scoreand Bispectral Index (BIS) were recorded. When the plasma concentration and Ce wereequal to the target Ce, and if the MOAA/S score did not change, the target Ce was increasedby 0.2 µg/ml; otherwise, the Ce was maintained for 2 min and then increased. This processwas repeated until the MOAA/S score became 0. RESULTS: No significant differences were observed in Ce values at each sedation level between both groups. Ce values for loss of consciousness (LOC) of groups C and N were 2.76± 0.29 and 2.67 ± 0.27 µg/ml (P = 0.285), respectively. However, the BIS value at LOC ofgroup C (63.87 ± 7.04) was lower than that (68.44 ± 6.01) of group N (P = 0.018). CONCLUSIONS: Neoadjuvant chemotherapy for breast cancer has no effect on the Ce ofpropofol for sedation.

Benzyl Isothiocyanate Attenuates Inflammasome Activation in Pseudomonas aeruginosa LPS-Stimulated THP-1 Cells and Exerts Regulation through the MAPKs/NF-κB Pathway.

Inflammasomes are a group of intracellular multiprotein platforms that play important roles in immune systems. Benzyl isothiocyanate (BITC) is a constituent of cruciferous plants and has been confirmed to exhibit various biological activities. The modulatory effects of BITC on inflammasome-mediated interleukin (IL)-1ß expression and its regulatory mechanisms in Pseudomonas aeruginosa (P. aeruginosa) LPS/ATP-stimulated THP-1 cells was investigated. Monocytic THP-1 cells were treated with phorbol myristate acetate (PMA) to induce differentiation into macrophages. Enzyme-linked immunosorbent assays (ELISA) were performed to measure the levels of IL-1ß produced in P. aeruginosa LPS/ATP-exposed THP-1 cells. Western blotting was performed to examine the BITC modulatory mechanisms in inflammasome-mediated signaling pathways. BITC inhibited IL-1ß production in P. aeruginosa LPS/ATP-induced THP-1 cells. BITC also inhibited activation of leucine-rich repeat protein-3 (NLRP3) and caspase-1 in P. aeruginosa LPS/ATP-induced THP-1 cells. Furthermore, we show that mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) activation in P. aeruginosa LPS was attenuated by BITC. These BITC-mediated modulatory effects on IL-1ß production may have therapeutic potential for inflammasome-mediated disorders such as a nasal polyp.

Effect of chemotherapy on effect-site concentration of propofol for loss of consciousness in patients with colorectal cancer.

BACKGROUND: The depth of anesthesia is an essential factor in surgical prognosis. The neurotoxic effect of chemotherapeutic drugs affects the sensitivity to anesthetics. This study was conducted to determine whether the effect-site concentration (Ce) of propofol for loss of consciousness (LOC) differs in patients undergoing preoperative chemotherapy. METHODS: A total of 60 patients scheduled for surgery for colorectal cancer under general anesthesia were included in this study. Patients who had received chemotherapy comprised the experimental (C) group, and those without a previous history of chemotherapy comprised the control (N) group. Propofol was administered as an effect-site target-controlled infusion, and the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scores were evaluated. When the plasma concentration and Ce were similar, and if the MOAA/S score did not change, the target Ce was increased by 0.2 µg/ml; otherwise, the Ce was maintained for 2 min and then increased. RESULTS: The Ce values of propofol for loss of verbal contact (LVC) in groups C and N were 2.40 ± 0.39 and 2.29 ± 0.39 µg/ml (P = 0.286), respectively, and those for LOC in groups C and N were 2.69 ± 0.43 and 2.50 ± 0.36 µg/ml (P = 0.069), respectively. No significant difference was observed in Ce values between the two groups. CONCLUSIONS: Chemotherapy had no effect on the Ce of propofol for LVC and LOC in patients with colorectal cancer. We do not recommend reducing the dose of propofol for the induction of LOC in patients with colorectal cancer undergoing chemotherapy.

Verification of the performance of the Bispectral Index as a hypnotic depth indicator during dexmedetomidine sedation.

BACKGROUND: Differences in the effects of propofol and dexmedetomidine sedation on electroencephalogram patterns have been reported previously. However, the reliability of the Bispectral Index (BIS) value for assessing the sedation caused by dexmedetomidine remains debatable. The purpose of this study is to evaluate the correlation between the BIS value and the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale in patients sedated with dexmedetomidine. METHODS: Forty-two patients (age range, 20-80 years) who were scheduled for elective surgery under spinal anesthesia were enrolled in this study. Spinal anesthesia was performed using 0.5% bupivacaine, which was followed by dexmedetomidine infusion (loading dose, 0.5-1 µg/kg for 10 min; maintenance dose, 0.3-0.6 µg/kg/h). The MOAA/S score was used to evaluate the level of sedation, and the Vital Recorder program was used to collect data (vital signs and BIS values). RESULTS: A total of 215082 MOAA/S scores and BIS data pairs were analyzed. The baseline variability of the BIS value was 7.024%, and the decrease in the BIS value was associated with a decrease in the MOAA/S score. The correlation coefficient and prediction probability between the two measurements were 0.566 (P < 0.0001) and 0.636, respectively. The mean ± standard deviation values of the BIS were 87.22 ± 7.06, 75.85 ± 9.81, and 68.29 ± 12.65 when the MOAA/S scores were 5, 3, and 1, respectively. Furthermore, the cut-off BIS values in the receiver operating characteristic analysis at MOAA/S scores of 5, 3, and 1 were 82, 79, and 73, respectively. CONCLUSION: The BIS values were significantly correlated with the MOAA/S scores. Thus, the BIS along with the clinical sedation scale might prove useful in assessing the hypnotic depth of a patient during sedation with dexmedetomidine.

Effect of dexamethasone gargle, intravenous dexamethasone, and their combination on postoperative sore throat: a randomized controlled trial.

BACKGROUND: Postoperative sore throat (POST) is a complication that decreases patient satisfaction and increases postoperative complaints. The present study was conducted to investigate effects of gargling with dexamethasone, intravenous dexamethasone injection and the combination of the two on the incidence and severity of POST. METHODS: Study participants were 96 patients who had undergone laparoscopic cholecystectomy, randomly allocated into three groups. Group G gargled with 0.05% dexamethasone solution and were infused intravenous 0.9% normal saline before general anesthesia; group I gargled with 0.9% normal saline and were infused intravenous 0.1 mg/kg dexamethasone; group GI gargled with 0.05% dexamethasone solution and were infused intravenous 0.1 mg/kg dexamethasone. The incidence and severity of POST, hoarseness and cough were evaluated and recorded at 1, 6, and 24 h after the surgery. RESULTS: There were no significant differences in the total incidence of POST up to 24 postoperative hours among Group G, Group I and Group GI (P = 0.367, Group G incidence = 34.38%, [95% confidence interval, 95% CI = 17.92-50.83], Group I incidence = 18.75%, [95% CI = 5.23-32.27], Group GI incidence = 28.13%, [95% CI = 12.55-43.70]). The other outcomes were comparable among the groups. CONCLUSIONS: In patients who had undergone laparoscopic cholecystectomy, gargling with 0.05% dexamethasone solution demonstrated the same POST prevention effect as intravenous injection of 0.1 mg/kg dexamethasone. The incidence and severity of POST were not significantly different between the combination of gargling with 0.05% dexamethasone solution and intravenous injection of 0.1 mg/kg dexamethasone and use of each of the preventive methods alone.

Osseointegration of magnesium-incorporated sand-blasted acid-etched implant in the dog mandible: Resonance frequency measurements and histomorphometric analysis.

The aim of this pilot study was to investigate the bone responses of novel magnesium (Mg)-incorporated sand-blasted and acid-etched (SLA) titanium (Ti) implant in an experimental animal model. Novel Mg-incorporated SLA Ti implant was obtained via vacuum arc source ion implantation method and Mg-ions were implanted into the SLA implant surface. Control group consisted of two commercial implants; resorbable blasting media (RBM) and SLA. Twelve implants from each group were placed into the mandibles of 6 mongrel dogs. Experimental animals were divided into 2 groups of 3 animals, with 4 weeks and 8 weeks healing time points. Resonance frequency analysis was performed at the time of fixture installation, 1, 2, 4, and 8 weeks after installation. Bone to implant contact (BIC) measurements were assessed at the 4 and 8 weeks healing time points. The overall implant survival rate was 97.2%. The Mg-incorporated SLA Ti implants showed more rapid osseointegration than control group implants at follow-up periods of 4 weeks. Histomorphometric analysis showed a tendency for BIC% values of Mg-incorporated SLA Ti implant to be higher than that of other the implant groups. The results of this study suggest that Mg-incorporated SLA Ti implant may be effective in enhancing the bone responses by rapid osseointegration in early healing periods.

Etiology of distinct membrane excitability in pre- and posthearing auditory neurons relies on activity of Cl- channel TMEM16A.

The developmental rehearsal for the debut of hearing is marked by massive changes in the membrane properties of hair cells (HCs) and spiral ganglion neurons (SGNs). Whereas the underlying mechanisms for the developing HC transition to mature stage are understood in detail, the maturation of SGNs from hyperexcitable prehearing to quiescent posthearing neurons with broad dynamic range is unknown. Here, we demonstrated using pharmacological approaches, caged-Ca(2+) photolysis, and gramicidin patch recordings that the prehearing SGN uses Ca(2+)-activated Cl(-) conductance to depolarize the resting membrane potential and to prime the neurons in a hyperexcitable state. Immunostaining of the cochlea preparation revealed the identity and expression of the Ca(2+)-activated Cl(-) channel transmembrane member 16A (TMEM16A) in SGNs. Moreover, null deletion of TMEM16A reduced the Ca(2+)-activated Cl(-) currents and action potential firing in SGNs. To determine whether Cl(-) ions and TMEM16A are involved in the transition between pre- and posthearing features of SGNs we measured the intracellular Cl(-) concentration [Cl(-)]i in SGNs. Surprisingly, [Cl(-)]i in SGNs from prehearing mice was ∼90 mM, which was significantly higher than posthearing neurons, ∼20 mM, demonstrating discernible altered roles of Cl(-) channels in the developing neuron. The switch in [Cl(-)]i stems from delayed expression of the development of intracellular Cl(-) regulating mechanisms. Because the Cl(-) channel is the only active ion-selective conductance with a reversal potential that lies within the dynamic range of SGN action potentials, developmental alteration of [Cl(-)]i, and hence the equilibrium potential for Cl(-) (ECl), transforms pre- to posthearing phenotype.

Epicardial delivery of VEGF and cardiac stem cells guided by 3-dimensional PLLA mat enhancing cardiac regeneration and angiogenesis in acute myocardial infarction.

Congestive heart failure is mostly resulted in a consequence of the limited myocardial regeneration capacity after acute myocardial infarction. Targeted delivery of proangiogenic factors and/or stem cells to the ischemic myocardium is a promising strategy for enhancing their local and sustained therapeutic effects. Herein, we designed an epicardial delivery system of vascular endothelial growth factor (VEGF) and cardiac stem cells (CSCs) using poly(l-lactic acid) (PLLA) mat applied to the acutely infarcted myocardium. The fibrous VEGF-loaded PLLA mat was fabricated by an electrospinning method using PLLA solution emulsified VEGF. This mat not only allowed for sustained release of VEGF for 4weeks but boosted migration and proliferation of both endothelial cells and CSCs in vitro. Furthermore, sustained release of VEGF showed a positive effect on in vitro capillary-like network formation of endothelial cells compared with bolus treatment of VEGF. PLLA mat provided a permissive 3-dimensional (3D) substratum that led to spontaneous cardiomyogenic differentiation of CSCs in vitro. Notably, sustained stimulation by VEGF-loaded PLLA mat resulted in a substantial increase in the expression of proangiogenic mRNAs of CSCs in vitro. The epicardially implanted VEGF-loaded PLLA mat showed modest effects on angiogenesis and cardiomyogenesis in the acutely infarcted hearts. However, co-implantation of VEGF and CSCs using the PLLA mat showed meaningful therapeutic effects on angiogenesis and cardiomyogenesis compared with controls, leading to reduced cardiac remodeling and enhanced global cardiac function. Collectively, the PLLA mat allowed a smart cargo that enabled the sustained release of VEGF and the delivery of CSCs, thereby synergistically inducing angiogenesis and cardiomyogenesis in acute myocardial infarction.

Genetic, cellular, and functional evidence for Ca2+ inflow through Cav1.2 and Cav1.3 channels in murine spiral ganglion neurons.

Spiral ganglion neurons (SGNs) of the eighth nerve serve as the bridge between hair cells and the cochlear nucleus. Hair cells use Cav1.3 as the primary channel for Ca(2+) inflow to mediate transmitter release. In contrast, SGNs are equipped with multiple Ca(2+) channels to mediate Ca(2+)-dependent functions. We examined directly the role of Cav1.3 channels in SGNs using Cav1.3-deficient mice (Cav1.3(-/-)). We revealed a surprising finding that SGNs functionally express the cardiac-specific Cav1.2, as well as neuronal Cav1.3 channels. We show that evoked action potentials recorded from SGNs show a significant decrease in the frequency of firing in Cav1.3(-/-) mice compared with wild-type (Cav1.3(+/+)) littermates. Although Cav1.3 is the designated L-type channel in neurons, whole-cell currents recorded in isolated SGNs from Cav1.3(-/-) mice showed a surprising remnant current with sensitivity toward the dihydropyridine (DHP) agonist and antagonist, and a depolarization shift in the voltage-dependent activation compared with that in the Cav1.3(+/+) mice. Indeed, direct measurement of the elementary properties of Ca(2+) channels, in Cav1.3(+/+) neurons, confirmed the existence of two DHP-sensitive single-channel currents, with distinct open probabilities and conductances. We demonstrate that the DHP-sensitive current in Cav1.3(-/-) mice is derived from Cav1.2 channel activity, providing for the first time, to our knowledge, functional data for the expression of Cav1.2 currents in neurons. Finally, using shRNA gene knockdown methodology, and histological analyses of SGNs from Cav1.2(+/-) and Cav1.3(+/-) mice, we were able to establish the differential roles of Cav1.2 and Cav1.3 in SGNs.