Real-Time Acoustic Simulation Framework for tFUS: A Feasibility Study Using Navigation System.

Transcranial focused ultrasound (tFUS), in which acoustic energy is focused on a small region in the brain through the skull, is a non-invasive therapeutic method with high spatial resolution and depth penetration. Image-guided navigation has been widely utilized to visualize the location of acoustic focus in the cranial cavity. However, this system is often inaccurate because of the significant aberrations caused by the skull. Therefore, acoustic simulations using a numerical solver have been widely adopted to compensate for this inaccuracy. Although the simulation can predict the intracranial acoustic pressure field, real-time application during tFUS treatment is almost impossible due to the high computational cost. In this study, we propose a neural network-based real-time acoustic simulation framework and test its feasibility by implementing a simulation-guided navigation (SGN) system. Real-time acoustic simulation is performed using a 3D conditional generative adversarial network (3D-cGAN) model featuring residual blocks and multiple loss functions. This network was trained by the conventional numerical acoustic simulation program (i.e., k-Wave). The SGN system is then implemented by integrating real-time acoustic simulation with a conventional image-guided navigation system. The proposed system can provide simulation results with a frame rate of 5 Hz (i.e., about 0.2 s), including all processing times. In numerical validation (3D-cGAN vs. k-Wave), the average peak intracranial pressure error was 6.8 ± 5.5%, and the average acoustic focus position error was 5.3 ± 7.7 mm. In experimental validation using a skull phantom (3D-cGAN vs. actual measurement), the average peak intracranial pressure error was 4.5%, and the average acoustic focus position error was 6.6 mm. These results demonstrate that the SGN system can predict the intracranial acoustic field according to transducer placement in real-time.

Aggressive hydration for preventing post-endoscopic retrograde cholangiopancreatography pancreatitis: trial sequential analysis.

BACKGROUND: Randomized controlled trials (RCTs) have demonstrated that aggressive hydration with lactated Ringer's (LR) solution reduces the frequency and severity of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). In this trial sequential analysis (TSA), we aimed to evaluate the prophylactic effect of aggressive hydration on PEP in specific patient subgroups and to determine the need for additional RCTs. METHODS: We conducted a systematic and comprehensive search to identify all randomized controlled studies published through August 2021 that examined the effectiveness of aggressive hydration for preventing PEP. The primary outcome was the frequency of PEP. We also performed TSA to calculate the required information size and assess whether our results were conclusive. RESULTS: The analysis included 12 studies involving 2,501 patients. According to the TSA, the overall frequency of PEP was significantly lower in the aggressive hydration group (5.6%; 74 of 1,327 patients) than in the control group (13.1%; 154 of 1,174 patients) (risk ratio [RR]: 0.458; 95% confidence interval [CI]: 0.350-0.599). In the subgroup analysis of patients with average risk, the cumulative Z curve crossed both the conventional test boundary and the trial sequential monitoring boundary. However, in the high-risk group and in patients with moderate-to-severe PEP, the Z curve did not cross the trial sequential monitoring boundary. CONCLUSIONS: This TSA indicates that aggressive hydration is effective in the overall prevention of PEP. However, additional RCTs are required to examine the prophylactic effect of aggressive hydration with LR on PEP in high-risk populations.

Effect of prophylactic endoscopic clipping for prevention of delayed bleeding after endoscopic papillectomy for ampullary neoplasm: a multicenter randomized trial.

BACKGROUND : Endoscopic clip placement is technically challenging using a duodenoscope, limiting their application for treatment of bleeding after endoscopic papillectomy. This study evaluated the efficacy of newly designed clips to prevent bleeding after endoscopic papillectomy. METHODS : Patients (n = 80) with suspected benign adenomas on the major papilla who were scheduled for endoscopic papillectomy with or without clipping were randomized. A new duodenoscope-compatible clip capable of being rotated, reopened, and repeatedly repositioned was used. The primary end point was incidence of delayed bleeding. RESULTS : The clipping procedure was successful in all patients. The incidence of delayed bleeding was nonsignificantly higher in the no-clipping group than in the clipping group (31.6 % [95 % confidence interval (CI) 19.1-47.5] vs. 15.0 % [95 %CI 7.1-29.1]). The incidence of post-endoscopic retrograde cholangiopancreatography pancreatitis did not differ significantly between the groups (clipping vs. no-clipping: 17.5 % [95 %CI 8.7-31.9] vs. 5.3 % [95 %CI 1.5-17.3]), and all cases were mild. CONCLUSIONS : Placement of the newly designed rotatable clip was technically feasible and tended to have a protective effect by preventing delayed bleeding after endoscopic papillectomy, although statistical significance was not reached.

Prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis with a combination of pharmacological agents based on rectal non-steroidal anti-inflammatory drugs: A systematic review and network meta-analysis.

BACKGROUND AND AIMS: Rectally administered non-steroidal anti-inflammatory drugs (NSAIDs) are effective but suboptimal in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis or PEP. New trials with the combination of rectal NSAIDs and other pharmacological agents have been conducted. This network meta-analysis (NMA) aimed to determine the relative efficacy of combination regimens and identify an optimal regimen for preventing PEP. METHODS: We performed a systematic and comprehensive search to identify and analyze all the randomized controlled studies published until October 15, 2019, examining rectal NSAIDs and their combination with other pharmacological agents for the prevention of PEP. The primary outcome was the frequency of PEP. We conducted an NMA to combine the direct and indirect comparisons of rectal NSAIDs and their combination with other pharmacological agents. RESULTS: The NMA included 24 studies evaluating 14 regimens in 11 321 patients. According to predictive interval plot and surface under the cumulative ranking curve values, indomethacin + lactated Ringer's solution, followed by diclofenac + nitrate and indomethacin + normal saline, is the most efficacious combination of pharmacological agents for the overall prevention of PEP. Rectal indomethacin alone is the most efficacious agent for prevention of moderate to severe PEP, and rectal diclofenac is the most useful agent for prevention of PEP among the high-risk group. CONCLUSIONS: Rectal indomethacin with intravenous hydration and rectal diclofenac with sublingual nitrate are the most efficacious combination regimens for the overall prevention of PEP.

Forward-viewing endoscope for ERCP in patients with Billroth II gastrectomy: a systematic review and meta-analysis.

BACKGROUND: The forward-viewing endoscope has been increasingly used to perform endoscopic retrograde cholangiopancreatography (ERCP) in patients who underwent Billroth II gastrectomy. This study intended to assess efficacy and safety of the forward-viewing endoscope for ERCP in Billroth II gastrectomy patients compared with conventional side-viewing endoscope using a systematic review and meta-analysis. METHODS: A systematic review was conducted for studies that evaluated the outcomes of ERCP for patients with Billroth II gastrectomy. Random-effect model meta-analyses with subgroup analyses were conducted. The methodological quality of the included publications was evaluated using the risk of bias assessment tool for non-randomized studies. The publication bias was assessed. RESULTS: In total, 25 studies (1 randomized, 18 retrospective, 1 prospective, and 5 case series studies) with 2446 patients (499 forward-viewing and 1947 side-viewing endoscopes) were analyzed. The pooled afferent loop intubation rate was higher with the forward-viewing endoscope (90.3%, 95% confidence interval (CI) 85.6-93.6 vs. 86.8%, 95% CI 82.8-89.9%). The pooled selective cannulation rate was higher with the side-viewing endoscope (92.3%, 95% CI 88.0-95.2 vs. 91.1%, 95% CI 87.2-93.9%). The pooled bowel perforation rate was higher with the side-viewing endoscope (3.6%, 95% CI 2.3-5.7 vs. 3.0%, 95% CI 1.7-5.3%). The pooled pancreatitis rate was higher with the forward-viewing endoscope (5.4%, 95% CI 3.6-8.0 vs. 2.5%, 95% CI 2.3-5.7%). The pooled bleeding rate was higher with the forward-viewing endoscope (3.0%, 95% CI 1.6-5.5 vs. 2.0%, 95% CI 1.4-3.0%). The heterogeneity among the studies was not significant. The publication bias was minimal. CONCLUSION: This meta-analysis indicates that the forward-viewing endoscope is as safe and effective as conventional side-viewing endoscope for ERCP in patients with Billroth II gastrectomy.

Prognostic Significance of Hemodynamic and Clinical Stages in the Prediction of Hepatocellular Carcinoma.

BACKGROUND & GOALS: Early identification of hepatocellular carcinoma (HCC) is associated with improved survival for patients with chronic liver disease (CLD). We evaluated the prognostic significance of hemodynamic stage (HS) and clinical stage (CS) in predicting HCC in CLD patients. METHODS: Between January 2006 and May 2014, 801 patients with CLD who underwent hepatic venous pressure gradient (HVPG) measurement were prospectively enrolled. HS was classified by HVPG (mm Hg) as follows: HS-1 (HVPG≤6), HS-2 (612 mm Hg (P=0.033, OR=2.17), CS>2 (P=0.039, OR=2.36), and alpha-fetoprotein (AFP; P=0.017, OR=1.01) were significant predictors of HCC development in all patients. For patients with cirrhosis, ascites aggravation (OR=2.51), HVPG >12 mm Hg (OR=2.46), and CS >2 (OR=2.62) were correlated with HCC development. Areas under receiver operating characteristic curves of the prediction-model, CS, HVPG score, and AFP were 0.797, 0.707, 0.701, and 0.653, respectively. CONCLUSIONS: HCC development correlates with advancing liver fibrosis or disease as measured by HS and CS. In addition, ascites aggravation and elevated AFP appears to be associated with increased incidence of HCC.

Prokinetics for the treatment of functional dyspepsia: Bayesian network meta-analysis.

BACKGROUND: Controversies persist regarding the effect of prokinetics for the treatment of functional dyspepsia (FD). This study aimed to assess the comparative efficacy of prokinetic agents for the treatment of FD. METHODS: Randomized controlled trials (RCTs) of prokinetics for the treatment of FD were identified from core databases. Symptom response rates were extracted and analyzed using odds ratios (ORs). A Bayesian network meta-analysis was performed using the Markov chain Monte Carlo method in WinBUGS and NetMetaXL. RESULTS: In total, 25 RCTs, which included 4473 patients with FD who were treated with 6 different prokinetics or placebo, were identified and analyzed. Metoclopramide showed the best surface under the cumulative ranking curve (SUCRA) probability (92.5%), followed by trimebutine (74.5%) and mosapride (63.3%). However, the therapeutic efficacy of metoclopramide was not significantly different from that of trimebutine (OR:1.32, 95% credible interval: 0.27-6.06), mosapride (OR: 1.99, 95% credible interval: 0.87-4.72), or domperidone (OR: 2.04, 95% credible interval: 0.92-4.60). Metoclopramide showed better efficacy than itopride (OR: 2.79, 95% credible interval: 1.29-6.21) and acotiamide (OR: 3.07, 95% credible interval: 1.43-6.75). Domperidone (SUCRA probability 62.9%) showed better efficacy than itopride (OR: 1.37, 95% credible interval: 1.07-1.77) and acotiamide (OR: 1.51, 95% credible interval: 1.04-2.18). CONCLUSIONS: Metoclopramide, trimebutine, mosapride, and domperidone showed better efficacy for the treatment of FD than itopride or acotiamide. Considering the adverse events related to metoclopramide or domperidone, the short-term use of these agents or the alternative use of trimebutine or mosapride could be recommended for the symptomatic relief of FD.

Spontaneous hemobilia after liver transplantation: Frequency, risk factors, and outcome of endoscopic management.

BACKGROUND AND AIM: Spontaneous hemobilia is an uncommon liver transplantation (LT)-related biliary complication. The frequency, etiology, and mechanism of spontaneous hemobilia after LT are not known. This study aimed to assess the outcome of endoscopic management for spontaneous hemobilia after LT, and to investigate its frequency and risk factors. METHODS: The records of patients who underwent endoscopic retrograde cholangiopancreatography to manage hemobilia after LT at the Asan Medical Center, Korea, between January 2006 and April 2014 were retrospectively reviewed. RESULTS: A total 2701 cases of LT was performed in the study period, and 33 LT patients with spontaneous hemobilia were included in the study group. Endoscopic nasobiliary drainage was achieved in 33 cases (100%). In 29 of 33 patients (87.9%), hemobilia was improved. The frequency of spontaneous hemobilia was 1.22% (33/2701). On multivariate analysis, United Network for Organ Sharing status I or IIa (odds ratio [OR] 3.095, 95% CI 1.097-8.732, P = 0.033), alcoholic liver cirrhosis (OR 3.942, 95% CI 1.261-12.324, P = 0.018), and body mass index < 24.5 kg/m2 (OR 2.329, 95% CI 1.005-5.397, P = 0.049) were significant risk factors for spontaneous hemobilia after LT. CONCLUSIONS: Endoscopic retrograde cholangiopancreatography and endoscopic nasobiliary drainage are feasible methods for the management of spontaneous hemobilia after LT. In patients with United Network for Organ Sharing status I and IIa, alcoholic liver cirrhosis, or body mass index < 24.5 kg/m2 , special attention should be paid to the occurrence of spontaneous hemobilia after LT.

Outcomes of ERCP in Billroth II gastrectomy patients.

BACKGROUND AND AIMS: ERCP is a difficult procedure to perform in Billroth II gastrectomy patients because of altered anatomy. We investigated the outcomes and risk factors for adverse events with ERCP using a cap-fitted forward-viewing endoscope with endoscopic papillary balloon dilation (EPBD) in Billroth II gastrectomy patients. METHODS: The records for Billroth II gastrectomy patients who underwent ERCP using a cap-fitted forward-viewing endoscope with EPBD at 5 institutions between August 2008 and April 2014 were retrospectively reviewed. The outcomes and risk factors for adverse events resulting from this treatment were analyzed. RESULTS: In total, 165 patients were identified. ERCP was technically successful in 144 patients (87.3%) and clinically successful in 141 patients (85.5%). Adverse events occurred in 38 patients (23.0%): perforation in 3 cases (1.8%), pancreatitis in 13 cases (7.9%), and asymptomatic hyperamylasemia in 22 patients (13.3%). In univariate analysis, ≥2 ERCP sessions, periampullary diverticulum, and common bile duct (CBD) stone size ≥ 12 mm were found to be associated with ERCP-related adverse events. In multivariate analysis, ≥2 ERCP sessions (odds ratio [OR], 4.762; 95% confidence interval [CI], 1.472-15.402; P = .009) and a CBD stone size ≥ 12 mm (OR, 3.213; 95% CI, 1.140-9.057; P = .027) were significant. CONCLUSIONS: ERCP using a cap-fitted forward-viewing endoscope with EPBD is feasible in Billroth II gastrectomy patients. In patients with ≥2 ERCP sessions or a CBD stone size ≥ 12 mm, special attention should be paid to the possible occurrence of significant adverse events.

An intrapericardial ectopic thyroid mimicking metastasis in a patient with papillary thyroid cancer: Localization, differential diagnosis by 18F-FDG PET/CT and ablation by 131I.

We report a very rare case of incidental intrapericardial thyroid in a papillary thyroid cancer patient. Post ablation scan revealed iodine-131 (131I) uptake in the mid-chest. Fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) was performed and showed a 18F-FDG avid lesion between the right atrium and the ascending aorta, (which was) shown to be an ectopic thyroid and not metastasis. The lesion disappeared on a 6 month follow-up 123I whole body scan while serum thyroglobulin was negative. Although intrapericardial ectopic thyroid is reported to show high iodine uptake, low 18F-FDG avidity of the lesion could be helpful in the exclusion of metastases.

Clinical features of pancreatic involvement in von Hippel-Lindau disease: a retrospective study of 55 cases in a single center.

BACKGROUND: von Hippel-Lindau (VHL) disease is an autosomal dominant disorder characterized by the development of multiple tumors in the central nervous system and visceral organs. In this study, we describe clinical features of pancreatic involvement in VHL disease, of which there have been few reported studies to date. METHODS: We reviewed medical records of 63 VHL patients, diagnosed at Asan Medical Center between January 1995 and December 2013. Demographic, genetic, and radiologic features, and the clinical course of VHL patients with pancreatic involvement were retrospectively analyzed. RESULTS: Among the 63 VHL patients, 55 (87.4%) had VHL-associated pancreatic lesions (male: female, 31:24; median age at onset, 33 years; range, 12-67 years). These presented as single simple cysts (n = 5, 9.1%), multiple simple cysts (n = 14, 25.5%), serous cystadenoma (n = 29, 52.7%), or neuroendocrine tumors (NETs) (n = 17, 30.9%). Genetic tests were performed on 35 of the 55 patients (63.6%) and VHL gene mutations were observed in 28 of them (80%). Of the 55 patients, 11 received surgical treatment, 2 received endoscopic ultrasonography-guided ethanol ablation therapy as local treatment for NET, and 42 patients were followed regularly without intervention (20%, 3.6%, and 76.4%, respectively). CONCLUSION: Pancreatic involvement in VHL disease is common, with a prevalence of 87.4%. Serial screening imaging studies for the early detection of VHL-associated NET are necessary in individuals at risk of VHL disease. A large-scale epidemiological study of VHL disease is needed to examine the natural course of the disease and the prognosis for pancreatic involvement.

Assessment of safety of non-anesthesiologist-assisted endoscopic retrograde cholangiopancreatography based on performance status in elderly patients.

BACKGROUND AND AIM: Endoscopic retrograde cholangiopancreatography (ERCP) has been increasingly performed in the elderly patients, yet little is known concerning objective criteria of safety. This study aimed to determine the potential predictors for the procedure-related outcomes. METHODS: Two hundred eighty-one patients older than 70 years who were indicated for ERCP (group A [n = 195], 70-79 years of age; group B [n = 86], ≥ 80 years of age) were prospectively enrolled and analyzed for the development of serious adverse events related to ERCP. RESULTS: ERCP was not performed in six patients at high risk for the procedure. There were significant differences between group A and B in Duke Activity Status Index (DASI) (23.1 vs 14.9, P < 0.01) and Eastern Cooperative Oncology Group performance status (3 and 4, 49/195 vs 33/86, P < 0.05). Major ERCP-related complications (hypotension, severe bradycardia, hypoxia, myocardial infarction, cerebral infarction) occurred in five patients from group B and three from group A. Post-ERCP pancreatitis occurred in one patient from group A and bleeding in one from group B. In univariate analysis, old age (≥ 80 years), American Society of Anesthesiologists score ≥ 3, and DASI < 10 were statistically significant predictors for overall serious events related to ERCP. In the multivariate analysis, DASI < 10 (only manage to ambulate) was independent predictor for overall serious events related to ERCP. CONCLUSION: DASI score is useful predictor for the feasibility assessment of safe ERCP in the elderly patients.

Early oral antibiotic switch compared with conventional intravenous antibiotic therapy for acute cholangitis with bacteremia.

BACKGROUND: Biliary decompression with antibiotic therapy is the mainstay treatment for acute cholangitis with bacteremia. A few studies have been conducted to investigate the optimal duration and route of antibiotic therapy in biliary tract infection with bacteremia. METHODS: Patients with acute cholangitis with bacteremia who achieved successful biliary drainage were randomly assigned to an early oral antibiotic switch group (group A, n = 29) and a conventional intravenous antibiotics group (group B, n = 30). Patients were discharged when they were afebrile over 2 days after oral antibiotic switch and showed consecutive improvement in the laboratory index. They were followed up and assessed at 30 days after diagnosis to evaluate the eradication of bacteria, recurrence of acute cholangitis, and 30-day mortality rate. RESULTS: There were no statistically significant differences between the two groups in baseline characteristics, clinical and laboratory index, severity of acute cholangitis, bacteria isolated from blood cultures, and clinical outcomes. The rate of eradication of bacteria was 93.1 % in group A and 93.3 % in group B, respectively (p = 0.97). Using non-inferiority tests, the rate of eradication of bacteria in group A was not inferior to that in group B (95 % CI -0.13 to 0.14, p = 0.97). There was no statistically significant difference in the recurrence of acute cholangitis and a 30-day mortality rate between the two groups. CONCLUSIONS: Early switch to oral antibiotic therapy following adequate biliary drainage for treatment of acute cholangitis with bacteremia was not inferior to conventional 10-day intravenous antibiotic therapy.

Sex Differences in Heart Rate Variability and Vascular Function Following High-Intensity Interval Training in Young Adults.

High-intensityintervaltraining (HIIT) issuperiortoothertrainingstrategies in both male andfemalehealthyindividuals. Understanding sex-specificdifferences in cardiac auto-regulation maycontributetothe optimal trainingstrategiesfor HIIT. The presentstudyaimedtoidentifysexdifferences in heart rate variability (HRV) andvascularfunctionfollowing HIIT in youngadults. Twenty-fourphysicallyactiveyoung male andfemaleadults (M: 12, F: 12, age: 19.5 yr, BMI: 22.1 kg·m-2) volunteeredtoparticipate in thestudy. Participantsperformed 10 boutsof HIIT including 20 s of high-intensitycycling at 115-130% Wmaxfollowedby 100 s ofrecovery. The cardiac auto-regulationsincluding HRV andvascularfunctionweremeasured at five different time points. The R-R interval, rMSSD, and SDNN wererecoveredfaster in malesthan in females after 15 min of HIIT. Thereweresexdifferences in theautonomicnervoussystemwhereln LF andln HF activitiesalongwithsympathovagalbalance (ln LF/HF) weregreater in femalescomparedwithmalesimmediatelyand 15 min after HIIT. However, nosignificantdifferences in bloodpressureand brachial-ankle pulse wavevelocitywereobservedbetween male andfemaleparticipants. Overall, HRV was moreactivated in femalesthan in malesfollowing HIIT, but theacuteresponse in vascularfunction was not different betweensexes. In futurestudies, sex-specificadaptationsofcardiacautoregulationfollowingrepeated HIIT mayneedtobeperformed.

A review of functional neuromodulation in humans using low-intensity transcranial focused ultrasound.

Transcranial ultrasonic neuromodulation is a rapidly burgeoning field where low-intensity transcranial focused ultrasound (tFUS), with exquisite spatial resolution and deep tissue penetration, is used to non-invasively activate or suppress neural activity in specific brain regions. Over the past decade, there has been a rapid increase of tFUS neuromodulation studies in healthy humans and subjects with central nervous system (CNS) disease conditions, including a recent surge of clinical investigations in patients. This narrative review summarized the findings of human neuromodulation studies using either tFUS or unfocused transcranial ultrasound (TUS) reported from 2013 to 2023. The studies were categorized into two separate sections: healthy human research and clinical studies. A total of 42 healthy human investigations were reviewed as grouped by targeted brain regions, including various cortical, subcortical, and deep brain areas including the thalamus. For clinical research, a total of 22 articles were reviewed for each studied CNS disease condition, including chronic pain, disorder of consciousness, Alzheimer's disease, Parkinson's disease, depression, schizophrenia, anxiety disorders, substance use disorder, drug-resistant epilepsy, and stroke. Detailed information on subjects/cohorts, target brain regions, sonication parameters, outcome readouts, and stimulatory efficacies were tabulated for each study. In later sections, considerations for planning tFUS neuromodulation in humans were also concisely discussed. With an excellent safety profile to date, the rapid growth of human tFUS research underscores the increasing interest and recognition of its significant potential in the field of non-invasive brain stimulation (NIBS), offering theranostic potential for neurological and psychiatric disease conditions and neuroscientific tools for functional brain mapping.

A review of algorithms and software for real-time electric field modeling techniques for transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS) is a device-based neuromodulation technique increasingly used to treat brain diseases. Electric field (E-field) modeling is an important technique in several TMS clinical applications, including the precision stimulation of brain targets with accurate stimulation density for the treatment of mental disorders and the localization of brain function areas for neurosurgical planning. Classical methods for E-field modeling usually take a long computation time. Fast algorithms are usually developed with significantly lower spatial resolutions that reduce the prediction accuracy and limit their usage in real-time or near real-time TMS applications. This review paper discusses several modern algorithms for real-time or near real-time TMS E-field modeling and their advantages and limitations. The reviewed methods include techniques such as basis representation techniques and deep neural-network-based methods. This paper also provides a review of software tools that can integrate E-field modeling with navigated TMS, including a recent software for real-time navigated E-field mapping based on deep neural-network models.

SlicerTMS: Real-Time Visualization of Transcranial Magnetic Stimulation for Mental Health Treatment.

We present a real-time visualization system for Transcranial Magnetic Stimulation (TMS), a non-invasive neuromodulation technique for treating various brain disorders and mental health diseases. Our solution targets the current challenges of slow and labor-intensive practices in treatment planning. Integrating Deep Learning (DL), our system rapidly predicts electric field (E-field) distributions in 0.2 seconds for precise and effective brain stimulation. The core advancement lies in our tool's real-time neuronavigation visualization capabilities, which support clinicians in making more informed decisions quickly and effectively. We assess our system's performance through three studies: First, a real-world use case scenario in a clinical setting, providing concrete feedback on applicability and usability in a practical environment. Second, a comparative analysis with another TMS tool focusing on computational efficiency across various hardware platforms. Lastly, we conducted an expert user study to measure usability and influence in optimizing TMS treatment planning. The system is openly available for community use and further development on GitHub: https://github.com/lorifranke/SlicerTMS.

Cytotoxicity of two fluoride-releasing adhesive tapes.

Sodium fluoride-polyvinyl alcohol (NaF-PVA) tape was developed to deliver fluoride to teeth by adding fluoride to polymer tape. Previous studies have demonstrated that tapes are effective and have antimicrobial properties. This study aimed to evaluate the cytotoxicity of two fluoride-releasing adhesive tapes. We investigated two polyvinyl alcohol (PVA) tapes: (i) a fluoride-PVA (F-PVA) tape, and (ii) a pullulan-incorporated F-PVA (PF-PVA) tape. The cytotoxicity test was conducted on human gingival fibroblasts (HGF) and human periodontal ligament (PDL) cells. Using an adhesive tape containing fluoride, we performed the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on these cells. Genetic analysis of the cells was performed to conduct a stability test on humans. In the MTT assay, PF-PVA had 66% greater cytotoxicity than control by PDL and 69% by HGF. F-PVA showed less cytotoxicity than PF-PVA by 29% in PDL and 33% in HGF. Gene ontology (GO) analysis and gene set enrichment analysis (GSEA) were performed as gene expression analyses. GO analysis indicated that PF-PVA displayed more expression changes of genes related to cytotoxicity than F-PVA. In addition, GSEA found more inflammatory response associations in PF-PVA than in F-PVA. MTT and genetic testing yielded comparable results.

Transcranial focused ultrasound stimulation enhances cerebrospinal fluid movement: Real-time in vivo two-photon and widefield imaging evidence.

BACKGROUND: Cerebrospinal fluid (CSF) flow is crucial for brain homeostasis and its dysfunction is highly associated with neurodegenerative diseases. Restoring CSF circulation is proposed as a key strategy for the treatment of the diseases. Among the methods to improve CSF circulation, focused ultrasound (FUS) stimulation has emerged as a promising non-invasive brain stimulation technique, with effectiveness evidenced by ex vivo studies. However, due to technical disturbances in in vivo imaging combined with FUS, direct evidence of real-time in vivo CSF flow enhancement by FUS remains elusive. OBJECTIVE: To investigate whether FUS administered through the skull base can enhance CSF influx in living animals with various real-time imaging techniques. METHODS: We demonstrate a novel method of applying FUS through the skull base, facilitating cortical CSF influx, evidenced by diverse in vivo imaging techniques. Acoustic simulation confirmed effective sonication of our approach through the skull base. After injecting fluorescent CSF tracers into cisterna magna, FUS was administered at the midline of the jaw through the skull base for 30 min, during which imaging was performed concurrently. RESULTS: Enhanced CSF influx was observed in macroscopic imaging, demonstrated by the influx area and intensity of the fluorescent dyes after FUS. In two-photon imaging, increased fluorescence was observed in the perivascular space (PVS) after stimulation. Moreover, particle tracking of microspheres showed more microspheres entering the imaging field, with increased mean speed after FUS. CONCLUSION: Our findings provide direct real-time in vivo imaging evidence that FUS promotes CSF influx and flow in the PVS.

Antimicrobial effect of two fluoride-releasing adhesive tapes on Streptococcus mutans biofilm.

Fluoride-releasing adhesive tapes have been developed as a new fluoride delivery agent. However, application as caries prevention agents remains underexplored. This study aimed at evaluating the antimicrobial activity of two fluoride-releasing adhesive tapes against S. mutans biofilm. Two polyvinyl alcohol (PVA) tapes were investigated: (i) a fluoride-PVA (F-PVA) tape, (ii) a pullulan incorporated F-PVA (PF-PVA) tape. S. mutan strains were cultured and treated with the tapes. Antimicrobial effects were evaluated using the agar diffusion test, field-emission scanning electron microscopy (FE-SEM), and confocal laser scanning microscopy (CLSM). F-PVA tapes showed higher inhibition-zone diameters than PF-PVA at 48 h and 72 h. However, there were no significant differences (p > 0.05) between the effects of F-PVA and PF-PVA. The bio-volume of S. mutans and extracellular polymeric substances significantly decreased in the F-PVA tapes than in the PF-PVA tapes (p < 0.05). FE-SEM micrographs revealed less S. mutans colonization in F-PVA. F-PVA exhibited better antimicrobial activity against S. mutans than PF-PVA.