Auricular vagus nerve stimulation (aVNS) is one of the promising neuromodulation techniques due to its non-invasiveness, convenience, and effectiveness. aVNS has been suggested as a potential treatment for neurodegenerative diseases showing impaired cerebrospinal fluid (CSF) dynamics. Improving CSF flow has been proposed as a key mechanism of the therapeutic effect on neurodegenerative diseases. However, aVNS parameters have been set empirically and the effective parameter that maximize the effect remains elusive. Here we show that 30 minutes of low-frequency aVNS increased arterial vasomotion events and enhanced cortical CSF influx along the branches of middle cerebral arteries. By using in vivo two photon imaging or widefield fluorescence microscopy with plasma and CSF tracers for visualizing blood vessels and perivascular spaces, arterial vasomotion and cortical CSF influx dynamics were acquired. The low-frequency (2 Hz) aVNS, but not middleand high-frequency (40 and 100 Hz) aVNS, significantly increased the number of vasomotion events compared to the sham group. Accordingly, in the CSF imaging, 2 Hz of aVNS markedly enhanced the CSF influx. Our findings demonstrate that lowfrequency aVNS is the effective parameter in respect to modulating vasomotion and CSF influx, resulting in brain clearance effect.

Auricular vagus nerve stimulation (aVNS) is one of the promising neuromodulation techniques due to its non-invasiveness, convenience, and effectiveness. aVNS has been suggested as a potential treatment for neurodegenerative diseases showing impaired cerebrospinal fluid (CSF) dynamics. Improving CSF flow has been proposed as a key mechanism of the therapeutic effect on neurodegenerative diseases. However, aVNS parameters have been set empirically and the effective parameter that maximize the effect remains elusive. Here we show that 30 minutes of low-frequency aVNS increased arterial vasomotion events and enhanced cortical CSF influx along the branches of middle cerebral arteries. By using in vivo two photon imaging or widefield fluorescence microscopy with plasma and CSF tracers for visualizing blood vessels and perivascular spaces, arterial vasomotion and cortical CSF influx dynamics were acquired. The low-frequency (2 Hz) aVNS, but not middleand high-frequency (40 and 100 Hz) aVNS, significantly increased the number of vasomotion events compared to the sham group. Accordingly, in the CSF imaging, 2 Hz of aVNS markedly enhanced the CSF influx. Our findings demonstrate that lowfrequency aVNS is the effective parameter in respect to modulating vasomotion and CSF influx, resulting in brain clearance effect.

Auricular vagus nerve stimulation (aVNS) is one of the promising neuromodulation techniques due to its non-invasiveness, convenience, and effectiveness. aVNS has been suggested as a potential treatment for neurodegenerative diseases showing impaired cerebrospinal fluid (CSF) dynamics. Improving CSF flow has been proposed as a key mechanism of the therapeutic effect on neurodegenerative diseases. However, aVNS parameters have been set empirically and the effective parameter that maximize the effect remains elusive. Here we show that 30 minutes of low-frequency aVNS increased arterial vasomotion events and enhanced cortical CSF influx along the branches of middle cerebral arteries. By using in vivo two photon imaging or widefield fluorescence microscopy with plasma and CSF tracers for visualizing blood vessels and perivascular spaces, arterial vasomotion and cortical CSF influx dynamics were acquired. The low-frequency (2 Hz) aVNS, but not middleand high-frequency (40 and 100 Hz) aVNS, significantly increased the number of vasomotion events compared to the sham group. Accordingly, in the CSF imaging, 2 Hz of aVNS markedly enhanced the CSF influx. Our findings demonstrate that lowfrequency aVNS is the effective parameter in respect to modulating vasomotion and CSF influx, resulting in brain clearance effect.

Auricular vagus nerve stimulation (aVNS) is one of the promising neuromodulation techniques due to its non-invasiveness, convenience, and effectiveness. aVNS has been suggested as a potential treatment for neurodegenerative diseases showing impaired cerebrospinal fluid (CSF) dynamics. Improving CSF flow has been proposed as a key mechanism of the therapeutic effect on neurodegenerative diseases. However, aVNS parameters have been set empirically and the effective parameter that maximize the effect remains elusive. Here we show that 30 minutes of low-frequency aVNS increased arterial vasomotion events and enhanced cortical CSF influx along the branches of middle cerebral arteries. By using in vivo two photon imaging or widefield fluorescence microscopy with plasma and CSF tracers for visualizing blood vessels and perivascular spaces, arterial vasomotion and cortical CSF influx dynamics were acquired. The low-frequency (2 Hz) aVNS, but not middleand high-frequency (40 and 100 Hz) aVNS, significantly increased the number of vasomotion events compared to the sham group. Accordingly, in the CSF imaging, 2 Hz of aVNS markedly enhanced the CSF influx. Our findings demonstrate that lowfrequency aVNS is the effective parameter in respect to modulating vasomotion and CSF influx, resulting in brain clearance effect.

Auricular vagus nerve stimulation (aVNS) is one of the promising neuromodulation techniques due to its non-invasiveness, convenience, and effectiveness. aVNS has been suggested as a potential treatment for neurodegenerative diseases showing impaired cerebrospinal fluid (CSF) dynamics. Improving CSF flow has been proposed as a key mechanism of the therapeutic effect on neurodegenerative diseases. However, aVNS parameters have been set empirically and the effective parameter that maximize the effect remains elusive. Here we show that 30 minutes of low-frequency aVNS increased arterial vasomotion events and enhanced cortical CSF influx along the branches of middle cerebral arteries. By using in vivo two photon imaging or widefield fluorescence microscopy with plasma and CSF tracers for visualizing blood vessels and perivascular spaces, arterial vasomotion and cortical CSF influx dynamics were acquired. The low-frequency (2 Hz) aVNS, but not middleand high-frequency (40 and 100 Hz) aVNS, significantly increased the number of vasomotion events compared to the sham group. Accordingly, in the CSF imaging, 2 Hz of aVNS markedly enhanced the CSF influx. Our findings demonstrate that lowfrequency aVNS is the effective parameter in respect to modulating vasomotion and CSF influx, resulting in brain clearance effect.

Background: Unlike the Mycoplasma IST2 kit (bioMérieux), the Mycoplasma IST3 kit has been updated to comply with the standardized antimicrobial susceptibility test (AST) method for Ureaplasma spp. (Up) and Mycoplasma hominis (Mh). We aimed to verify the use of the Mycoplasma IST3 kit for genital mycoplasma cultures. Methods: From September 2023 to January 2024, the R1 medium remaining after inoculation with IST2 was refrigerated until the next day. For IST2-positive samples, 300 μL of residual R1 medium was inoculated into the IST3. Species identification, enumeration, and AST results obtained using IST3 were compared with those obtained using IST2. Results: A total of 48 IST2-positive samples were inoculated into IST3, including 35, 1, and 12 Up-only, Mh-only, and both Up- and Mh-positive samples, respectively. Among Up-only samples, 2.8%, 91.4%, and 100.0% were susceptible to ciprofloxacin, tetracycline, and erythromycin, respectively. With IST3, 45 (93.8%) samples grew genital mycoplasmas; 42 (89.4%) of the 47 Up-positive samples and 6 (46.2%) of the 13 Mh-positive samples showed growth of the same organisms. All seven samples that failed to grow Mh were from mixed cultures, of which four Mh concentrations of < 104 /mL. Up was susceptible to levofloxacin, tetracycline, and erythromycin at the rates of 64.3 %, 88.1 %, and 95.2 %, respectively. Conclusion IST3 showed good performance in detecting genital Mycoplasma except for its tendency to not detect Mh of low concentrations in mixed cultures. IST3 is preferable to IST2 because it can accurately screen for erythromycin resistance in Up and reduce falseresistances for fluoroquinolone.

Objective: Diagnosis and assessment of depression rely on scoring systems based on questionnaires, either self-reported by patients or administered by clinicians, and observation of patient facial expressions during the interviews plays a crucial role in making impressions in clinical settings. Deep learning driven approaches can assist clinicians in the course of diagnosis of depression by recognizing subtle facial expressions and emotions in depression patients. Methods: Seventeen simulated patients who acted as depressed patients participated in this study. A trained psychiatrist structurally interviewed each participant with moderate depression in accordance with a prepared scenario and without depressive features. Interviews were video-recorded, and a facial emotion recognition algorithm was used to classify emotions of each frame. Results: Among seven emotions (anger, disgust, fear, happiness, neutral, sadness, and surprise), sadness was expressed in a higher proportion on average in the depression-simulated group compared to the normal group. Neutral and fear were expressed in higher proportions on average in the normal group compared to the normal group. The overall distribution of emotions between the two groups was significantly different (p ＜ 0.001). Variance in emotion was significantly less in the depression-simulated group (p ＜ 0.05). Conclusion This study suggests a novel and practical approach to understand the emotional expression of depression patients based on deep learning techniques. Further research would allow us to obtain more perspectives on the emotional profiles of clinical patients, potentially providing helpful insights in making diagnosis of depression patients.

Cancer chemotherapy often triggers peripheral neuropathy in patients, leading to neuropathic pain in the extremities. While previous research has explored various nerve stimulation to alleviate chemotherapy-induced peripheral neuropathy (CIPN), evidence on the effectiveness of noninvasive auricular vagus nerve stimulation (aVNS) remains uncertain. This study aimed to investigate the efficacy of non-invasive aVNS in relieving CIPN pain. To induce CIPN in experimental animals, oxaliplatin was intraperitoneally administered to rats (6 mg/kg). Mechanical and cold allodynia, the representative symptoms of neuropathic pain, were evaluated using the von Frey test and acetone test, respectively. The CIPN animals were randomly assigned to groups and treated with aVNS (5 V, square wave) at different frequencies (2, 20, or 100 Hz) for 20 minutes. Results revealed that 20 Hz aVNS exhibited the most pronounced analgesic effect, while 2 or 100 Hz aVNS exhibited weak effects. Immunohistochemistry analysis demonstrated increased c-Fos expression in the locus coeruleus (LC) in the brain of CIPN rats treated with aVNS compared to sham treatment. To elucidate the analgesic mechanisms involving the adrenergic descending pathway, α 1 -, α 2 -, or β-adrenergic receptor antagonists were administered to the spinal cord before 20 Hz aVNS. Only the β-adrenergic receptor antagonist, propranolol, blocked the analgesic effect of aVNS.These findings suggest that 20 Hz aVNS may effectively alleviate CIPN pain through β-adrenergic receptor activation.

This study aimed to identify metabolic biomarkers and investigate changes in intestinal microbiota in the feces of healthy participants following administration of Lactococcus lactis GEN-001. GEN-001 is a single-strain L. lactis strain isolated from the gut of a healthy human volunteer. The study was conducted as a parallel, randomized, phase 1, open design trial. Twenty healthy Korean males were divided into five groups according to the GEN-001 dosage and dietary control.Groups A, B, C, and D1 received 1, 3, 6, and 9 GEN-001 capsules (1 × 1011 colony forming units), respectively, without dietary adjustment, whereas group D2 received 9 GEN-001 capsules with dietary adjustment. All groups received a single dose. Fecal samples were collected 2 days before GEN-001 administration to 7 days after for untargeted metabolomics and gut microbial metagenomic analyses; blood samples were collected simultaneously for immunogenicity analysis. Levels of phenylalanine, tyrosine, cholic acid, deoxycholic acid, and tryptophan were significantly increased at 5–6 days after GEN-001 administration when compared with predose levels. Compared with predose, the relative abundance (%) of Parabacteroides and Alistipes significantly decreased, whereas that of Lactobacillus and Lactococcus increased; Lactobacillus and tryptophan levels were negatively correlated. A single administration of GEN-001 shifted the gut microbiota in healthy volunteers to a more balanced state as evidenced by an increased abundance of beneficial bacteria, including Lactobacillus, and higher levels of the metabolites that have immunogenic properties.