Classification of laryngeal diseases including laryngeal cancer, benign mucosal disease, and vocal cord paralysis by artificial intelligence using voice analysis.

Voice change is often the first sign of laryngeal cancer, leading to diagnosis through hospital laryngoscopy. Screening for laryngeal cancer solely based on voice could enhance early detection. However, identifying voice indicators specific to laryngeal cancer is challenging, especially when differentiating it from other laryngeal ailments. This study presents an artificial intelligence model designed to distinguish between healthy voices, laryngeal cancer voices, and those of the other laryngeal conditions. We gathered voice samples of individuals with laryngeal cancer, vocal cord paralysis, benign mucosal diseases, and healthy participants. Comprehensive testing was conducted to determine the best mel-frequency cepstral coefficient conversion and machine learning techniques, with results analyzed in-depth. In our tests, laryngeal diseases distinguishing from healthy voices achieved an accuracy of 0.85-0.97. However, when multiclass classification, accuracy ranged from 0.75 to 0.83. These findings highlight the challenges of artificial intelligence-driven voice-based diagnosis due to overlaps with benign conditions but also underscore its potential.

Phenolic changes in a combined herbal extract of Lithospermum erythrorhizon, Houttuynia cordata, and Spirodela polyrhiza and alleviation of DNCB-induced atopic dermatitis in BALB/c mice.

Atopic dermatitis (AD) is an inflammatory skin disease showing skin barrier dysfunction, eczematous lesions, severe itching, and abnormal immune responses. The aim of this study was to determine whether an herb combination of Lithospermum erythrorhizon (LE), Houttuynia cordata (HC), and Spirodela polyrhiza (SP) has a superior anti-AD effect. Forty-two compounds were identified in LE, HC, SP, and a combined herb extract of LE, HC, and SP (LHS) using ultra-high-pressure liquid chromatography (UHPLC)-Orbitrap mass spectrometer (MS). The concentration of flavonoid glycosides including orientin (luteolin-8-C-glucoside), quercetin-3-O-rhamnoside, and luteolin-7-O-glucoside in the LHS was increased than in individual extracts. Furthermore, the treatment of LHS most effectively inhibited the increase of epidermal thickness, the number of mast cells, and the release of immunoglobulin E compared with that with each extract. These results suggest that the potential anti-AD effects of the LHS are due to the changes of bioactive compounds by the combination of herbs. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01329-7.

Umbelliferone Ameliorates Memory Impairment and Enhances Hippocampal Synaptic Plasticity in Scopolamine-Induced Rat Model.

Alzheimer's disease (AD) is a neurodegenerative disorder, characterized by memory loss and cognitive decline. Among the suggested pathogenic mechanisms of AD, the cholinergic hypothesis proposes that AD symptoms are a result of reduced synthesis of acetylcholine (ACh). A non-selective antagonist of the muscarinic ACh receptor, scopolamine (SCOP) induced cognitive impairment in rodents. Umbelliferone (UMB) is a Apiaceae-family-derived 7-hydeoxycoumarin known for its antioxidant, anti-tumor, anticancer, anti-inflammatory, antibacterial, antimicrobial, and antidiabetic properties. However, the effects of UMB on the electrophysiological and ultrastructure morphological aspects of learning and memory are still not well-established. Thus, we investigated the effect of UMB treatment on cognitive behaviors and used organotypic hippocampal slice cultures for long-term potentiation (LTP) and the hippocampal synaptic ultrastructure. A hippocampal tissue analysis revealed that UMB attenuated a SCOP-induced blockade of field excitatory post-synaptic potential (fEPSP) activity and ameliorated the impairment of LTP by the NMDA and AMPA receptor antagonists. UMB also enhanced the hippocampal synaptic vesicle density on the synaptic ultrastructure. Furthermore, behavioral tests on male SD rats (7-8 weeks old) using the Y-maze test, passive avoidance test (PA), and Morris water maze test (MWM) showed that UMB recovered learning and memory deficits by SCOP. These cognitive improvements were in association with the enhanced expression of BDNF, TrkB, and the pCREB/CREB ratio and the suppression of acetylcholinesterase activity. The current findings indicate that UMB may be an effective neuroprotective reagent applicable for improving learning and memory against AD.

Study on relationship between self-recognition of voice disorder and mental health status: Korea National Health and Nutrition Examination Survey.

BACKGROUND: The voice has been thought to be associated with emotions, but conducting large-scale research on this relationship has some limitations. To overcome these limitations, questionnaires have been utilized as a research tool. METHODS: A population-based cross-sectional study was done. A total of 15,977 participants completed questionnaires regarding self-recognition of voice disorder (SRVD), and mental health status. RESULTS: 1053(6.6 %) participants answered that they had SRVD. In the multivariate Cox proportional hazard model, psychological stress (Hazard ratio (HR) = 1.371, 95 % confidence interval (CI) = 1.154-1.629), depressive symptoms (HR = 1.626, 95 % CI = 1.323-1.997), suicidal ideation (HR = 1.739, 95 % CI = 1.418-2.133), and suicide attempt (HR =2.206, 95 % CI = 1.067-4.56) were all associated with SRVD. In SRVD lasting over three weeks, psychological stress (HR = 1.604, 95 % CI = 1.278-2.014), depressive symptoms (HR = 1.807, 95 % CI = 1.384-2.36), and suicidal ideation (HR = 2.073, 95 % CI = 1.587-2.709) were also significant factors. As the number of mental health problems increased, the odds ratio of both SRVD (OR = 2.49, 95 % CI = 1.839-3.37) and SRVD lasting over three weeks (OR = 3.254, 95 % CI = 2.242-4.725) increased, respectively. LIMITATIONS: SRVD and mental health status were judged only by simple questionnaires. Cross-sectional design and retrospective data could not draw causal relationships. CONCLUSIONS: SRVD and SRVD lasting over three weeks had a significant relationship with mental health status, including psychological stress, depressive symptoms, and suicidal ideation. There is a need to consider psychiatric treatment for individuals who visit hospitals with voice disorders.

Guideline for the Surgical Management of Locally Invasive Differentiated Thyroid Cancer From the Korean Society of Head and Neck Surgery.

The aim of this study was to develop evidence-based recommendations for determining the surgical extent in patients with locally invasive differentiated thyroid cancer (DTC). Locally invasive DTC with gross extrathyroidal extension invading surrounding anatomical structures may lead to several functional deficits and poor oncological outcomes. At present, the optimal extent of surgery in locally invasive DTC remains a matter of debate, and there are no adequate guidelines. On October 8, 2021, four experts searched the PubMed, Embase, and Cochrane Library databases; the identified papers were reviewed by 39 experts in thyroid and head and neck surgery. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the quality of evidence, and to develop and report recommendations. The strength of a recommendation reflects the confidence of a guideline panel that the desirable effects of an intervention outweigh any undesirable effects, across all patients for whom the recommendation is applicable. After completing the draft guidelines, Delphi questionnaires were completed by members of the Korean Society of Head and Neck Surgery. Twenty-seven evidence-based recommendations were made for several factors, including the preoperative workup; surgical extent of thyroidectomy; surgery for cancer invading the strap muscles, recurrent laryngeal nerve, laryngeal framework, trachea, or esophagus; and surgery for patients with central and lateral cervical lymph node involvement. Evidence-based guidelines were devised to help clinicians make safer and more efficient clinical decisions for the optimal surgical treatment of patients with locally invasive DTC.

Naringin enhances long-term potentiation and recovers learning and memory deficits of amyloid-beta induced Alzheimer's disease-like behavioral rat model.

Alzheimer's disease (AD), as the most typical type of dementia, is a chronic neurodegenerative disorder characterized by progressive learning and memory impairment. It is known that the main causes of AD are the accumulation of ß-amyloid (Aß) plaques and neurofibrillary tangles (NFT) containing hyperphosphorylated tau protein. Naringin is a flavonoid from citrus fruits, especially in grapefruit, which has anti-inflammatory, antioxidant, anti-apoptotic, and neuroprotective activities. However, the effect of naringin in AD caused by Aß has not been clearly studied, and there are few studies on the electrophysiological aspect. Thus, we investigated the ex vivo neuroprotective effect of naringin through the long-term potentiation (LTP) on organotypic hippocampal slice cultures. We evaluated the in vivo effects of naringin (100 mg/kg/day) orally treated for 20 days on learning, memory, and cognition which was impaired by bilateral CA1 subregion injection of Aß. Cognitive behaviors were measured 2 weeks after Aß injection using behavioral tests and the hippocampal expression of apoptotic and neurotrophic regulators were measured by immunoblotting. In hippocampal tissue slices, naringin dose-dependently increased the field excitatory postsynaptic potential (fEPSP) after theta burst stimulation and attenuated Aß-induced blockade of fEPSP in the hippocampal CA1 area. In Aß injected rats, naringin improved object recognition memory in the novel object test, avoidance memory in the passive avoidance test and spatial recognition memory in the Morris water maze test. In the hippocampus, naringin attenuated the Aß-induced cyclooxygenase-2, Bax activation and Bcl-2, CREB, BDNF and TrkB inhibition. These results suggest that naringin has therapeutic potential to reduce neuronal inflammation and apoptosis induced by Aß related with the BDNF/TrkB/CREB signaling.

Association of smoking status, duration and amount with the risk of head and neck cancer subtypes: a national population-based study.

Smoking is positively associated with multiple cancer types including head and neck cancer (HNC). We sought to confirm the effect of smoking in HNC and subtypes through big data analysis. All data used in this study originated from the Korean National Health Insurance Service database. We analyzed subjects who had undergone health check-ups in 2009 with follow-up until 2018 (n=10,585,852). We collected data on smoking and other variables that could affect the risk of HNC. The overall incidence of HNC was highest in current smokers (HR: 1.822, 95% CI: 1.729-1.920), followed by ex-smokers (HR: 1.242, 95% CI: 1.172-1.317). Laryngeal cancer, hypopharynx cancer, oral cancer, oropharyngeal cancer, and salivary gland cancer showed increasing incidence rates from ex-smokers to current smokers. Smoking duration and amount showed a dose-dependent relationship with the occurrence of HNC. However, the incidence of HNC did not increase significantly when smoking duration was less than 10 years, or when the smoking amount was less than 10 pack-years in ex-smokers. Smoking is associated with the risk of HNC. Smoking cessation before 10 years or 10 pack-years can prevent the development of HNC.

Association of Estimated Glomerular Filtration Rate with Risk of Head and Neck Cancer: A Nationwide Population-Based Study.

In this study, through a cohort study of 10 million people, we investigated the association between estimated glomerular filtration rate (eGFR) and head and neck cancer (HNC) incidence. This is an observational cohort study using data from the national health claims database established by the Korean National Health Insurance Service (NHIS). We selected 9,598,085 participants older than 20 years who had undergone health checkups in 2009. A health checkup involves the history of any diseases, current health status, and results of several physical and blood exams including eGFR. We investigated the presence of HNC diagnosis in their national health insurance data from 2010 to 2018. Of the 9,598,085 participants, 10,732 had been newly diagnosed with HNC in the 9-year follow-up. In the multivariate Cox proportional hazard model, participants with elevated eGFR were associated with a risk of HNC incidence (HR = 1.129; 95% CI = 1.075−1.186 for eGFR = 90−104 mL/min/1.73 m2 and HR = 1.129; 95% CI = 1.076−1.194 for eGFR ≥ 105 mL/min/1.73 m2) compared with those with eGFR 60−89 mL/min/1.73 m2. Among HNC, the incidences of oral cavity, oropharyngeal, hypopharyngeal, and laryngeal cancers were significantly increased in the elevated eGFR group. According to the subgroup analysis, participants with eGFR ≥ 60 mL/min/1.73 m2 were correlated with risk of HNC incidence in middle age, non/mild drinker, low BMI, no diabetes, and no hypertension patients compared with those with eGFR < 60 mL/min/1.73 m2. Elevated eGFR was associated with the risk of some type of HNC, even in individuals with adjusted hypertension and diabetes without chronic diseases. The results of this study have implications for etiological investigations and preventive strategies.

Associations of Body Mass Index and Waist Circumference with the Risk of Head and Neck Cancer: A National Population-Based Study.

Background: We investigated the association between BMI and HNC subtype incidence in a cohort study of ten million people, adjusting for the effect of smoking and drinking. We also investigated the relationship between waist circumference (WC) and HNC subtype. Methods: All data used in this study originated from the Korean National Health Insurance Service database. We analysed subjects who had undergone health check-ups in 2009 and monitored subjects until 2018 (n = 10,585,852). Finally, 9,598,085 subjects were included after exclusions. We collected variables that could affect the risk of HNC. Cox proportional hazards regression analysis was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: The overall incidence of HNC was higher in the low BMI category (BMI < 18.5 according to WHO recommendations for Asian people) (HR: 1.322; 95% CI: 1.195−1.464) compared with the normal BMI category. Among the HNC cases, the incidence rates of laryngeal (HR: 1.3; 95% CI: 1.085−1.558), oral cavity (HR: 1.277; 95% CI: 1.011−1.611), and oropharyngeal (HR: 1.584; 95% CI: 1.25−2.008) cancers were higher in the low BMI category compared with the normal BMI category. No significant association was detected between low BMI and sinus cancer, salivary gland cancer, or nasopharyngeal cancer. The low WC category (<80 cm in men and <75 cm in women) was related to a risk of hypopharyngeal (HR: 1.268; 95% CI: 1.061−1.514) and laryngeal (HR: 1.118; 95% CI: 1.007−1.241) cancers. The HR for occurrence of HNC was high in underweight participants according to smoking status (1.219 for never smoker vs. 1.448 for ever smoker, p for interaction = 0.0015) and drinking status (1.193 for never drinker vs. 1.448 for ever drinker, p for interaction = 0.0044). Conclusions: Low BMI was associated with the risk of some types of HNC. The results of this study could assist etiological investigations and prevention strategies.

Association between γ-Glutamyltransferase and Head and Neck Cancer in Korean Population: A National Population-Based Study.

BACKGROUND: Gamma-glutamyltransferase (GGT) is positively associated with several cancer types. The objective of this study was to investigate the association between GGT and head and neck cancer (HNC) incidence in a cohort of 10 million people, considering effects of smoking and alcohol consumption. METHODS: All data used in this study were obtained from the Korean National Health Insurance Service database. We analyzed subjects who underwent health check-ups in 2009 and monitored them until 2018 (n = 9,597,952). Using proportional hazards models, quartiles of GGT as independent predictors for HNC incidence were evaluated. RESULTS: The overall incidence of HNC increased in the highest quartile [r-GPT ≥ 40 U/L; HR, 1.452; 95% confidence interval (CI), 1.354-1.557]. Among HNC cases, the HR for hypopharyngeal cancer (HR, 2.364; 95% CI, 1.818-3.074) was significantly higher. HRs for HNC (larynx, sino-nasal, oropharynx, oral cavity, and nasopharynx, except salivary glands) were also significant. CONCLUSIONS: Elevated GGT was associated with the risk of some types of HNCs, such as hypopharyngeal, laryngeal, sinonasal, oropharyngeal, oral cavity, and nasopharyngeal cancer. IMPACT: Results of this study have implications for etiologic investigations and preventive strategies.

Close Surgical Margins in Oral and Oropharyngeal Cancer: Do They Impact Prognosis?

Introduction. Mucosal margins exhibit a mean shrinkage of 30−40% after resection of oral and oropharyngeal cancers, and an adequate in situ surgical margin frequently results in a pathological close margin. However, the impact on prognosis remains unclear. We investigated the impact of a pathological close margin on disease-free survival (DFS) and overall survival (OS). Methods. We retrospectively reviewed the clinicopathological data of 418 patients diagnosed with squamous cell carcinomas of the oral cavity or oropharynx who underwent initial surgery (with curative intent) at our institute between 2010 and 2016. Results. Of the total population, the pathological marginal status of 290 (69.4%) patients was reported as clear (>5 mm), 61 (14.6%) as close (>1 mm, ≤5 mm), and 67 (16.0%) as positive (≤1 mm). The 5-year DFSs were 79.3%, 65.1%, and 52% in patients in the negative margin (group 1), close margin (group 2), and positive margin (group 3) groups, respectively. The difference between groups 1 and 2 was not significant (p = 0.213) but the difference between groups 2 and 3 was (p = 0.034). The 5-year OSs were 79.4%, 84%, and 52.3% in groups 1, 2, and 3, respectively. The difference between groups 1 and 2 was not significant (p = 0.824) but the difference between groups 2 and 3 was (p = 0.001). In multivariate analysis, older age, advanced T stage, and a positive margin were independently prognostic of the 5-year DFS and OS. Conclusion. In conclusion, the OS of patients with close margins was no different than that of others when appropriate postoperative adjuvant and/or salvage treatment were/was prescribed. However, we could not determine the impact of close margins on locoregional recurrence given various biases in our study setting. A future prospective study is needed.

Astrocyte ethanol exposure reveals persistent and defined calcium response subtypes and associated gene signatures.

Astrocytes play a critical role in brain function, but their contribution during ethanol (EtOH) consumption remains largely understudied. In light of recent findings on the heterogeneity of astrocyte physiology and gene expression, an approach with the ability to identify subtypes and capture this heterogeneity is necessary. Here, we combined measurements of calcium signaling and gene expression to define EtOH-induced astrocyte subtypes. In the absence of a demonstrated EtOH receptor, EtOH is believed to have effects on the function of many receptors and downstream biological cascades that underlie calcium responsiveness. This mechanism of EtOH-induced calcium signaling is unknown and this study provides the first step in understanding the characteristics of cells displaying these observed responses. To characterize underlying astrocyte subtypes, we assessed the correlation between calcium signaling and astrocyte gene expression signature in response to EtOH. We found that various EtOH doses increased intracellular calcium levels in a subset of astrocytes, distinguishing three cellular response types and one nonresponsive subtype as categorized by response waveform properties. Furthermore, single-cell RNA-seq analysis of astrocytes from the different response types identified type-enriched discriminatory gene expression signatures. Combining single-cell calcium responses and gene expression analysis identified specific astrocyte subgroups among astrocyte populations defined by their response to EtOH. This result provides a basis for identifying the relationship between astrocyte susceptibility to EtOH and corresponding measurable markers of calcium signaling and gene expression, which will be useful to investigate potential subgroup-specific influences of astrocytes on the physiology and pathology of EtOH exposure in the brain.

Bilateral Vocal Fold Paralysis After COVID-19 mRNA Vaccination: A Case Report.

Since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was noted to cause coronavirus disease 2019 (COVID-19) in 2019, there have been many trials to develop vaccines against the virus. Messenger ribonucleic acid (mRNA) vaccine as a type of the vaccine has been developed and commercialized rapidly, but there was not enough time to verify the long-term safety. An 82-year-old female patient was admitted to the emergency room with dyspnea accompanied by stridor three days after the 3rd COVID-19 mRNA vaccination (Comirnaty, Pfizer-BioNTech, USA). The patient was diagnosed with bilateral vocal fold paralysis (VFP) by laryngoscope. Respiratory distress was improved after the intubation and tracheostomy in sequence. The brain, chest, and neck imaging tests, serological tests, cardiological analysis, and immunological tests were performed to evaluate the cause of bilateral VFP. However, no definite cause was found except for the precedent vaccination. Because bilateral VFP can lead to a fatal condition, a quick evaluation is necessary in consideration of VFP when dyspnea with stridor occurs after vaccination.

Sex Differences in the Prevalence of Head and Neck Cancers: A 10-Year Follow-Up Study of 10 Million Healthy People.

Background: Descriptive epidemiologists have repeatedly reported that males are more susceptible to head and neck cancers. However, most published data are those of cross-sectional studies, and no population-based cohort study has yet been published. The aim of this study was to compare the prevalence of head and neck cancers in healthy males with females. Methods: A retrospective cohort study using the Korean National Health Insurance Service database on 9,598,085 individuals who underwent regular health checkups from 1 January to 31 December 2009. We sought head and neck cancers developed during the 10-year follow-up. Results: A total of 10,732 (incidence rate (IR) per 1000 person-years 0.25) individuals were newly diagnosed with head and neck cancer among the 9,598,085 individuals during the 10-year follow-up. The IR was 0.19 in males (8500 affected) and 0.06 in females (2232 affected). Notably, the male−female ratio increased with age below 70 years but decreased thereafter. The male−female difference was most apparent for laryngeal cancer; the male IR was 11-fold higher in the 40 s and 20-fold higher in the 60 s, followed by hypopharyngeal cancer (6.8- and 24.2-fold). Males smoked more and drank more alcohol than females (p < 0.0001 *, p < 0.0001 *). When never-smokers/-drinkers (only) were compared, males remained at a 2.9-fold higher risk of head and neck cancer than females. The hazard ratios for head and neck cancers in males tended to increase in the lower part of the upper aerodigestive tract: larynx (13.9) > hypopharynx (10.9) > oropharynx (4.4) > nasopharynx (2.9) > sinonasal region (1.8) > oral (1.6). Only the salivary gland cancer incidence did not differ between the sexes; the gland is not in the upper aerodigestive tract. Conclusion: Males are much more susceptible to head and neck cancers than females regardless of whether they drink alcohol or smoke tobacco. Sex differences in the incidence of head and neck cancer are most evident in the 60 s in the lower part of the upper aerodigestive tract, such as the larynx and hypopharynx.

Comparison of Surgical Outcomes Between Ossicle-Cartilage Composite Graft and Synthetic Ossicular Prosthesis for Ossicular Reconstruction.

OBJECTIVE: To propose a modified technique of ossiculoplasty using an ossicle-cartilage composite graft (OCCG) and compare its hearing outcome and protrusion rate with those of a synthetic prosthesis. METHODS: Autologous tragal or homologous septal cartilage was combined with an ossicle to create an umbrella shape OCCG. A total of 302 ossiculoplasty surgeries performed in a single university hospital between 1997 and 2006 were retrospectively reviewed based on the prosthesis type-OCCG or polymaleinate ionomeric prosthesis (IONOS®). Data includes demographic profiles, audiometric outcomes, intraoperative findings, and post-operative complications and was categorized by the follow-up periods. RESULTS: Ossicle-cartilage composite graft was used for 175 patients and IONOS® for 127 patients. The mean post-operative air-bone gap (ABG) of the OCCG group was 22.36 dB, which was better than the IONOS® group of 25.08 dB (P = .015). The successful ABG closure rate of less than 20 dB was also higher in the OCCG group compared to the IONOS® group (38.3% vs 26.8%, P = .036). The ABG between the pre- and post-operative conditions exhibited a significant difference between the 2 groups (P = .006). In the data divided into 3 groups according to the follow-up period, the OCCG group showed a better outcome in the long-term follow-up with 0 cases of protrusion during the follow-up period in the OCCG group compared to 8 cases of the IONOS® group (P = .018). CONCLUSION: Ossiculoplasty with OCCG exhibited satisfactory audiometric outcomes and low complication rates. Ossicle-cartilage composite graft can be a good option with sufficient informed consent and preliminary screening of transmitted diseases.

Changes in metabolic syndrome status and risk of laryngeal cancer: A nationwide cohort study.

BACKGROUND: Whether dynamic changes of metabolic syndrome (MetS) affects the subsequent laryngeal cancer occurrence remains unknown. OBJECTIVE: This study investigated the effects of changes of MetS on the incidence of laryngeal cancer due to a lack of knowledge regarding the development of MetS in Korean population. METHODS: A total of 6,757,048 individuals who received national health checkup in 2009 and follow-up health examination in 2011 were analyzed and followed up until 2018. MetS status included the following categories: MetS-chronic (n = 941,609), MetS-developed (n = 614,229), MetS-recovery (n = 455,835), and MetS-free (n = 4,745,375). RESULTS: With a median follow-up duration of 6.403 years, 1,350 subjects were newly diagnosed with laryngeal cancer. Compared to participants without MetS, adjusted hazard ratios (HR) (95% confidence interval) for those with MetS were 1.320 (1.17-1.489) for laryngeal cancer. The HR of laryngeal cancer was found to be increased with increasing number of MetS components. The MetS-developed group had a significantly higher risk of laryngeal cancer than the MetS-free group (HR: 1.296; 95% CI: 1.093-1.537). The MetS-recovery group within two years also had an increased risk of laryngeal cancer compared with the MetS-free group (HR: 1.220; 95% CI: 1.008-1.476). Among MetS components, abdominal obesity had the highest risk of laryngeal cancer (HR: 1.374; 95% CI: 1.123-1.681). CONCLUSION: Changes in MetS status were associated with the risk of laryngeal cancer. Results of this study have implications for etiological investigations and prevention strategies.

Astrocytes promote ethanol-induced enhancement of intracellular Ca2+ signals through intercellular communication with neurons.

Ethanol (EtOH) abuse induces significant mortality and morbidity worldwide because of detrimental effects on brain function. Defining the contribution of astrocytes to this malfunction is imperative to understanding the overall EtOH effects due to their role in homeostasis and EtOH-seeking behaviors. Using a highly controllable in vitro system, we identify chemical signaling mechanisms through which acute EtOH exposure induces a modulatory feedback loop between neurons and astrocytes. Neuronally-derived purinergic signaling primed a subpopulation of astrocytes to respond to subsequent acute EtOH exposures (SEastrocytes: signal enhanced astrocytes) with greater calcium signal strength. Generation of SEastrocytes arose from astrocytic hemichannel-derived ATP and accumulation of its metabolite adenosine within the astrocyte microenvironment to modulate adenylyl cyclase and phospholipase C activity. These results highlight an important role of astrocytes in shaping the overall physiological responsiveness to EtOH and emphasize the unique plasticity of astrocytes to adapt to single and multiple exposures of EtOH.

Sulforaphane enhances long-term potentiation and ameliorate scopolamine-induced memory impairment.

Increases in human life expectancy have led to increases in the prevalence of senile dementia and neurodegenerative diseases. This is a major problem because there are no curative treatments for these diseases, and patients with unmanaged cognitive and neurodegenerative symptoms experience many social problems. Sulforaphane is a type of organosulfur compound known as an isothiocyanate. It is derived from glucoraphanin, a compound found in cruciferous vegetables such as broccoli, brussels sprouts, and cabbages, via an enzymatic reaction that is triggered by plant damage (e.g., chewing). Sulforaphane exhibits activity against cancer, inflammation, depression, and severe cardiac diseases. It can also alleviate oxidative stress and neural dysfunction in the brain. However, there is insufficient knowledge about the electrophysiological and behavioral basis of the effects of sulforaphane on learning and memory. Therefore, we evaluated whether acute sulforaphane administration affected long-term potentiation (LTP) in organotypic cultured rat hippocampal tissues. We also measured the effect of sulforaphane on the performance of three behavioral tests, the Y-maze test, the passive avoidance test, and the Morris water maze, which assess short-term memory, avoidance memory, and short and long-term spatial memory, respectively. We found that sulforaphane increased the total field excitatory postsynaptic potential (fEPSP) in a dose-dependent manner after high frequency stimulation and attenuated scopolamine-induced interference of the fEPSP in the hippocampal CA1 area. Sulforaphane also restored cognitive function and inhibited memory impairment as indicated by the alleviation of the negative neurological effects of scopolamine, i.e, a lowered ratio of spontaneous alternation in the Y-maze, a reduced step-through latency in the passive avoidance test, and an increased navigation time in the Morris water maze. These results indicate that sulforaphane can effectively prevent the attenuation of LTP and cognitive abilities induced by cholinergic and muscarinic receptor blockade. Further research is warranted to explore the potential therapeutic and prophylactic utility of sulforaphane for improving learning and memory, especially in those suffering from neurodegenerative disorders.

MR-Based Electrical Conductivity Imaging of Liver Fibrosis in an Experimental Rat Model.

BACKGROUND: Liver fibrosis is characterized by the excessive accumulation of extracellular matrix proteins. Electrical conductivity imaging at low frequency can provide novel contrast because the contrast mechanisms originate from the changes in the concentration and mobility of ions in the extracellular space. PURPOSE: To evaluate the feasibility of an MR-based electrical conductivity imaging that can detect the changes in a tissue condition associated with the progression of liver fibrosis. STUDY TYPE: Prospective phantom and animal study. ANIMAL MODEL: Fibrosis was induced by weekly intraperitoneal injection of dimethylnitrosamine (DMN) in 45 male Sprague-Dawley rats. FIELD STRENGTH/SEQUENCE: 3T MRI with a multispin-echo pulse sequence. ASSESSMENT: The percentage change of conductivity (Δσ, %) in the same region-of-interest (ROI) was calculated from the DMN-treated rats based on the values of the normal control rats. The percentage change was also calculated between the ROIs in each DMN-treated group. STATISTICAL TESTS: One-way analysis of variance (ANOVA) and a two-sample t-test were performed. RESULTS: Liver tissues in normal control rats showed a uniform conductivity distribution of 56.6 ± 4.4 (mS/m). In rats more than 5 weeks after induction, the fibrous region showed an increased conductivity of ≥12% compared to that of the corresponding normal control rats. From regional comparisons in the same liver, the fibrous region showed an increased conductivity of ≥11% compared to the opposite, less induced region of rats more than 5 weeks after induction. Liver samples from the fibrous region represent tissue damages such as diffuse centrilobular congestion with marked dilatation of central veins from the histological findings. Immunohistochemistry revealed significant levels of attenuated fibrosis and increased inflammatory response. DATA CONCLUSION: The increased conductivity in the fibrous region is related to the changes of the extracellular space. The correlation between the collagen deposition and conductivity changes is essential for future clinical studies. Level of Evidence 2 Technical Efficacy Stage 2 J. MAGN. RESON. IMAGING 2021;53:554-563.