Real-time in vivo thoracic spinal glutamate sensing during myocardial ischemia.

In the spinal cord, glutamate serves as the primary excitatory neurotransmitter. Monitoring spinal glutamate concentrations offers valuable insights into spinal neural processing. Consequently, spinal glutamate concentration has the potential to emerge as a useful biomarker for conditions characterized by increased spinal neural network activity, especially when uptake systems become dysfunctional. In this study, we developed a multichannel custom-made flexible glutamate-sensing probe for the large-animal model that is capable of measuring extracellular glutamate concentrations in real time and in vivo. We assessed the probe's sensitivity and specificity through in vitro and ex vivo experiments. Remarkably, this developed probe demonstrates nearly instantaneous glutamate detection and allows continuous monitoring of glutamate concentrations. Furthermore, we evaluated the mechanical and sensing performance of the probe in vivo, within the pig spinal cord. Moreover, we applied the glutamate-sensing method using the flexible probe in the context of myocardial ischemia-reperfusion (I/R) injury. During I/R injury, cardiac sensory neurons in the dorsal root ganglion transmit excitatory signals to the spinal cord, resulting in sympathetic activation that potentially leads to fatal arrhythmias. We have successfully shown that our developed glutamate-sensing method can detect this spinal network excitation during myocardial ischemia. This study illustrates a novel technique for measuring spinal glutamate at different spinal cord levels as a surrogate for the spinal neural network activity during cardiac interventions that engage the cardio-spinal neural pathway.NEW & NOTEWORTHY In this study, we have developed a new flexible sensing probe to perform an in vivo measurement of spinal glutamate signaling in a large animal model. Our initial investigations involved precise testing of this probe in both in vitro and ex vivo environments. We accurately assessed the sensitivity and specificity of our glutamate-sensing probe and demonstrated its performance. We also evaluated the performance of our developed flexible probe during the insertion and compared it with the stiff probe during animal movement. Subsequently, we used this innovative technique to monitor the spinal glutamate signaling during myocardial ischemia and reperfusion that can cause fatal ventricular arrhythmias. We showed that glutamate concentration increases during the myocardial ischemia, persists during the reperfusion, and is associated with sympathoexcitation and increases in myocardial substrate excitability.

GABAergic Signaling during Spinal Cord Stimulation Reduces Cardiac Arrhythmias in a Porcine Model.

BACKGROUND: Neuraxial modulation, including spinal cord stimulation, reduces cardiac sympathoexcitation and ventricular arrhythmogenesis. There is an incomplete understanding of the molecular mechanisms through which spinal cord stimulation modulates cardiospinal neural pathways. The authors hypothesize that spinal cord stimulation reduces myocardial ischemia-reperfusion-induced sympathetic excitation and ventricular arrhythmias through γ-aminobutyric acid (GABA)-mediated pathways in the thoracic spinal cord. METHODS: Yorkshire pigs were randomized to control (n = 11), ischemia-reperfusion (n = 16), ischemia-reperfusion plus spinal cord stimulation (n = 17), ischemia-reperfusion plus spinal cord stimulation plus γ-aminobutyric acid type A (GABAA) or γ-aminobutyric acid type B (GABAB) receptor antagonist (GABAA, n = 8; GABAB, n = 8), and ischemia-reperfusion plus GABA transaminase inhibitor (GABAculine, n = 8). A four-pole spinal cord stimulation lead was placed epidurally (T1 to T4). GABA modulating pharmacologic agents were administered intrathecally. Spinal cord stimulation at 50 Hz was applied 30 min before ischemia. A 56-electrode epicardial mesh was used for high-resolution electrophysiologic recordings, including activation recovery intervals and ventricular arrhythmia scores. Immunohistochemistry and Western blots were performed to measure GABA receptor expression in the thoracic spinal cord. RESULTS: Cardiac ischemia led to myocardial sympathoexcitation with reduction in activation recovery interval (mean ± SD, -42 ± 11%), which was attenuated by spinal cord stimulation (-21 ± 17%, P = 0.001). GABAA and GABAB receptor antagonists abolished spinal cord stimulation attenuation of sympathoexcitation (GABAA, -9.7 ± 9.7%, P = 0.043 vs. ischemia-reperfusion plus spinal cord stimulation; GABAB, -13 ± 14%, P = 0.012 vs. ischemia-reperfusion plus spinal cord stimulation), while GABAculine alone caused a therapeutic effect similar to spinal cord stimulation (-4.1 ± 3.7%, P = 0.038 vs. ischemia-reperfusion). The ventricular arrhythmia score supported these findings. Spinal cord stimulation during ischemia-reperfusion increased GABAA receptor expression with no change in GABAB receptor expression. CONCLUSIONS: Thoracic spinal cord stimulation reduces ischemia-reperfusion-induced sympathoexcitation and ventricular arrhythmias through activation of GABA signaling pathways. These data support the hypothesis that spinal cord stimulation-induced release of GABA activates inhibitory interneurons to decrease primary afferent signaling from superficial dorsal horn to sympathetic output neurons in the intermediolateral nucleus.

Association and dose-response relationship between exposure to alcohol advertising media and current drinking: a nationwide cross-sectional study of Japanese adolescents.

BACKGROUND: Underage drinking is a public health concern. However, few studies have examined the association between alcoholic beverage advertising and underage drinking, particularly in countries with low underage drinking rates, such as Japan. Therefore, we aimed to investigate the relationship between exposure to advertising in various media and alcohol drinking among Japanese adolescents. METHODS: We conducted a cross-sectional study involving 15,683 adolescents (51% girls) using data from a nationwide lifestyle survey in 2021 among junior and senior high schools across Japan. Media types were websites, stores, and public transportation. We defined current drinking as alcohol consumption of ≥1 day in the 30 days preceding the survey. Multivariable logistic regression was used to examine the association between exposure to alcohol advertisements and current drinking, adjusting for sex, grades, school area, lifestyle (bedtime and having fun at school), and addictive behaviors (smoking status and parents' alcohol consumption). RESULTS: The prevalence of current drinking was 2.2% (2.3% of boys and 2.0% of girls). Students who were exposed to any alcohol advertising media had higher odds of current drinking compared with those who were not (odds ratio, 1.48; 95% confidence interval [CI], 1.18-1.87). Students who were exposed to web, in-store, and public transportation advertisements had odds ratios of 1.44 (95% CI, 1.14-1.81), 1.62 (1.28-2.05), and 1.45 (1.06-1.98) of current drinking, respectively, compared with those who were not. The association of exposure to alcohol advertising media with the prevalence of current drinking was similar among boys and girls (all p for sex interaction >0.1), except for that of exposure to web advertisements; its association with current drinking was more pronounced in girls (p for sex interaction = 0.046). Exposure to a larger cumulative number of different alcohol advertising media was independently associated with a higher prevalence of current drinking among all students, boys, and girls (p-values for trend <0.001, 0.031, and <0.001, respectively; p for sex interaction = 0.085). CONCLUSIONS: We found an association with a dose-response relationship between exposure to alcohol advertisements and current drinking among adolescents in junior and senior high schools across Japan. Our findings highlight the need for further advertising regulations to prevent underage drinking.

Effectiveness of nurse-delivered screening and brief alcohol intervention in the workplace: A randomized controlled trial at five Japan-based companies.

BACKGROUND: Excessive alcohol use is a leading cause of global morbidity and premature mortality. This study evaluated the effectiveness of two types of nurse-delivered interventions to reduce excessive alcohol consumption among screened participants using the alcohol use disorders identification test (AUDIT) in the workplace. METHODS: A randomized controlled trial involving AUDIT-positive employees of five Japan-based companies was conducted. A total of 351 participants were randomized into groups that received a patient information leaflet (PIL), 5 min of brief advice, or 15 min of brief advice and counseling. Outcomes (weekly alcohol consumption and drinking and binge drinking frequency in the previous 30 days) were evaluated at 6 and 12-month follow-up. RESULTS: The follow-up rates were 96.3% (n = 338) and 94.9% (n = 333) at 6 and 12 months, respectively. At 6 months, the mean change in weekly alcohol consumption was -38.1 g (-1.64 US fluid oz/week) in the 15-min brief advice and counseling group, which differed significantly from the PIL group. The reduction in the advice and counseling group persisted at 12-month follow-up but was no longer significantly different from the PIL group. There was no significant change in alcohol consumption observed in the 5-min brief advice group. Improvement in drinking and binge drinking frequency was observed in all three groups. CONCLUSIONS: Nurse-delivered 15-min brief advice and counseling was effective over a 6-month period in reducing alcohol consumption in a workplace setting. This finding suggests that the implementation of workplace screening and brief intervention could play a useful role in preventing the burden of harmful alcohol use.

Abstaining from annual health check-ups is a predictor of advanced cancer diagnosis: a retrospective cohort study.

BACKGROUND: Cancer prevention is a crucial challenge in preventive medicine. Several studies have suggested that voluntary health check-ups and recommendations from health professionals are associated with increased participation in cancer screening. In Japan, it is recommended that individuals aged 40-74 years should undergo annual health check-ups; however, the compliance to this recommendation is approximately <50%. According to the national survey, individuals who do not undergo annual health check-ups are at a higher risk for cancer. However, to the best of our knowledge, no previous study has investigated the association between the use of health check-ups and the incidence rate of cancer. We hypothesised that not undergoing periodic health check-ups and/or less use of outpatient medical services are predictors for advanced cancer. METHODS: To explore the relationship between health check-up or outpatient service utilisation and cancer incidence, this retrospective cohort study used data at two time points-baseline in 2014 and endpoint in 2017-from the National Health Insurance (NHI) claims and cancer registry. A multivariable logistic regression analysis was performed to investigate whether cancer diagnosis was associated with health check-up or outpatient service utilisation. RESULTS: A total of 72,171 participants were included in the analysis. The results of the multivariable logistic regression showed that individuals who skipped health check-ups had a higher risk of cancer diagnosis (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.04-1.40). Moreover, not undergoing health check-ups increased the risk of advanced-stage cancer (OR, 1.78; 95% CI, 1.29-2.44). Furthermore, increased rate of outpatient service utilisation was negatively associated with advanced cancer diagnosis. CONCLUSIONS: This is the first study reporting that not undergoing health check-ups is a predictor of cancer diagnosis and advanced cancer stage. Primary prevention strategies for NHI members who do not undergo health check-ups must be reassessed. Moreover, future research should examine secondary prevention strategies, such as health education and recommendations from health professionals to facilitate adequate utilisation of preventive health services.

Immunological features of circulating monocyte subsets in patients with squamous cell carcinoma of the head and neck.

BACKGROUND: Circulating monocytes are classified into three subsets according to their CD14 and CD16 expressions. Here we investigated all three subsets in patients with squamous cell carcinoma of the head and neck (SCCHN). METHODS: Peripheral blood from 54 patients with SCCHN and 24 healthy donors (HDs) was tested for flowcytometry. Immunohistochemical staining of the primary tumor was performed. SCCHN cells were co-cultured with human monocytes in vitro. RESULTS: The level of intermediate monocytes was significantly lower in SCCHN than in HDs. The expression levels of HLA-G, PD-L1, and CD51 on intermediate monocytes was evidently greater in patients with SCCHN. In vitro co-culturing of SCCHN cells with monocytes revealed a significant increase in CD51 expression levels on monocytes. The decrease in expression levels of the maturation markers CX3CR1 and CD68 was significantly correlated to poor clinical outcomes. CONCLUSION: The level of intermediate monocytes was decreased in cancer patients in favor of immature and expressed immunosuppressive molecules.

Heated Tobacco Product Smokers in Japan Identified by a Population-Based Survey.

BACKGROUND: In this study, we aim to estimate the prevalence of heated tobacco product (HTP) smokers 3 years after the launch of HTPs in Japan. METHODS: Our study, performed in February 2018 in Japan, had a cross-sectional population-based design. A total of 4,628 adult participants (2,121 men and 2,507 women) were randomly sampled from all regions of Japan. The response rate was 57.9%. Interviews were conducted by trained investigators who visited participants' homes. A survey on current (past 30 days) and lifetime tobacco use (including e-cigarettes and HTPs), as well as numerous sociodemographic factors, was conducted. RESULTS: The age-adjusted rates and estimated number of lifetime-HTP smokers were 14.1% (95% confidence interval [CI], 12.5-15.6%; 7.11 million men) and 3.7% (95% CI, 2.9-4.4%; 1.99 million women). The age-adjusted rates for current HTP smokers were 8.3% (95% CI, 7.1-9.6%; 4.21 million men) and 1.9% (95% CI, 1.3-2.4%; 1.02 million women). Multiple variables were found to be associated with a higher prevalence of current HTP use, including being male, aged 20-39 years, a current Internet user, a risky drinker, or a heavy episodic drinker. HTP use was also higher among men with 10 years or more of education, women with 15 years or less of education, and men with middle- or high-level household incomes. CONCLUSION: We concluded that HTP use has increased substantially in Japan. However, regulations for HTPs are weaker than those for combustible cigarettes in Japan. Thus, HTPs should be subjected to the same regulations as combustible tobacco products.

Heat-not-burn tobacco, electronic cigarettes, and combustible cigarette use among Japanese adolescents: a nationwide population survey 2017.

BACKGROUND: From among the global public health concerns, smoking remains one of the most crucial challenges. Especially for adolescents, the increase in the use of electronic cigarettes is controversial, as its use may lead to established smoking. In Japan, where a unique tobacco regulation system exists, the heat-not-burn tobacco market has been growing. However, the prevalence and association of combustible cigarettes and new tobacco-related products have not yet been closely investigated among Japanese adolescents. This study aimed to clarify the prevalence of smoking among adolescents, including new types of tobacco-related products, and to compare the characteristics of their users. METHODS: The 2017 Lifestyle Survey of Adolescents is a nationally-representative survey collected in Japan. From the national school directory, 98 junior high schools and 86 high schools were randomly sampled throughout Japan. The students completed an anonymous questionnaire at school. We calculated the prevalence of use for each type of tobacco product. Then, the use of a combination of products and the characteristics of different types of products were examined. RESULTS: In total, 64,152 students from 48 junior high schools and 55 high schools were included the analysis (school response rate = 56%, Mage = 15.7 years, 53.9% boys). The age-adjusted rate of ever (current) use of electronic cigarettes was 2.1% (0.7%) in junior high school and 3.5% (1.0%) in high school; that of combustible cigarettes was 2.6% (0.6%) in junior high school and 5.1% (1.5%) in high school. The rate of heat-not-burn tobacco use was lower relative to other products: 1.1% (0.5%) in junior high school and 2.2% (0.9%) in high school. An examination of the combined use of the three products identified a high number of dual users. Comparisons between different types of users indicated different backgrounds for combustible cigarette users and new product users. CONCLUSIONS: The prevalence of new tobacco-alternative products is growing in popularity among Japanese adolescents. Dual use is common, and many adolescents use new products only. Moreover, e-cigarettes might attract a broader range of groups to smoking. Continuous monitoring and research are needed to investigate their influence as a possible gateway to tobacco smoking.

Changes in smoking behavior among victims after the great East Japan earthquake and tsunami.

BACKGROUND: In areas affected by the tsunami of the great East Japan Earthquake, smoking behavior may have deteriorated due to high stress and drastic changes in living environment. Surveys were conducted to reveal changes in smoking behaviors among victims. METHODS: A population-based random-sample home-visit interview survey of victims in Iwate and Miyagi Prefectures affected by the tsunami disaster was conducted in 2012 (n = 1978), while a population-based nationwide survey was conducted in 2013 (n = 1082). A panel survey in 2014 was conducted with respondents of the 2012 survey (n = 930). Multiple logistic regression analysis was performed to reveal factors related to smoking status after the disaster. RESULTS: There was high smoking prevalence of both sexes in the tsunami disaster area (current smoking rate in coastal area, 50.0% for male, 21.4% for female; inland area, 34.7% for male, 7.6% for female). Low prevalence of male quitters was observed (quitter rate in coastal area, 20.8% for male, 8.0% for female; inland area, 23.4% for male, 5.5% for female). The prevalence of nicotine-dependent people assessed by FTND (Fagerström Test for Nicotine Dependence) in the coastal area was also higher than in the inland area or other areas of Japan. Smoking behavior among victims worsened after the disaster and did not improve 3 years from the disaster. Post-disaster factors related to smoking were living in coastal area, complete destruction of house, and living in temporary housing. CONCLUSIONS: Smoking prevalence and the level of nicotine dependence of tsunami victims were still high even 3 years after the disaster. It is important to emphasize measures for smoking control in the disaster areas for an extended time period.

Nonlinear polarization evolution using time-dependent density functional theory.

We propose a theoretical and computational approach to investigate temporal behavior of a nonlinear polarization in a perturbative regime induced by an intense and ultrashort pulsed electric field. First-principles time-dependent density functional theory is employed to describe the electron dynamics. Temporal evolution of third-order nonlinear polarization is extracted from a few calculations of electron dynamics induced by pulsed electric fields with the same time profile but different amplitudes. We discuss characteristic features of the nonlinear polarization evolution as well as an extraction of nonlinear susceptibilities and time delays by fitting the polarization. We also carry out a decomposition of temporal and spatial changes in the electron density in power series with respect to the field amplitude. It helps to get insight into the origin of the nonlinear polarization in atomic scale.

Impairments of long-term depression induction and motor coordination precede Aß accumulation in the cerebellum of APPswe/PS1dE9 double transgenic mice.

Alzheimer's disease (AD) is a neurodegenerative disorder that represents the most common type of dementia among elderly people. Amyloid beta (Aß) peptides in extracellular Aß plaques, produced from the amyloid precursor protein (APP) via sequential processing by ß- and γ-secretases, impair hippocampal synaptic plasticity, and cause cognitive dysfunction in AD patients. Here, we report that Aß peptides also impair another form of synaptic plasticity; cerebellar long-term depression (LTD). In the cerebellum of commonly used AD mouse model, APPswe/PS1dE9 mice, Aß plaques were detected from 8 months and profound accumulation of Aß plaques was observed at 18 onths of age. Biochemical analysis revealed relatively high levels of APP protein and Aß in the cerebellum of APPswe/PS1dE9 mice. At pre-Aß accumulation stage, LTD induction, and motor coordination are disturbed. These results indicate that soluble Aß oligomers disturb LTD induction and cerebellar function in AD mouse model.

Association between multimorbidity and utilization of medical and long-term care among older adults in a rural mountainous area in Japan.

Objective: With the accelerated population aging, multimorbidity has become an important healthcare issue. However, few studies have examined multimorbidity and its impact on the use of medical and long-term care services in Japan. Therefore, this study aimed to examine the association between multimorbidity and the use of medical and long-term care services among older adults living in the depopulated mountainous areas of Japan. Patients and Methods: A cross-sectional study was conducted using insurance claims data from late-stage medical insurance and long-term care insurance (April 2017 to March 2018) for older adults ≥75 years residing in a mountainous area in the Tottori prefecture. In addition to the descriptive analysis, multiple generalized linear regressions with family gamma and log-link functions were used to examine the association between the number of morbidities and total annual medical and long-term care expenditures. Results: A total of 970 participants ≥75 years were included in the analysis. Participants who had two or more morbidities constituted 86.5% of the total sample. Furthermore, participants with mental disorders were found to have more comorbidities. The number of comorbidities is associated with higher medical and long-term care expenditures. Conclusion: Multimorbidity was dominant among late-stage older adults living in depopulated mountainous areas of Japan, and the number of morbidities was associated with higher economic costs of medical and long-term care services. Mitigating the impact of multimorbidity among older adults in depopulated regions of Japan is an urgent challenge. Future research should investigate the degree and effectiveness of social protections for vulnerable older adults living in remote areas.

Lifestyle factors associated with presenteeism among city government office workers: a cross-sectional study.

OBJECTIVES: Presenteeism is a critical issue in occupational health. This study aimed to examine the association between presenteeism and subjective sleep quality, smoking status, and alcohol consumption. METHODS: Anonymous data of 777 workers in a Japanese city were retrospectively obtained from City Government Office A. They included variables like absolute presenteeism scores (measured using the Japanese version of the World Health Organization Health and Work Performance Questionnaire short form), gender, age, family status, subjective sleep quality, smoking status, and alcohol consumption. A binary logistic regression analysis was performed with gender, age, family status, subjective sleep quality, smoking status, and alcohol consumption as the independent variables, and absolute presenteeism scores equal to or below 40 as the dependent variable. A gender-stratified binary logistic regression analysis was also performed. RESULTS: The logistic regression analysis results revealed that absolute presenteeism was positively associated with poor subjective sleep quality among all respondents (odds ratio [OR], 1.70; 95% CI, 1.18-2.44) and men (OR, 1.85; 95% CI, 1.12-3.05) and with current drinkers among women (OR, 3.49; 95% CI, 1.36-8.92); it was negatively associated with age among those who were ≥50 years old (OR, 0.50; 95% CI, 0.27-0.93) and with current drinkers among men (OR, 0.43; 95% CI, 0.20-0.92). CONCLUSIONS: The factors associated with presenteeism differed between men and women office workers, suggesting that gender differences need to be considered when working toward improving workers' productivity.

Ventricular arrhythmia inducibility in porcine infarct model after stereotactic body radiation therapy.

BACKGROUND: Ventricular arrhythmia (VA) is the primary mechanism of sudden death in patients with structural heart disease. Cardiac stereotactic body radiation therapy (SBRT) delivered to the scar in the left ventricle significantly reduces the burden of VA. OBJECTIVE: The goal of this study was to investigate the impact of SBRT on scar morphology and VA inducibility in a porcine infarct model. METHODS: Myocardial infarction (MI) was created in 10 Yorkshire pigs involving the left anterior descending artery territory. Cardiac positron emission tomography and computed tomography were performed for targeted SBRT. Alternative pigs received SBRT at 25 Gy in a single fraction. The terminal experiment included endocardial mapping, programmed ventricular stimulation, and tissue harvesting. RESULTS: Of the 10 pigs infarcted, 2 died prematurely after MI and 8 (4 MI and 4 MI+SBRT) survived. Mean time from MI to SBRT was 48 ± 12 days, and mean time from SBRT to harvest was 32 ± 12 days. Scar was localized on intracardiac mapping in all pigs, and the scar was denser in the MI+SBRT compared with the MI-only group (33% ± 20% vs 14% ± 11%; P = .07). All 4 MI pigs had inducible VA during programmed stimulation, whereas only 1 of 4 pigs had inducible VA in the MI+SBRT arm (100% vs 25%; P = .07). No myocardial fibrosis was seen in the remote areas in either group. CONCLUSION: SBRT reduced VA inducibility in pigs with scarring after MI. Endocardial mapping revealed denser scar in pigs receiving SBRT compared with those that did not, suggesting that SBRT suppresses VA inducibility through better scar homogenization.

Spatial and Economic Proximity of Cigarette Sales to School Children in Mongolia.

Background: The Western Pacific Region has the highest rate of cigarette smoking in the world. In this region, Mongolia has ratified the WHO FCTC treaty and, as part of treaty implementation, has monitored school tobacco use in children using the 2014 Global Youth Tobacco Survey (GYTS) and 2019 GYTS. Our objective was to examine the spatial and economic factors associated with cigarette use in schoolchildren of Mongolia. Methods: The 2014 and 2019 GYTS are the most recent and comprehensive national surveys of tobacco use in schoolchildren in Mongolia and are cross-sectional, stratified, multi-stage cluster surveys of 13-15 year-old schoolchildren (7,298 in 2014, 4,146 in 2019) selected from urban and rural schools. For each survey, we conducted logistic regression modelling to examine whether spatial (proximity of cigarette sales to schools), economic (pocket money available to school children), and other environmental/contextual factors were predictors of cigarette use (all, single sticks) in schoolchildren. Results: We found that 1)the prevalence of vendors selling cigarettes near schools increased from 65% in the 2014 GYTS to 94% in the 2019 GYTS, 2) sales of cigarettes near schools were associated with increased current smoking of all cigarettes and this effect increased from a marginal 31% increase in odds in 2014 (OR [95% confidence interval(CI)]=1.31 [0.99, 1.73]) to a 416% increase in odds in 2019 (OR [95% CI]=5.16[3.31, 8.05]), 3) sales of cigarettes near schools were associated with a substantial increase in odds of smoking single cigarettes in 2014 (OR [95% CI]=1.87 [1.14,3.06]) and in 2019 (OR[95% CI]=2.70 [1.42, 5.12]). We also found that smoking of all cigarettes was higher when student pocket money exceeded the price of the cigarette pack (approximately 1.8 USD) and also when parents and/or peers were smokers. Conclusions: Despite the 2012 National Tobacco Laws banning sales of cigarettes and single cigarettes to schoolchildren near schools, the most recent national surveys (2014-2019) have shown that these sales are increasing. We provide new findings indicating that despite the higher pricing of cigarette packs (relative to the region), illicit sales of single cigarettes are targeting schoolchildren near their schools.

Propofol anesthesia decreases the incidence of new-onset postoperative atrial fibrillation compared to desflurane in patients undergoing video-assisted thoracoscopic surgery: A retrospective single-center study.

BACKGROUND: Postoperative atrial fibrillation (POAF) increases postoperative morbidity, mortality, and length of hospital stay. Propofol is reported to modulate atrial electrophysiology and the cardiac autonomic nervous system. Therefore, we retrospectively examined whether propofol suppresses POAF in patients undergoing video-assisted thoracoscopic surgery (VATS) compared to desflurane. METHODS: We retrospectively recruited adult patients who underwent VATS during the period from January 2011 to May 2018 in an academic university hospital. Between continuous propofol and desflurane administration during anesthetic maintenance, we investigated the incidence of new-onset POAF (within 48 hours after surgery) before and after propensity score matching. RESULTS: Of the 482 patients, 344 received propofol, and 138 received desflurane during anesthetic maintenance. The incidence of POAF in the propofol group was less than that in the desflurane group (4 [1.2%] vs. 8 patients [5.8%], odds ratio [OR]; 0.161, 95% confidence interval (CI), 0.040-0.653, p = 0.011) in the present study population. After adjustment for propensity score matching (n = 254, n = 127 each group), the incidence of POAF was still less in propofol group than desflurane group (1 [0.8%] vs. 8 patients [6.3%], OR; 0.068, 95% CI: 0.007-0.626, p = 0.018). CONCLUSIONS: These retrospective data suggest propofol anesthesia significantly inhibits POAF compared to desflurane anesthesia in patients undergoing VATS. Further prospective studies are needed to elucidate the mechanism of propofol on the inhibition of POAF.

Did Depression, Schizophrenia, and Alcohol Use Increase During the COVID-19 Pandemic Even in Low-Risk Regions? An Analysis of the 2017-2020 National Health Insurance Data in Tottori Prefecture.

Background: This study aimed to determine whether the COVID-19 pandemic increased the number of medical consultations for depression, schizophrenia, and alcohol dependence in low-risk regions. Methods: National Health Insurance enrolments from March 2017 to March 2021 in Tottori Prefecture, Japan, where there were minimal COVID-19 cases in 2020, were included in this study. The all-cause mortality and proportion of National Health Insurance members with depression, schizophrenia, and alcohol dependence in the financial years (FY) 2017, 2018, 2019, and 2020 were calculated. The proportion in FY 2020 was compared with the average proportion from FY2017 to FY2019 and the proportion in FY2019. Results: The all-cause mortality for men aged 80-99 years and women aged 70-89 years decreased in FY2020. The proportion of men aged 20-29 years with depression increased to 4.1% in FY2020 compared with 3.0% in FY2019, while the proportion of women aged 20-29 years with depression was 4.4% in FY2017, 4.8% in FY2018, 4.8% in FY2019, and 5.5% in FY2020, confirming an increasing trend from before the COVID-19 pandemic. The proportion of men aged 30-39 years and 60-69 years with schizophrenia increased and that of women aged 40-49 years, 60-69 years, and 90-99 years with schizophrenia also increased, even before the pandemic. The proportion of people with alcohol use disorder has not changed significantly since FY2017. Conclusion: The pandemic has led to an increased proportion of men aged 20-29 years with depression, even in low-risk regions.

Thoracic dorsal root ganglion stimulation reduces acute myocardial ischemia induced ventricular arrhythmias.

Background: Dorsal root ganglion stimulation (DRGS) may serve as a novel neuromodulation strategy to reduce cardiac sympathoexcitation and ventricular excitability. Objective: In this pre-clinical study, we investigated the effectiveness of DRGS on reducing ventricular arrhythmias and modulating cardiac sympathetic hyperactivity caused by myocardial ischemia. Methods: Twenty-three Yorkshire pigs were randomized to two groups, which was control LAD ischemia-reperfusion (CONTROL) or LAD ischemia-reperfusion + DRGS (DRGS) group. In the DRGS group (n = 10), high-frequency stimulation (1 kHz) at the second thoracic level (T2) was initiated 30 min before ischemia and continued throughout 1 h of ischemia and 2 h of reperfusion. Cardiac electrophysiological mapping and Ventricular Arrhythmia Score (VAS) were assessed, along with evaluation of cFos expression and apoptosis in the T2 spinal cord and DRG. Results: DRGS decreased the magnitude of activation recovery interval (ARI) shortening in the ischemic region (CONTROL: -201 ± 9.8 ms, DRGS: -170 ± 9.4 ms, p = 0.0373) and decreased global dispersion of repolarization (DOR) at 30 min of myocardial ischemia (CONTROL: 9546 ± 763 ms2, DRGS: 6491 ± 636 ms2, p = 0.0076). DRGS also decreased ventricular arrhythmias (VAS-CONTROL: 8.9 ± 1.1, DRGS: 6.3 ± 1.0, p = 0.038). Immunohistochemistry studies showed that DRGS decreased % cFos with NeuN expression in the T2 spinal cord (p = 0.048) and the number of apoptotic cells in the DRG (p = 0.0084). Conclusion: DRGS reduced the burden of myocardial ischemia-induced cardiac sympathoexcitation and has a potential to be a novel treatment option to reduce arrhythmogenesis.

Real-time in vivo thoracic spinal glutamate sensing reveals spinal hyperactivity during myocardial ischemia.

Myocardial ischemia-reperfusion (IR) can cause ventricular arrhythmias and sudden cardiac death via sympathoexcitation. The spinal cord neural network is crucial in triggering these arrhythmias and evaluating its neurotransmitter activity during IR is critical for understanding ventricular excitability control. To assess the real-time in vivo spinal neural activity in a large animal model, we developed a flexible glutamate-sensing multielectrode array. To record the glutamate signaling during IR injury, we inserted the probe into the dorsal horn of the thoracic spinal cord at the T2-T3 where neural signals generated by the cardiac sensory neurons are processed and provide sympathoexcitatory feedback to the heart. Using the glutamate sensing probe, we found that the spinal neural network was excited during IR, especially after 15 mins, and remained elevated during reperfusion. Higher glutamate signaling was correlated with the reduction in the cardiac myocyte activation recovery interval, showing higher sympathoexcitation, as well as dispersion of the repolarization which is a marker for increased risk of arrhythmias. This study illustrates a new technique for measuring the spinal glutamate at different spinal cord levels as a surrogate for the spinal neural network activity during cardiac interventions that engage the cardio-spinal neural pathway.

Thoracic Dorsal Root Ganglion Application of Resiniferatoxin Reduces Myocardial Ischemia-Induced Ventricular Arrhythmias.

BACKGROUND: A myocardial ischemia/reperfusion (IR) injury activates the transient receptor potential vanilloid 1 (TRPV1) dorsal root ganglion (DRG) neurons. The activation of TRPV1 DRG neurons triggers the spinal dorsal horn and the sympathetic preganglionic neurons in the spinal intermediolateral column, which results in sympathoexcitation. In this study, we hypothesize that the selective epidural administration of resiniferatoxin (RTX) to DRGs may provide cardioprotection against ventricular arrhythmias by inhibiting afferent neurotransmission during IR injury. METHODS: Yorkshire pigs (n = 21) were assigned to either the sham, IR, or IR + RTX group. A laminectomy and sternotomy were performed on the anesthetized animals to expose the left T2-T4 spinal dorsal root and the heart for IR intervention, respectively. RTX (50 µg) was administered to the DRGs in the IR + RTX group. The activation recovery interval (ARI) was measured as a surrogate for the action potential duration (APD). Arrhythmia risk was investigated by assessing the dispersion of repolarization (DOR), a marker of arrhythmogenicity, and measuring the arrhythmia score and the number of non-sustained ventricular tachycardias (VTs). TRPV1 and calcitonin gene-related peptide (CGRP) expressions in DRGs and CGRP expression in the spinal cord were assessed using immunohistochemistry. RESULTS: The RTX mitigated IR-induced ARI shortening (-105 ms ± 13 ms in IR vs. -65 ms ± 11 ms in IR + RTX, p = 0.028) and DOR augmentation (7093 ms2 ± 701 ms2 in IR vs. 3788 ms2 ± 1161 ms2 in IR + RTX, p = 0.020). The arrhythmia score and VT episodes during an IR were decreased by RTX (arrhythmia score: 8.01 ± 1.44 in IR vs. 3.70 ± 0.81 in IR + RTX, p = 0.037. number of VT episodes: 12.00 ± 3.29 in IR vs. 0.57 ± 0.3 in IR + RTX, p = 0.002). The CGRP expression in the DRGs and spinal cord was decreased by RTX (DRGs: 6.8% ± 1.3% in IR vs. 0.6% ± 0.2% in IR + RTX, p < 0.001. Spinal cord: 12.0% ± 2.6% in IR vs. 4.5% ± 0.8% in IR + RTX, p = 0.047). CONCLUSIONS: The administration of RTX locally to thoracic DRGs reduces ventricular arrhythmia in a porcine model of IR, likely by inhibiting spinal afferent hyperactivity in the cardio-spinal sympathetic pathways.