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.
Low-intensity, low-frequency ultrasound (LILFU) is the next-generation, non-invasive brain stimulation technology for treating various neurological and psychiatric disorders. However, the underlying ...cellular and molecular mechanism of LILFU-induced neuromodulation has remained unknown. Here, we report that LILFU-induced neuromodulation is initiated by opening of TRPA1 channels in astrocytes. The Ca2+ entry through TRPA1 causes a release of gliotransmitters including glutamate through Best1 channels in astrocytes. The released glutamate activates NMDA receptors in neighboring neurons to elicit action potential firing. Our results reveal an unprecedented mechanism of LILFU-induced neuromodulation, involving TRPA1 as a unique sensor for LILFU and glutamate-releasing Best1 as a mediator of glia-neuron interaction. These discoveries should prove to be useful for optimization of human brain stimulation and ultrasonogenetic manipulations of TRPA1.
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•Ultrasound-induced neuromodulation is initiated by opening of TRPA1 in astrocytes•The Ca2+ entry through TRPA1 causes a release of glutamate through Best1 channels•The released glutamate activates NMDA receptors in neighboring neurons
Oh et al. show that TRPA1 is the molecular sensor and transducer for low-intensity, low-frequency ultrasound (LILFU). With TRPA1’s unique co-localization and cooperation with the glutamate-releasing Ca2+-activated Best1 at the microdomains of astrocytes, LILFU is capable of eliciting neuromodulation as a consequence of neuronal NMDAR activation.
Whether dynamic changes of metabolic syndrome (MetS) affects the subsequent laryngeal cancer occurrence remains unknown. 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. 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). 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). Changes in MetS status were associated with the risk of laryngeal cancer. Results of this study have implications for etiological investigations and prevention strategies.
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.
Due to the improvement of medical level, life expectancy increased. But the increased incidence of cognitive disorders is an emerging social problem. Current drugs for dementia treatment can only ...delay the progress rather than cure. p-Coumaric acid is a phenylpropanoic acid derived from aromatic amino acids and known as a precursor for flavonoids such as resveratrol and naringenin. It was shown to reduce oxidative stress, inhibit genotoxicity and exert neuroprotection. Based on these findings, we evaluated whether p-coumaric acid can protect scopolamine induced learning and memory impairment by measuring LTP in organotypic hippocampal slice and cognitive behaviors in rats. p-Coumaric acid dose-dependently increased the total activity of fEPSP after high frequency stimulation and attenuated scopolamine-induced blockade of fEPSP in the hippocampal CA1 area. In addition, while scopolamine shortened the step-through latency in the passive avoidance test and prolonged the latency as well as reduced the latency in the target quadrant in the Morris water maze test, co-treatment of p-coumaric acid improved avoidance memory and long-term retention of spatial memory in behavioral tests. Since p-coumaric acid improved electrophysiological and cognitive functional deterioration by scopolamine, it may have regulatory effects on central cholinergic synapses and is expected to improve cognitive problems caused by abnormality of the cholinergic nervous system.
•p-Coumaric acid protects scopolamine-induced spatial and avoidance memory disruption.•p-coumaric acid improved LTP impairments induced by scopolamine.•p-Coumaric acid may have therapeutic value to improve memory impairements.
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•A piezocapacitive biodegradable pressure sensor has been fabricated.•Device targets low pressure measurements in tactile range of 0 < P < 5 kPa.•Nanofibrous PLGA-PCL membrane has ...been used as elastomeric dielectric.•It was used for wrist pulse monitoring and pressure mapping array applications.•7 days of degradation caused a 19.5% decrease in sensitivity in low pressure range.
High performance biodegradable electronic devices are becoming popular due to their enormous applications as biomedical implants or short term communication devices. They are biocompatible and eco-friendly. For example wearable or implantable biodegradable pressure sensors are very useful for cardiovascular or blood flow monitoring. But unfortunately very few previous researches have focused on developing biodegradable pressure sensors. Here we propose a composite of Polylactic-co-glycolic acid (PLGA) and Polycaprolactone (PCL) for biodegradable piezo-capacitive pressure sensor fabrication for low pressure measurement in tactile ranges of (0 < P < 5 kPa). An electrospun PLGA-PCL composite membrane has been used as elastomeric dielectric sandwiched between two biodegradable iron-zinc (Fe-Zn) bilayer electrodes, deposited on degradable Polyvinyl alcohol (PVA) substrate using electron beam deposition, and encapsulated in PLGA thin films for device fabrication. PLGA-PCL nanofibrous dielectric membrane is highly compressible and porous having tunable mechanical as well as dielectric properties and has been reported first ever for biodegradable pressure sensor application. The sensitivity of the sensor was found to be 0.863 ± 0.025 kPa−1 in the low pressure region (0 < P ≤ 1.86 kPa) which is quite high as compared to previous literature on biodegradable sensors so far while it adapted to a value of 0.062 ± 0.005 kPa−1 for high pressure region (1.86 kPa < P ≤ 4.6 kPa). The lowest detected value was 1.24 Pa (at 10mgf). Sensor showed good average response and recovery times of 251 ms and 170 ms respectively. In vitro degradation studies of the sensor were performed in PBS solution and sensor lost 60% of its initial weight during first two weeks of degradation and continued to degrade even after that. After one week of incubation sensor showed a 19.5% decrease in low pressure measurement range while there was no significant difference in upper detection range. It has been used to measure the arterial pulse wave on wrist and a 4 × 4 pressure sensor array was made to demonstrate its use in mapping different pressure points.
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.
Curcumin is a major diarylheptanoid component of Curcuma longa with traditional usage for anxiety and depression. It has been known for the anti-inflammatory, antistress, and neurotropic effects. ...Here we examined curcumin effect in neural plasticity and cell viability. 60-channel multielectrode array was applied on organotypic hippocampal slice cultures (OHSCs) to monitor the effect of 10 μM curcumin in long-term depression (LTD) through low-frequency stimulation (LFS) to the Schaffer collaterals and commissural pathways. Cell viability was assayed by propidium iodide uptake test in OHSCs. In addition, the influence of oral curcumin administration on rat behavior was assessed with the forced swim test (FST). Finally, protein expression levels of brain-derived neurotrophic factor (BDNF) and cyclooxygenase-2 (COX-2) were measured by Western blot in chronically stressed rats. Our results demonstrated that 10 μM curcumin attenuated LTD and reduced cell death. It also recovered the behavior immobility of FST, rescued the attenuated BDNF expression, and inhibited the enhancement of COX-2 expression in stressed animals. These findings indicate that curcumin can enhance postsynaptic electrical reactivity and cell viability in intact neural circuits with antidepressant-like effects, possibly through the upregulation of BDNF and reduction of inflammatory factors in the brain.
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.
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.
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