K+ Channel Modulatory Subunits KChIP and DPP Participate in Kv4-Mediated Mechanical Pain Control.

The K+ channel pore-forming subunit Kv4.3 is expressed in a subset of nonpeptidergic nociceptors within the dorsal root ganglion (DRG), and knockdown of Kv4.3 selectively induces mechanical hypersensitivity, a major symptom of neuropathic pain. K+ channel modulatory subunits KChIP1, KChIP2, and DPP10 are coexpressed in Kv4.3+ DRG neurons, but whether they participate in Kv4.3-mediated pain control is unknown. Here, we show the existence of a Kv4.3/KChIP1/KChIP2/DPP10 complex (abbreviated as the Kv4 complex) in the endoplasmic reticulum and cell surface of DRG neurons. After intrathecal injection of a gene-specific antisense oligodeoxynucleotide to knock down the expression of each component in the Kv4 complex, mechanical hypersensitivity develops in the hindlimbs of rats in parallel with a reduction in all components in the lumbar DRGs. Electrophysiological data further indicate that the excitability of nonpeptidergic nociceptors is enhanced. The expression of all Kv4 complex components in DRG neurons is downregulated following spinal nerve ligation (SNL). To rescue Kv4 complex downregulation, cDNA constructs encoding Kv4.3, KChIP1, and DPP10 were transfected into the injured DRGs (defined as DRGs with injured spinal nerves) of living SNL rats. SNL-evoked mechanical hypersensitivity was attenuated, accompanied by a partial recovery of Kv4.3, KChIP1, and DPP10 surface levels in the injured DRGs. By showing an interdependent regulation among components in the Kv4 complex, this study demonstrates that K+ channel modulatory subunits KChIP1, KChIP2, and DPP10 participate in Kv4.3-mediated mechanical pain control. Thus, these modulatory subunits could be potential drug targets for neuropathic pain.SIGNIFICANCE STATEMENT Neuropathic pain, a type of moderate to severe chronic pain resulting from nerve injury or disorder, affects 6.9%-10% of the global population. However, less than half of patients report satisfactory pain relief from current treatments. K+ channels, which act to reduce nociceptor activity, have been suggested to be novel drug targets for neuropathic pain. This study is the first to show that K+ channel modulatory subunits KChIP1, KChIP2, and DPP10 are potential drug targets for neuropathic pain because they form a channel complex with the K+ channel pore-forming subunit Kv4.3 in a subset of nociceptors to selectively inhibit mechanical hypersensitivity, a major symptom of neuropathic pain.

Influence of Temperature on the Formation of Silver Nanoparticles by using a Seed-Free Photochemical Method under Sodium-Lamp Irradiation.

Silver nanoparticles can be prepared by using a seed-free photo-assisted citrate reduction method under the irradiation of a sodium lamp. Under the same irradiation intensity, bath temperatures are crucial in influencing the reaction rate, morphologies of final products, and shape evolution of the silver nanostructures. For example, when the bath temperature is 80 °C, the product yields of silver nanoplates, nanorods, and nanodecahedra are 38±6 %, 35±10 %, and 12±8 %, respectively. However, when the bath temperature is 30 °C, the product yields of silver nanoplates, nanorods, and nanodecahedra are 6±3 %, 0 %, and 83±16 %, respectively. Time-dependent UV/Vis spectra and TEM images show that silver nanoplates were formed at the earlier reaction stage and greatly decreased in amount at the later stage when the bath temperatures are less than or equal to 40 °C. This indicates that the silver nanoplates, which can be regarded as intermediates, are kinetically favored products. They are not thermodynamically favored products at these relatively low bath temperatures. The SERS spectra of crystal violet (CV) show that all the silver colloids synthesized at various temperatures exhibit good enhancement factors and that the colloids prepared at lower bath temperatures have a higher enhancement factor.

Transcutaneous Laryngeal Ultrasound for Assessing Hyaluronic Acid Status in Patients Undergoing Injection Laryngoplasty.

OBJECTIVE: Injection laryngoplasty (IL) with hyaluronic acid (HA) is an effective treatment for patients with glottic insufficiency. The duration of HA maintenance in the vocal fold remains unknown. In this study, transcutaneous laryngeal ultrasound (TLUS) was used to evaluate the absorption and migration of HA after IL. Subsequent management might be provided based on the TLUS finding. METHODS: Patients diagnosed with unilateral vocal fold paralysis (UVFP) or vocal fold atrophy were recruited. All patients underwent IL with HA in an office-based setting along with TLUS to monitor the status of HA. The schedule of TLUS included assessments before and after IL until non-visualization. RESULTS: The study population comprised 38 women and 17 men. Of the patients, 54.1% underwent IL for UVFP, whereas 45.9% underwent IL for vocal fold atrophy. Multivariate Cox regression analysis for factors affecting HA absorption revealed that the cause of injection was the most important independent predictor (hazard ratio [HR], 2.15; 95% confidence interval [CI], 1.03-4.46; p = 0.040). The duration of HA maintenance was significantly longer in patients with UVFP than in those with vocal fold atrophy (8.77 vs. 4.70 months, HR, 2.33; 95% CI, 5.47-8.18; p = 0.002). CONCLUSION: TLUS is an objective assessment method for patients undergoing IL with HA. Subsequent tailor-made management could be offered based on the TLUS findings during follow-up. For patients at high risk of upper respiratory tract infection or who are intolerant to flexible nasopharyngoscopy, TLUS can be used as an alternative tool to evaluate the condition of the glottis after IL with HA. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:4682-4687, 2024.

Use of YouTube by academic medical centres during the COVID-19 pandemic: an observational study in Taiwan.

OBJECTIVES: YouTube has been of immense importance in conveying essential information on COVID-19 and promoting the latest healthcare policies during the outbreak. However, there have been few studies that have focused on how healthcare organisations have used YouTube to communicate with the public and increase their awareness during the pandemic, as well as its effectiveness. DESIGN: A nationwide observational study. SETTINGS: We analysed all YouTube video posts culled from the official accounts of all medical centres in Taiwan from December 2019 to August 2021. PARTICIPANTS: All YouTube videos were categorised as either COVID-19 or non-COVID-19 related. The COVID-19-related videos were divided into five categories, and detailed metrics for each video were recorded. For comparison, we also surveyed all YouTube video posts placed by the Ministry of Health and Welfare and the Taiwan Centers for Disease Control (TCDC). RESULTS: We analysed official YouTube channels from 17 academic medical centres, involving a total of 943 videos. We found a relationship between the quantity of YouTube videos uploaded by the TCDC and the trend of confirmed cases (Pearson's correlation coefficient was 0.25, p=0.02). Data from private hospitals revealed that they posted more COVID-19 videos (103 vs 56) when compared with public hospitals. In addition, multivariate linear regression showed that more 'likes' (estimate 41.1, 95% CI 38.8 to 43.5) and longer lengths (estimate 10 800, 95% CI 6968.0 to 14 632.0) of COVID-19-related videos correlated significantly with an increased number of 'views'. CONCLUSIONS: This nationwide observational study, performed in Taiwan, demonstrates well the trend and effectiveness of academic medical centres in promoting sound healthcare advice regarding COVID-19 through YouTube due to the channel's easy accessibility and usability.

Extra-major salivary gland pleomorphic adenoma of the head and neck: a 10-year experience and review of the literature.

Pleomorphic adenomas, or benign mixed tumors, make up 65% of all salivary gland tumors. They also can be found as solid tumors in other parts of the head and neck region, such as the auditory canal, the eyelids, and the orbital area. In this study, we investigated extra-major salivary gland pleomorphic adenomas of the head and neck region retrospectively at a tertiary care center. Between March 1998 and June 2009, 37 patients underwent primary surgery for extra-major salivary gland pleomorphic adenoma of the head and neck. The duration of symptoms, radiographic findings, operative procedures, and pathologic findings were documented. Of the 37 patients enrolled, 22 were male and 15 were female, with a median age of 57 years. Tumors were found in the soft palate, hard palate, nasopharynx, orbital area, trachea, buccal mucosa, cheek, nasal septum, upper lip, lower eyelid, and external auditory canal. Cellular variant of the pleomorphic adenoma was found in four patients, while the remaining patients presented with the classic variant. No myxoid subgroup was noted in our study. Carcinoma ex pleomorphic adenoma was observed only in one patient for whom radical surgery was performed. Twenty-eight patients (76%) had long-term follow-ups, with the average follow-up period being 4.5 years. Local recurrence was observed in three patients, and they underwent revision surgery during the follow-up period. Our results indicate that extra-major salivary gland pleomorphic adenomas are most commonly found in the soft palate. Wide excision was the treatment of choice, although its efficacy might be compromised with cosmetics and functional structures of the head and neck. Therefore, long-term follow-up of patients is necessary.

Compositional RL Agents That Follow Language Commands in Temporal Logic.

We demonstrate how a reinforcement learning agent can use compositional recurrent neural networks to learn to carry out commands specified in linear temporal logic (LTL). Our approach takes as input an LTL formula, structures a deep network according to the parse of the formula, and determines satisfying actions. This compositional structure of the network enables zero-shot generalization to significantly more complex unseen formulas. We demonstrate this ability in multiple problem domains with both discrete and continuous state-action spaces. In a symbolic domain, the agent finds a sequence of letters that satisfy a specification. In a Minecraft-like environment, the agent finds a sequence of actions that conform to a formula. In the Fetch environment, the robot finds a sequence of arm configurations that move blocks on a table to fulfill the commands. While most prior work can learn to execute one formula reliably, we develop a novel form of multi-task learning for RL agents that allows them to learn from a diverse set of tasks and generalize to a new set of diverse tasks without any additional training. The compositional structures presented here are not specific to LTL, thus opening the path to RL agents that perform zero-shot generalization in other compositional domains.

Microstructure and Hardness of Spark Plasma Sintered Inconel 625-NbC Composites for High-Temperature Applications.

The study focuses on obtaining Inconel 625-NbC composites for high-temperature applications, e.g., jet engines, waste-to-energy combusting systems or gas engine turbines, and characterizing them in terms of their microstructure and hardness improvement. Synthesis was performed utilizing Spark Plasma Sintering (SPS) at 1150 °C under the load of 45 MPa in medium vacuum (under 10-3 MPa) for a total time of 60 min. Four sets of samples with different Inconel 625 to NbC weight ratios were prepared (5, 10, 20, and 30 wt.%), followed by a reference sample containing no ceramic reinforcement. Obtained materials were hot-rolled at 1150 °C with a 10% reduction step and later cut and polished to perform characterization utilizing scanning electron microscopy (SEM) equipped with energy dispersive spectroscopy (EDS) module and microhardness testing device equipped with Vickers indenter. Hardness was improved proportionally to NbC addition achieving an increase of up to 20% of reference values. Additional heat treatment was conducted on the hot-rolled samples at 1200 °C in an argon atmosphere to further observe the interaction between reinforcement and alloy. Their microstructure revealed the coarsening of precipitates within the metal matrix and partial reinforcement dissolution, which proved to be crucial to obtaining the highest quality composites with homogenous hardness improvement.

The Effect of Post-Processes on the Microstructure and Creep Properties of Alloy718 Built Up by Selective Laser Melting.

The selective laser melting (SLM) process was used to fabricate an Alloy718 specimen. The microstructure and creep properties were characterized in both the as-built and post-processed SLM materials. Post-processing involved several heat treatments and a combination of hot isostatic pressing (HIP) and solution treatment and aging (STA) to homogenize the microstructure. The experimental results showed that the originally recommended heat treatment process, STA-980 °C, for cast and wrought materials was not effective for SLM-processed specimens. Obvious grain growth structures were obtained in the STA-1180 °C/1 h and STA-1180 °C/4 h specimens. However, the grain size was uneven since heavy distortion or high-density dislocation formed during the SLM process, which would be harmful for the mechanical properties of SLM-fabricated materials. The HIP+ direct aging process was the most effective method among the post-processes to improve the creep behavior at 650 °C. The creep rupture life of the HIP+ direct aging condition approached 800 h since the HIP process had the benefit of being free of pores, thus preventing microcrack nucleation and the formation of a serrated grain boundary.

Neck dissection and stroke in patients with oral cavity cancer: A population-based cohort study.

BACKGROUND: Oral cavity cancer is one of the most common head and neck cancers in the world. The purpose of this study was to determine the incidence and risk factors for stroke after surgery in patients with oral cavity cancer with a focus on the effect of neck dissection. METHODS: Data from the Taiwan National Health Insurance Research Database for newly diagnosed oral cavity cancer between January 1, 2005, and December 31, 2007, were included. RESULTS: Neck dissection did not increase the risk of stroke after treatment. Patients with ages older than 44 years, hypertension, diabetes mellitus, coronary artery disease, previous stroke, or postoperative chemoradiotherapy had a significantly higher risk of stroke (p < .05). CONCLUSION: Our data demonstrate that neck dissection does not increase the risk of stroke in patients with oral cavity cancer. Patients have higher risk of stroke after cancer treatment because of their older age, specific comorbidities, and/or type of postoperative treatment. © 2016 Wiley Periodicals, Inc. Head Neck 39: 63-70, 2017.

Revisiting the quantitative features of surface-assisted laser desorption/ionization mass spectrometric analysis.

Surface-assisted laser desorption/ionization (SALDI) coupled with mass spectrometry (MS) is frequently used to analyse small organics owing to its clean background. Inorganic materials can be used as energy absorbers and the transfer medium to facilitate the desorption/ionization of analytes; thus, they are used as SALDI-assisting materials. Many studies have demonstrated the usefulness of SALDI-MS in quantitative analysis of small organics. However, some characteristics occurring in SALDI-MS require certain attention to ensure the reliability of the quantitative analysis results. The appearance of a coffee-ring effect in SALDI sample preparation is the primary factor that can affect quantitative SALDI-MS analysis results. However, to the best of our knowledge, there are no reports relating to quantitative SALDI-MS analysis that discuss or consider this effect. In this study, the coffee-ring effect is discussed using nanoparticles and nanostructured substrates as SALDI-assisting materials to show how this effect influences SALDI-MS analysis results. Potential solutions for overcoming the existing problems are also suggested.This article is part of the themed issue 'Quantitative mass spectrometry'.

Functional gold nanoparticle-based antibacterial agents for nosocomial and antibiotic-resistant bacteria.

AIM: Medical treatments for bacterial-infections have become challenging because of the emergence of antibiotic-resistant bacterial strains. Thus, new therapeutics and antibiotics must be developed. MATERIALS & METHODS: Arginine and tryptophan can target negatively-charged bacteria and penetrate bacterial cell membrane, respectively. Synthetic-peptides containing arginine, tryptophan and cysteine termini, in other words, (DVFLG)2REEW4C and (DVFLG)2REEW2C, as starting materials were mixed with aqueous tetrachloroauric acid to generate peptide-immobilized gold nanoparticles (i.e., [DVFLG]2REEW4C-AuNPs and [DVFLG]2REEW2C-AuNPs) through one-pot reactions. RESULTS & DISCUSSION: The peptide immobilized AuNPs exhibit targeting capacity and antibacterial activity. Furthermore, (DVFLG)2REEW4C-AuNPs immobilized with a higher number of tryptophan molecules possess more effective antibacterial capacity than (DVFLG)2REEW2C-AuNPs. Nevertheless, they are not harmful for animal cells. The feasibility of using the peptide-AuNPs to inhibit the cell growth of bacterium-infected macrophages was demonstrated. CONCLUSION: These results suggested that the proposed antibacterial AuNPs are effective antibacterial agents for Staphylococci, Enterococci and antibiotic-resistant bacterial strains. [Formula: see text].

Relationship between idiopathic sudden sensorineural hearing loss and subsequent stroke.

OBJECTIVES/HYPOTHESIS: The correlation between idiopathic sudden sensorineural hearing loss and subsequent stroke is unclear. This study aimed to review stroke incidence after idiopathic sudden sensorineural hearing loss among patients admitted to a tertiary referral center and aimed to compare the characteristics of patients with and without stroke. STUDY DESIGN: Individual retrospective cohort study. METHODS: Between January 2000 and April 2004, a total of 349 patients diagnosed with idiopathic sudden sensorineural hearing loss were admitted to Taipei Veterans General Hospital and followed up until May 31, 2009. The patients were divided into two groups: a stroke group and a nonstroke group. Cox proportional hazards regression was used for analysis after adjusting for age, sex, hypertension, diabetes mellitus, coronary artery disease, and prior stroke history. RESULTS: The average follow-up duration was 81.7 ± 15.0 months, and the average annual stroke incidence rate was 0.6%. The number of patients with older age, hypertension, coronary artery disease, and prior stroke history was significantly higher in the stroke group than in the nonstroke group. Prior stroke history was the most important risk factor for stroke after idiopathic sudden sensorineural hearing loss. CONCLUSIONS: Idiopathic sudden sensorineural hearing loss did not increase stroke risk. The average annual stroke incidence rate after idiopathic sudden sensorineural hearing loss was comparable with that in the general Taiwanese population. The study patients experienced stroke because they carried the risk factors for stroke. In patients with modified risk factors for stroke, efforts should be made to prevent stroke rather than idiopathic sudden sensorineural hearing loss.

Partial laryngopharyngectomy in the treatment of squamous cell carcinoma of hypopharynx: analysis of the oncologic results and laryngeal preservation rate.

CONCLUSION: Partial laryngopharyngectomy (PLP) provides acceptable oncologic results and laryngeal preservation rate in selected patients with squamous cell carcinoma of the hypopharynx. Even when local recurrence develops, the chance of successful salvage is still high. OBJECTIVES: To evaluate the oncologic results and laryngeal preservation rate in patients with squamous cell carcinoma of the hypopharynx who underwent PLP. METHODS: The results of 39 patients who underwent PLP were compared with those of 91 patients who underwent total laryngectomy (TL). RESULTS: The distribution of the primary T stages were 23 (59%) pT2, 9 (23%) pT3, and 7 (18%) pT4; the pathologic stages were 8 patients (21%) stage II, 9 (23%) stage III, and 22 (56%) stage IV. All of the patients also had ipsilateral or bilateral neck dissections. Eighteen patients (46%) received postoperative adjuvant therapy. After a median follow-up of 39 months, 17 patients (44%) had recurrence, including 12 local, 2 regional, and 3 distant lesions. The 5-year overall and disease-specific survival were 44% and 56%, respectively; functional preservation was 62%. The recurrence rate was similar in patients treated with PLP and TL (44% vs 36%, p = 0.431); the local recurrence rate was higher after PLP than after TL (31% vs 8%, p = 0.001). The salvage surgery was successful in four of the six patients (67%). After salvage treatment, the 5-year overall survival (44% vs 47%) and disease-specific survival (56% vs 62%) were similar in the two groups.

Re-evaluation of CO2 laser myringotomy for managing children with persistent acute otitis media.

BACKGROUND: This study aimed to re-evaluate the utility of CO(2) laser myringotomy in children with persistent acute otitis media (PAOM). METHODS: From September 2002 to April 2008, 40 children with PAOM received CO(2) laser myringotomy. PAOM was defined as continuing symptoms and signs after systemic antibiotic treatment. Before laser myringotomy, the eardrums were checked under videotelescopy, pure tone audiometry or behavior audiometry and tympanometry. Middle ear effusions were collected using our own designed bottle culture device after laser myringotomy. The patients were followed up at outpatient clinics for 3 months. Cultured middle ear pathogens, healing time of the eardrums, hospital course (for admitted patients), and the development of middle ear effusions were recorded. RESULTS: Forty children with 53 ears with PAOM were enrolled. Eight patients (20%) had bilateral disease and underwent bilateral laser myringotomy. The overall culture rate was 28.3%, and Streptococcus pneumoniae was the most common pathogen. Eight patients (20%) were admitted for intravenous antibiotics. The average eardrum healing time was 22 days in those with positive cultures, and 16.4 days in those with negative cultures (p=0.125). All eardrums healed in 1 month. The resolution rate was 62.5% at 1 month. Patients with bilateral PAOM were prone to have positive middle ear culture (5/8) compared with those with unilateral PAOM (8/32) (p=0.086). CONCLUSION: CO(2) laser myringotomy is an applicable means of treating PAOM. S pneumoniae is the most common pathogen in PAOM. CO(2) laser myringotomy allows for the drainage and culture sampling of middle ear effusion, relieving the need of taking prolonged medication.