Recent application of CRISPR-Cas12 and OMEGA system for genome editing.

In 2012, it was discovered that precise gene editing could be induced in target DNA using the reprogrammable characteristics of the CRISPR system. Since then, several studies have investigated the potential of the CRISPR system to edit various biological organisms. For the typical CRISPR system obtained from bacteria and archaea, many application studies have been conducted and have spread to various fields. To date, orthologs with various characteristics other than CRISPR-Cas9 have been discovered and are being intensively studied in the field of gene editing. CRISPR-Cas12 and its varied orthologs are representative examples of genome editing tools and have superior properties in terms of in vivo target gene editing compared with Cas9. Recently, TnpB and Fanzor of the OMEGA (obligate mobile element guided activity) system were identified to be the ancestor of CRISPR-Cas12 on the basis of phylogenetic analysis. Notably, the compact sizes of Cas12 and OMEGA endonucleases allow adeno-associated virus (AAV) delivery; hence, they are set to challenge Cas9 for in vivo gene therapy. This review is focused on these RNA-guided reprogrammable endonucleases: their structure, biochemistry, off-target effects, and applications in therapeutic gene editing.

Cumulative effect of impaired fasting glucose on the risk of dementia in middle-aged and elderly people: a nationwide cohort study.

The relationship between prediabetes and dementia remains controversial. We aimed to examine the association between cumulative exposure to impaired fasting glucose (IFG) and the risk of dementia in the general population. 1,463,066 middle-aged and elderly subjects who had had health examinations for four consecutive years were identified from a Korean nationwide population-based cohort database. IFG was defined as fasting blood glucose 100-125 mg/dL, and the risk of dementia-according to the number of IFG exposure (range 0-4)-was analyzed using the multivariable Cox proportional-hazards model. During the median 6.4 years of follow-up, 7614 cases of all-cause dementia, 5603 cases of Alzheimer's disease, and 1257 cases of vascular dementia occurred. There was a significant trend towards a higher risk of all-cause dementia (P for trend = 0.014) and Alzheimer's disease ( Pfor trend = 0.005) according to the cumulative exposure to IFG, but with a modest (approximately 7-14%) increase in the hazards. A significant stepwise increase in the risk of all-cause dementia and Alzheimer's disease was seen in non-obese subjects, whereas no significant association was observed in obese subjects. This study supports the association between prediabetes and incident dementia and emphasizes that even mild hyperglycemia should not be overlooked.

Long-Term Cumulative Exposure to High γ-Glutamyl Transferase Levels and the Risk of Cardiovascular Disease: A Nationwide Population-Based Cohort Study.

Background: Elevated γ-glutamyl transferase (γ-GTP) levels are associated with metabolic syndrome. We investigated the association of cumulative exposure to high γ-GTP with the risk of cardiovascular disease (CVD) in a large-scale population. Methods: Using nationally representative data from the Korean National Health Insurance system, 1,640,127 people with 4 years of consecutive γ-GTP measurements from 2009 to 2012 were included and followed up until the end of 2019. For each year of the study period, participants were grouped by the number of exposures to the highest γ-GTP quartile (0-4), and the sum of quartiles (0-12) was defined as cumulative γ-GTP exposure. The hazard ratio for CVD was evaluated using the Cox proportional hazards model. Results: During the 6.4 years of follow-up, there were 15,980 cases (0.97%) of myocardial infarction (MI), 14,563 (0.89%) of stroke, 29,717 (1.81%) of CVD, and 25,916 (1.58%) of death. Persistent exposure to high γ-GTP levels was associated with higher risks of MI, stroke, CVD, and death than those without such exposure. The risks of MI, stroke, CVD, and mortality increased in a dose-dependent manner according to total cumulative γ-GTP (all P for trend <0.0001). Subjects younger than 65 years, with a body mass index <25 kg/m2, and without hypertension or fatty liver showed a stronger relationship between cumulative γ-GTP and the incidence of MI, CVD, and death. Conclusion: Cumulative γ-GTP elevation is associated with CVD. γ-GTP could be more widely used as an early marker of CVD risk, especially in individuals without traditional CVD risk factors.

Comparison of accuracy of breeding value for cow from three methods in Hanwoo (Korean cattle) population.

In Korea, Korea Proven Bulls (KPN) program has been well-developed. Breeding and evaluation of cows are also an essential factor to increase earnings and genetic gain. This study aimed to evaluate the accuracy of cow breeding value by using three methods (pedigree index [PI], pedigree-based best linear unbiased prediction [PBLUP], and genomic-BLUP [GBLUP]). The reference population (n = 16,971) was used to estimate breeding values for 481 females as a test population. The accuracy of GBLUP was 0.63, 0.66, 0.62 and 0.63 for carcass weight (CWT), eye muscle area (EMA), back-fat thickness (BFT), and marbling score (MS), respectively. As for the PBLUP method, accuracy of prediction was 0.43 for CWT, 0.45 for EMA, 0.43 for MS, and 0.44 for BFT. Accuracy of PI method was the lowest (0.28 to 0.29 for carcass traits). The increase by approximate 20% in accuracy of GBLUP method than other methods could be because genomic information may explain Mendelian sampling error that pedigree information cannot detect. Bias can cause reducing accuracy of estimated breeding value (EBV) for selected animals. Regression coefficient between true breeding value (TBV) and GBLUP EBV, PBLUP EBV, and PI EBV were 0.78, 0.625, and 0.35, respectively for CWT. This showed that genomic EBV (GEBV) is less biased than PBLUP and PI EBV in this study. In addition, number of effective chromosome segments (Me) statistic that indicates the independent loci is one of the important factors affecting the accuracy of BLUP. The correlation between Me and the accuracy of GBLUP is related to the genetic relationship between reference and test population. The correlations between Me and accuracy were -0.74 in CWT, -0.75 in EMA, -0.73 in MS, and -0.75 in BF, which were strongly negative. These results proved that the estimation of genetic ability using genomic data is the most effective, and the smaller the Me, the higher the accuracy of EBV.

Diabetes Mellitus and Acute Facial Palsy: A Nationwide Population-Based Study.

INTRODUCTION: Acute facial palsy, characterized by sudden hemifacial weakness, significantly impacts an individual's quality of life. Despite several predisposing factors identified for acute facial palsy, the specific relationship between diabetes mellitus (DM) and acute facial palsy has not been comprehensively explored in recent studies. The aim of the study was to assess the risk of acute facial palsy in patients with DM using a nationwide population sample cohort. METHODS: DM cohort and non-DM cohort were built using the Korean National Health Insurance Service-Sample Cohort which represents the entire population of the Republic of Korea from January 2002 to December 2019. The DM cohort comprised 92,872 patients with a record of medication and a diagnosis of DM. Individuals who had facial palsy before the diagnosis of DM were excluded. A comparison cohort comprised 1,012,021 individuals without DM matched sociodemographically in a 1:4 ratio. The incidence of Bell's palsy (BP) and Ramsay Hunt syndrome (RHS) were evaluated in both cohorts. The risk factors for acute facial palsy were also assessed. RESULTS: Among the 92,868 patients in the DM cohort, the incidence rate (IR) of BP and RHS were 31.42 (confidence interval [CI], 30.24-32.63) and 4.58 per 10,000 person-years (CI, 4.14-5.05), respectively. Among the 371,392 individuals in the non-DM cohort, the IR of BP was 22.11 per 10,000 person-years (CI, 21.62-22.59) and the IR of RHS was 2.85 per 10,000 person-years (CI, 2.68-3.02). IR ratios for BP and RHS were 1.42 (CI, 1.36-1.48) and 1.61 (CI, 1.43-1.80). In multivariate analysis, DM (hazard ratio [HR] 1.428), age (HR 1.008), and high comorbidity score (HR 1.051) were associated with increased risk of BP, and male (HR 0.803) and living in metropolis (HR 0.966) decreased the risk of BP. And DM (HR 1.615), high comorbidity score (HR 1.078), and living in metropolis (HR 1.201) were associated with increased risk for RHS. CONCLUSION: This study suggests that patients with DM had an increased risk of acute facial palsy including BP and RHS.

Relationship between Loudness Dependence of Auditory-evoked Potentials and Suicidality.

Objective: : Serotonin concentration is associated with suicide in patients with major depressive disorder. Loudness dependence of auditory-evoked potentials (LDAEPs), a representative neurophysiological indicator, is related to serotonin activity. Therefore, this study aimed to investigate the relationship between LDAEPs and suicidal ideation, suicide attempts, and the severity of depression. Methods: : We evaluated the scalp N1, P2, and N1/P2 LDAEPs along with standardized low-resolution brain electromagnetic tomography (sLORETA)-localized N1, P2, and N1/P2 LDAEPs of 221 patients with major depressive disorder. The demographic and clinical data of the patients, including data on suicidal ideation and previous suicide attempts, were obtained from clinical interviews and medical records. The severity of depression was assessed using the Beck Depression Inventory and Hamilton Depression Rating Scale, whereas suicidal ideation was evaluated using the Beck Scale for Suicidal Ideation (BSS). Results: : The total BSS score was associated with low N1/P2 LDAEP (p = 0.045), whereas P2 sLORETA-LDAEP was associated with lower previous suicide attempts (p = 0.043). In addition, suicide attempt was correlated with an elevated P2 left sLORETA-LDAEP (coefficient = 4.638, p = 0.038). Conclusion: : These findings suggest that suicidal ideation is associated with decreased LDAEP, whereas suicide attempt is associated with increased LDAEP.

A prognostic value of estimated pulse wave velocity in idiopathic sudden sensorineural hearing loss.

PURPOSE: Arterial stiffness, represented by estimated pulse wave velocity (ePWV), is the independent surrogate marker for cardiovascular event. The aim of the study was to investigate the significance of ePWV in the treatment outcome of idiopathic sudden sensorineural hearing loss (SSNHL). METHODS: One hundred and ten patients with idiopathic SSNHL who hospitalized between April 2019 and March 2022 were evaluated. Arterial stiffness was calculated with formula for ePWV and other cardiovascular parameters of body mass index (BMI), and serum lipid level was determined. All patients received systemic high-dose steroid therapy and intratympanic steroid injections as a salvage management. Treatment outcome was assessed at 6 months after treatment, and classified as recovery and nonrecovery groups according to hearing recovery. RESULTS: The initial pure-tone hearing threshold was 72.6 ± 23.8 dB and final hearing threshold was 52.63 ± 31.10 dB. After treatment, 60 (54.5%) patients included in recovery group and other 50 (45.5%) were classified as nonrecovery group. Age, days of onset to treatment, BMI, waist circumference, and ePWV were higher in the nonrecovery group compared to recovery group in univariate analysis (p = 0.039, p = 0.049, p = 0.003, p = 0.004, p = 0.007, respectively). In multivariate analysis, days of onset to treatment, BMI, and ePWV were associated with recovery (p = 0.030, p = 0.007, p = 0.022). CONCLUSION: Higher ePWV, a measure of arterial stiffness, was associated with a poor hearing recovery of SSNHL.

Expanding the therapeutic landscape: ezetimibe as non-statin therapy for dyslipidemia.

Dyslipidemia is a significant risk factor for atherosclerotic cardiovascular disease (ASCVD), and statins are the primary therapeutic options for reducing low-density lipoprotein cholesterol (LDL-C) levels. However, it can be challenging to achieve optimal LDL-C goals with statin monotherapy. Ezetimibe, a cholesterol absorption inhibitor, offers a potential non-statin therapy to optimize LDL-C management. Key clinical trials, such as IMPROVE-IT and RACING, have demonstrated that the addition of ezetimibe to statin therapy leads to further decreases in LDL-C or significant decreases in major adverse cardiovascular events (MACEs), particularly in patients with high ASCVD risk. Subsequent meta-analyses and clinical trials have further supported the beneficial effect of ezetimibe, suggesting additive decreases in LDL-C and MACEs, as well as pleiotropic effects. This review provides a comprehensive analysis of the clinical implications of ezetimibe for managing dyslipidemia; it also evaluates the available evidence that supports the role of ezetimibe as an adjunct non-statin therapy for long-term use. However, the long-term pleiotropic effects of ezetimibe remain controversial because of limited clinical data. Therefore, additional research is needed to clarify its potential benefits beyond LDL-C reduction. Nonetheless, an understanding of the role of ezetimibe in dyslipidemia management will help clinicians to develop effective treatment strategies.

Sudden Hearing Loss and Vertigo With Silent Pontine Infarction: A Case Report.

Most cases of sudden sensorineural hearing loss (SSNHL) occur without a specific identifiable cause, although vascular factors may serve as potential etiological contributors. Silent infarction refers to ischemic changes observed on imaging studies without accompanying clinical symptoms; however, this condition is clinically significant owing to the increased risk of future stroke. We report a case of left-sided SSNHL accompanied by dizziness in a 62-year-old male patient who was diagnosed with left pontine infarction without any other neurological symptoms. The cochlea and pons receive blood supply from the anterior inferior cerebellar artery; the cochlea lacks collateral vessels and is therefore susceptible to fluctuations in blood flow. This case report provides evidence to support the vascular hypothesis as the etiology underlying SSNHL.

Kaempferol Alleviates Mitochondrial Damage by Reducing Mitochondrial Reactive Oxygen Species Production in Lipopolysaccharide-Induced Prostate Organoids.

Common prostate diseases such as prostatitis and benign prostatic hyperplasia (BPH) have a high incidence at any age. Cellular stresses, such as reactive oxygen species (ROS) and chronic inflammation, are implicated in prostate enlargement and cancer progression and development. Kaempferol is a flavonoid found in abundance in various plants, including broccoli and spinach, and has been reported to exhibit positive biological activities, such as antioxidant and anti-inflammatory properties. In the present study, we introduced prostate organoids to investigate the protective effects of kaempferol against various cellular stresses. The levels of COX-2, iNOS, p-IκB, a pro-inflammatory cytokine, and ROS were increased by LPS treatment but reversed by kaempferol treatment. Kaempferol activated the nuclear factor erythroid 2-related factor 2(Nrf2)-related pathway and enhanced the mitochondrial quality control proteins PGC-1α, PINK1, Parkin, and Beclin. The increase in mitochondrial ROS and oxygen consumption induced by LPS was stabilized by kaempferol treatment. First, our study used prostate organoids as a novel evaluation platform. Secondly, it was demonstrated that kaempferol could alleviate the mitochondrial damage in LPS-induced induced prostate organoids by reducing the production of mitochondrial ROS.

Identification of Missense Variants Affecting Carcass Traits for Hanwoo Precision Breeding.

This study aimed to identify causal variants associated with important carcass traits such as weight and meat quality in Hanwoo cattle. We analyzed missense mutations extracted from imputed sequence data (ARS-UCD1.2) and performed an exon-specific association test on the carcass traits of 16,970 commercial Hanwoo. We found 33, 2, 1, and 3 significant SNPs associated with carcass weight (CW), backfat thickness (BFT), eye muscle area (EMA), and marbling score (MS), respectively. In CW and EMA, the most significant missense SNP was identified at 19,524,263 on BTA14 and involved the PRKDC. A missense SNP in the ZFAND2B, located at 107,160,304 on BTA2 was identified as being involved in BFT. For MS, missense SNP in the ACVR2B gene, located at 11,849,704 in BTA22 was identified as the most significant marker. The contribution of the most significant missense SNPs to genetic variance was confirmed to be 8.47%, 2.08%, 1.73%, and 1.19% in CW, BFT, EMA, and MS, respectively. We generated favorable and unfavorable haplotype combinations based on the significant SNPs for CW. Significant differences in GEBV (Genomic Estimated Breeding Values) were observed between groups with each favorable and unfavorable haplotype combination. In particular, the missense SNPs in PRKDC, MRPL9, and ANKFN1 appear to significantly affect the protein's function and structure, making them strong candidates as causal mutations. These missense SNPs have the potential to serve as valuable markers for improving carcass traits in Hanwoo commercial farms.

Identification of potential biomarkers associated with meat tenderness in Hanwoo (Korean cattle): An expression quantitative trait loci analysis.

Meat tenderness is considered the most important trait contributing to beef quality, level of consumer satisfaction, willingness to pay premium prices and industry profit. Genomic selection method would be helpful for genetic improvement of traits with low heritability and that are difficult to measure. The identification of core genes can aid genomic selection for complex traits with low heritability that are difficult to measure. We performed statistical analysis of associations between longissimus dorsi muscle tenderness and gene expression in 20 Hanwoo cattle, using Warner-Bratzler shear force and RNAseq data, respectively. We found a total of 166 core genes, from which six (ASAP1, CAPN5, ELN, SUMF2, TTC8 and MGAT4A) were regulated by 16 cis-expression quantitative trait loci (eQTL) SNPs. Notably, we found that a cis-eQTL SNP of the ELN gene contained an MFZ-1 binding site in its putative promoter region. These findings provide useful information for genomic prediction of beef tenderness in Hanwoo cattle.

Risk of data leakage in estimating the diagnostic performance of a deep-learning-based computer-aided system for psychiatric disorders.

Deep-learning approaches with data augmentation have been widely used when developing neuroimaging-based computer-aided diagnosis (CAD) systems. To prevent the inflated diagnostic performance caused by data leakage, a correct cross-validation (CV) method should be employed, but this has been still overlooked in recent deep-learning-based CAD studies. The goal of this study was to investigate the impact of correct and incorrect CV methods on the diagnostic performance of deep-learning-based CAD systems after data augmentation. To this end, resting-state electroencephalogram (EEG) data recorded from post-traumatic stress disorder patients and healthy controls were augmented using a cropping method with different window sizes, respectively. Four different CV approaches were used to estimate the diagnostic performance of the CAD system, i.e., subject-wise CV (sCV), overlapped sCV (oSCV), trial-wise CV (tCV), and overlapped tCV (otCV). Diagnostic performances were evaluated using two deep-learning models based on convolutional neural network. Data augmentation can increase the performance with all CVs, but inflated diagnostic performances were observed when using incorrect CVs (tCV and otCV) due to data leakage. Therefore, the correct CV (sCV and osCV) should be used to develop a deep-learning-based CAD system. We expect that our investigation can provide deep-insight for researchers who plan to develop neuroimaging-based CAD systems for psychiatric disorders using deep-learning algorithms with data augmentation.

Risk of Cause-Specific Mortality across Glucose Spectrum in Elderly People: A Nationwide Population-Based Cohort Study.

BACKGRUOUND: This study investigated the risk of cause-specific mortality according to glucose tolerance status in elderly South Koreans. METHODS: A total of 1,292,264 individuals aged ≥65 years who received health examinations in 2009 were identified from the National Health Information Database. Participants were classified as normal glucose tolerance, impaired fasting glucose, newly-diagnosed diabetes, early diabetes (oral hypoglycemic agents ≤2), or advanced diabetes (oral hypoglycemic agents ≥3 or insulin). The risk of system-specific and disease-specific deaths was estimated using multivariate Cox proportional hazards analysis. RESULTS: During a median follow-up of 8.41 years, 257,356 deaths were recorded. Diabetes was associated with significantly higher risk of all-cause mortality (hazard ratio [HR], 1.58; 95% confidence interval [CI], 1.57 to 1.60); death due to circulatory (HR, 1.49; 95% CI, 1.46 to 1.52), respiratory (HR, 1.51; 95% CI, 1.47 to 1.55), and genitourinary systems (HR, 2.22; 95% CI, 2.10 to 2.35); and neoplasms (HR, 1.30; 95% CI, 1.28 to 1.32). Diabetes was also associated with a significantly higher risk of death due to ischemic heart disease (HR, 1.70; 95% CI, 1.63 to 1.76), cerebrovascular disease (HR, 1.46; 95% CI, 1.41 to 1.50), pneumonia (HR, 1.69; 95% CI, 1.63 to 1.76), and acute or chronic kidney disease (HR, 2.23; 95% CI, 2.09 to 2.38). There was a stepwise increase in the risk of death across the glucose spectrum (P for trend <0.0001). Stroke, heart failure, or chronic kidney disease increased the risk of all-cause mortality at every stage of glucose intolerance. CONCLUSION: A dose-dependent association between the risk of mortality from various causes and severity of glucose tolerance was noted in the elderly population.

New Class of Tyrosinase Inhibitors, Rotenoids, from Amorpha fruticosa.

A series of rotenoids including a new one from the seeds of Amorpha fruticosa were found to have significant potential as tyrosinase inhibitors. All of the isolated rotenoids (1-6) displayed inhibitory activity against tyrosinase, both as a monophenolase for the oxidation of l-tyrosine and as a diphenolase for the oxidation of l-DOPA. The three most active compounds (1, 5, and 6) showed significant monophenolase inhibition with IC50 values of 2.1, 1.7, and 1.2 µM, respectively. They also inhibited diphenolase function with IC50 values in the range of 9.5-21.5 µM. The inhibition kinetics established all compounds to be competitive inhibitors of both oxidation processes. All rotenoids formed the Emet·I complex effectively around their IC50 values with long lag times. Tyrosinase inhibition of the new rotenoid 6 was additionally demonstrated using high-performance liquid chromatography (HPLC) analysis with N-acetyl-l-tyrosine. Molecular docking disclosed that the sugar moiety of 5 interacted with the bottom of the catalytic gorge.

Nanorod/nanodisk-integrated liquid crystalline systems for starvation, chemodynamic, and photothermal therapy of cancer.

Indocyanine green (ICG), glucose oxidase (GOx), and copper(II) sulfate (Cu)-installed hybrid gel based on organic nanorod (cellulose nanocrystal [CNC]) and inorganic nanodisk (Laponite [LAP]) was developed to perform a combination of starvation therapy (ST), chemodynamic therapy (CDT), and photothermal therapy (PTT) for localized cancers. A hybrid CNC/LAP network with a nematic phase was designed to enable instant gelation, controlled viscoelasticity, syringe injectability, and longer in vivo retention. Moreover, ICG was introduced into the CNC/LAP gel system to induce hyperthermia of tumor tissue, amplifying the CDT effect; GOx was used for glucose deprivation (related to the Warburg effect); and Cu was introduced for hydroxyl radical generation (based on Fenton-like chemistry) and cellular glutathione (GSH) degradation in cancer cells. The ICG/GOx/Cu-installed CNC/LAP gel in combination with near-infrared (NIR) laser realized improved antiproliferation, cellular reactive oxygen species (ROS) generation, cellular GSH degradation, and apoptosis induction in colorectal cancer (CT-26) cells. In addition, local injection of the CNC/ICG/GOx/Cu/LAP gel into the implanted CT-26 tumor while irradiating it with NIR laser provided strong tumor growth suppression effects. In conclusion, the designed hybrid nanorod/nanodisk gel network can be efficiently applied to the local PTT/ST/CDT of cancer cells.

The TNFα/TNFR2 axis mediates natural killer cell proliferation by promoting aerobic glycolysis.

Natural killer (NK) cells are predominant innate lymphocytes that initiate the early immune response during infection. NK cells undergo a metabolic switch to fuel augmented proliferation and activation following infection. Tumor necrosis factor-alpha (TNFα) is a well-known inflammatory cytokine that enhances NK cell function; however, the mechanism underlying NK cell proliferation in response to TNFα is not well established. Here, we demonstrated that upon infection/inflammation, NK cells upregulate the expression of TNF receptor 2 (TNFR2), which is associated with increased proliferation, metabolic activity, and effector function. Notably, IL-18 can induce TNFR2 expression in NK cells, augmenting their sensitivity toward TNFα. Mechanistically, TNFα-TNFR2 signaling upregulates the expression of CD25 (IL-2Rα) and nutrient transporters in NK cells, leading to a metabolic switch toward aerobic glycolysis. Transcriptomic analysis revealed significantly reduced expression levels of genes involved in cellular metabolism and proliferation in NK cells from TNFR2 KO mice. Accordingly, our data affirmed that genetic ablation of TNFR2 curtails CD25 upregulation and TNFα-induced glycolysis, leading to impaired NK cell proliferation and antiviral function during MCMV infection in vivo. Collectively, our results delineate the crucial role of the TNFα-TNFR2 axis in NK cell proliferation, glycolysis, and effector function.

A content analysis of YouTube videos on tinnitus in South Korea.

More people use the internet for medical information, especially YouTube. Nevertheless, no study has been conducted to analyze the quality of YouTube videos about tinnitus in Korea. This study aims to review the contents and quality of YouTube videos on tinnitus. The top 100 Korean YouTube videos on tinnitus were reviewed by a tinnitus expert. This study assessed video details: title, creator, length, and popularity indicators-subscribers, views, and likes. The contents of the video clips were analyzed to determine the relevance, understandability, actionability, and quality of information. Out of 100 tinnitus videos, 27 were created by otolaryngologists, 25 by traditional Korean medicine doctors, 25 by other medical professionals, and 3 by lay persons. Sensorineural tinnitus was frequently dealt, and hearing loss, stress, and noise were introduced as main causes of tinnitus. Otolaryngologists' videos covered verified treatments, but others suggested unproven therapies including herbal medicine or acupressure. Otolaryngologists' videos showed significantly higher understandability and quality of information compared to others (p < 0.001). This study found that tinnitus YouTube videos frequently present low-quality and incorrect material, which could have an adverse effect on patients. Results highlight the need for tinnitus specialists to provide accurate information.

Weight loss and side-effects of liraglutide and lixisenatide in obesity and type 2 diabetes mellitus.

AIMS: Glucagon-like peptide-1 receptor agonist (GLP-1 RA) is used to treat obesity or type 2 diabetes mellitus (DM). We compared weight loss and side-effects between patients with and without DM using GLP-1 RA. METHODS: This was a retrospective cohort study based on electronic medical records. Patients were categorized into three groups: liraglutide without DM (LiRa_NL), liraglutide with DM (LiRa_DM), and lixisenatide with DM (LiXi_DM). Six-month outcomes were evaluated for weight loss, side-effect types, and onset discontinuation of GLP-1 RA. RESULTS: We enrolled 356 (190 LiRa_NL, 95 LiRa_DM, and 71 LiXi_DM) patients (women, 72.5 %; mean age, 43.7 ± 12.7 years; mean body mass index, 30.7 ± 5.2 kg/m2). The mean glycated hemoglobin (HbA1c) participants were 7.7 ± 2.1 %. Average weight loss was 2.9 ± 0.3 kg. The change in HbA1c was lower in the LiXi_DM group than in the LiRa_DM group (- 1.1 ± 0.2 % vs. - 0.4 ± 0.1 %, P < 0.05). The LiRa_DM group showed a more effective weight loss (- 3.0 ± 0.4 kg) than the LiXi_DM group (- 0.9 ± 0.4 kg) (P < 0.05). Approximately 30 % of the patients reported experiencing side-effects, with gastrointestinal side-effects being the most frequent (20.5 %). The median side-effect onset was 1.9 ± 0.1 months from first treatment. The rate of GLP-1 RA discontinuation was 72.8 %. Discontinuation rates due to side-effects were 75.7 %, 68.9 %, and 64.4 % in the LiRa_NL, LiRa_DM, and LiXi_DM groups, respectively. CONCLUSIONS: The LiRa_NL group showed the most weight loss, although the discontinuation rate was high. Most side-effects occurred at 1-2 months. When prescribing GLP-1 RA, education concerning side-effects and discontinuation is needed to enhance treatment adherence.