The formation of lamellar body-like structures may be a trigger of cetylpyridinium chloride-induced cell death and inflammatory response.

Cetylpyridinium chloride (CPC) is a quaternary ammonium compound used widely in health and personal care products. Meanwhile, due to its increasing use, its potential adverse health effects are emerging as a topic of public concern. In this study, we first administered CPC by pharyngeal aspiration to determine the survival level (the maximum concentration at which no death is observed) and then administered CPC to mice repeatedly for 28 days using the survival level as the highest concentration. CPC increased the total number of pulmonary cells secreting pro- and anti-inflammatory cytokines and chemokines. Infiltration of inflammatory cells, production of foamy alveolar macrophages, and chronic inflammatory lesions were found in the lung tissue of male and female mice exposed to the highest dose of CPC. We also investigated the toxicity mechanism using BEAS-2B cells isolated from normal human bronchial epithelium. At 6 h after exposure to CPC, the cells underwent non-apoptotic cell death, especially at concentrations greater than 2 µg/mL. The expression of the transferrin receptor was remarkably enhanced, and the expression of proteins that contribute to intracellular iron storage was inhibited. The expression of both mitochondrial SOD and catalase increased with CPC concentration, and PARP protein was cleaved, suggesting possible DNA damage. In addition, the internal structure of mitochondria was disrupted, and fusion between damaged organelles was observed in the cytoplasm. Most importantly, lamellar body-like structures and autophagosome-like vacuoles were found in CPC-treated cells, with enhanced expression of ABCA3 protein, a marker for lamellar body, and a docking score between ABCA3 protein and CPC was considered to be approximately -6.8969 kcal/mol. From these results, we propose that mitochondrial damage and iron depletion may contribute to CPC-induced non-apoptotic cell death and that pulmonary accumulation of cell debris may be closely associated with the inflammatory response. Furthermore, we hypothesize that the formation of lamellar body-like structures may be a trigger for CPC-induced cell death.

Air pollution and survival in patients with malignant mesothelioma and asbestos-related lung cancer: a follow-up study of 1591 patients in South Korea.

BACKGROUND: Despite significant advancements in treatments such as surgery, radiotherapy, and chemotherapy, the survival rate for patients with asbestos-related cancers remains low. Numerous studies have provided evidence suggesting that air pollution induces oxidative stress and inflammation, affecting acute respiratory diseases, lung cancer, and overall mortality. However, because of the high case fatality rate, there is limited knowledge regarding the effects of air pollution exposures on survival following a diagnosis of asbestos-related cancers. This study aimed to determine the effect of air pollution on the survival of patients with malignant mesothelioma and asbestos-related lung cancer. METHODS: We followed up with 593 patients with malignant mesothelioma and 998 patients with lung cancer identified as asbestos victims between 2009 and 2022. Data on five air pollutants-sulfur dioxide, carbon monoxide, nitrogen dioxide, fine particulate matter with a diameter < 10 µm, and fine particulate matter with a diameter < 2.5 µm-were obtained from nationwide atmospheric monitoring stations. Cox proportional hazard models were used to estimate the association of cumulative air pollutant exposure with patient mortality, while adjusting for potential confounders. Quantile-based g-computation was used to assess the combined effect of the air pollutant mixture on mortality. RESULTS: The 1-, 3-, and 5-year survival rates for both cancer types decreased with increasing exposure to all air pollutants. The estimated hazard ratios rose significantly with a 1-standard deviation increase in each pollutant exposure level. A quartile increase in the pollutant mixture was associated with a 1.99-fold increase in the risk of malignant mesothelioma-related mortality (95% confidence interval: 1.62, 2.44). For lung cancer, a quartile increase in the pollutant mixture triggered a 1.87-fold increase in the mortality risk (95% confidence interval: 1.53, 2.30). CONCLUSION: These findings support the hypothesis that air pollution exposure after an asbestos-related cancer diagnosis can negatively affect patient survival.

Reliability and Validity of the Korean version of the Center for Neurologic Study Bulbar Function Scale (K-CNS-BFS): An observational study.

Bulbar dysfunction in amyotrophic lateral sclerosis (ALS) significantly affects daily life, leading to weight loss and reduced survival. Methods for evaluating bulbar dysfunction, including videofluoroscopic swallowing studies and the bulbar component of the ALS Functional Rating Scale-Revised (ALSFRS-R), have been employed; however, Korean-specific tools are lacking. The Center for Neurologic Study Bulbar Function Scale (CNS-BFS) comprehensively evaluates bulbar symptoms. This study aimed to develop and validate the Korean version of the CNS-BFS (K-CNS-BFS) to assess bulbar dysfunction in Korean patients with ALS. Twenty-seven patients with ALS were recruited from a tertiary hospital in South Korea based on revised El Escorial criteria. Demographic, clinical, and measurement data were collected. The K-CNS-BFS was evaluated for reliability and validity. Reliability assessment revealed strong internal consistency (Cronbach alpha) for the K-CNS-BFS subscales and total score. Test-retest reliability showed significant correlation. Content validity index was excellent, and convergent validity demonstrated significant correlations between the K-CNS-BFS and relevant measures. Discriminant validity was observed between the K-CNS-BFS and motor/respiratory subscores of the ALSFRS-R. Construct validity demonstrated significant correlations between the K-CNS-BFS subscales and total score. This is the first study to investigate the reliability and validity of the Korean version of the CNS-BFS, which showed consistent and reliable scores that correlated with tests for bulbar or general dysfunction. The K-CNS-BFS effectively measured bulbar dysfunction similar to the original CNS-BFS. The K-CNS-BFS is a reliable and valid tool for assessing bulbar dysfunction in patients with ALS in South Korea.

Impact of COVID-19 Infection and Its Association With Previous Vaccination in Patients With Myasthenia Gravis in Korea: A Multicenter Retrospective Study.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, patients with myasthenia gravis (MG) were more susceptible to poor outcomes owing to respiratory muscle weakness and immunotherapy. Several studies conducted in the early stages of the COVID-19 pandemic reported higher mortality in patients with MG compared to the general population. This study aimed to investigate the clinical course and prognosis of COVID-19 in patients with MG and to compare these parameters between vaccinated and unvaccinated patients in South Korea. METHODS: This multicenter, retrospective study, which was conducted at 14 tertiary hospitals in South Korea, reviewed the medical records and identified MG patients who contracted COVID-19 between February 2022 and April 2022. The demographic and clinical characteristics associated with MG and vaccination status were collected. The clinical outcomes of COVID-19 infection and MG were investigated and compared between the vaccinated and unvaccinated patients. RESULTS: Ninety-two patients with MG contracted COVID-19 during the study. Nine (9.8%) patients required hospitalization, 4 (4.3%) of whom were admitted to the intensive care unit. Seventy-five of 92 patients were vaccinated before contracting COVID-19 infection, and 17 were not. During the COVID-19 infection, 6 of 17 (35.3%) unvaccinated patients were hospitalized, whereas 3 of 75 (4.0%) vaccinated patients were hospitalized (P < 0.001). The frequencies of ICU admission and mechanical ventilation were significantly lower in the vaccinated patients than in the unvaccinated patients (P = 0.019 and P = 0.032, respectively). The rate of MG deterioration was significantly lower in the vaccinated patients than in the unvaccinated patients (P = 0.041). Logistic regression after weighting revealed that the risk of hospitalization and MG deterioration after COVID-19 infection was significantly lower in the vaccinated patients than in the unvaccinated patients. CONCLUSION: This study suggests that the clinical course and prognosis of patients with MG who contracted COVID-19 during the dominance of the omicron variant of COVID-19 may be milder than those at the early phase of the COVID-19 pandemic when vaccination was unavailable. Vaccination may reduce the morbidity of COVID-19 in patients with MG and effectively prevent MG deterioration induced by COVID-19 infection.

Perfluorooctanoic acid inhibits cell proliferation through mitochondrial damage.

Grown evidence has shown that the liver and reproductive organs were the main target organs of perfluorooctanoic acid (PFOA). Herein, we studied a toxic mechanism of PFOA using HeLa Chang liver epithelial cells. When incubated with PFOA for 24 h or 48 h, cell proliferation was inhibited in a concentration- and time-dependent fashion, but interestingly, the feature of dead cells was not notable. Mitochondrial volume was increased with concentration and time, whereas the mitochondrial membrane potential and produced ATP amounts were significantly reduced. Autophagosome-like vacuoles and contraction of the mitochondrial inner membrane were observed in PFOA-treated cells. The expression of acetyl CoA carboxylase (ACC) and p-ACC proteins rapidly decreased, and that of mitochondrial dynamics-related proteins increased. The expression of solute carrier family 7 genes, ChaC glutathione-specific gamma-glutamylcyclotransferase 1, and 5S ribosomal RNA gene was up-regulated the most in cells exposed to PFOA for 24 h, and the KEGG pathway analysis revealed that PFOA the most affected metabolic pathways and olfactory transduction. More importantly, PPAR alpha, fatty acid binding protein 1, and CYP450 family 1 subfamily A member 1 were identified as the target proteins for binding between PFOA and cells. Taken together, we suggest that disruption of mitochondrial integrity and function may contribute closely to PFOA-induced cell proliferation inhibition.

Efficacy of leuprorelin in spinal and bulbar muscular atrophy: a 3-year observational study.

OBJECTIVE: This study aimed to investigate the long-term effects and functional outcomes of androgen suppression therapy using leuprorelin among Korean patients with spinal and bulbar muscular atrophy (SBMA). METHODS: This observational study enrolled patients with genetically confirmed SBMA who provided informed consent. Leuprorelin was administered via subcutaneous injection every 12 weeks. The primary outcome measure was the change in total Spinal and Bulbar Muscular Atrophy Functional Rating Scale (SBMAFRS) scores. RESULTS: A total of 48 SBMA patients were evaluated in this study. Among them, 39 patients underwent androgen suppression therapy over a 3-year period. The total SBMAFRS score decreased from 41.72 ± 5.55 to 36.74 ± 7.74 (p < 0.001) in patients who completed their treatment. The subgroup with a baseline SBMAFRS score of ≥ 42 had a significantly lower decline in SBMAFRS score than did those with a baseline SBMAFRS score of ≤ 41. We determined that at a baseline, SBMAFRS cutoff value of 41.5 could predict good prognosis, with a corresponding area under the curve of 0.689. CONCLUSION: Despite androgen suppression therapy, all enrolled participants exhibited a decrease in the overall SBMAFRS score. However, those with a baseline SBMAFRS of ≥ 42 showed a mild decrease in scores, indicating a more favorable prognosis. These findings suggest that a higher baseline motor function was a key prognostic indicator in SBMA treatment and that initiating early leuprorelin treatment in patients with high baseline function may lead to good clinical outcomes.

Association between oil spill clean-up work and thyroid cancer: Nine years of follow-up after the Hebei Spirit oil spill accident.

In 2007, an unprecedented oil spill occurred in Taean, Korea. Although crude oil contains chemicals that could increase thyroid cancer risk, few studies have examined the long-term effects of oil exposure during clean-up and thyroid cancer incidence. We investigated the long-term thyroid cancer incidence among participants involved in clean-up work. 1798 participants engaged in at least two surveys since the baseline was tracked from 2008 to 2018. Participants reported the days they participated in oil clean-up works and cancer diagnoses. Cox proportional hazard models were used to estimate the hazard ratios between clean-up work duration and thyroid cancer. Over the 9-year follow-up, 30 thyroid cancer cases were diagnosed. A positive association was observed between clean-up duration and thyroid cancer risk. This effect was more pronounced among residents living <50 m from traffic roads. Our results indicate that crude oil clean-up work participation may increase the thyroid cancer risk.

Clinicopathological Reclassification of Idiopathic Inflammatory Myopathy to Match the Serological Results of Myositis-Specific Antibodies.

BACKGROUND AND PURPOSE: Advances in serological tests are transforming the classification of idiopathic inflammatory myopathy (IIM). The new criteria suggested by the 119th European Neuromuscular Center international workshop divide IIM cases into four main diseases according to clinical and pathological findings, adding immune-mediated necrotizing myositis and nonspecific myositis to the classic categories of polymyositis and dermatomyositis. METHODS: Seventy one cases of IIM with sufficient available clinical and pathological data were reviewed to be reclassified according to the new criteria. RESULTS: Most of the cases previously classified as polymyositis (77.8%, 35/45) were reclassified as immune-mediated necrotizing myopathy. The results of myositis-specific antibodies matched well with the new clinicopathological classification. CONCLUSIONS: This new clinicopathological classification for IIM in combination with serological test results could be applied to our previous case series. Adoption of the new criteria will lead to a better understanding of the disease and hence new therapeutic insights.

Ocular and Plasma Pharmacokinetics of Enavogliflozin Ophthalmic Solution in Preclinical Species.

An enavogliflozin ophthalmic solution (DWRX2008) is being developed to treat diabetic retinopathy and macular edema. This study evaluated the ocular distribution and plasma pharmacokinetics (PKs) of enavogliflozin in animal species. A sample of [14C] enavogliflozin was ocularly administered to two rabbits per time point at single doses of 600 µg/eye to evaluate ocular PK, which was evaluated using autoradiography until 48 h post-dose. Plasma concentrations after ocular administration in six rabbits, three rats, and three beagle dogs with single doses of 400 µg, 25 µg, and 100 µg, respectively, were investigated for 24 h. The retinal concentration of [14C] enavogliflozin reached Cmax at 2.0 h with an elimination half-life of 32.5 h, which remained above the IC50 value of sodium-dependent glucose transporter 2 until 24 h post-dose. In the plasma of rabbits, the fastest Tmax of 0.5 h and a 3.6 h half-life were observed among animal species. The relative bioavailability in rabbits after ocular administration was 3.4 compared to oral administration. Ocular administration of enavogliflozin could be a potential therapeutic route for diabetic retinal complications, based on relative bioavailability and effective delivery to the posterior ocular segment. DWRX2008 would be applicable to humans with favorable PK profiles and minimal systemic adverse effect.

Identification and characterization of novel ERBB4 variant associated with sporadic amyotrophic lateral sclerosis (ALS).

Amyotrophic Lateral Sclerosis (ALS) is the most common type of motor neuron disease characterized by progressive motor neuron degeneration in brain and spinal cord. Most cases are sporadic in ALS and 5-10% of cases are familiar. >50 genes are known to be associated with ALS and one of them is ERBB4. In this paper, we report the case of a 53-year-old ALS patient with progressive muscle weakness and fasciculation, but he had no cognitive decline. We performed the next generation sequencing (NGS) and in silico analysis, it predicted a highly pathogenic variant, c.2116 A > G, p.Asn706Asp (N706D) in the ERBB4 gene. The amino acid residue is highly conserved among species. ERBB4 is a member of the ERBB family of receptor tyrosine kinases. ERBB4 has multiple tyrosine phosphorylation sites, including an autophosphorylation site at tyrosine 1284 residue. Autophosphorylation of ERBB4 promotes biological activity and it associated with NRG-1/ERBB4 pathway. It is already known that tyrosine 128 phosphorylation of ERBB4 is decreased in patients who have ALS-associated ERBB4 mutations. We generated ERBB4 N706D construct using site-directed mutagenesis and checked the phosphorylation level of ERBB4 N706D in NSC-34 cells. We found that the phosphorylation of ERBB4 N706D was decreased compared to ERBB4 wild-type, indicating a loss of function mutation in ERBB4. We report a novel variant in ERBB4 gene leading to ALS through dysfunction of ERBB4.

Whole-Body Muscle Magnetic Resonance Imaging in 81 Patients with Spinal and Bulbar Muscular Atrophy: A Prospective Study.

OBJECTIVE: Spinal and bulbar muscular atrophy (SBMA) is characterized by slow, progressive bulbar and limb muscle weakness; however, the pattern of progression of muscle fat infiltration remains unclear. We assessed the progression of muscle involvement in 81 patients with SBMA using whole-body muscle magnetic resonance imaging (MRI), alongside clinical and laboratory findings. METHODS: This prospective study included patients with genetically confirmed SBMA who underwent whole-body muscle MRI. We analyzed muscle fat infiltration and the pattern of involved muscles using cluster analysis, visualizing the sequential progression of fat infiltration. Muscle clusters demonstrated correlation with clinical scales and laboratory findings. Additionally, linear regression analysis was performed to identify the MRI section most strongly associated with 6-minute walk test (6MWT). RESULTS: We included 81 patients with SBMA (age = 54.3 years). After categorizing the patients into 6 clusters based on the pattern of muscle fat infiltration, we observed that muscle involvement began in the posterior calf and progressed to the posterior thigh, pelvis, trunk, anterior thigh, medial thigh, anterior calf, and upper extremity muscles. These muscle clusters correlated significantly with disease duration (τ = 0.47, p < 0.001), 6MWT (τ = -0.49, p < 0.001), and serum creatinine level (τ = -0.46, p < 0.001). The whole-body MRI indicated the thigh as the section most significantly correlated with 6MWT. INTERPRETATION: We used whole-body muscle MRI to determine the sequential progression of the fat infiltration in SBMA. Our findings may enable the identification of objective and reliable imaging outcome measures in the study of the natural history or future clinical trials of SBMA. ANN NEUROL 2024;95:596-606.

Long-term effects of the Hebei Spirit oil spill on the prevalence and incidence of allergic disorders.

The Hebei Spirit oil spill accident occurred in December 2007, approximately 10 km off the coast of Taean, South Korea, a location notably close to residential areas. Crude oil substances have been detected in various environmental mediums since the accident, yet previous studies have primarily focused on the acute effects of oil exposure due to the short latency period of allergic diseases. Therefore, this study evaluated the long-term effects of oil spill exposure on allergic disorders. Our study included adult residents who had participated in the Health Effects Research on Hebei Spirit Oil Spill (HEROS) study up to five years post-incident, which was a prospective cohort to monitor the health status of Taean residents. We used two indicators to assess oil spill exposure, namely the distance from the initial contaminated coastline to each participant's residence and the number of days participants had engaged in oil clean-up work. Current symptoms such as asthma, allergic rhinitis, atopic dermatitis, allergic conjunctivitis, and multimorbidity were considered allergic disorders. In the baseline survey, the prevalence of asthma, allergic rhinitis, atopic dermatitis, allergic conjunctivitis, and allergic multimorbidity symptoms was associated with both exposure indicators; however, these associations were not observed in the two consecutive surveys. Significant longitudinal associations between oil spill exposure indicators and the four allergic disorders, as well as multimorbidity incidences, were observed during a five-year follow-up period. Our results suggest that oil spill exposure can affect acute and long-term allergic symptoms in residents near the accident site.

Neurofilament light chain as a biomarker in neuromyelitis optica spectrum disorder: a comprehensive review and integrated analysis with glial fibrillary acidic protein.

BACKGROUND: In the context of neuromyelitis optica spectrum disorder (NMOSD), there are several measures that serve as a biomarker. However, each of the methods has the intrinsic limitations. While neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) have emerged as an additional biomarker for NMOSD, a thorough investigation of their role remains incomplete. Our aim is to provide a comprehensive review of the current literature regarding NfL and GFAP as a biomarker and explore their potential utility in NMOSD. METHODS: We performed a comprehensive search using PubMed and Google Scholar to identify peer-reviewed articles investigating NfL and GFAP as a biomarker in NMOSD. RESULTS: Our search identified 13 relevant studies. NfL consistently showed promise in distinguishing NMOSD patients from healthy individuals, although it had limited specificity in distinguishing NMOSD from other demyelinating diseases. NfL offered certain advantages over GFAP, notably its ability to predict disability worsening during attacks. In contrast, GFAP provided valuable insight, particularly in distinguishing NMOSD from multiple sclerosis and identifying clinical relapses. In addition, GFAP showed predictive potential for future attacks. Some studies even suggested that NfL may serve as an indicator of treatment response in NMOSD. CONCLUSIONS: NfL and GFAP hold promise as biomarkers for NMOSD, demonstrating their usefulness in distinguishing patients from healthy individuals, assessing disease severity, and possibly reflecting treatment response. However, it is important to recognize that NfL and GFAP may, at some point, have different roles.

Measurement device hacking-free mutual quantum identity authentication over a deployed optical fiber.

Quantum identity authentication serves as a crucial technology for secure quantum communication, but its security often faces challenges due to quantum hacking of measurement devices. This study introduces a measurement-device-independent mutual quantum identity authentication (MDI MQIA) scheme capable of ensuring secure user authentication, despite the use of measurement devices vulnerable to quantum hacking. To realize the MDI MQIA scheme, we proposed and applied a modified Bell state measurement based on linear optics, enabling the probabilistic measurement of all Bell states. Furthermore, the proposed experimental setup adopted a plug-and-play architecture, thus efficiently establishing the indistinguishability of two photons prepared by the communication members. Finally, we successfully performed a proof-of-principle experimental demonstration of the proposed scheme using a field-deployed fiber, achieving quantum bit error rates of less than 3%.

Eco-Friendly Dispersant-Free Purification Method of Boron Nitride Nanotubes through Controlling Surface Tension and Steric Repulsion with Solvents.

Boron nitride nanotubes (BNNTs) were purified without the use of a dispersant by controlling the surface tension and steric repulsion of solvent molecules. This method effectively enhanced the difference in solubilities of impurities and BNNTs. The purification process involved optimizing the alkyl-chains of alcohol solvents and adjusting the concentration of alcohol solvent in water to regulate surface tension and steric repulsion. Among the solvents tested, a 70 wt% t-butylalcohol in water mixture exhibited the highest selective isolation of BNNTs from impurities based on differences in solubilities. This favorable outcome was attributed to the surface tension matching with BNNTs, steric repulsion from bulky alkyl chain structures, and differences in interfacial energy between BNNT-liquid and impurity-liquid interfaces. Through this optimized purification process, impurities were removed to an extent of up to 93.3%. Additionally, the purified BNNTs exhibited a distinct liquid crystal phase, which was not observed in the unpurified BNNTs.

Subway station dust-induced pulmonary inflammation may be due to the dysfunction of alveolar macrophages: Possible contribution of bound elements.

With its increasing value as a means of public transportation, the health effects of the air in subway stations have attracted public concern. In the current study, we investigated the pulmonary toxicity of dust collected from an air purifier installed on the platform of the busiest subway station in Seoul. We found that the dust contained various elements which are attributable to the facilities and equipment used to operate the subway system. Particularly, iron (Fe), chromium (Cr), zirconium (Zr), barium (Ba), and molybdenum (Mo) levels were more notable in comparison with those in dust collected from the ventilation chamber of a subway station. To explore the health effects of inhaled dust, we first instilled via the trachea in ICR mice for 13 weeks. The total number of pulmonary macrophages increased significantly with the dose, accompanying hematological changes. Dust-laden alveolar macrophages and inflammatory cells accumulated in the perivascular regions in the lungs of the treated mice, and pulmonary levels of CXCL-1, TNF-α, and TGF-ß increased clearly compared with the control. The CCR5 and CD54 level expressed on BAL cell membranes was also enhanced following exposure to dust, whereas the CXCR2 level tended to decrease in the same samples. In addition, we treated the dust to alveolar macrophages (known as dust cells), lysosomal and mitochondrial function decreased, accompanied by cell death, and NO production was rapidly elevated with concentration. Moreover, the expression of autophagy- (p62) and anti-oxidant (SOD-2)-related proteins increased, and the expression of inflammation-related genes was dramatically up-regulated in the dust-treated cells. Therefore, we suggest that dysfunction of alveolar macrophages may importantly contribute to dust-induced inflammatory responses and that the exposure concentrations of Cr, Fe, Mo, Zr, and Ba should be considered carefully when assessing the health risks associated with subway dust. We also hypothesize that the bound elements may contribute to dust-induced macrophage dysfunction by inhibiting viability.

Subchronic pulmonary toxicity of ambient particles containing cement production-related elements.

Chronic respiratory disease is among the most common non-communicable diseases, and particulate materials (PM) are a major risk factor. Meanwhile, evidence of the relationship between the physicochemical characteristics of PM and pulmonary toxicity mechanism is still limited. Here, we collected particles (CPM) from the air of a port city adjacent to a cement factory, and we found that the CPM contained various elements, including heavy metals (such as arsenic, thallium, barium, and zirconium) which are predicted to have originated from a cement plant adjacent to the sampling site. We also delivered the CPM intratracheally to mice for 13 weeks to investigate the pulmonary toxicity of inhaled CPM. CPM-induced chronic inflammatory lesions with an increased total number of cells in the lung of mice. Meanwhile, among inflammatory mediators measured in this study, levels of IL-1ß, TNF-α, CXCL-1, and IFN-γ were elevated in the treated group compared with the controls. Considering that the alveolar macrophage (known as dust cell) is a professional phagocyte that is responsible for the clearance of PM from the respiratory surfaces, we also investigated cellular responses following exposure to CPM in MH-S cells, a mouse alveolar macrophage cell line. CPM inhibited cell proliferation and formed autophagosome-like vacuoles. Intracellular calcium accumulation and oxidative stress, and altered expression of pyrimidine metabolism- and olfactory transduction-related genes were observed in CPM-treated cells. More interestingly, type I-LC3B and full-length PARP proteins were not replenished in CPM-treated cells, and cell cycle changes, apoptotic and necrotic cell death, and caspase-3 cleavage were not significantly detected in cells exposed to CPM. Taken together, we conclude that dysfunction of alveolar macrophages may contribute to CPM-induced pulmonary inflammation. In addition, given the possible transformation of heart tissue observed in CPM-treated mice, we suggest that further study is needed to clarify the systemic pathological changes and the molecular mechanisms following chronic exposure to CPM.

Incidence and prevalence of Spinal and bulbar muscular atrophy in South Korea: a nationwide population-based study.

Spinal and bulbar muscular atrophy (SBMA), or Kennedy's disease, is a rare X-linked neuromuscular disorder predominantly affecting males and caused by a mutation in the androgen receptor gene. The epidemiology and comorbidities associated with SBMA in different ethnicities remain poorly understood. This study investigated the prevalence, incidence, and comorbidities associated with SBMA in the South Korean population using the Health Insurance Review and Assessment Service (HIRA) database. We retrospectively reviewed diagnosed cases of SBMA (G12.25 code of the Korean Classification of Diseases-7th edition) registered from January 1, 2016, to December 31, 2019, to calculate incidence and prevalence rates and concomitant comorbidities. Additionally, we surveyed SBMA patients (questionnaire group) visiting our clinic in 2022 to compare comorbidities with the HIRA data. The mean incidence rate of SBMA in the Korean population was 0.36/100,000 males from 2018 to 2019, while the prevalence rate was approximately 0.46/100,000 males from 2016 to 2019. The most common comorbidities identified in HIRA were gastritis and duodenitis (99.7%), gastroesophageal reflux (90.5%), hyperlipidemia (88.4%), and liver disorders (75.2%), which showed similar results in the questionnaire group. Additionally, gastric cancer was the most common type of cancer reported in SBMA in South Korea; although indeterminate, age-related factors may contribute to the development of cancer in these patients. Our findings provide valuable insights into the epidemiology and associated comorbidities of SBMA within the Korean population, which could inform clinical practice and future clinical research.