BACKGROUND/AIMS: Bile reflux (BR) can influence the gastric environment by altering gastric acidity and possibly the gastric microbiota composition. This study investigated the correlation between bile acids and microbial compositions in the gastric juice of 50 subjects with differing gastric pathologies. METHODS: This study included 50 subjects, which were categorized into three groups based on the endoscopic BR grading system. The primary and secondary bile acid concentrations in gastric juice samples were measured, and microbiota profiling was conducted using 16 S rRNA gene sequencing. RESULTS: Significant differences were observed in each bile acid level in the three endoscopic BR groups (P < 0.05). The Shannon index demonstrated a significant decrease in the higher BR groups (P < 0.05). Analysis of the ß-diversity revealed that BR significantly altered the gastric microbiota composition. The presence of neoplastic lesions and the presence of H. pylori infection impacted the ß-diversity of the gastric juice microbiota. The abundance of the Streptococcus and Lancefielfdella genera exhibited positive correlations for almost all bile acid components(P < 0.05). In addition, the abundance of Slobacterium, Veillonella, and Schaalia showed positive correlations with primary unconjugated bile acids (P < 0.05). CONCLUSION: Changes in microbial diversity in the gastric juice were associated with BR presence in the stomach. This result suggests that the degree of BR should be considered when studying the gastric juice microbiome.
Small plaque psoriasis is the typical form of chronic plaque psoriasis affecting adults in South Korea. The effectiveness of calcipotriol/betamethasone dipropionate (Cal/BD) aerosol foam for large and small psoriasis plaques has not previously been examined. We performed a post hoc analysis of a recent, 4-week observational study of Cal/BD aerosol foam use in routine clinical practice in South Korea. Investigator Global Assessment response ([IGA] 0/1 at week 4), Patient Global Assessment response ([PaGA] 0/1 at week 4), change in Psoriasis Area and Severity Index (PASI), changes in psoriasis symptom scores, change in the Dermatology Life Quality Index (DLQI), and the proportion of patients achieving DLQI ≤5 were analyzed for patients with small (≤5 cm; n = 131) or large (>5 cm; n = 35) baseline plaque size. IGA response rates were similar for patients with small and large plaques (59.5% and 51.4% respectively). Similarly, there was no significant difference between the small and large groups in mean change in PASI (-2.20 vs -3.34), the proportions of patients with DLQI ≤5 (62.3% vs 54.3%) or PaGA 0/1 (29.2% vs 40.0%). Mean improvements in DLQI (-4.04 vs -6.20) and in psoriasis symptoms including itching (-1.50 vs -2.83), sleep loss (-0.67 vs -1.89), dryness (-1.57 vs -2.97), scaling (-1.21 vs -3.57), and redness (-1.17 vs -3.11) were greater in patients with large plaques than those with small plaques. Itching and DLQI differences were not statistically significant after adjustment for baseline characteristics. Stratification by body surface area affected eliminated statistically significant differences between the groups for most outcomes. In conclusion, this analysis suggests that Cal/BD aerosol foam is an effective, well-accepted treatment for adult patients with the small plaques typical of chronic plaque psoriasis in South Korea, as well as for those with large plaques.
Rotator cuff tendon tears are a leading cause of shoulder pain. They are challenging to treat, and tendon-bone healing has a high failure rate despite successful surgery. Tendons connect the muscles and bones, which make them important for the body's overall mobility and stability. Metabolic diseases, including diabetes or high blood pressure, can affect the healing process after repair of a damaged tendon. With a global incidence of 9.3%, diabetes is considered as a significant risk factor for rotator cuff tendon healing because it causes structural, inflammatory, and vascular changes in the tendon. However, the mechanisms of how diabetes affects tendon healing remain unknown. Several factors have been suggested, including glycation product accumulation, adipokine dysregulation, increased levels of reactive oxygen species, apoptosis, inflammatory cytokines, imbalanced matrix-metalloproteinase-to-tissue-inhibitor ratio, and impaired angiogenesis and differentiation of the tendon sheath. Despite the effects of diabetes on tendon function and healing, few treatments are available to improve recovery in these patients. This review summarizes the current literature on the pathophysiological changes of the tendon in diabetes and hyperlipidemia. Preclinical and clinical evidence regarding the association between diabetes and tendon healing is presented. Moreover, current approaches to improve tendon healing in patients with diabetes are reviewed.
Endoscopic middle meatal antrostomy (MMA) is commonly used for maxillary sinus (MS) fungal ball removal. For challenging cases involving anterior or inferior recess, an additional inferior meatal approach (IMA) might be needed. We analyzed the differences in MS dimensions on CT scans according to the surgical approach to suggest preoperative variables that could facilitate an additional IMA. CT scans of 281 adult patients who underwent ESS for the MS fungal ball (139 MMA, 62 MMA & IMA) were evaluated for comparative analysis of 8 MS measurements based on the surgical approach. Complete removal was achieved in all cases. Age and sex didn't differ significantly (p > 0.05). The maximum distances between the anterior-posterior walls, the inferior ostium border to the lateral recess, and the ostium to the inferior wall of the MS were statistically greater in the MMA & IMA group compared to the MMA group (p = 0.003, p = 0.005, and p = 0.010, respectively), especially among females. This study underscores the clinical importance of specific measurements-anterior to posterior wall, medial wall to lateral recess, and ostium to inferior wall of the maxillary sinus-for guiding optimal surgical approaches in MS lesions.
Endoscopy , Maxillary Sinus , Tomography, X-Ray Computed , Humans , Female , Male , Maxillary Sinus/surgery , Maxillary Sinus/diagnostic imaging , Maxillary Sinus/microbiology , Middle Aged , Adult , Endoscopy/methods , Aged , Retrospective Studies , Maxilla/surgery , Maxilla/diagnostic imaging , Mycoses/surgery , Mycoses/diagnostic imaging
BACKGROUND: A wide array of histone deacetylase (HDAC) inhibitors and aryl hydrocarbon receptor (AHR) agonists commonly arrest experimental autoimmune encephalomyelitis (EAE). However, it is not known whether HDAC inhibition is linked to the AHR signaling pathway in EAE. METHODS: We investigated how the pan-HDAC inhibitor SB939 (pracinostat) exerted immunoregulatory action in the myelin oligodendrocyte glycoprotein 35-55 (MOG35-55)-induced EAE mouse model by evaluating changes in of signal transducer and activator of transcription 3 (STAT3) acetylation and the expression of indoleamine 2,3-dioxygenase 1 (IDO1) and AHR in inflamed spinal cords during EAE evolution. We proved the involvement of IDO1 and the AHR in SB939-mediated immunosuppression using Ido1-/- and Ahr-/- mice. RESULTS: Administration with SB939 halted EAE progression, which depended upon IDO1 expression in neurons of the central nervous system (CNS). Our in vitro and in vivo studies demonstrated that SB939 sustained the interleukin-6-induced acetylation of STAT3, resulting in the stable transcriptional activation of Ido1. The therapeutic effect of SB939 also required the AHR, which is expressed mainly in CD4+ T cells and macrophages in CNS disease lesions. Finally, SB939 was shown to markedly reduce the proliferation of CD4+ T cells in inflamed neuronal tissues but not in the spleen or draining lymph nodes. CONCLUSIONS: Overall, our results suggest that IDO1 tryptophan metabolites produced by neuronal cells may act on AHR in pathogenic CD4+ T cells in a paracrine fashion in the CNS and that the specific induction of IDO1 expression in neurons at disease-afflicted sites can be considered a therapeutic approach to block the progression of multiple sclerosis without affecting systemic immunity.
Aspergillus subgenus Nidulantes with nine section forms the second largest subgenus of the fungi that comes under the genus Aspergillus. Species in this group of fungi are important as they are reported to play several important roles in the environment including influencing air quality in confined spaces, food spoilage, production of mycotoxins as well as in human pathogenicity. In the present study, 53 strains of Aspergillus subgenus Nidulantes (section: Nidulantes & Usti) isolated from Korea and preserved at the Korean Agricultural Culture Collection (KACC) were subjected to re-identification by using a combined dataset of partial ß-tubulin (BenA), Calmodulin (CaM) gene sequences as well as their morphological data. We confirmed 14 species from 53 isolates in Korea. Of them, eleven species were reported in Korea previously (A. amoenus, A. baeticus, A. calidoustus, A. creber, A. insuetus, A. jensenii, A. nidulans, A. protuberus, A. sydowii, A. tabacinus and A. unguis), and three species (A. griseoaurantiacus, A. puulaauensis and A. sublatus) were previously unreported from Korea. We detailed the characteristic features of these three species, that remain unexplored in Korea.
OBJECTIVES: This study aimed to identify predictors for the recurrence of spontaneous intracranial hypotension (SIH) after epidural blood patch (EBP). BACKGROUND: Epidural blood patch is the main treatment option for SIH; however, the characteristics of patients who experience relapse after successful EBP treatment for SIH remain understudied. METHODS: In this exploratory, retrospective, case-control study, we included 19 patients with SIH recurrence after EBP and 36 age- and sex-matched patients without recurrence from a single tertiary medical institution. We analyzed clinical characteristics, neuroimaging findings, and volume changes in intracranial structures after EBP treatment. Machine learning methods were utilized to predict the recurrence of SIH after EBP treatment. RESULTS: There were no significant differences in clinical features between the recurrence and no-recurrence groups. Among brain magnetic resonance imaging signs, diffuse pachymeningeal enhancement and cerebral venous dilatation were more prominent in the recurrence group than no-recurrence group after EBP (14/19 [73%] vs. eight of 36 [22%] patients, p = 0.001; 11/19 [57%] vs. seven of 36 [19%] patients, p = 0.010, respectively). The midbrain-pons angle decreased in the recurrence group compared to the no-recurrence group after EBP, at a mean (standard deviation [SD]) of -12.0 [16.7] vs. +1.8[18.3]° (p = 0.048). In volumetric analysis, volume changes after EBP were smaller in the recurrence group than in the no-recurrence group in intracranial cerebrospinal fluid (mean [SD] -11.6 [15.3] vs. +4.8 [17.1] mL, p = 0.001) and ventricles (mean [SD] +1.0 [2.0] vs. +2.0 [2.5] mL, p = 0.003). Notably, the random forest classifier indicated that the model constructed with brain volumetry was more accurate in discriminating SIH recurrence (area under the curve = 0.80 vs. 0.52). CONCLUSION: Our study suggests that volumetric analysis of intracranial structures may aid in predicting recurrence after EBP treatment in patients with SIH.
Blood Patch, Epidural , Intracranial Hypotension , Magnetic Resonance Imaging , Recurrence , Humans , Intracranial Hypotension/therapy , Intracranial Hypotension/diagnostic imaging , Female , Male , Retrospective Studies , Adult , Middle Aged , Case-Control Studies , Machine Learning
Photonic nanomaterials, characterized by their remarkable photonic tunability, empower a diverse range of applications, including cutting-edge advances in cancer nanomedicine. Recently, ferroptosis has emerged as a promising alternative strategy for effectively killing cancer cells with minimizing therapeutic resistance. Novel design of photonic nanomaterials that can integrate photoresponsive-ferroptosis inducers, -diagnostic imaging, and -synergistic components provide significant benefits to effectively trigger local ferroptosis. This review provides a comprehensive overview of recent advancements in photonic nanomaterials for image-guided ferroptosis cancer nanomedicine, offering insights into their strengths, constraints, and their potential as a future paradigm in cancer treatment.
The utilization of electromagnetic waves is rapidly advancing into the millimeter-wave frequency range, posing increasingly severe challenges in terms of electromagnetic pollution prevention and radar stealth. However, existing millimeter-wave absorbers are still inadequate in addressing these issues due to their monotonous magnetic resonance pattern. In this work, rare-earth La3+ and non-magnetic Zr4+ ions are simultaneously incorporated into M-type barium ferrite (BaM) to intentionally manipulate the multi-magnetic resonance behavior. By leveraging the contrary impact of La3+ and Zr4+ ions on magnetocrystalline anisotropy field, the restrictive relationship between intensity and frequency of the multi-magnetic resonance is successfully eliminated. The magnetic resonance peak-differentiating and imitating results confirm that significant multi-magnetic resonance phenomenon emerges around 35 GHz due to the reinforced exchange coupling effect between Fe3+ and Fe2+ ions. Additionally, Mössbauer spectra analysis, first-principle calculations, and least square fitting collectively identify that additional La3+ doping leads to a profound rearrangement of Zr4+ occupation and thus makes the portion of polarization/conduction loss increase gradually. As a consequence, the La3+-Zr4+ co-doped BaM achieves an ultra-broad bandwidth of 12.5 + GHz covering from 27.5 to 40 + GHz, which holds remarkable potential for millimeter-wave absorbers around the atmospheric window of 35 GHz.
Particulate matter (PM), released into the air by a variety of natural and human activities, is a key indicator of air pollution. Although PM is known as the extensive health hazard to affect a variety of illness, few studies have specifically investigated the effects of PM10 exposure on schizophrenic development. In the present study, we aimed to investigate the impact of PM10 on MK-801, N-methyl-D-aspartate (NMDA) receptor antagonist, induced schizophrenia-like behaviors in C57BL/6 mouse. Preadolescent mice were exposed PM10 to 3.2â¯mg/m3 concentration for 4â¯h/day for 2 weeks through a compartmentalized whole-body inhalation chamber. After PM10 exposure, we conducted behavioral tests during adolescence and adulthood to investigate longitudinal development of schizophrenia. We found that PM10 exacerbated schizophrenia-like behavior, such as psychomotor agitation, social interaction deficits and cognitive deficits at adulthood in MK-801-induced schizophrenia animal model. Furthermore, the reduced expression levels of brain-derived neurotrophic factor (BDNF) and the phosphorylation of BDNF related signaling molecules, extracellular signal-regulated kinase (ERK) and cAMP response element-binding protein (CREB), were exacerbated by PM10 exposure in the adult hippocampus of MK-801-treated mice. Thus, our present study demonstrates that exposure to PM10 in preadolescence exacerbates the cognitive impairment in animal model of schizophrenia, which are considered to be facilitated by the decreased level of BDNF through reduced ERK-CREB expression.
Brain-Derived Neurotrophic Factor , Cyclic AMP Response Element-Binding Protein , Dizocilpine Maleate , Mice, Inbred C57BL , Particulate Matter , Schizophrenia , Signal Transduction , Animals , Brain-Derived Neurotrophic Factor/metabolism , Schizophrenia/chemically induced , Particulate Matter/toxicity , Dizocilpine Maleate/pharmacology , Mice , Male , Signal Transduction/drug effects , Cyclic AMP Response Element-Binding Protein/metabolism , Air Pollutants/toxicity , Behavior, Animal/drug effects , Extracellular Signal-Regulated MAP Kinases/metabolism , Disease Models, Animal , Hippocampus/drug effects , Hippocampus/metabolism
PURPOSE: To investigate the effect of age on visual outcomes after the bilateral implantation of trifocal intraocular lenses (IOLs). METHODS: A total of 290 patients (580 eyes) who underwent bilateral implantation of a trifocal IOL were enrolled in this retrospective case-control study. Patients were divided into five age groups: 45 to 49, 50 to 54, 55 to 59, 60 to 64, and 65 years and older. Postoperative monocular uncorrected and corrected distance visual acuity (UDVA and CDVA, respectively), uncorrected near visual acuity (UNVA), binocular distance-corrected defocus curve, spectacle dependence for near and distance vision, and patient satisfaction scores were compared among the five groups. RESULTS: The 45 to 49 years group had significantly better mean UDVA (0.02 ± 0.05 logMAR) and UNVA (0.02 ± 0.04 logMAR) than the 65 years and older group (0.06 ± 0.09 and 0.09 ± 0.09 logMAR; P = .029 and P < .001; respectively). However, no significant differences were observed in the mean CDVA among the groups. Binocular visual performance of the 45 to 49 years group was better than that of the 65 years and older age group at defocuses of +1.00, +0.50, -1.00, and -3.00 D. No significant differences were observed in spectacle dependence for near and distance vision or in patient satisfaction scores among the five groups. CONCLUSIONS: Bilateral implantation of trifocal IOLs can provide excellent near and distance vision in both young and older patients. However, UDVA and UNVA revealed considerably worse results in the older group, although no significant difference was observed in CDVA and postoperative refractive errors by age. [J Refract Surg. 2024;40(4):e270-e277.].
Lenses, Intraocular , Phacoemulsification , Humans , Aged , Middle Aged , Refraction, Ocular , Lens Implantation, Intraocular , Eyeglasses , Retrospective Studies , Case-Control Studies , Vision, Binocular , Patient Satisfaction , Prosthesis Design
Probiotics should possess specific properties to exert beneficial effects, and their safety must be ensured for human consumption. The purpose of this study was to evaluate the probiotic properties and safety of Limosilactobacillus mucosae NK41 and Bifidobacterium longum NK46 isolated from human feces in vitro. Both strains exhibited high resistance to simulated gastrointestinal fluid. Furthermore, probiotic-related cell surface characteristics including auto-aggregation and cell surface hydrophobicity were assessed by measuring the absorbance at a wavelength of 600 nm, which demonstrated good auto-aggregation ability and affinity for xylene, indicating their effective adhesion to Caco-2 cells. In addition, hemolytic, gelatinase, and ß-glucuronidase activities were found to be negative in both strains. The susceptibility to nine commonly used antibiotics was assessed using the broth macrodilution method, which demonstrated that both strains were susceptible to all tested antibiotics. Furthermore, L. mucosae NK41 and B. longum NK46 produced significantly higher levels of L-lactate (71.8 ± 0.7% and 97.8 ± 0.4%) than D-lactate (28.2 ± 0.7% and 2.2 ± 0.4%, respectively). Using PCR amplification to investigate genes associated with virulence factors, we found that neither strain harbored any virulence genes. These findings suggest that L. mucosae NK41 and B. longum NK46 have the potential to be used as probiotics and are considered safe for human consumption.
Colorectal endoscopic submucosal dissection (ESD) is a promising but challenging procedure. It is not widely performed due to its technical difficulty. We aimed to find the predictive factors associated with technical difficulty in colorectal ESD before the procedure. Clinical data from patients who underwent ESD for colorectal tumors in 5 hospitals in Honam province of South Korea between 2015 and 2020 were reviewed retrospectively. Technically difficult colorectal ESD procedure was defined in 3 points. Long procedure time (longer than 60 minutes), occurrence of perforation, and failure of en bloc resection. Factors associated with technically difficult ESD were included as main outcome measure. 1446 patients were identified and their data were analyzed. Median procedure time was 30.0 minutes and median long axis of the tumor was 20.1 mm. Technically difficult procedures including long procedure time were 231 cases (16.0%), perforation occurred in 34 cases (2.3%), and en bloc resection was done in 1292 cases (89.3%). Tumor size larger than 35 mm (odd ratio [OR]: 1.474, P = .047), central depression or ulceration in the lesion (OR: 1.474, P = .013), previous endoscopic mucosal resection (EMR) or polypectomy procedure (OR: 2.428, P = .020) were associated with technically difficult ESD. Descending colon-located tumor (OR: 5.355, P < .001), and use of IT knife (OR: 4.157, P = .003) were associated with perforation. Recognizing factors associated with technically difficult ESD can help in planning the ESD procedure beforehand.
Colorectal Neoplasms , Endoscopic Mucosal Resection , Humans , Endoscopic Mucosal Resection/methods , Endoscopic Mucosal Resection/adverse effects , Male , Female , Colorectal Neoplasms/surgery , Middle Aged , Retrospective Studies , Aged , Republic of Korea/epidemiology , Operative Time , Risk Factors , Colonoscopy/methods , Colonoscopy/adverse effects
Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.
Asian People , Colorectal Neoplasms , Genetic Predisposition to Disease , Genome-Wide Association Study , Polymorphism, Single Nucleotide , Quantitative Trait Loci , White People , Humans , Colorectal Neoplasms/genetics , Asian People/genetics , White People/genetics , Exome Sequencing , Case-Control Studies , Transcriptome , Chromosome Mapping , Male , Female , East Asian People
OBJECTIVE: To examine associations between serum oxylipins, which regulate tissue repair and pain signalling, and knee pain/radiographic osteoarthritis (OA) at baseline and knee pain at 3 year follow-up. METHOD: Baseline, and 3 year follow-up, knee pain phenotypes were assessed from 154 participants in the Knee Pain in the Community (KPIC) cohort study. Serum and radiographic Kellgren and Lawrence (KL) and Nottingham line drawing atlas OA scores were collected at baseline. Oxylipin levels were quantified using liquid chromatography coupled with mass spectrometry. Associations were measured by linear regression and receiver operating characteristics (ROC). RESULTS: Serum levels of 8,9-epoxyeicosatrienoic acid (EET) (ß(95% confidence intervals (CI)) = 1.809 (-0.71 to 2.91)), 14,15-dihydroxyeicosatrienoic acid (DHET) (ß(95%CI) = 0.827 (0.34-1.31)), and 12-hydroxyeicosatetraenoic acid (HETE) (ß(95%CI) = 4.090 (1.92-6.26)) and anandamide (ß(95%CI) = 3.060 (1.35-4.77)) were cross-sectionally associated with current self-reported knee pain scores (numerical rating scale (NRS) item 3, average pain). Serum levels of 9- (ß(95%CI) = 0.467 (0.18-0.75)) and 15-HETE (ß(95%CI) = 0.759 (0.29-1.22)), 14-hydroxydocosahexaenoic acid (ß(95%CI) = 0.483(0.24-0.73)), and the ratio of 8,9-EET:DHET (ß(95%CI) = 0.510(0.19-0.82)) were cross-sectionally associated with KL scores. Baseline serum concentrations of 8,9-EET (ß(95%CI) = 2.166 (0.89-3.44)), 5,6-DHET (ß(95%CI) = 152.179 (69.39-234.97)), and 5-HETE (ß(95%CI) = 1.724 (0.677-2.77) showed positive longitudinal associations with follow-up knee pain scores (NRS item 3, average pain). Combined serum 8,9-EET and 5-HETE concentration showed the strongest longitudinal association (ß(95%CI) = 1.156 (0.54-1.77) with pain scores at 3 years, and ROC curves distinguished between participants with no pain and high pain scores at follow-up (area under curve (95%CI) = 0.71 (0.61-0.82)). CONCLUSIONS: Serum levels of a combination of hydroxylated metabolites of arachidonic acid may have prognostic utility for knee pain, providing a potential novel approach to identify people who are more likely to have debilitating pain in the future.
The COVID-19 Vaccine Safety Research Committee (CoVaSC) was established in November 2021 to address the growing need for independent, in-depth scientific evidence on adverse events (AEs) following coronavirus disease 2019 (COVID-19) vaccination. This initiative was requested by the Korea Disease Control and Prevention Agency and led by the National Academy of Medicine of Korea. In September 2022, the COVID-19 Vaccine Safety Research Center was established, strengthening CoVaSC's initiatives. The center has conducted various studies on the safety of COVID-19 vaccines. During CoVaSC's second research year, from September 29, 2022 to July 19, 2023, the center was restructured into 4 departments: Epidemiological Research, Clinical Research, Communication & Education, and International Cooperation & Policy Research. Its main activities include (1) managing CoVaSC and the COVID-19 Vaccine Safety Research Center, (2) surveying domestic and international trends in AE causality investigation, (3) assessing AEs following COVID-19 vaccination, (4) fostering international collaboration and policy research, and (5) organizing regular fora and training sessions for the public and clinicians. Causality assessments have been conducted for 27 diseases, and independent research has been conducted after organizing ad hoc committees comprising both epidemiologists and clinical experts on each AE of interest. The research process included protocol development, data analysis, interpretation of results, and causality assessment. These research outcomes have been shared transparently with the public and healthcare experts through various fora. The COVID-19 Vaccine Safety Research Center plans to continue strengthening and expanding its research activities to provide reliable, high-quality safety information to the public.
