Do toenail manganese and iron levels reflect brain metal levels or brain metabolism in welders?

Inhalation of welding fumes can cause metal accumulation in the brain, leading to Parkinsonian-like symptoms. Metal accumulation and altered neurochemical profiles have been observed using magnetic resonance imaging (MRI) in highly exposed welders, being associated with decreased motor function and cognition. While MRI is impractical to use as a health risk assessment tool in occupational settings, toenail metal levels are easier to assess and have been demonstrated to reflect an exposure window of7-12 months in the past. Yet, it is unclear whether toenail metal levels are associated with brain metal levels or changes in metabolism, which are the root of potential health concerns. This study investigates whether toenail manganese (Mn) and iron (Fe) levels, assessed at several time points, correlate with brain Mn and Fe levels, measured by MRI, as well as brain GABA, glutamate (Glu), and glutathione (GSH) levels, measured by Magnetic Resonance Spectroscopy (MRS), in seventeen Mn-exposed welders. Quantitative T1 and R2* MRI maps of the whole brain, along with GABA, Glu, and GSH MRS measurements from the thalamus and cerebellum were acquired at baseline (T0). Toenail clippings were collected at T0 and every three months after the MRI for a year to account for different exposure periods being reflected by toenail clippings and MRI. Spearman correlations of toenail metal levels were run against brain metal and metabolite levels, but no significant associations were found for Mn at any timepoint. Cerebellar GSH positively correlated with toenail Fe clipped twelve months after the MRI (p = 0.05), suggesting an association with Fe exposure at the time of the MRI. Neither thalamic GABA nor Glu correlated with toenail Fe levels. In conclusion, this study cannot support toenail Mn as a proxy for brain Mn levels or metabolic changes, while toenail Fe appears linked to brain metabolic alterations, underscoring the importance of considering other metals, including Fe, in studying Mn neurotoxicity.

Sucralose Influences the Productive Performance, Carcass Traits, Blood Components, and Gut Microflora Using 16S rRNA Sequencing of Growing APRI-Line Rabbits.

This study investigated how sucralose influenced rabbit intestine and caecal microbial activity, blood parameters, growth performance, carcass characteristics, and digestibility. In total, 160 5-week-old rabbits from the APRI line weighing 563.29 gm were randomly assigned to four experimental groups with four replicates-5 males and 5 females in each. Four experimental groups were used, as follows: SUC1, SUC2, and SUC3 got 75, 150, and 300 mg of sucralose/kg body weight in water daily, while the control group ate a basal diet without supplements. The results showed that both the control and SUC1 groups significantly (p < 0.05) increased daily weight gain and final body weight. Sucralose addition significantly improved feed conversion ratio (p < 0.05) and decreased daily feed intake (gm/d). The experimental groups do not significantly differ in terms of mortality. Furthermore, nutrient digestibility was not significantly affected by sucralose treatment, with the exception of crud protein digestion, which was significantly reduced (p < 0.05). Additionally, without altering liver or kidney function, sucralose administration dramatically (p < 0.05) decreased blood serum glucose and triglyceride levels while increasing total lipids, cholesterol, and malonaldehyde in comparison to the control group. Furthermore, the addition of sucrose resulted in a significant (p < 0.05) increase in the count of total bacteria, lactobacillus, and Clostridium spp., and a decrease in the count of Escherichia coli. Further analysis using 16S rRNA data revealed that sucralose upregulated the expression of lactobacillus genes but not that of Clostridium or E. Coli bacteria (p < 0.05). Therefore, it could be concluded that sucralose supplementation for rabbits modifies gut microbiota and boosts beneficial bacteria and feed conversion ratios without side effects. Moreover, sucralose could decrease blood glucose and intensify hypercholesterolemia and should be used with caution for human consumption.

PIEZO1 activation may serve as an early tissue biomarker for the prediction of irradiation-induced salivary gland dysfunction.

Irradiation (IR)-induced xerostomia is the most common side effect of radiation therapy in patients with head and neck cancer (HNC). Xerostomia diagnosis is mainly based on the patient's medical history and symptoms. Currently, no direct biomarkers are available for the early prediction of IR-induced xerostomia. Here, we identified PIEZO1 as a novel predictive tissue biomarker for xerostomia. Our data demonstrate that PIEZO1 is significantly upregulated at the gene and protein levels during IR-induced salivary gland (SG) hypofunction. Notably, PIEZO1 upregulation coincided with that of inflammatory (F4/80) and fibrotic markers (fibronectin and collagen fibers accumulation). These findings suggest that PIEZO1 upregulation in SG tissue may serve as a novel predictive marker for IR-induced xerostomia.

Genomic insights into novel Erwinia bacteriophages: unveiling their Henunavirus membership and host infection strategies.

Erwinia amylovora, the primary causative agent of blight disease in rosaceous plants, poses a significant threat to agricultural yield worldwide, with limited effective countermeasures. The emergence of sustainable alternative agents such as bacteriophages is a promising solution for fire blight that specifically targets Erwinia. In this study, we isolated pEp_SNUABM_01 and pEa_SNUABM_55 from a South Korean apple orchard soil, analyzed their genomic DNA sequences, and performed a comprehensive comparative analysis of Hena1 in four distinct sections. This study aimed to unveil distinctive features of these phages, with a focus on host recognition, which will provide valuable insights into the evolution and characteristics of Henunavirus bacteriophages that infect plant pathogenic Erwinia spp. By elucidating the distinct genomic features of these phages, particularly in terms of host recognition, this study lays a foundation for their potential application in mitigating the risks associated with fire blight in Rosaceae plants on a global scale.

Blood Fluke Infection (Spirorchidiasis) and Systemic Granulomatous Inflammation: A Case Study of Green Sea Turtles (Chelonia mydas) on Jeju Island, South Korea.

Despite the precarious state of marine turtles as a highly endangered species, our understanding of their diseases remains limited. This case report presents a detailed pathological investigation of spirorchiidiasis, a blood fluke infection that poses a substantial threat to marine turtles. This retrospective study examined three cases of spirorchiid-infected sea turtles, specifically, green sea turtles stranded on Jeju Island, South Korea. Premortem examination of the three spirorchiid-infected green sea turtles demonstrated nonspecific clinical symptoms; blood analysis revealed dehydration, malnutrition, and anemia. Computed tomography scans provided insights into severe pulmonary and extrapulmonary manifestations, including the mass present in the joint region. Post-mortem examinations consistently indicated severe lung lesions and systemic manifestations, with histopathological examination confirming the presence of spirorchiid ova across various organs. Despite the global prevalence of spirorchiidiasis in sea turtles, disease severity varies regionally. This report provides a detailed demonstration of the pathology of spirorchiidiasis in sea turtles from Northeast Asia.

Ingestion of fishing gear and Anisakis sp. infection in a beached Indo-Pacific finless porpoise (Neophocaena phocaenoides) in the Jeju Island, Republic of Korea: findings from post-mortem computed tomography and necropsy.

BACKGROUND: Human fishing activities have significantly affect environmental concern for marine ecosystems, conservation of marine mammals, and human health. Coastal cetaceans are highly vulnerable to ingestion of fishing gear, bycatching, or entanglement, all of which can be fatal for these animals. In particular, certain coastal dolphins and porpoises are heavily impacted by fishing gear such as angling gear or stownet, as their food often overlap with the target fish species of human fisheries. CASE PRESENTATION: This study presents a case of an Indo-Pacific finless porpoise (Neophocaena phocaenoides) beached on the coast of Jeju Island, Republic of Korea, with ingestion of fishing gear and severe Anisakis infection. Although this species inhabits waters ranging from the Persian Gulf to Taiwan, several stranded carcasses have been reported on Jeju Island in recent years. Post-mortem computed tomography revealed a bundle of four fishing hooks in the forestomach, along with nylon lines and steel lines with connectors, which were assumed to be angling gear for Jeju hairtail (Trichiurus lepturus). Further necroscopic investigation revealed that the forestomach contained a large number of Anisakis spp. (Nematoda: Anisakidae). Histological examination revealed a thickened forestomach wall with pinpoint and volcanic ulcerations, a thickened layer of stratified squamous epithelium, and infiltrated stroma in the squamous epithelium. CONCLUSIONS: This study emphasizes the urgent need to address the impact of fishing activities on marine mammals, marine litter pollution, and the bycatch problem in Korean seawater. In addition, the occurrence of N. phocaenoides in seawater around Jeju Island should be raised in future geographical ecology or veterinary pathology studies and when its distribution is updated.

Supplemental effect of Pediococcus acidilactici CNCM I-4622 probiotic on the laying characteristics and calcium and phosphorus metabolism in laying hens.

The close link between intestinal microbiota and bone health ('gut-bone' axis) has recently been revealed: the modulation of the amount and nature of bacteria present in the intestinal tract has an impact on bone health and calcium (Ca) metabolism. Probiotics are known to favorably impact the intestinal microbiota. The objective of this study was to investigate the effect of Pediococcus acidilactici CNCM I-4622 (PA) on laying performance, egg/eggshell quality, Ca metabolism and bone mineralization and resistance in relatively old layers (50 wks old at the beginning of the experiment) during 14 weeks. 480 Hy Line brown layers were divided into 2 groups (CON and PA: 3 layers/rep, 80 rep/group) and fed with a diet formulated to be suboptimal in calcium (Ca) and phosphorus (P) (- 10% of the requirements). The total egg weight was improved by 1.1% overall with PA, related to an improvement of the weight of marketable eggs (+ 0.9%). PA induced a decreased % of downgraded eggs, mainly broken eggs (- 0.4 pts) and FCR improvement (- 0.8% for all eggs, - 0.9% for marketable eggs). PA also led to higher Haugh units (HU: + 7.4%). PA tended to decrease crypt depth after the 14 weeks of supplementation period in the jejunum (- 25.2%) and ileum (- 17.6%). As a consequence, the VH/CD ratio appeared increased by PA at the end of the trial in the jejunum (+ 63.0%) and ileum (+ 48.0%). Ca and P retention were increased by 4 pts following PA supplementation, translating into increased bone hardness (+ 19%), bone cohesiveness (+ 43%) and bone Ca & P (+ 1 pt) for PA-supplemented layers. Blood Ca and P were respectively improved by 5% and 12% with PA. In addition, blood calcitriol and osteocalcin concentrations were respectively improved by + 83% and + 3% in PA group at the end of the trial, compared to CON group. There was no difference between the 2 groups for ALP (alkaline phosphatase) and PTH (parathyroid hormone). PA significantly decreased the expression of the following genes: occludin in the small intestine, calbindin 1 in the ovarian tissue and actin B in the bone. PA therefore improved zootechnical performance of these relatively old layers, and egg quality. The parallel increase in Ca and P in the blood and in the bone following PA supplementation suggests an improvement of the mineral supply for eggshell formation without impacting bone integrity, and even increasing bone resistance.

Effect of phytase supplementation on performance, fecal excretion, and compost characteristics in broilers fed diets deficient in phosphorus and calcium.

This study investigated the effect of dietary supplementation with phytase on growth performance, fecal excretion, and compost nutrition on broilers fed available phosphorus (avP)- and calcium (Ca)-deficient diets. A total of 750 one-day-old broiler chicks were randomly divided into five dietary groups having ten replications in a floor house. Diets of the groups were formulated with positive control (PC), negative control (NC; low avP and Ca), and NC supplemented with phytase levels; 500 (NC500), 1,000 (NC1000), and 1,500 FTU/kg (NC1500). A three-phase feeding program was used in the trial. Average daily gain (ADG) and average daily feed intake (ADFI) in the groups fed diets supplemented with phytase were significantly (p < 0.05) higher than those fed NC and the increase was equivalent to those fed PC. Serum levels of Ca and phosphorus (P) were higher (p < 0.05) in broilers fed NC1000 and NC1500 than in those fed NC. Interleukin (IL) level was the lowest in the group fed NC. Plasma myo-inositol (INS) concentrations in the NC1500 group were higher (p < 0.05) than PC, NC, and NC500 groups. Crude protein (CP) excretion was notably (p < 0.05) lower in the NC1500 group than in PC and NC groups. A lower (p < 0.05) concentration of P2O5 was observed in compost from the group fed NC1500 than the groups fed PC and NC. Accordingly, we suggest that phytase supplementation in lower avP and Ca levels of broiler diet can improve their productive performance and reduce environmental pollution.

Effect of dietary heat-killed Lactiplantibacillus plantarum VSG3 on growth, immunity, antioxidant status, and immune-related gene expression in pathogen-aggravated Cyprinus carpio.

Heat-killed probiotics offer an alternative approach to enhance growth and disease resistance in farmed fish. In this study, we isolated Lactiplantibacillus plantarum VSG3 from the gut of Labeo rohita to investigate the effects of heat-killed L. plantarum (HK-LP) on the health and growth performance of Cyprinus carpio fingerlings. Different concentrations of HK-LP (0, 50, 100, 200, 300, and 400 mg/kg) were administered to the fish, followed by a challenge with Aeromonas hydrophila after 8 weeks of feeding. Notably, the LP200 group exhibited significantly improved percentage weight gain and specific growth rate, accompanied by the lowest feed conversion ratio. Post-challenge survival rates were considerably enhanced in the LP200 group, reaching 60.65%. Moreover, serum analysis indicated significantly higher levels of total protein and albumin in the LP200 group than in the control group. Although HK-LP had no substantial impact on certain serum parameters (glucose, total cholesterol, cortisol, and alanine aminotransferase), aspartate aminotransferase levels were considerably low in the LP200 group. Intestinal protease and trypsin activities significantly increased in the LP200 group, while no significant changes were observed in lipase and amylase activities post-pathogen challenge. Serum immunological indices, including lysozyme, alternative complement pathway, and phagocytic activity, improved considerably in the LP200 group. Additionally, serum antioxidant enzyme activities (superoxide dismutase [SOD], glutathione peroxidase [GPx], catalase [CAT], and myeloperoxidase) were significantly elevated in the LP200 group, while malondialdehyde level was reduced. Gene expression analysis in liver tissue indicated strong upregulation of antioxidant-related genes (SOD, CAT, nuclear factor erythroid 2 [NFE2]-related factor 2 [Nrf2], Kelch-like ECH-associated protein 1[Keap1]) in the LP100 and LP200 groups. Pro-inflammatory cytokines (IL-1ß and TNF-α) were considerably downregulated in the kidneys of the LP200 post-challenged fish, although the anti-inflammatory cytokine IL-10 showed an increased expression. Quadratic regression analysis identified the optimal dietary HK-LP level for maximizing growth and immune performance (200.381-270.003 mg/kg). In summary, our findings underscore the potential of HK-LP as a valuable dietary supplement for enhancing carp aquaculture, particularly at the appropriate concentration.

The incidences of nausea and vomiting after general anesthesia with remimazolam versus sevoflurane: a prospective randomized controlled trial.

Background: Postoperative nausea and vomiting (PONV) refers to nausea and vomiting that occurs within 24-h after surgery or in the post-anesthesia care unit (PACU). Previous studies have reported that the use of remimazolam, a newer benzodiazepine (BDZ) hypnotic, for anesthesia results in less PONV. In this study, we compared the rate of PONV between sevoflurane and remimazolam after general anesthesia. Methods: In this prospective randomized controlled trial (RCT), participants aged 20-80 years who underwent elective laparoscopic cholecystectomy or hemicolectomy were randomized to either the remimazolam or sevoflurane group. The primary outcome was PONV incidence for 24-h after surgery. Secondary outcomes comprised of PONV at 30-min post-surgery, postoperative additional antiemetic use, and Quality of Recovery-15 (QOR-15) score at 24-h postoperatively. Results: Forty patients were enrolled in the study. The remimazolam group exhibited significantly lower rates of PONV for 24-h after surgery than did the sevoflurane group (remimazolam group vs. sevoflurane group; 5% vs. 45%, P = 0.003, respectively). The use of dexamethasone, a rescue antiemetic administered within 24 h of surgery, was substantially lower in the remimazolam group than in the sevoflurane group (0% in remimazolam vs. 30% in sevoflurane, P = 0.020). The QOR-15 score at 24-h after surgery showed no significant difference between the two groups. Conclusions: Compared to sevoflurane, opting for remimazolam as an intraoperative hypnotic may decrease the incidence of PONV and reduce antiemetic use for 24 h after laparoscopic surgery.

Left Atrium Volume Measured with Multislice Computed Tomography as a Prognostic Predictor for Atrial Fibrillation Catheter Ablation Outcomes.

Background: Current guidelines consider atrial fibrillation (AF) type as the prognostic factor for a recommendation of catheter ablation. We aimed to determine whether LA and LA appendage (LAA) volumes measured using multislice computed tomography (MSCT) were related to long-term outcomes in AF following radiofrequency catheter ablation (RFCA). Methods: We evaluated 152 consecutive patients with drug-refractory AF (median age, 55.8 ± 9.6 years), including 110 male patients, who underwent RFCA in a single center. All patients underwent MSCT imaging for anatomical assessment. The endpoint of this study was documented AF recurrence after RFCA. Results: The overall procedure success rate was 77.6% (n = 118) during a mean follow-up period of 12.6 months. The LA volume was significantly larger for those who experienced AF recurrence after RFCA than for the patients without recurrent AF after the procedure (153.8 ± 29.9 mL vs. 139.2 ± 34.1 mL, p = 0.025). However, LAA volumes were nearly equivalent between the patients with and without AF recurrence after RFCA (16.2 ± 6.3 mL and 14.7 ± 6.5 mL, respectively; p = 0.235). LA volume ≥ 153.2 mL was the optimal cutoff value for estimating AF recurrence after RFCA, with 94% sensitivity and 66% specificity. LA volume remained an independent predictor of both AF recurrence and permanent AF. Conclusions: LA volume as assessed by MSCT might be helpful for identifying patients likely to achieve successful AF ablation. LA volume ≥ 153.2 mL, but not LAA volume, showed good accuracy in predicting AF recurrence after RFCA.

Size-selective sampler combined with an immunochromatographic assay for the rapid detection of airborne Legionella pneumophila.

Airborne biological aerosols (also called bioaerosols) are found in various environmental and occupational settings. Among these, pathogenic bioaerosols can cause diseases such as legionellosis, influenza, measles, and tuberculosis. To prevent or minimize people's exposure to these pathogenic bioaerosols in the field, a rapid detection method is required. In this study, a size-selective bioaerosol (SSB) sampler was combined with the immunochromatographic assay (ICA). The SSB sampler can collect bioaerosols on the sampling swab and the lateral flow test kit used in ICA can rapidly detect the pathogens in bioaerosols collected on the swab. Before testing the combined method, the lower limit of detection (LOD) of the lateral flow test kit was determined. Legionella pneumophila (L. pneumophila) was used as a target pathogen. The results show that at least 1.3 × 103L. pneumophila cells are required to be detected by the lateral flow test kit. To test the developed method, L. pneumophila suspension was aerosolized in the sampling chamber and collected using two SSB samplers with different sampling times (10 and 20 min). The developed method could detect aerosolized L. pneumophila and also estimate the concentrations from the lower LOD, sampling time, and formation of a positive line on a test strip. When positive results were obtained from sampling for 10 min and 20 min, concentrations of respirable L. pneumophila were estimated ≥5.2 × 104 CFUresp/m3 and ≥2.6 × 104 CFUresp/m3, respectively. The conventional sampler Andersen impactor with colony counting was also used for comparison. In all cases, the estimated concentrations obtained by the developed method were higher than those obtained by the conventional method. These findings confirm that the developed method can overcome the limitations of conventional methods and eventually benefit environmental and occupational health by providing a better method for risk assessment.

First report of kyphoscoliosis in the narrow-ridged finless porpoises (Neophocaena asiaeorientalis): Findings from congenital and degenerative cases comparison using post-mortem computed tomography.

INTRODUCTION: Spinal deformities, including kyphoscoliosis, have been consistently documented in cetaceans. However, the majority of reported cases of kyphoscoliosis in cetaceans pertain to bottlenose dolphins, with limited information on its occurrence in narrow-ridged finless porpoise (NFP) (Neophocaena asiaeorientalis). MATERIALS AND METHODS: In November 2021, two deceased NFPs were discovered stranded on the shores of the Republic of Korea. As part of the pioneer stranded cetacean imaging programme in the Republic of Korea, both carcasses underwent post-mortem computed tomography (PMCT), revealing congenital and degenerative traumatic kyphoscoliosis, respectively. RESULTS: Although kyphoscoliosis may not have directly caused the demise of these individuals, it is hypothesized that the reduced spinal range of motion and mobility associated with kyphoscoliosis may have contributed to their deaths. CONCLUSION: This case report presents the first documented cases of kyphoscoliosis in two NFPs stranded in Korean waters, utilizing PMCT as an efficient methodology for assessing skeletal abnormalities in cetaceans.

Factors Associated with Reaching Mid-Parental Height in Patients Diagnosed with Inflammatory Bowel Disease in Childhood and Adolescent Period.

Background/Aims: The recent update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease initiative has added normal growth in children as an intermediate target in Crohn's disease and ulcerative colitis. We aimed to investigate factors associated with reaching mid-parental height (MPH) in patients diagnosed with inflammatory bowel disease in childhood and the adolescent period. Methods: This multicenter retrospective observational study included pediatric patients with inflammatory bowel disease that had reached adult height. Factors associated with reaching MPH were investigated by logistic regression analyses. Results: A total of 166 patients were included in this study (128 Crohn's disease and 38 ulcerative colitis). Among them, 54.2% (90/166) had reached their MPH. Multivariable logistic regression analysis revealed that height Z-score at diagnosis and MPH Z-score were independently associated with reaching MPH (odds ratio [OR], 8.45; 95% confidence interval [CI], 4.44 to 17.90; p<0.001 and OR, 0.11; 95% CI, 0.04 to 0.24; p<0.001, respectively). According to the receiver operating characteristic curve analysis, the optimal cutoff level of "height Z-score at diagnosis minus MPH Z-score" that was associated with reaching MPH was -0.01 with an area under the curve of 0.889 (95% CI [0.835 to 0.944], sensitivity 88.9%, specificity 84.2%, positive predictive value 87.0%, negative predictive value 86.5%, p<0.001). Conclusions: Height Z-score at diagnosis and MPH Z-score were the only factors associated with reaching MPH. Efforts should be made to restore growth in pediatric patients who present with a negative "height Z-score at diagnosis minus MPH Z-score."

Adhesive Bowel Obstruction (ABO) in a Stranded Narrow-Ridged Finless Porpoise (Neophocaena asiaeorientalis sunameri).

In this case report, we present a rare occurrence of a narrow-ridged finless porpoise (Neophocaena asiaeorientalis sunameri), discovered on the coast of Jeju Island, Republic of Korea, that was afflicted with adhesive bowel obstruction (ABO), a life-threatening condition that has scarcely been reported in cetaceans. Diagnosis of ABO was confirmed via radiological and clinical assessments. Post-mortem computed tomography and necropsy revealed ABO between two loops of the jejunum at the L8 level. The mesenteric tissue covering the intestinal lesion was severely thickened with increased tension. Both bowel loops were fixed to the mesentery and acutely angulated, leading to asymmetrical thickening of the cross-sectional bowel walls. The intestinal lumen was stenosed because of pressure from the firm mesenteric band, and no fecal matter was observed in the lumen of the posterior bowel or rectum. Calcified nodules were detected, and histological analysis suggested parasitic or suspected post-parasitic infections. The primary cause of the intestinal lesions is presumed to be a reaction related to parasitic infection. However, further investigations would establish a definitive link between parasitic infections and ABO in this species. This case highlights the importance of studying rare medical conditions in wildlife, providing valuable insights into marine mammal health.

Optimizing the formulation of Erwinia bacteriophages for improved UV stability and adsorption on apple leaves.

Fire blight is a bacterial disease that affects plants of the Rosaceae family and causes significant economic losses worldwide. Although antibiotics have been used to control the disease, concerns about their environmental impact and the potential to promote antibiotic resistance have arisen. Bacteriophages are being investigated as an alternative to antibiotics; however, their efficacy can be affected by environmental stresses, such as UV radiation. In this study, we optimized the formulation of Erwinia phages to enhance their stability in the field, focusing on improving their UV stability and adsorption using adjuvants. Our results confirmed that 4.5 % polysorbate 80 and kaolin improve phage stability under UV stress, resulting in an 80 % increase in PFU value and improved UV protection efficacy. Adsorption assays also demonstrated that polysorbate 80 and kaolin improved the absorption efficiency, with phages detected in plant for up to two weeks. These findings demonstrate the effectiveness of the auxiliary formulation of Erwinia bacteriophages against environmental stress.

Effect of statin use on head and neck cancer prognosis in a multicenter study using a Common Data Model.

Few studies have found an association between statin use and head and neck cancer (HNC) outcomes. We examined the effect of statin use on HNC recurrence using the converted Observational Medical Outcome Partnership (OMOP) Common Data Model (CDM) in seven hospitals between 1986 and 2022. Among the 9,473,551 eligible patients, we identified 4669 patients with HNC, of whom 398 were included in the target cohort, and 4271 were included in the control cohort after propensity score matching. A Cox proportional regression model was used. Of the 4669 patients included, 398 (8.52%) previously received statin prescriptions. Statin use was associated with a reduced rate of 3- and 5-year HNC recurrence compared to propensity score-matched controls (risk ratio [RR], 0.79; 95% confidence interval [CI], 0.61-1.03; and RR 0.89; 95% CI 0.70-1.12, respectively). Nevertheless, the association between statin use and HNC recurrence was not statistically significant. A meta-analysis of recurrence based on subgroups, including age subgroups, showed similar trends. The results of this propensity-matched cohort study may not provide a statistically significant association between statin use and a lower risk of HNC recurrence. Further retrospective studies using nationwide claims data and prospective studies are warranted.

Statistical methods for handling nondetected results in food chemical monitoring data to improve food risk assessments.

Chemical risk assessment is important for risk management, and estimates of chemical exposure must be as accurate as possible. Chemical concentrations in food below the limit of detection are known as nondetects and result in left-censored data. During statistical analysis, the method used for handling values below the limit of detection is important. Many risk assessors employ widely used substitution methods to treat left-censored data, as recommended by international organizations. The National Institute of Food and Drug Safety Evaluation of South Korea also recommends these methods, which are currently used for chemical exposure assessments. However, these methods have statistical limitations, and international organizations recommend more advanced alternative statistical approaches. In this study, we assessed the validity of currently used statistical methods for handling nondetects. To identify the most suitable statistical method for handling nondetection, we created virtual data and conducted simulation studies. Based on both simulation and case studies, the Maximum Likelihood Estimation (MLE) and Robust Regression on Order Statistics (ROS) methods were found to be the best options. The statistical values obtained from these methods were similar to those obtained from the commonly used 1/2 Limit of Detection (LOD) substitution method for nondetection treatment. In three case studies, we compared the various methods based on the root mean squared error. The data for all case studies were from the same source, to avoid heterogeneity. Across various sample sizes and nondetection rates, the mean and 95th percentile values for all treatment methods were similar. However, "lognormal maximum likelihood estimation" method was not suitable for estimating the mean. Risk assessors should consider statistical processing of monitoring data to reduce uncertainty. Currently used substitution methods are effective and easy to apply to large datasets with nondetection rates <80%. However, advanced statistical methods are required in some circumstances, and national guidelines are needed regarding their use in risk assessments.

Self-organized insulin-producing ß-cells differentiated from human omentum-derived stem cells and their in vivo therapeutic potential.

BACKGROUND: Human omentum-derived mesenchymal stem cells (hO-MSCs) possess great potential to differentiate into multiple lineages and have self-renewal capacity, allowing them to be utilized as patient-specific cell-based therapeutics. Although the use of various stem cell-derived ß-cells has been proposed as a novel approach for treating diabetes mellitus, developing an efficient method to establish highly functional ß-cells remains challenging. METHODS: We aimed to develop a novel cell culture platform that utilizes a fibroblast growth factor 2 (FGF2)-immobilized matrix to regulate the adhesion and differentiation of hO-MSCs into insulin-producing ß-cells via cell-matrix/cell-cell interactions. In our study, we evaluated the in vitro differentiation potential of hO-MSCs cultured on an FGF2-immobilized matrix and a round-bottom plate (RBP). Further, the in vivo therapeutic efficacy of the ß-cells transplanted into kidney capsules was evaluated using animal models with streptozotocin (STZ)-induced diabetes. RESULTS: Our findings demonstrated that cells cultured on an FGF2-immobilized matrix could self-organize into insulin-producing ß-cell progenitors, as evident from the upregulation of pancreatic ß-cell-specific markers (PDX-1, Insulin, and Glut-2). Moreover, we observed significant upregulation of heparan sulfate proteoglycan, gap junction proteins (Cx36 and Cx43), and cell adhesion molecules (E-cadherin and Ncam1) in cells cultured on the FGF2-immobilized matrix. In addition, in vivo transplantation of differentiated ß-cells into animal models of STZ-induced diabetes revealed their survival and engraftment as well as glucose-sensitive production of insulin within the host microenvironment, at over 4 weeks after transplantation. CONCLUSIONS: Our findings suggest that the FGF2-immobilized matrix can support initial cell adhesion, maturation, and glucose-stimulated insulin secretion within the host microenvironment. Such a cell culture platform can offer novel strategies to obtain functional pancreatic ß-cells from patient-specific cell sources, ultimately enabling better treatment for diabetes mellitus.

Compositional variations in metal nanoparticle components of welding fumes impact lung epithelial cell toxicity.

Welding fumes contain harmful metals and gas by-products associated with development of lung dysfunction, asthma, bronchitis, and lung cancer. Two prominent welding fume particulate metal components are nanosized iron (Fe) and manganese (Mn) which might induce oxidative stress and inflammation resulting in pulmonary injury. Welding fume toxicity may be dependent upon metal nanoparticle (NP) components. To examine toxicity of welding fume NP components, a system was constructed for controlled and continuous NP generation from commercial welding and customized electrodes with varying proportions of Fe and Mn. Aerosols generated consisted of nanosized particles and were compositionally consistent with each electrode. Human alveolar lung A459 epithelial cells were exposed to freshly generated metal NP mixtures at a target concentration of 100 µg/m3 for 6 hr and then harvested for assessment of cytotoxicity, generation of reactive oxygen species (ROS), and alterations in the expression of genes and proteins involved in metal regulation, inflammatory responses, and oxidative stress. Aerosol exposures decreased cell viability and induced increased ROS production. Assessment of gene expression demonstrated variable up-regulation in cellular mechanisms related to metal transport and storage, inflammation, and oxidative stress based upon aerosol composition. Specifically, interleukin-8 (IL-8) demonstrated the most robust changes in both transcriptional and protein levels after exposure. Interleukin-8 has been determined to serve as a primary cytokine mediating inflammatory responses induced by welding fume exposures in alveolar epithelial cells. Overall, this study demonstrated variations in cellular responses to metal NP mixtures suggesting compositional variations in NP content within welding fumes may influence inhalation toxicity.