Uremic toxin indoxyl sulfate induces trained immunity via the AhR-dependent arachidonic acid pathway in end-stage renal disease (ESRD).

Trained immunity is the long-term functional reprogramming of innate immune cells, which results in altered responses toward a secondary challenge. Despite indoxyl sulfate (IS) being a potent stimulus associated with chronic kidney disease (CKD)-related inflammation, its impact on trained immunity has not been explored. Here, we demonstrate that IS induces trained immunity in monocytes via epigenetic and metabolic reprogramming, resulting in augmented cytokine production. Mechanistically, the aryl hydrocarbon receptor (AhR) contributes to IS-trained immunity by enhancing the expression of arachidonic acid (AA) metabolism-related genes such as arachidonate 5-lipoxygenase (ALOX5) and ALOX5 activating protein (ALOX5AP). Inhibition of AhR during IS training suppresses the induction of IS-trained immunity. Monocytes from end-stage renal disease (ESRD) patients have increased ALOX5 expression and after 6 days training, they exhibit enhanced TNF-α and IL-6 production to lipopolysaccharide (LPS). Furthermore, healthy control-derived monocytes trained with uremic sera from ESRD patients exhibit increased production of TNF-α and IL-6. Consistently, IS-trained mice and their splenic myeloid cells had increased production of TNF-α after in vivo and ex vivo LPS stimulation compared to that of control mice. These results provide insight into the role of IS in the induction of trained immunity, which is critical during inflammatory immune responses in CKD patients.

Tebuconazole Induces Mouse Fetal Testes Damage via ROS Generation in an Organ Culture Method.

The fungicide tebuconazole (TEB) poses risks to human and animal health via various exposure routes. It induces toxicity in multiple organs and disrupts reproductive health by affecting steroid hormone synthesis and fetal development. In this study, we investigated the impact of TEB on fetal testes using in vitro models, focusing on germ, Sertoli, and Leydig cells, and explored the mechanisms underlying cellular damage. The results revealed significant damage to germ cells and disruption of Leydig cell development. TEB exposure led to a decrease in germ cell numbers, as indicated by histological and immunostaining analyses. TEB induced the up- and down-regulation of the expression of fetal and adult Leydig cell markers, respectively. Additionally, TEB-treated fetal testes exhibited increased expression of oxidative-stress-related genes and proteins. However, co-treatment with the antioxidant N-acetylcysteine mitigated TEB-induced germ cell damage and prevented abnormal Leydig cell development. These findings suggest that administration of antioxidants can prevent the intratesticular damage typically caused by TEB exposure.

Risk of Cardiovascular Events Associated with Chronic Obstructive Pulmonary Disease and/or Metabolic Syndrome: A Large-Scale Nationwide Population-Based Cohort Study.

Purpose: Chronic obstructive pulmonary disease (COPD) and metabolic syndrome (MetS) are among the most prevalent conditions that might predispose individuals to life-threatening events. We aimed to examine their associations with cardiovascular (CV) events and mortality using a large-scale population dataset from the National Health Information Database in Korea. Patients and Methods: This population-based cohort study enrolled adults aged ≥40 years who had undergone more than two health examinations between 2009 and 2011. They were divided into four groups based on the presence of COPD and MetS. Analysis of the outcomes and CV events or deaths was performed from 2014 to 2019. We compared CV event incidence and mortality rates using a multivariate Cox proportional hazards model and Kaplan-Meier curves. Results: Totally, 5,101,810 individuals were included, among whom 3,738,458 (73.3%) had neither COPD nor MetS, 1,193,014 (23.4%) had only MetS, 125,976 (2.5%) had only COPD, and 44,362 (0.9%) had both. The risk of CV events was significantly higher in individuals with both COPD and MetS than in those with either COPD or MetS alone (HRs: 2.4 vs 1.6 and 1.8, respectively; all P <0.001). Similarly, among those with both COPD and MetS, all-cause and CV mortality risks were also elevated (HRs, 2.9 and 3.0, respectively) compared to the risks in those with either COPD (HRs, 2.6 and 2.1, respectively) or MetS (HRs, 1.7 and 2.1, respectively; all P <0.001). Conclusion: The comorbidity of MetS in patients with COPD increases the incidence of CV events and all-cause and cardiovascular mortality rates.

Comparative clinical outcomes of irrigation techniques in burr-hole craniostomy for chronic subdural hemorrhage: a multicenter cohort study.

BACKGROUND: Chronic Subdural Hemorrhage(cSDH) is often treated with surgical blood drainage, but concerns about recurrence and outcomes persist. Surgical techniques, including irrigation, vary. This study compares the outcomes of irrigation in cSDH surgery. MATERIALS AND METHODS: From September 2020 to September 2022, 92 cSDH patients underwent surgery. Two different irrigation methods were used: extensive irrigation (IG) and non-irrigation (NIG). Method of irrigation was selected by each surgeon's preference. Parameters measured included volume of hematoma changes, midline shifting, complications, and basic demographics. Recurrence was defined as symptomatic or hematoma expansion more than double the volume before surgery. Factors predicting recurrence and irrigation method impact were analyzed. RESULTS: Eleven patients were excluded because of bilateral or related to other disease. We analyzed 81 patients (44 NIG, 37 IG). Recurrence occurred in 6 IG cases (16.2%) and 1 NIG case (2.3%). Irrigation method significantly affected recurrence (P = 0.043). Age, gender, medication, medical history, and preoperative measurements had no major impact on recurrence. NIG had unexpected cases of intracerebral hemorrhage. CONCLUSION: Extensive irrigation may increase recurrence in cSDH drainage. Non-irrigation drainage had fewer recurrences, but unexpected complications arose. Careful drainage in non-irrigated cases is crucial.

Hierarchically porous and single Zn atom-embedded carbon molecular sieves for H2 separations.

Hierarchically porous materials containing sub-nm ultramicropores with molecular sieving abilities and microcavities with high gas diffusivity may realize energy-efficient membranes for gas separations. However, rationally designing and constructing such pores into large-area membranes enabling efficient H2 separations remains challenging. Here, we report the synthesis and utilization of hybrid carbon molecular sieve membranes with well-controlled nano- and micro-pores and single zinc atoms and clusters well-dispersed inside the nanopores via the carbonization of supramolecular mixed matrix materials containing amorphous and crystalline zeolitic imidazolate frameworks. Carbonization temperature is used to fine-tune pore sizes, achieving ultrahigh selectivity for H2/CO2 (130), H2/CH4 (2900), H2/N2 (880), and H2/C2H6 (7900) with stability against water vapor and physical aging during a continuous 120-h test.

IL-1 Receptor Dynamics in Immune Cells: Orchestrating Immune Precision and Balance.

IL-1, a pleiotropic cytokine with profound effects on various cell types, particularly immune cells, plays a pivotal role in immune responses. The proinflammatory nature of IL-1 necessitates stringent control mechanisms of IL-1-mediated signaling at multiple levels, encompassing transcriptional and translational regulation, precursor processing, as well as the involvement of a receptor accessory protein, a decoy receptor, and a receptor antagonist. In T-cell immunity, IL-1 signaling is crucial during both the priming and effector phases of immune reactions. The fine-tuning of IL-1 signaling hinges upon two distinct receptor types; the functional IL-1 receptor (IL-1R) 1 and the decoy IL-1R2, accompanied by ancillary molecules such as the IL-1R accessory protein (IL-1R3) and IL-1R antagonist. IL-1R1 signaling by IL-1ß is critical for the differentiation, expansion, and survival of Th17 cells, essential for defense against extracellular bacteria or fungi, yet implicated in autoimmune disease pathogenesis. Recent investigations emphasize the physiological importance of IL-1R2 expression, particularly in its capacity to modulate IL-1-dependent responses within Tregs. The precise regulation of IL-1R signaling is indispensable for orchestrating appropriate immune responses, as unchecked IL-1 signaling has been implicated in inflammatory disorders, including Th17-mediated autoimmunity. This review provides a thorough exploration of the IL-1R signaling complex and its pivotal roles in immune regulation. Additionally, it highlights recent advancements elucidating the mechanisms governing the expression of IL-1R1 and IL-1R2, underscoring their contributions to fine-tuning IL-1 signaling. Finally, the review briefly touches upon therapeutic strategies targeting IL-1R signaling, with potential clinical applications.

Vomiting-induced pharyngeal perforation during bowel preparation for colonoscopy: A case report.

BACKGROUND: Effective bowel cleansing is essential for a successful colonoscopy. Laxatives, such as polyethylene glycol, are commonly used for bowel preparation. Vomiting is a frequent complication during bowel preparation, and forceful vomiting can potentially lead to esophageal perforation, as reported in several previous cases. However, pharyngeal perforation during bowel preparation has not been previously documented. Here, we present a case of pharyngeal perforation induced by forceful vomiting during bowel preparation. CASE SUMMARY: A 38-year-old man with a history of hypertension, dyslipidemia, diabetes mellitus, and end-stage renal disease on hemodialysis was admitted for evaluation of recurrent abdominal pain. The patient complained of sudden pain in the neck, throat, and anterior chest following forceful vomiting during bowel preparation. Physical examination revealed crepitus under the skin of the neck and anterior chest on palpation, and upper gastrointestinal endoscopy revealed pharyngeal perforation. The perforation site was located above the upper esophageal sphincter, which distinguished it from Boerhaave's syndrome. Conservative medical management was chosen after consultation with a thoracic surgeon and an otolaryngologist, considering the patient's mild symptoms, stable vital signs, and the small size of the lesion; the perforation resolved without endoscopic or surgical intervention. The patient was discharged from hospital two weeks after the perforation. CONCLUSION: Despite its rarity, pharyngeal perforation should be considered a potential complication of bowel preparation for colonoscopy.

Prescribing trends of glaucoma medication in Korea from 2007 to 2020: A nationwide population-based study.

PURPOSE: Investigating long-term trends in glaucoma medication. METHODS: All patients diagnosed with glaucoma and prescribed glaucoma eye drops between 2007 and 2020 in Korea's Health Insurance Review and Assessment Service database participated in this study. A weight was assigned to each prescription using the reciprocal of the total number of prescriptions received by the individual in that year. The number of patients who received each type of glaucoma eye drop prescription was calculated by summing the weights for each year. RESULTS: During the study period, prostaglandin analog eye drop monotherapy was the most frequently given type of glaucoma eye drop prescription. Until 2008, the second most frequently given type of glaucoma eye drop prescription was beta blocker eye drop monotherapy; thereafter, it changed to carbonic anhydrase inhibitor/beta blocker fixed-combination eye drop monotherapy. The prescription proportion of single-ingredient glaucoma eye drops decreased (-1.290%/year, P < 0.001), whereas that of fixed-combination glaucoma eye drops increased (1.291%/year, P < 0.001). The number of glaucoma eye drops prescribed per patient remained constant (-0.00030/year, P = 0.167) with an average of 1.302, while the number of active ingredients prescribed per patient increased (0.01737/year, P < 0.001) from 1.659 in 2007 to 1.896 in 2020. CONCLUSION: Over 14 years, there was no change in the number of glaucoma eye drops prescribed to individual patients in Korea. However, the number of active ingredients prescribed increased owing to the increased prescription of fixed-combination eye drops. The current trends in glaucoma medication are expected to help establish future treatment strategies.

Developing an eyeball positioning method in the eye orbit for craniofacial identification in Korean population.

We analysed the skulls and faces of Korean subjects using anthropometric methods to understand the anatomical characteristics of the eyeball and eye orbit region of Korean population and to determine the correlations between the hard and soft tissues around the eyeball and eye orbit region. In total, 82 sections in the region were measured to determine the correlations; among them, 34 showed significant differences by sex, and 6 showed significant differences by age. As the distance from the centre of the eye lens to the eye orbit is calculated as a ratio, we determined that the centre of the eye lens is located relatively on the lateral and superior position in each eye orbit in front view. Fourteen sections that could be used for craniofacial reconstruction/approximation in men and women were selected. Regression equations were derived according to the correlation of each section, and their reliabilities were verified by out of sample validation tests. Therefore, our results increase the accuracy of eyeball position determination, which would be useful for more efficient craniofacial reconstruction/approximation of the Korean population and should improve the efficiency of facial recognition.

International scope of biomedical research ethics review.

Many countries consider long-term implications for society.

Benefits of Hepatitis C Viral Eradication: A Real-World Nationwide Cohort Study in Taiwan.

BACKGROUND: Chronic hepatitis C (CHC) increases the risk of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). This nationwide cohort study assessed the effectiveness of viral eradication of CHC. METHODS: The Taiwanese chronic hepatitis C cohort and Taiwan hepatitis C virus (HCV) registry are nationwide HCV registry cohorts incorporating data from 23 and 53 hospitals in Taiwan, respectively. This study included 27,577 individuals from these cohorts that were given a diagnosis of CHC and with data linked to the Taiwan National Health Insurance Research Database. Patients received either pegylated interferon and ribavirin or direct-acting antiviral agent therapy for > 4 weeks for new-onset LC and liver-related events. RESULTS: Among the 27,577 analyzed patients, 25,461 (92.3%) achieved sustained virologic response (SVR). The mean follow-up duration was 51.2 ± 48.4 months, totaling 118,567 person-years. In the multivariable Cox proportional hazard analysis, the hazard ratio (HR) for incident HCC was 1.39 (95% confidence interval [CI]: 1.00-1.95, p = 0.052) among noncirrhotic patients without SVR compared with those with SVR and 1.82 (95% CI 1.34-2.48) among cirrhotic patients without SVR. The HR for liver-related events, including HCC and decompensated LC, was 1.70 (95% CI 1.30-2.24) among cirrhotic patients without SVR. Patients with SVR had a lower 10-year cumulative incidence of new-onset HCC than those without SVR did (21.7 vs. 38.7% in patients with LC, p < 0.001; 6.0 vs. 18.4% in patients without LC, p < 0.001). CONCLUSION: HCV eradication reduced the incidence of HCC in patients with and without LC and reduced the incidence of liver-related events in patients with LC.

A Historical Survey of Key Epidemiological Studies of Ionizing Radiation Exposure.

In this article we review the history of key epidemiological studies of populations exposed to ionizing radiation. We highlight historical and recent findings regarding radiation-associated risks for incidence and mortality of cancer and non-cancer outcomes with emphasis on study design and methods of exposure assessment and dose estimation along with brief consideration of sources of bias for a few of the more important studies. We examine the findings from the epidemiological studies of the Japanese atomic bomb survivors, persons exposed to radiation for diagnostic or therapeutic purposes, those exposed to environmental sources including Chornobyl and other reactor accidents, and occupationally exposed cohorts. We also summarize results of pooled studies. These summaries are necessarily brief, but we provide references to more detailed information. We discuss possible future directions of study, to include assessment of susceptible populations, and possible new populations, data sources, study designs and methods of analysis.

Relationship between Presentation, Attitude, and In-Flight Meal Food Healthiness: Moderating Role of Familiarity.

This work focused on the perception of the food healthiness of in-flight meals. This work adopts presentation as the determinant. This work also employs attitude as the consequence of food healthiness. This research also examines the moderating effect of familiarity on the relationship between food presentation and food healthiness. This research used a survey, and survey participants were recruited via a Clickworker platform service. Survey participants were experienced with in-flight meals. The number of observations was 317. Moreover, this research tested the research hypotheses using the Hayes process macro Model 7. The results revealed that food healthiness is positively influenced by presentation and that food healthiness positively affects attitude. Moreover, the results revealed that the type of presentation has a positive influence on attitude. Familiarity was a significant moderating variable for the relationship between food presentation and food healthiness. This work sheds light on the literature by identifying the associations among four attributes of in-flight meals. Additionally, the results of this study could be used as a reference to develop better in-flight meals.

Hemodialysis-induced positional changes in lamina cribrosa.

This study is aimed to investigate the effect of hemodialysis (HD) on the lamina cribrosa (LC) of the optic nerve head (ONH) using swept-source optical coherence tomography (SS-OCT) and other ophthalmological parameters in patients with end-stage kidney disease (ESKD). This prospective observational study included 29 patients who underwent HD for ESKD. ONH parameters including neural canal diameter (NCD), peripapillary vertical height (PVH), and anterior LC depth (LCD), were assessed using SS-OCT. Changes in the ONH parameters before and after HD were statistically analysed. Correlations between changes in the LCD and other ocular and systemic measurements were identified using Pearson's correlation analyses. The mean anterior LCD significantly decreased from 441.6 ± 139.8 µm before HD to 413.5 ± 141.7 µm after HD (P = 0.001). Mean NCD and PVH did not show significant changes after HD (P = 0.841 and P = 0.574, respectively). A significant correlation was found between changes in the anterior LCD and the mean ocular perfusion pressure (r = 0.397, P = 0.036). We observed a significant decrease in anterior LCD after HD. Our study suggests that HD can influence the ONH, especially in the LC.

A Rare Case of Delayed Ventriculoperitoneal Shunt Catheter Migration Into the Heart: A Case Report.

The treatment of hydrocephalus with a ventriculoperitoneal (VP) shunt can lead to complications such as shunt migration. A 67-year-old male, who had previously undergone VP shunt surgery for normal-pressure hydrocephalus, presented approximately five years later with symptoms of general weakness and abdominal pain. Imaging revealed shunt malpositioning, with the catheter passing through an abnormal route to the heart. The catheter was successfully removed under fluoroscopic guidance while monitoring patient's electrocardiogram to prevent potential secondary complications. Although rare, cardiac migration of VP shunts can lead to life-threatening secondary complications. Our case highlights the possibility of delayed upward migration of the shunt catheter in patients with VP shunts, emphasizing the need for various strategies to address and manage this issue.

Nomogram for radiation-induced lymphopenia in patients receiving intensity-modulated radiotherapy based-chemoradiation therapy for newly diagnosed glioblastoma: A multi-institutional study.

Purpose: Severe lymphopenia (SLP) has emerged as a significant prognostic factor in glioblastoma. Intensity-modulated radiation therapy (IMRT)-based radiation therapy (RT) is suggested to minimize the risk of SLP. This study aimed to evaluate SLP incidence based on multi-institutional database in patients with GBM treated with IMRT and develop a predictive nomogram. Patients and methods: This retrospective study reviewed data from 348 patients treated with IMRT-based concurrent chemoradiation therapy (CCRT) at two major hospitals from 2016 to 2021. After multivariate regression analysis, a nomogram was developed and internally validated to predict SLP risk. Results: During treatment course, 21.0% of patients developed SLP and SLP was associated with poor overall survival outcomes in patients with GBM. A newly developed nomogram, incorporating gender, pre-CCRT absolute lymphocyte count, and brain mean dose, demonstrated fair predictive accuracy (AUC 0.723). Conclusions: This study provides the first nomogram for predicting SLP in patients with GBM treated with IMRT-based CCRT, with acceptable predictive accuracy. The findings underscore the need for dose optimization and radiation planning to minimize SLP risk. Further external validation is crucial for adopting this nomogram in clinical practice.

Species identification and pyrethroid resistance genotyping of recently resurgent Cimex lectularius and Cimex hemipterus in Korea.

The global resurgence of bed bug infestations, exacerbated by increasing international travel, trade, and insecticide resistance, has significantly impacted Korea. This study identified the bed bug species and performed pyrethroid resistance genotyping of recently resurgent bed bugs in Korea. Thirty-one regional bed bug samples were collected from 5 administrative regions: Gyeonggi-do (n=14), Seoul (n=13), Busan (n=2), Jeonllanam-do (n=1), and Chungcheongbuk-do (n=1). The samples underwent morphological and molecular identification. Twenty-four regional samples (77.4%) were identified as the tropical bed bug, Cimex hemipterus, and the remaining 7 regional samples (22.6%) were identified as the common bed bug, Cimex lectularius. The C. hemipterus regional samples carried at least three mutations associated with knockdown resistance (kdr), including 2 super-kdr mutations. The 7 C. lectularius regional samples possessed at least one of the 3 kdr-related mutations associated with pyrethroid resistance. This study confirms that the prevalent bed bug species recently in Korea is C. hemipterus, replacing the previously endemic C. lectularius. Additionally, the rise in bed bug populations with pyrethroid resistance underscores the necessity of introducing alternative insecticides.

Structural and functional characterization of Hdh-HSBP1 and its involvement in heat stress and early development in Pacific abalone, Haliotis discus hannai.

Heat shock factor binding protein 1 (HSBP1) is known to regulate the activity of heat shock factor 1 (HSF1) and the early development of organisms. To understand the involvement of HSBP1 in the heat shock response and embryonic and larval development of Pacific abalone (Haliotis discus hannai), the Hdh-HSBP1 gene was sequenced from the digestive gland (DG) tissue. The full-length sequence of Hdh-HSBP1 encompassed 738 nucleotides, encoding an 8.42 kDa protein consisting of 75 deduced amino acids. The protein contains an HSBP1 domain and a coiled-coil domain, which are conserved features in the HSBP1 protein family. Protein-protein molecular docking revealed that the coiled-coil region of Hdh-HSBP1 binds to the coiled-coil region of Hdh-HSF1. Tissue expression analysis demonstrated that the highest Hdh-HSBP1 expression occurred in the DG, whereas seasonal expression analysis revealed that this gene was most highly expressed in summer. In heat-stressed abalone, the highest expression of Hdh-HSBP1 occurred at 30 °C. Moreover, time-series analysis revealed that the expression of this gene began to increase significantly at 6 h post-heat stress, with higher expression observed at 12 h and 24 h post-heat stress. Furthermore, Hdh-HSBP1 mRNA expression showed a link to ROS production. Additionally, the expression of Hdh-HSBP1 showed significantly higher expression in the early stages of embryonic development in Pacific abalone. These results suggest that Hdh-HSBP1 plays a crucial role in the stress physiology of Pacific abalone by interacting with Hdh-HSF1, as well as its embryonic development.

The Clinical Effects of C2 and C3 Medial Branch Block for Medically Intractable Headache : a Retrospective Study.

Objective: This study aimed to evaluate the clinical effects of medial branch blocks (MBB) C2 and C3 in treating patients with medically intractable headaches. Methods: The medical records of 81 patients with medically intractable headaches who underwent a C2/3 MBB between January 2019 and March 2022 were retrospectively reviewed. The degrees of pain were evaluated using a visual analogue scale (VAS) score (rating 0-10) on baseline and after procedures. To evaluate patients' satisfaction for the treatment, self-reporting measurements were examined and were categorized as excellent (>90% pain relief), good (50%-90% pain relief), fair (10%-50% pain relief), and none (<10% pain relief). Results: The total number of MBB procedure was 107. The average baseline VAS score was 7.4 ±1.5, which improved significantly to 2.6 ±2.3, 3.6 ±2.6, and 4.5 ±3.2 on 1-3 days, 3-7 days, and 3 months after the procedure, respectively (Wilks' lambda within group test, P <0.001). For the subjective feeling of pain relief, percentages of "excellent" response in the self-reporting measurements were significantly decreased over time (chi-square test; P= 0.001). Conclusion: This study demonstrates clinical effectiveness of C2/3 MBB in patients with medically intractable headaches, with both early and prolonged benefits.