Primary Agent Research Articles

Inhibitory effect of hydroxychloroquine on glucocorticoid‐induced osteoporosis in lupus therapy

AbstractObjectivesSystemic lupus erythematosus (SLE) is a chronic and severe autoimmune disease characterised by persistent inflammation. Hydroxychloroquine (HCQ) and glucocorticoids (GCs) are the primary agents commonly used in combination as the first‐line treatment for SLE. Nevertheless, the specific mechanisms responsible for the effectiveness of this combined therapy with HCQ and GCs have not been fully elucidated. This study aimed to reveal the mechanism behind combined HCQ and GC treatment in lupus.MethodsAn SLE IgG‐induced inflammation model was used to investigate the anti‐inflammatory effects of HCQ and dexamethasone (DXM). A glucocorticoid‐induced osteoporosis (GIOP) model was used to investigate the inhibitory effect of HCQ on osteoclastogenesis. Inflammation was assessed by haematoxylin and eosin staining. Bone metabolism was determined structurally via microcomputer tomography and in bone marrow‐derived osteoclast cultures.ResultsAn SLE IgG‐induced inflammation model demonstrated that HCQ could not ameliorate inflammation alone but could enhance the anti‐inflammatory effect of GCs by decreasing the expression of FcγRI on macrophages. HCQ inhibited osteoclastogenesis induced by GCs and RANKL by upregulating nuclear factor erythroid 2‐related factor 2 and limiting reactive oxygen species formation, which mitigated GC‐induced bone loss.ConclusionThe results indicate that HCQ improved the anti‐inflammatory effects of GCs and inhibits the osteoclastogenesis in experimental lupus. This study offers valuable insights into the mechanisms underlying the combined treatment of lupus with HCQ and GCs.

Recent Advances in Marine-Derived Nanoformulation for the Management of Glioblastoma.

Glioma is the most common and aggressive type of central nervous system tumor as categorized by the World Health Organization. Glioblastoma (GBA), in general, exhibits a grim prognosis and short life expectancy, rarely exceeding 14months. The dismal prognosis is primarily attributed to the development of chemoresistance to temozolomide, the primary therapeutic agent for GBA treatment. Hence, it becomes imperative to develop novel drugs with antitumor efficacy rooted in distinct mechanisms compared to temozolomide. The vast marine environment contains a wealth of naturally occurring compounds from the sea (known as marine-derived natural products), which hold promise for future research in the quest for new anticancer drugs. Ongoing advancements in anticancer pharmaceuticals have led to an upswing in the isolation and validation of numerous pioneering breakthroughs and improvements in anticancer therapeutics. Nonetheless, the availability of FDA-approved marine-derived anticancer drugs remains limited, owing to various challenges and constraints. Among these challenges, drug delivery is a prominent hurdle. This review delves into an alternative approach for delivering marine-derived drugs using nanotechnological formulations and their mechanism of action for treating GBA.

Middle Meningeal Artery Embolization for Chronic Subdural Hematoma Using N-Butyl Cyanoacrylate With a D5W Push Technique: A Multicentric North American Study of 269 Patients

BACKGROUND AND OBJECTIVES: As the aging population increases, the incidence of chronic subdural hematomas (cSDHs) is expected to rise. Surgical evacuation, though effective, sees up to 30% recurrence. Middle meningeal artery (MMA) embolization, particularly with n-butyl cyanoacrylate (n-BCA) glue diluted in D5W for distal penetration, has shown promise in reducing recurrences. Limited reports have investigated the safety and technical feasibility of n-BCA as a primary liquid embolic agent using the D5W push technique in cSDH. This series is the largest in the literature investigating the outcomes of this technique in cSDH. METHODS: A multicenter retrospective database analysis was conducted on consecutive patients who underwent MMA embolization using n-BCA embolisate. Data collected included patient demographics, procedural information, angiographic data, and periprocedural complications. RESULTS: The study included 269 patients with a median age of 76 years. Nearly half of the patients had previous surgeries, and 93 underwent contralateral embolization for bilateral cSDH. Successful MMA embolization with effective distal penetration was achieved in all cases. The complication rate was 2.2%. Significant improvements were noted at a 60-day follow-up, with a median reduction in cSDH diameter of 40.6% (P < .001) and 53% of patients showing neurological improvement. No recurrent cSDH or need for retreatment was observed in patients who underwent follow-up. CONCLUSION: MMA embolization using n-BCA with the D5W push technique is safe and technically feasible. It can be used adjunctively or as an alternative to surgery in patients with cSDH, resulting in decreased recurrence, high technical success, improved distal penetration, and low complication rates.

Research Note: Development of a reverse transcriptase recombinase-aided amplification method for detection of Parrot Borna Virus 4

The Parrot Borna virus 4 (PaBV-4) is the primary causative agent of parrot developmental disorder (PDD), leading to symptoms such as bloating, undigested feed in stool, decreased appetite, diarrhea, and weight loss. Its impact on the parrot industry has been significant, therefore, it is imperative to develop a rapid detection method for PaBV-4. The detection of PaBV-4 was achieved through the development of an RT-RAA assay, which involved the design of specific probes and primers targeting the N gene. This method allows for detection at 41°C within 30 min and has a minimum detection threshold of 8.56 × 101 copies/μL. The RT-RAA method demonstrated specific detection of PaBV-4 without any cross-reactivity observed with H5N6, H7N9, H9N2 avian influenza virus, newcastle disease virus (NDV), avian infectious bronchitis virus (IBV) and Parrot Borna virus 2 (PaBV-2). The coefficient of variation for the 3 repeatability experiments was below 10%. Tissue samples from 28 suspected cases of PaBV related deaths in parrots were analyzed using both RT-RAA and RT-qPCR methods. The sensitivity and specificity of both methods were 100%, demonstrating perfect agreement between them as indicated by a kappa value of 1. In conclusion, this study created a RT-RAA method for PaBV-4 detection successfully.

Unveiling the Hidden Enemies: Morphological and Molecular Characterization of Pod Rot Pathogens in Groundnut (Arachis hypogea L.) in India

Pod rot of groundnut is a complex disease caused by multiple pathogens causes significant economic losses. Present study was undertaken to know the pathogens associated with the disease. In Chittoor, Andhra Pradesh, roving survey against pod rot of groundnut revealed association of three fungal species: Sclerotium rolfsii, Rhizoctonia bataticola and Fusarium spp. Molecular analysis with modified CTAB method and performing PCR using ITS1 and ITS4 primers yielded DNA bands of 650-700 bp, 550-600 bp, and 500-600 bp for Sclerotium, Rhizoctonia and Fusarium species, respectively. Sequencing of the rDNA ITS region confirmed the identities of the pathogens as Sclerotium rolfsii, Rhizoctonia bataticola, Fusarium solani, Fusarium oxysporum, and Fusarium keratoplasticum, based on similarity with NCBI reference sequences. This study confirms that Sclerotium rolfsii, Rhizoctonia bataticola and Fusarium spp. are the primary causal agents of pod rot disease in Andhra Pradesh.

Novel, active, and uncultured hydrocarbon-degrading microbes in the ocean.

Given the vast quantity of oil and gas input to the marine environment annually, hydrocarbon degradation by marine microorganisms is an essential ecosystem service. Linkages between taxonomy and hydrocarbon degradation capabilities are largely based on cultivation studies, leaving a knowledge gap regarding the intrinsic ability of uncultured marine microbes to degrade hydrocarbons. To address this knowledge gap, metagenomic sequence data from the Deepwater Horizon (DWH) oil spill deep-sea plume was assembled to which metagenomic and metatranscriptomic reads were mapped. Assembly and binning produced new DWH metagenome-assembled genomes that were evaluated along with their close relatives, all of which are from the marine environment (38 total). These analyses revealed globally distributed hydrocarbon-degrading microbes with clade-specific substrate degradation potentials that have not been reported previously. For example, methane oxidation capabilities were identified in all Cycloclasticus. Furthermore, all Bermanella encoded and expressed genes for non-gaseous n-alkane degradation; however, DWH Bermanella encoded alkane hydroxylase, not alkane 1-monooxygenase. All but one previously unrecognized DWH plume member in the SAR324 and UBA11654 have the capacity for aromatic hydrocarbon degradation. In contrast, Colwellia were diverse in the hydrocarbon substrates they could degrade. All clades encoded nutrient acquisition strategies and response to cold temperatures, while sensory and acquisition capabilities were clade specific. These novel insights regarding hydrocarbon degradation by uncultured planktonic microbes provides missing data, allowing for better prediction of the fate of oil and gas when hydrocarbons are input to the ocean, leading to a greater understanding of the ecological consequences to the marine environment.IMPORTANCEMicrobial degradation of hydrocarbons is a critically important process promoting ecosystem health, yet much of what is known about this process is based on physiological experiments with a few hydrocarbon substrates and cultured microbes. Thus, the ability to degrade the diversity of hydrocarbons that comprise oil and gas by microbes in the environment, particularly in the ocean, is not well characterized. Therefore, this study aimed to utilize non-cultivation-based 'omics data to explore novel genomes of uncultured marine microbes involved in degradation of oil and gas. Analyses of newly assembled metagenomic data and previously existing genomes from other marine data sets, with metagenomic and metatranscriptomic read recruitment, revealed globally distributed hydrocarbon-degrading marine microbes with clade-specific substrate degradation potentials that have not been previously reported. This new understanding of oil and gas degradation by uncultured marine microbes suggested that the global ocean harbors a diversity of hydrocarbon-degrading bacteria, which can act as primary agents regulating ecosystem health.

Incidence and Characteristics of Dermatophytosis Lesions in Cats (Felis catus) at Go Pet Care Animal Clinic (2020-2022)

Dermatophytosis, a dermatological condition caused by dermatophyte fungi, affects the superficial keratinized structures of the skin. The primary etiological agents include the genera Microsporum, Trichophyton, and Epidermophyton. This study examines the incidence and characteristics of dermatophytosis lesions in domestic cats (Felis catus) at Go Pet Care Animal Clinic from 2020 to 2022. The research utilized secondary data from the clinic's medical records, which is a significant reference institution in Kabupaten Bandung Barat, to assess the prevalence and features of dermatophytosis within this population. The findings revealed a prevalence of 7.5% in 2020, 11.3% in 2021, and 3.7% in 2022. The incidence was highest in cats under 1 year of age, with a notable frequency in Persian breed cats and males. Common lesions identified included localized alopecia primarily in the ear region, alopecia in the back region, and crust formation also in the back area. This study provides critical insights into the epidemiology and clinical presentation of dermatophytosis in domestic cats, offering guidance for improved diagnosis and management of the condition.

Hydrogen-peroxide intercalated expanded graphite facilitates large enhancement in thermal conductivity of polyetherimide/graphite nanocomposites

In this work, we prepared expanded graphite (EG) filler using hydrogen peroxide (H2O2) as an oxidizing agent to study its impact on the thermal conductivity (k) of polyetherimide (PEI) composite, compared to EG prepared using sodium chlorate (NaClO3). Sulfuric acid was used as the primary intercalating agent for both synthesis routes. The use of H2O2 prepared EG (EG-H2O2) led to a remarkable ∼4030% enhancement (9.5 Wm−1K−1) in k of the PEI/EG composite, while the use of NaClO3 prepared EG (EG-NaClO3) led to a much smaller enhancement of ∼2190% (5.3 Wm−1K−1), at 10 wt% EG composition compared to kPEI (∼0.23 Wm−1K−1). Such findings exceed the current state-of-art in EG-based polymer composites. Detailed characterization was performed to understand the properties of EG-H2O2 and EG-NaClO3. Raman analysis revealed that H2O2 resulted in relatively defect-free EG (ID/IG ratio ∼0.04), thus preserving the k of graphite (∼2000 Wm−1K−1). Use of NaClO3, however, led to a large defect density (ID/IG ratio ∼0.25), yielding graphite with significantly diminished k. Furthermore, through-plane thermal diffusivity of EG-H2O2 paper was measured to be 9.5 mm2s-1 while that of NaClO3 case was measured to be 6.7 mm2s-1, thus directly confirming the beneficial impact of H2O2 in preserving the high k of graphene. X-ray photoelectron spectroscopy (XPS) revealed that the higher number of defects in EG-NaClO3 are due to the higher degree of oxidation induced by NaClO3. The results demonstrate the potential of EG-H₂O₂ as an efficient filler for achieving high thermal conductivity polymer composites.

277 Estimating the potential effect of Mycoplasma hyopneumoniae infection on swine sustainability

Abstract Mycoplasma hyopneumoniae is the primary causative agent of enzootic pneumonia, one of the most common bacterial pathogens affecting pigs and the main contributor to respiratory comorbidities. Infection with M. hyopneumoniae, commonly observed in growing pigs, results in decreased feed intake and an increase in the number of days to reach market weight. Based on extended days to market, pigs infected with M. hyopneumoniae will have a greater life cycle carbon emissions and water usage than that of non-infected pigs. However, the magnitude of additional carbon footprint and water use in pigs infected with M. hyopneumoniae has never been calculated. Therefore, the objective of this study was to estimate the potential variation in carbon emissions and water footprint generated by M. hyopneumoniae infected pigs. This study was conducted using data from previous publications on M. hyopneumoniae infected pigs in experimental and commercial conditions. The carbon footprint and water usage of pork production was obtained from the literature and was used as a baseline (3,470 kg of CO2 eq and 1,678 m3 water eq; both per 1,000 kg of pork carcass weight). The change in average daily gain was estimated and additional days on feed to reach market weight were used to calculate potential carbon and water impact for pigs infected with M. hyopneumoniae. The estimated carbon emissions and water usage of M. hyopneumoniae infected pigs increased in a range of 84.69 to 142.93 kg of CO2 eq/1,000 kg of pork carcass weight and 40.95 to 69.12 m3 eq/1,000 kg of pork carcass weight respectively, compared with the carbon emissions of non-infected pigs (Table 1). Results of this study showed an increased carbon footprint for M. hyopneumoniae infected pigs by 2 to 4% and water usage increased by 2.5 to 4.1% suggesting that the sustainability of pork production was negatively affected by this bacterial infection. Previous literature on the impact of controlling vaccine-preventable diseases has shown similar results for other swine respiratory pathogens. In addition, these data only included M. hyopneumoniae infected pigs, thus the effect of respiratory co-infections was not estimated and the impact on sustainability metrics may be greater than currently calculated. The application of sustainable practices in animal production, including disease prevention, is key to ensuring a secure food supply for future generations. The carbon and water footprints of swine production are measurements of sustainability, with average daily gain being an important factor.

Blood pressure management strategies and podocyte health.

Hypertension (HTN) is one of the key global cardiovascular risk factors, which is tightly linked to kidney health and disease development. Podocytes, glomerular epithelial cells that play a pivotal role in maintenance of the renal filtration barrier, are significantly affected by increased glomerular capillary pressure in HTN. Damage or loss of these cells causes proteinuria, which marks the initiation of the HTN-driven renal damage. It goes without saying that effective BP management should not only mitigate cardiovascular risks but also preserve renal function by protecting podocyte integrity. This review offers a comprehensive examination of current blood pressure (BP) management strategies and their implications for podocyte structure and function and emphasizes strategies for the reduction of proteinuria in HTN. We explore primary and secondary antihypertensive agents, including ACE inhibitors, ARBs, calcium channel blockers, diuretics, as well as newer therapies (SGLT2 blocking and endothelin receptor antagonism), emphasizing their mechanistic roles in safeguarding podocytes and curtailing proteinuria.

One-pot construction of α-Fe2O3/ZnNiFe2O4 heterojunction by incomplete sol/gel-self-propagating method with choline chloride-ethylene glycol media and its photo-degradation performance

A magnetic α-Fe2O3/ZnNiFe2O4 composite photocatalyst was synthesized through a one-pot reaction employing choline chloride-ethylene glycol deep eutectic solvents and an incomplete sol-gel self-propagating method. The photocatalytic performance was assessed by removing methylene blue (MB) under 40 W visible light. With a 1.0 g/L catalyst dosage, 10 mg/L MB concentration, and pH levels of 6 and 12, removal rates of 97 % and 99 % were achieved within 90 min, respectively. The composite also demonstrated effective degradation of methyl orange (MO) and malachite green (MG). Stability tests revealed minimal reduction in photocatalytic activity after four cycles. Active species analysis identified ·O2⁻ and ·OH as the primary agents in the photocatalytic process. XRD, XPS, UV–VIS DRS, HRTEM, PL, and EIS analyses confirmed the formation of a Z-scheme heterojunction between ZnNiFe2O4 and α-Fe2O3, which enhanced the specific surface area, electron transport capacity, and narrowed the band gap. This heterojunction improved the separation efficiency of photogenerated electron-hole pairs, resulting in enhanced photocatalytic activity and stability. This study presents a novel approach for preparing Z-scheme heterojunction photocatalysts through a one-pot reaction.

Fatty Imidazolines as a Green Corrosion Inhibitor of Bronze Exposed to Acid Rain

Acid rain is one of the primary corrosive agents on bronze exposed to the atmosphere. Bronze naturally forms a layer of oxides on its surface called patina, protecting it from corrosion. However, when exposed to acid rain, this layer dissolves, making it necessary to use a corrosion inhibitor or stabilize the patina. This study investigated fatty imidazolines derived from agro-industrial waste bran as a corrosion inhibitor of SAE-62 bronze in simulated acid rain (pH of 4.16 ± 0.1). Electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization curve (PC) measurements were used to evaluate corrosion inhibition efficiency, which was 90% for an inhibitor concentration of 50 ppm. The EIS measurements showed that the fatty imidazolines formed a protective film that stabilized the patina on the bronze surface to a certain extent by hindering the charge transfer process. SEM–EDS analyzed the morphology and composition of the protective oxide layer. The results were complemented by Raman spectroscopy and XRD analysis, indicating cuprite, tenorite, cassiterite, and covellite in the patina layer formed on the bronze surface. The SEM analysis showed that the protective coating on the bronze surface was homogeneous using a 50-ppm inhibitor concentration. The XRD analysis suggested the presence of an organic complex that stabilizes the corrosion products formed on the bronze surface.

Prevalence, spatial distribution and determinants of complete childhood pneumococcal conjugate vaccination in Ethiopia: spatial and multilevel analyses

IntroductionPneumococcal disease is a serious global public health concern. The primary causative agent of severe illnesses such as pneumonia, meningitis, acute otitis media, and bacteremia is the pneumococcus bacterium. The pneumococcal conjugate vaccine is a key strategy to reduce the burden of pneumococcal disease. Understanding the spatial distribution of complete childhood pneumococcal conjugate vaccine utilization and its associated factors is crucial for designing strategies to improve vaccination implementation. Therefore, this study aimed to determine the spatial distribution of complete childhood pneumococcal conjugate vaccination coverage and identify its determinants in Ethiopia.MethodA spatial and multilevel analysis was conducted using data from the 2019 Ethiopian Mini Demographic and Health Survey. The analysis included a total of 2,055 weighted children. The association between the outcome variable and the explanatory variables was determined by calculating adjusted odds ratios at a 95% confidence interval. Explanatory variables were considered significantly associated with the outcome if the p-value was less than 0.05.ResultThe prevalence of complete childhood pneumococcal conjugate vaccination in Ethiopia was 53.94% (95% CI: 51.77, 56.08). Higher complete childhood pneumococcal vaccination coverage was observed in the Addis Ababa, Tigray, Amhara, Benishangul-Gumuz, and Oromia regions, while lower coverage was seen in the Afar, Somali, and SNNPR regions of Ethiopia. Factors significantly associated with complete childhood pneumococcal conjugate vaccination included maternal age, antenatal care visits, place of delivery, region, community women’s literacy level, community poverty level, and community antenatal care utilization.ConclusionThe distribution of complete childhood pneumococcal conjugate vaccination exhibited spatial variability across Ethiopia. Approximately half of children aged twelve to thirty-five months received the full dose of the childhood pneumococcal conjugate vaccine in the country. Several factors were identified as statistically significant determinants of complete childhood pneumococcal conjugate vaccination, including maternal age, antenatal care visits, place of delivery, region, community women’s literacy level, community poverty level, and community ANC utilization. Therefore, policies and strategies aimed at combating pneumococcal disease should consider these determinants and address areas with low vaccination coverage.

Mitochondrial Dysfunction in Aristolochic Acid I-Induced Kidney Diseases: What We Know and What We Do Not Know

Aristolochic acids, compounds derived from Aristolochiaceae plant species, are associated with significant renal nephrotoxicity and carcinogenicity. Aristolochic acid I (AAI), the most predominant and potent of these compounds, is a primary etiological agent in acute and chronic kidney diseases such as Aristolochic Acid Nephropathy (AAN) and Balkan Endemic Nephropathy (BEN). Due to the kidneys’ critical role in xenobiotic excretion, they are the primary organs affected by AAI toxicity. Recent in vitro and in vivo studies have highlighted mitochondrial dysfunction as a crucial factor in the pathogenesis of these kidney diseases. This review provides an update on the recent advances in understanding the causes of acquired mitochondrial dysfunction within the context of AAN and BEN. Key findings include the identification of mitochondrial DNA depletion, loss of mitochondrial membrane potential, and decreased ATP production as significant contributors to kidney damage. Additionally, oxidative stress markers and inflammatory mediators have been implicated in disease progression. Potential therapeutic approaches, such as the use of antioxidants like vitamin C and catalpol, have shown promise in mitigating AAI-induced cytotoxicity. Furthermore, future predictive approaches like pharmacogenomics could pave the way for novel mitochondria-targeted treatments. A comprehensive characterization of mitochondrial function, its underlying molecular mechanisms, and specific biomarkers could offer valuable insights and potential therapeutic options, significantly impacting the current management of AAN and BEN.

Nitrogen-sulfur co-doped magnetic biochar efficiently activates hydrogen peroxide for the degradation of sulfamethazine

To address the issue of low activation efficiency of magnetic biochar (MBC), this research synthesized nitrogen-sulfur co-doped magnetic biochar (NSMBC) using sawdust as the primary material via impregnation pyrolysis method. NSMBC effectively activated hydrogen peroxide and exhibited significant oxidation and degradation capabilities towards sulfamethazine (SMT), a sulfonamide antibiotic. The results demonstrate that under optimal conditions, NSMBC achieves a removal rate of 99.7 % for SMT within 2 h, with a reaction rate constant 8.5 times higher than that of MBC/H2O2 system. Mechanistic investigations unveiled that hydroxyl radicals (·OH) were the primary agents responsible for the degradation of sulfamethazine within the NSMBC/H2O2 system, contributing to 83.26 % of the removal efficiency. Furthermore, the nitrogen-sulfur co-doping facilitates the increase in Fe(II) content, augmentes the defect density, and enriches the number of oxygen-containing functional groups, thereby enhancing the utilization efficiency of H2O2 and consequently boosting the activation performance of magnetic biochar. Notably, the NSMBC/H2O2 system demonstrated excellent degradation efficiency towards various antibiotics, exhibiting potent broad-spectrum activity. Minimal influence on the NSMBC/H2O2 system was observed under conditions of coexisting natural organic matter and anions, rendering it suitable for practical application in the treatment of aquaculture wastewater and providing a novel technology for the application of magnetic biochar in actual water pollution control scenarios.

Controllable preparation of red phosphorus nanoribbons for enhanced photocatalytic degradation of Methyl Orange and Tetracycline.

Nanoribbons (NRs), leveraging the flexibility of one-dimensional materials and the expansive surface area of two-dimensional materials, offer heightened exposure to edge sites and superior charge transfer rates. Consequently, they present promising prospects within the domain of photocatalysis. Crystalline red phosphorus (cRP), dcharacterized by its layered and fibrous structure, lends itself readily to the production of nanoribbons. Our study demonstrates a robust method for achieving high-yield, high-quality cRP by concurrently introducing mineralizing agent I2 and Si wafers into the Chemical Vapor Transport (CVT) synthesis process. Through ultrasound assistance, we transformed high-quality cRP into crystalline red phosphorus nanoribbons (cRP NRs) with an average thickness ranging from 7.5 to 17.5nm and an average width between 75 and 175nm. cRP NRs (I2 and Si) showcased impressive degradation capabilities towards Methyl Orange (MO) and Tetracycline (TC), achieving a remarkable 99% degradation of MO within 18min under the simulated visible-light irradiation. The reactive species capturing experiments confirmed that ·O2- was the primary active agent responsible for the photocatalytic degradation of MO.

Evaluation of virulence of Aeromonas veronii strain GZ21-2 and development of a highly effective vaccine for grass carp with the potential for industrial application

Bacterial septicemia represents a significant disease affecting cultured grass carp culture, with the primary etiological agent identified as the Gram-negative bacterium Aeromonas veronii. In response to an outbreak of septicemia in Guangzhou, we developed a formaldehyde-inactivated vaccine against an A. veronii strain designated AV-GZ21-2. This strain exhibited high pathogenicity in experimental infections across at all developmental stages of grass carp. Mortality rates for grass carp weighing 15 ± 5 g ranged from 16 % to 92 % at exposure temperatures of 19 °C–34 °C, respectively. The median lethal dose (LD50) for grass carp groups weighing 15 ± 5 g, 60 ± 10 g, 150 ± 30 g and 500 ± 50 g were determined to be 1.43, 2.52, 4.65 and 7.12 × 107(CFU/mL), respectively. We investigated the inactivated vaccine in conbination with aluminum hydroxide gel (AV-AHG), Montanide ISA201VG (AV-201VG), and white oil (AV-WO) adjuvants. This study aimed to optimize inactivation conditions and identify the adjuvant that elicits the most robust immune response. The AV-GZ21-2 inactivated bacterial solution (AV),when combined with various adjuvants, was capable of inducing a strong specific immune response in grass carp. The relative percent survival (RPS) following a lethal challenge with AV-GZ21-2 were 94 % for AV-AHG, 88 % for AV-201VG, 84 % for AV-WO and 78 % for AV alone. The minimum immunization dose of the AV-AHG vaccine was determined to be 6.0 × 107 CFU per fish, providing immunity for a duration of six months with an immune protection level exceeding 75 %. Furthermore, the AV-AHG vaccine demonstrated significant protective efficacy against various epidemic isolates of A. veronii. Consequently, we developed an inactivated vaccine targeting a highly pathogenic strain of A. veronii, incorporating an aluminum hydroxide gel adjuvant, which resulted in high immune protection and a duration of immunity exceeding six months. These findings suggest that the AV-AHG vaccine holds substantial potential for industrial application.

397. TREATMENT OUTCOMES OF IMMUNE CHECKPOINT INHIBITORS AS PRIMARY THERAPY FOR UNRESECTABLE OR RECURRENT ESOPHAGEAL CANCER

Abstract Background For the primary treatment of unresectable or recurrent esophageal cancer, combination therapy with immune checkpoint inhibitors (ICI) such as pembrolizumab (Pem) with CF (cisplatin and 5-fluorouracil), nivolumab (Nivo) with CF, and Nivo with ipilimumab (Ipi) has been shown the significantly improve prognosis compared to standard CF therapy in international collaborative phase III trials. As a result, these ICIs have been approved as primary treatment agents in Japan, with treatment guidelines strongly recommending therapies including ICIs. We evaluated the treatment outcomes at our institute and discussed their utility. Methods We examined the treatment outcomes of 26 esophageal cancer patients who underwent primary treatment with Pem+CF, Nivo+CF, or Nivo+Ipi from January 2018 to January 2023. The median observation period was 7.0 months. Results There were 20 male and 6 female patients, with a median age of 69 years. Histologically, there were 24 cases of squamous cell carcinoma and 2 cases of adenocarcinoma. Of the 26 patients, 9 were postoperative recurrences and 17 were unresectable diseases. They were treated with Pem+CF (12 cases), Nivo+CF (7 cases), or Nivo+Ipi (7 cases) as primary therapy. The initial response was complete response (CR) in 1 case, partial response (PR) in 14 cases, stable disease (SD) in 2 cases, and progressive disease (PD) in 9 cases, resulting in an overall response rate of 57.6%. The median progression-free survival was 5.0 months, and the median overall survival was 15.2 months. There was no significant difference in prognosis according to the regimens. Grade 3 or higher adverse events included neutropenia in 3 cases, pituitary insufficiency in 1 case, and adrenal insufficiency in 1 case. One case with lung metastasis and two cases with para-aortic lymph node metastasis showed disappearance of metastatic lesions after chemotherapy including ICIs, leading to conversion esophagectomy. One case had anastomotic failure, but no other postoperative complications were observed. All patients are currently under observation without recurrence. Conclusion ICIs for unresectable or recurrent esophageal cancer showed a prolongation of prognosis in real-world clinical practice, suggesting their significance as part of a multimodal treatment approach including conversion surgery.

Development of Heutogogy Model as a Framework to Prepare Self-Determined Educator: A Case Study in Indonesia

This study aims to develop a heutogogy learning model which determines indigenous resources to improve numeracy literacy for high school educator to prepare their educator against disruptive education. This type of research is development research by using the ADDIE method according to two stages, namely (a) exploratory research to identify educator characteristics and needs, and (b) development research to develop a heutogogy model based on educators' needs. Heutogogy model succeeded in increasing educator numeracy literacy in high school as a preparation to create competent educators in a disruptive education era. This model has also succeeded in improving the literacy-numerical skills of teachers as primary agents of the information literacy movement in schools. By improving the educators' numerical skills, the model contributes to their overall information literacy, empowering them to better guide students in the rapidly evolving educational landscape characterized by disruptive changes. Need further research to implement this model on the different competencies with more deep user validation. This research can boost educators' literacy-numerical abilities, which are needed by the world of education in the next 10 years.

Ideals and Reality of Public Health Nursing in Korea: Influence of U.S. Nurse Advisors, 1945~1961.

South Korea's national healthcare system after liberation often described as transformation from 'sanitation' to 'public health'. The U.S. military government introduced public health nursing as the primary vehicle for communicating the newly introduced concept of public health to the Korean public. This meant that nursing, which had been in a subordinate position within the healthcare system during the Japanese occupation, had to be repositioned within the healthcare system as an independent and leading professional agent of healthcare. At the same time creating positions for public health nurses within the newly envisioned health center system, and convincing the public that nurses were the primary agents of public health activities. Yet, in resource limited setting, the role of public health nurses was significantly scaled back. Initial plans for institutionalized, community-wide health care through home visits shifted to addressing the challenges facing Korean society, including maternal and child health and infectious disease prevention. Ironically, the expansion of health centers during late 1950s diminished the position of public health nurses within local government health systems, who were gradually replaced by male administrative staff. The role of public health nurses was greatly curtailed in the 1960s, but they laid the groundwork for later community nursing and health care efforts. At the same time, public health nurses were assigned with new role of 'visiting' local health centers for observation, education, and management. Public health nursing allows to look beyond the ideological and institutional dimensions to examine how new concepts and practices of "public health" were actually transmitted to communities in post-liberation Korea.