Development of an AI-Assisted Embryo Selection System Using Iberian Ribbed Newts for Embryo-Fetal Development Toxicity Testing.

Background: The 3Rs (Reduction, Refinement, Replacement) principle is driving the need for alternative methods in animal testing. Despite advancements in in vitro testing, complex systemic toxicity tests still necessitate in vivo approaches. The aim of this study was to develop a developmental toxicity test protocol using the Iberian ribbed newt (Pleurodeles waltl) as a model organism, integrating AI image analysis for embryo selection to improve test accuracy and reproducibility. Methods: We established a developmental toxicity test protocol based on the zebrafish test. Gonadotropin was administered to induce ovulation, and in vitro fertilization was performed. Embryos were imaged at 5-6 and 6-7 h post-fertilization. AI image analysis was utilized to assess embryo viability. The test chemical was administered 24-48 h post-fertilization, and morphological changes were observed daily until day 8. Additionally, a time-lapse photography system was constructed to monitor embryonic development. Results: Out of 24 cultured embryos, 75% developed normally to the late tail bud stage or initial hatching stage, whereas 25% experienced developmental arrest or death. AI image analysis achieved high accuracy in classifying embryos, with overall accuracies of 92.0% and 92.9% for two learning models. The AI system demonstrated higher precision in the selection of viable embryos compared to visual inspection. Conclusion: The Iberian ribbed newt presents a viable alternative model for developmental toxicity testing, adhering to the 3Rs principles. The integration of AI image analysis substantially enhances the accuracy and reproducibility of embryo selection, providing a reliable method for evaluating developmental toxicity in pharmaceuticals.

Lactobacillus gasseri PA-3 reduces serum uric acid levels in patients with marginal hyperuricemia.

Several studies have reported that Lactobacillus gasseri PA-3 reduces the level of serum uric acid (SUA) in patients with hyperuricemia. However, it remains unknown how PA-3 affects uric acid metabolism. In the present study, we examined effects of PA-3-containing yoghurt on uric acid metabolism in patients with marginal hyperuricemia. Sixteen patients with SUA > 357 µmol/L (marginal hyperuricemia) were enrolled. PA-3-containing yoghurt was administered for 8 weeks. Uric acid metabolism was evaluated just before and 8 weeks after the administration and at 4 weeks after the administration ended (post-administration). SUA levels after the administration were significantly lower than that before the administration and remained low at post-administration. Urinary uric acid concentration (Uur) after the administration were significantly lower than that before the administration. However, post-administration Uur levels were comparable to those before the administration. Therefore, PA-3-containing yoghurt significantly reduced the levels of SUA and Uur in patients with marginal hyperuricemia.

The Influence of Illumination Color on the Subjective Visual Recognition of Biological Specimens.

BACKGROUND: Visual examination by the naked eye is integral to medical diagnosis and surgery. The illumination in conditioned color is widely used for visual inspection in the industry but has not been introduced to the biomedical context. The color that can enhance the visual recognition of individual tissues is still unknown. Therefore, we carried out a visual recognition experiment on biological specimens to determine the subjective preference for illumination color based on questionnaires. METHODS: Twenty healthy subjects were asked to compare the visual recognizability of several rat tissues between the illuminations in test colors and white. The rats were anesthetized, and the femoral vein and abdominal cavity were exposed. Seven tissues were selected for a visual recognition test. Illumination was generated using a multi-color LED light. The subjects observed the tissues under the illuminations of white and one of the test colors alternately and reported which illumination is suitable for visual recognition using a questionnaire. RESULTS: The analysis of the questionnaires showed that the blue test color was more effective than white illumination in the visual recognition of fine structures such as the branching of blood vessels and nerves, and red illumination disturbed the visual recognizability of the same tissues. On the other hand, the red but not the blue illumination improved the visual recognizability of the vein beneath the intact skin. As to the recognition of individual tissues in the abdominal cavity, the white illumination gave a better visual recognizability compared to every other test color. CONCLUSION: This study shows that the illumination color influences the visual recognition of biological specimens and the adequate color for the visual recognition of specific tissue parts is distinct among biological specimens. Using the lighting system to make fine adjustments to the illumination color may be useful in medical diagnosis and surgery.

A single nucleotide polymorphism in the carboxylesterase gene is associated with the responsiveness to imidapril medication and the promoter activity.

Imidapril is an angiotensin-converting enzyme inhibitor that is widely used in treating hypertension, although the responses vary among individuals. We investigated whether a single nucleotide polymorphism at position -816 of the carboxylesterase 1 (CES1) gene, which activates imidapril in the liver, is involved in the responsiveness to imidapril medication. A total of 105 Japanese hypertensives with systolic/diastolic blood pressures (SBP/DBP) of 140/90 mmHg or higher were prescribed 5-10 mg/day of imidapril. At baseline, blood pressure levels were not different between patients with and those without the -816C allele (AA vs. AC+ CC groups). After 8 weeks of treatment, we classified the responders and non-responders based on the decline in their blood pressures, and found that the responder rate was significantly higher in the AC+CC group than in the AA group (p=0.0331). Also, the reduction in SBP was significantly greater in the AC+CC group than in the AA group (24.7+/-11.8 vs. 17.6+/-16.8 mmHg, p=0.0184). Furthermore, an in vitro reporter assay revealed that the -816C construct had significantly higher promoter activity (p<0.0001). These findings suggest that the A(-816)C polymorphism affects the transcriptional activity, and that this may account for the responsiveness to imidapril.