Preliminary investigation into long-term stress by isolated captivity-related changes of reproduction hormones in Cynomolgus monkey.

BACKGROUND: Stress profoundly affects physical and emotional well-being, extending its physiological influence to the female menstrual cycle, impeding the hypothalamus-pituitary-gonadal (HPG) axis, and affecting fertility by suppressing sex-stimulating hormones. METHODS: In this study, we meticulously analyzed menstrual cycles and corresponding hormonal fluctuations in three female Cynomolgus monkeys. RESULTS: The preliminary findings indicated lower-than-normal levels of cortisol, follicle-stimulating hormone (FSH), and estradiol. Anovulatory bleeding occurred in one monkey, which could be linked to stress. In contrast to cortisol, alkaline phosphatase (ALP), which is correlated to cortisol levels, was consistently elevated in menstruating monkeys, suggesting its potential as a stress indicator. The non-menstruating group exhibited stress-related weight loss, emphasizing the observed ALP trends. CONCLUSIONS: Non-menstruating monkeys may experience more stress than menstruating monkeys. The implications of this study extend beyond the confines of primate studies and offer a valuable method for enhancing the welfare of female Cynomolgus monkeys.

Potential Food Inclination of Crab-Eating Macaques in Laboratory Environments: Enhancing Positive Reinforcement Training and Health Optimization.

Positive reinforcement and training for health optimization are pivotal for successful studies with monkeys. Potential food inclination is important for studies on crab-eating macaques in laboratory environments, but evaluations remain scarce. We explored crab-eating macaques' potential food inclination to establish a reward system for future behavioral assessments. Twelve male and three female monkeys underwent a food inclination assessment in which they were offered four food categories-fruits, vegetables, proteins, and nuts. The monkeys exhibited a higher inclination for plant-based foods, particularly fruits and vegetables, over animal-based proteins like chicken and tuna (p < 0.0001), with a notable inclination for nuts (eaten/provided = 100%). Additionally, the consistency of potential food inclination after repeated offerings was investigated, revealing a time-dependent increase in inclination for protein items. Food consumption ratios correlated positively with caloric intake (r = 0.59, p = 0.02), implying that individuals with a regular high caloric intake and increased body weight are more likely to accept food during positive reinforcement training. Our findings suggest fruits, vegetables, protein-rich foods, and nuts can help with health optimization. However, animal-based protein-rich foods initially had a low preference, which may increase over time. Our study can provide guidelines for positive reinforcement training and health optimization.

Regular medical checkup program (in K-MEDI hub) to enhance the welfare of laboratory dogs and pigs.

BACKGROUND: The importance of animal welfare is being recognized worldwide. Recently, the increasing demand for enhanced laboratory animal welfare has led to clinically featured transformations of animal research institutes. This study aims to describe the process and findings of veterinary medical check-ups and its influence on laboratory dogs and pigs welfare. Regular medical checkups were conducted by the attending veterinarian twice a year to ensure the health and welfare of dogs and pigs in our animal research institute. Based on the findings from the medical checkup, we assessed the current health of dogs and pigs,providing reasonable treatments to prevent the risk of complications. RESULTS: Blood tests and physical examinations revealed clinically relevant findings. Some of these findings were due to insufficient postoperative care after invasive surgical experiments and the remaining were predictable side effects after surgical experiments. However, one finding involved severe gum bleeding due to retained deciduous teeth. This animal was euthanized because it was judged to reach the humane endpoint. Majority of the dogs and pigs at our animal research institute were considered to be healthy, based on the comprehensive results of the medical checkups. CONCLUSIONS: Regular medical checkups by the attending veterinarian established enhanced animal welfare, ensuring the accuracy and reproducibility of animal studies. This pioneering veterinary animal care program can serve as a potential advanced guideline for animal research institutes to improve dogs and pigs welfare.

Assessment of Stress Caused by Environmental Changes for Improving the Welfare of Laboratory Beagle Dogs.

Animal stress is influenced by environmental factors, yet only a few studies have evaluated the effects of environmental stress on captive dogs. This study aimed to evaluate the effects of environmental and social enrichment on the stress levels of captive dogs housed in a lab. We assessed stress levels in eight Beagle dogs by measuring their body weight, cortisol levels, a stress hormone, the alkaline phosphatase activity in serum, the number of steps per hour, as well as clinical sign observations in a changed environment for 6 weeks. Four dogs assigned to a control group were raised alone in a relatively narrow place without toys; four dogs assigned to an experimental group were raised together in a relatively large place with toys. The body weight of the control group remained unchanged, while that of the experimental group decreased. Cortisol levels in the control group increased throughout, whereas those in the experimental group increased for up to 2 weeks and decreased thereafter. Consequently, cortisol levels in the experimental group significantly decreased compared to the control group at 6 weeks (p = 0.048). Fighting was observed among the dogs in the experimental group at 3 weeks; thus, one dog was separated from the group. The number of steps per hour was more than twice as high in the experimental than in the control group. Thereby, we determined that social housing, with appropriate companions and environmental enrichment materials, can reduce stress levels in captive dogs more efficiently than in single housing without such materials. Our study provides useful insights for captive animal organizations, such as kenneled dogs' management, to improve animal welfare.

Multiple time-dependent pathophysiological changes in a rabbit model of high-fat diet-induced hyperlipidemia.

High-fat diets (HFD) adversely affect organ systems. Several studies have examined HFD-related disorders in animals but only in a few organs and time points. Herein, we evaluated disease development with time-dependent HFD-induced pathological, cardiovascular, and morphological changes in rabbits with lipid metabolism similar to that in humans for 9 weeks. The body weights and waist ratio of the HFD group were higher than those in the control group. HFD significantly increased the total cholesterol, low-density lipoprotein, high-density lipoprotein, and phospholipid levels after 3 weeks. Liver enzyme levels increased with hepatomegaly, steatosis, and fibrosis after 3 or 6 weeks. RBCs and hemoglobin decreased, while platelets increased in the HFD group with atherosclerosis and inflammatory cell infiltration in the aorta after 6 weeks. Ejection fraction and fractional shortening values decreased in the HFD group after 9 weeks. Creatinine increased with glomerulosclerosis in the kidneys of the HFD groups after 3 weeks, indicating renal dysfunction. Lipid accumulation was found in the pancreas after 9 weeks. Lipid accumulation and hypertrophy were observed in the adrenal glands after 3 weeks. Overall, our findings provide global reference data on the time-dependent effects of HFD on the body and may serve as a guide for future HFD risk prevention.

Stress Evaluation of Mouse Husbandry Environments for Improving Laboratory Animal Welfare.

Animal welfare is recognized as essential for the coexistence of humans and animals. Considering the increased demand and interest in animal welfare, many methods for improving animal welfare are being devised, but which method reduces animal stress has not been scientifically verified. Therefore, reducing animal stress by providing a proper breeding environment and environmental enrichment can be the basis for animal study. In this study, stress levels were assessed based on the mouse-breeding environment. We considered that the higher the body weight and the lower the corticosterone concentration, the lower the stress. According to the results, animals in the individual ventilation cages were determined to have lower serum cortisol concentrations, while the body weight of the animals was increased when in individual ventilation cages compared with individual isolated cages and when providing environmental enrichment compared with group breeding or not providing environmental enrichment. The results provide appropriate guidelines for improving laboratory animal welfare.

Attending veterinarians improve the research capability and psychological well-being of researchers in animal research institutes.

The use of laboratory animals in biomedical research has significantly advanced scientific understanding, yet it raises ethical concerns about animal welfare and the mental health of researchers Recent research has highlighted the potential for stress and compassion fatigue among researchers working with distressed animals. Attending veterinarians (AVs) are crucial in mitigating the pain and stress experienced by animals and, by extension, researchers. However, the impact of AVs on researchers' psychological well-being remains understudied. This study explores how AVs contribute to researchers' research capability and psychological well-being in animal research institutions. AVs oversee animal housing, health, and welfare; their involvement is mandated or strongly recommended in developed countries. AVs enhance animal welfare by ensuring proper housing, nutrition, and social interaction. They monitor animal health, educate researchers on pain assessment, and promote compliance with post-surgical care. AVs also contribute to researchers' well-being by addressing euthanasia procedures, which can be emotionally challenging. Programs for rehoming animals after experiments offer an alternative to euthanasia and positively impact researchers' psychological well-being. Moreover, AVs promote workplace well-being by fostering positive workplace cultures, offering peer counseling, and providing social support. Programs considering animal welfare and researchers' emotions are crucial for a healthy research environment. In conclusion, AVs are essential in balancing scientific progress with animal welfare and researchers' psychological well-being. Therefore, their role should be recognized as vital in achieving social equity that considers the welfare of humans and laboratory animals.

Toxicologic Evaluation for Amorphous Silica Nanoparticles: Genotoxic and Non-Genotoxic Tumor-Promoting Potential.

Amorphous silica nanoparticles (SiO2NPs) have been widely used in medicine including targeted drug/DNA delivery, cancer therapy, and enzyme immobilization. Nevertheless, SiO2NPs should be used with caution due to safety concerns associated with unique physical and chemical characteristics. The objective of this study was to determine the effects of SiO2NPs on genotoxic and non-genotoxic mechanisms associated with abnormal gap junctional intercellular communication (GJIC) in multistage carcinogenesis. The SiO2NPs exhibited negative responses in standard genotoxicity tests including the Ames test, chromosome aberration assay, and micronucleus assay. In contrast, the SiO2NPs significantly induced DNA breakage in comet assay. Meanwhile, SiO2NPs inhibited GJIC based on the results of scrape/loading dye transfer assay for the identification of non-genotoxic tumor-promoting potential. The reduction in expression and plasma membrane localization of Cx43 was detected following SiO2NP treatment. Particularly, SiO2NP treatment increased Cx43 phosphorylation state, which was significantly attenuated by inhibitors of extracellular signal-regulated kinases 1/2 (ERK1/2) and threonine and tyrosine kinase (MEK), but not by protein kinase C (PKC) inhibitor. Taken together, in addition to a significant increase in DNA breakage, SiO2NP treatment resulted in GJIC dysregulation involved in Cx43 phosphorylation through the activation of mitogen-activated protein kinase (MAPK) signaling. Overall findings of the genotoxic and non-genotoxic carcinogenic potential of SiO2NPs provide useful toxicological information for clinical application at an appropriate dose.

Morphologic changes in the anterior segment after phacovitrectomy for proliferative diabetic retinopathy.

PURPOSE: To determine whether combined phacoemulsification and intraocular lens implantation with pars plana vitrectomy (PPV) (phacovitrectomy) in patients with proliferative diabetic retinopathy (PDR) causes morphologic changes in the anterior segment and to evaluate whether there is a relationship between the anatomic changes and inflammatory complications. SETTING: Department of Ophthalmology, Chonnam National University Hospital, Gwangju, South Korea. METHODS: Patients who had uneventful surgery for PDR were divided into 2 groups (phacovitrectomy and PPV only). Morphologic changes in the ciliary regions were measured by ultrasound biomicroscopy (UBM) 1 day before surgery and 1, 2, 3, 5 days, 2 weeks, 1 and 2 months after surgery. The UBM parameters and inflammatory complications in the 2 groups were compared. RESULTS: The study comprised 60 patients; 30 had phacovitrectomy and 30, PPV only. The frequency of supraciliary effusions was higher in the phacovitrectomy group (24/30, 80%) than in the PPV-only group (14/30, 46%) (P = .015). The decrease in angle opening and anterior chamber depth was more prominent after phacovitrectomy. The incidence of complications was higher in the phacovitrectomy group than in the PPV-only group (60% versus 30%, abnormal intraocular pressure; 30% versus 7%, intraocular fibrin and posterior synechia formation); the complications were associated with supraciliary effusions. CONCLUSIONS: The results indicate that phacovitrectomy for PDR may induce more morphologic changes in the anterior segment. Supraciliary effusions were associated with inflammatory complications. Appropriate control of postsurgical inflammation is necessary in phacovitrectomy for PDR.

Intravitreal triamcinolone reduces the morphologic changes of ciliary body after pars plana vitrectomy for retinal vascular diseases.

PURPOSE: To investigate the early postoperative changes in ciliary body after pars plana vitrectomy (PPV) for retinal vascular disease and to determine whether intravitreal triamcinolone acetonide (IVTA) affects postvitrectomy changes of the ciliary body. DESIGN: Prospective interventional case-control study. METHODS: We recruited 46 patients who underwent uncomplicated PPV for retinal vascular disease (35 with proliferative diabetic retinopathy (PDR) and 11 with branch retinal vein occlusion) and divided the patients into two groups according to the use of IVTA at the end of the PPV. The morphologic changes of the anterior segments were measured by ultrasound biomicroscopy (UBM) one day before and one day, two days, three days, five days, two weeks, one month, and two months after the PPV. The main outcome measures were the thickness and area of the ciliary body, the frequency of supraciliary effusions (SEs), angle-opening, and anterior chamber depth (ACD). We compared the UBM parameters between the two groups. RESULTS: The thickness and area of the ciliary body significantly increased from day 1 to day 5 postoperatively. Nineteen of 46 eyes had SEs that were frequently associated with divergent alterations of postoperative intraocular pressure (IOP). The angle-opening and ACD were significantly decreased and dependent upon the findings of ciliary body thickness and SEs. The degree of the morphologic changes of the ciliary body and the frequency of SEs were significantly lower and of shorter duration in the IVTA group compared to the non-IVTA group. CONCLUSIONS: The PPV for retinal vascular disease induces the morphologic changes of the ciliary body associated with postoperative abnormalities in IOP during the early postoperative period. Administration of IVTA at the end of the PPV effectively reduces or shortens the duration of the postvitrectomy changes of the ciliary body.

An epidemic of chronic pseudophakic endophthalmitis due to Ochrobactrum anthropi: clinical findings and managements of nine consecutive cases.

PURPOSE: To report an epidemic of O. anthropi pseudophakic endophthalmitis. METHODS: The medical records of nine patients with culture-proven O. anthropi endophthalmitis were reviewed. RESULTS: The presenting features were compatible to chronic endophthalmitis. Two patients showed coinfections with P. acnes. Antibiotics sensitivity test revealed susceptibility to quinolones. Pars plana vitrectomy (PPV) with partial capsulectomy (PC) cured infections in seven patients without coinfection of P. acnes. Final visual acuity was 20/40 or better in five patients. CONCLUSIONS: O. anthropi should be considered in cases with chronic pseudophakic endophthalmitis. PPV with PC should be the initial therapeutic option for O. anthropi endophthalmitis.

Percutaneous modular stent-grafts in the treatment of abdominal aortic aneurysms.

PURPOSE: To describe a newly designed bifurcated modular stent-graft and assess the feasibility and safety of its use in the treatment of abdominal aortic aneurysms (AAA). METHODS: Thirteen patients (10 men; mean age 61.2+/-16 years, range 57-78) with AAAs underwent treatment with a bifurcated stent-graft consisting of 4 components: an unsupported bifurcated stent-graft, an inner bare stent, and 2 stent-grafts. The system was placed sequentially through a percutaneously introduced 12-F sheath; the preloaded bifurcated main body of the stent-graft was deployed first, followed by the inner bare stent and individual stent-graft limbs through separate 10-F sheaths. Spiral computed tomography (CT) was performed before treatment and at 1 week, 3 months, and then at 6-month intervals. RESULTS: The stent-grafts were successfully deployed in all patients, although 3 types of procedure-related adverse events occurred: left limb kinking in 1, postimplantation syndrome (fever, leukocytosis, and decreased platelet count) in 5, and a small access site arteriovenous fistula in 1. Postprocedural angiography and 1-week follow-up CT scanning did not identify any endoleaks. At a mean 9.2+/-4.6-month follow-up, all devices were intact, with complete exclusion of the aneurysms and no endoleaks. CONCLUSIONS: This newly designed bifurcated modular stent-graft appears to be effective for percutaneous AAA repair; further investigation is warranted.