Effect of sedatives or anesthetics on the measurement of resting brain function in common marmosets.

Common marmosets are promising laboratory animals for the study of higher brain functions. Although there are many opportunities to use sedatives and anesthetics in resting brain function measurements in marmosets, their effects on the resting-state network remain unclear. In this study, the effects of sedatives or anesthetics such as midazolam, dexmedetomidine, co-administration of isoflurane and dexmedetomidine, propofol, alfaxalone, isoflurane, and sevoflurane on the resting brain function in common marmosets were evaluated using independent component analysis, dual regression analysis, and graph-theoretic analysis; and the sedatives or anesthetics suitable for the evaluation of resting brain function were investigated. The results show that network preservation tendency under light sedative with midazolam and dexmedetomidine is similar regardless of the type of target receptor. Moreover, alfaxalone, isoflurane, and sevoflurane have similar effects on resting state brain function, but only propofol exhibits different tendencies, as resting brain function is more preserved than it is following the administration of the other anesthetics. Co-administration of isoflurane and dexmedetomidine shows middle effect between sedatives and anesthetics.

The Japan Monkey Centre Primates Brain Imaging Repository of high-resolution postmortem magnetic resonance imaging: The second phase of the archive of digital records.

A comparison of neuroanatomical features of the brain between humans and our evolutionary relatives, nonhuman primates, is key to understanding the human brain system and the neural basis of mental and neurological disorders. Although most comparative MRI studies of human and nonhuman primate brains have been based on brains of primates that had been used as subjects in experiments, it is essential to investigate various species of nonhuman primates in order to elucidate and interpret the diversity of neuroanatomy features among humans and nonhuman primates. To develop a research platform for this purpose, it is necessary to harmonize the scientific contributions of studies with the standards of animal ethics, animal welfare, and the conservation of brain information for long-term continuation of the field. In previous research, we first developed a gated data-repository of anatomical images obtained using 9.4-T ex vivo MRI of postmortem brain samples from 12 nonhuman primate species, and which are stored at the Japan Monkey Centre. In the present study, as a second phase, we released a collection of T2-weighted images and diffusion tensor images obtained in nine species: white-throated capuchin, Bolivian squirrel monkey, stump-tailed macaque, Tibet monkey, Sykes' monkey, Assamese macaque, pig-tailed macaque, crested macaque, and chimpanzee. Our image repository should facilitate scientific discoveries in the field of comparative neuroscience. This repository can also promote animal ethics and animal welfare in experiments with nonhuman primate models by optimizing methods for in vivo and ex vivo MRI scanning of brains and supporting veterinary neuroradiological education. In addition, the repository is expected to contribute to conservation, preserving information about the brains of various primates, including endangered species, in a permanent digital form.

Housing relocation does not have to induce a significant stress response in captive Japanese macaques (Macaca fuscata).

BACKGROUND: Previous studies suggest that housing relocation may be stressful for captive non-human primates. Our study investigated the stress levels of Japanese macaques during a housing relocation by measuring their daily fecal cortisol metabolites, which are often used as an indicator of stress. METHODS: Ten adult Japanese macaques, single-housed for research purposes, were relocated to a new facility. Fecal samples were collected daily for 7 days. Cortisol metabolite concentrations were determined via enzyme immunoassay. RESULTS: No significant differences in cortisol metabolite levels were found in 7 days, but concentration levels showed that the highest median was associated to the relocation day. CONCLUSIONS: The minimal cortisol metabolite increase suggests that there was a slight activity increase in the hypothalamic-pituitary-adrenal axis. Techniques encouraging cooperation of the monkeys, the short time duration of the relocation, and consistency in the environment may have contributed to the minimal stress levels observed.

The effect of different body positions on the cardiothoracic ratios obtained by chest radiography in Japanese macaques (Macaca fuscata) and rhesus macaques (Macaca mulatta).

BACKGROUND: Although some studies have reported cardiac diseases in macaques, an adequate screening method for cardiac enlargement has not yet been established. This study aimed to evaluate the positioning of macaques for radiographs and establish reference intervals for the cardiothoracic ratio (CTR). MATERIALS AND METHODS: We developed a device for chest radiography in the sitting position and performed chest radiography in 50 Japanese and 48 rhesus macaques to evaluate the CTR and chest cavity size. RESULTS: In Japanese and rhesus macaques, the thorax height was significantly larger, the heart width was significantly smaller, and the mean CTR was significantly smaller in the sitting position than in the prone position. The reference intervals for CTR in the sitting position were 51.6 ± 4.6% and 52.2 ± 5.1% in Japanese and rhesus macaques, respectively. CONCLUSION: Thoracic radiographic images obtained in a sitting position resulted in a smaller CTR and a larger thorax height, which could be useful for detecting pulmonary and cardiac abnormalities.

Primate veterinarians' knowledge and attitudes regarding pain in macaques.

BACKGROUND: Assessment of pain in macaques is challenging. The aims of this study were (1) to investigate current knowledge and attitudes of primate veterinarians concerning acute pain in macaques; (2) to synthesise current knowledge and opinion to facilitate pain assessment. A primary question of interest was whether more confident individuals differ in their knowledge and attitudes from less-confident individuals. METHODS: An online survey was conducted amongst primate veterinarians serving both laboratories and zoos/sanctuaries. The questionnaire consisted of demographic information, attitudes towards pain, pain rating and analgesics, pain recognition and confidence in recognising pain and sources of information used. RESULTS AND CONCLUSIONS: There was generally good use of analgesia by respondents. More confident individuals reported that they recognise pain both behaviourally and in facial expressions, rated all pain signs more highly and used more analgesics. Specialist support networks aimed at increasing veterinarian confidence in macaque pain assessment could be beneficial.

Pharmacokinetics and effects on clinical and physiological parameters following a single bolus dose of propofol in common marmosets (Callithrix jacchus).

The objectives of this study were (a) to establish a population pharmacokinetic model and (b) to investigate the clinical and physiological effects of a single bolus dose of propofol in common marmosets. In Study 1, pharmacokinetic analysis was performed in six marmosets under sevoflurane anaesthesia. 8 mg/kg of propofol was administrated at a rate of 4 mg kg-1  min-1 . Blood samples were collected 2, 5, 15, 30, 60, 90, 120 or 180 min after starting propofol administration. Plasma concentration was measured, and population pharmacokinetic modelling was performed. A two-compartment model was selected as the final model. The population pharmacokinetic parameters were as follows: V1  = 1.14 L, V2  = 77.6 L, CL1  = 0.00182 L/min, CL2  = 0.0461 L/min. In Study 2, clinical and physiological parameters were assessed and recorded every 2 min after 12 mg/kg of propofol was administrated at a rate of 4 mg kg-1  min-1 . Immobilization was sustained for 5 min following propofol administration without apparent bradycardia. While combination of propofol and sevoflurane caused apnoea in Study 1, apnoea was not observed following single administration of propofol in Study 2. These data provide bases for further investigation on intravenous anaesthesia using propofol in common marmosets.

Evaluation of anaesthetic and cardiorespiratory effects after intramuscular administration of alfaxalone alone, alfaxalone-ketamine and alfaxalone-butorphanol-medetomidine in common marmosets (Callithrix jacchus).

BACKGROUND: Anaesthesia is often required in common marmosets undergoing various procedures. The aim of this study was to evaluate anaesthetic and cardiopulmonary effects of alfaxalone, alfaxalone-ketamine and alfaxalone-butorphanol-medetomidine in common marmosets. METHODS: The following treatments were repeatedly administered to seven female common marmosets: Treatment A, alfaxalone (12 mg kg-1 ) alone; treatment AK, alfaxalone (1 mg animal-1 ) plus ketamine (2.5 mg animal-1 ); treatment AMB, alfaxalone (4 mg kg-1 ), medetomidine (50 µg kg-1 ) plus butorphanol (0.3 mg kg-1 ); and treatment AMB-Ati, AMB with atipamezole at 45 minutes. RESULTS AND CONCLUSIONS: Marmosets became laterally recumbent and unresponsive for approximately 30 minutes in A and AK and for approximately 60 minutes in AMB. The animals showed rapid recovery following atipamezole injection in AMB-Ati. The decrease in heart rate and SpO2 was significantly greater in AMB compared to A and AK. Oxygen supplementation, anaesthetic monitors and atipamezole should be available especially when AMB is administered.

Hematological and blood chemistry values in captive Japanese macaques (Macaca fuscata fuscata).

BACKGROUND: Biological information about captive Japanese macaques, including hematology and blood chemistry, is still lacking despite the fact that ethological and ecological data have accumulated during decades of field research. METHODS: Hematological (511 examinations of 280 Japanese macaques) and blood chemistry data (between 33 and 284 examinations from between 29 and 257 individual macaques) in clinically healthy, simian retrovirus-free Japanese macaques tested between 2009 and 2013 were reviewed. RESULTS AND CONCLUSIONS: Specific hematological and blood chemistry data for Japanese macaques without clinical signs of disease were provided in this study. Averages presented can be used as hematological parameters for Japanese macaques. Some differences between Japanese macaques and other closely related macaque species were found. Some parameters varied according to macaque age and sex, as well as regional origin. The data in this study will provide useful clinical indices for Japanese macaques in captive and similar conditions.

Hepatic neuroendocrine carcinoma in a Japanese macaque (Macaca fuscata).

Primary neuroendocrine neoplasm of the liver is extremely rare in both humans and non-human primates. The present report describes the clinical and pathological findings of an aged Japanese macaque (Macaca fuscata) with hepatic neuroendocrine carcinoma. To our knowledge, this is the first report of hepatic neuroendocrine neoplasm in macaques.

Impaired Air Conditioning within the Nasal Cavity in Flat-Faced Homo.

We are flat-faced hominins with an external nose that protrudes from the face. This feature was derived in the genus Homo, along with facial flattening and reorientation to form a high nasal cavity. The nasal passage conditions the inhaled air in terms of temperature and humidity to match the conditions required in the lung, and its anatomical variation is believed to be evolutionarily sensitive to the ambient atmospheric conditions of a given habitat. In this study, we used computational fluid dynamics (CFD) with three-dimensional topology models of the nasal passage under the same simulation conditions, to investigate air-conditioning performance in humans, chimpanzees, and macaques. The CFD simulation showed a horizontal straight flow of inhaled air in chimpanzees and macaques, contrasting with the upward and curved flow in humans. The inhaled air is conditioned poorly in humans compared with nonhuman primates. Virtual modifications to the human external nose topology, in which the nasal vestibule and valve are modified to resemble those of chimpanzees, change the airflow to be horizontal, but have little influence on the air-conditioning performance in humans. These findings suggest that morphological variation of the nasal passage topology was only weakly sensitive to the ambient atmosphere conditions; rather, the high nasal cavity in humans was formed simply by evolutionary facial reorganization in the divergence of Homo from the other hominin lineages, impairing the air-conditioning performance. Even though the inhaled air is not adjusted well within the nasal cavity in humans, it can be fully conditioned subsequently in the pharyngeal cavity, which is lengthened in the flat-faced Homo. Thus, the air-conditioning faculty in the nasal passages was probably impaired in early Homo members, although they have survived successfully under the fluctuating climate of the Plio-Pleistocene, and then they moved "Out of Africa" to explore the more severe climates of Eurasia.

Carbon and nitrogen stable isotopic offsets between diet and hair/feces in captive chimpanzees.

RATIONALE: Estimation of the stable isotopic offsets between tissue and diet is important for dietary reconstructions. Although stable isotopic studies of chimpanzees (Pan troglodytes) are increasing, the isotopic offsets in chimpanzees have never been studied. In this study, the carbon and nitrogen stable isotopic offset values in hair and feces were measured for 13 captive chimpanzees for the first time. METHODS: All consumed food items and quantities were recorded for each individual for 1 week. Food samples were typically collected three times, hair was collected 3 weeks after the experimental week, and feces were collected ad libitum during the experimental week. The stable carbon and nitrogen isotope ratios were measured using elemental analyzer-isotope ratio mass spectrometry (EA-IRMS). RESULTS: As the results of Monte Carlo analysis, the estimated carbon and nitrogen offsets between the hair and diet were +3.0 to +3.9‰ and +2.8 to +3.7‰, respectively, for the 95% confidence intervals (CIs). The 95% CIs of the carbon and nitrogen offset values between the feces and diet were -1.6 to 0.0‰ and +1.2 to +2.7‰, respectively. CONCLUSIONS: These offset values are generally consistent with those of the other primate species reported in previous studies. However, potential variations in the offset values due to dietary and physiological factors should be studied in detail in the future. Copyright © 2016 John Wiley & Sons, Ltd.

Hepatocellular carcinoma with intracranial metastasis in a Japanese macaque (Macaca fuscata).

BACKGROUND: A 23-year-old male Japanese macaque (Macaca fuscata) showed left ptosis, which progressed to exophthalmos. METHODS: The macaque underwent a clinical examination, CT and MRI, and was euthanized. Necropsy and histopathological examination were performed after euthanasia. RESULTS: The CT revealed and MRI confirmed an intracranial mass at the skull base with orbital extension. At necropsy, there were a large hepatic mass and an intracranial mass compressing the left temporal lobe of the brain. Histopathological and immunohistological examinations revealed that the masses were hepatocellular carcinoma (HCC) and a metastatic lesion. In both the primary and metastatic lesions, neoplastic hepatocytes were arranged mainly in a trabecular pattern. Immunohistochemically, the tumor cells were positive for cytokeratin (AE1/AE3 and CAM5.2) and hepatocyte paraffin 1 and negative for cytokeratin 7 and 20 and vimentin. CONCLUSION: To our knowledge, this is the first case report of HCC with intracranial metastasis in a macaque.

Association between preoperative characteristics and risk of anaesthesia-related death in dogs in small-animal referral hospitals in Japan.

OBJECTIVE: To explore the major risk factors linking preoperative characteristics and anaesthesia-related death in dogs in referral hospitals in Japan. STUDY DESIGN: Observational cohort study. ANIMALS: From April 1, 2010 to March 31, 2011, 4323 dogs anaesthetized in 18 referral hospitals in Japan. METHODS: Questionnaire forms were collated anonymously. Death occurring within 48 hours after extubation was considered as an anaesthesia-related death. Patient outcome (alive or dead) was set as the outcome variable. Preoperative general physical characteristics, complete blood cell counts, serum biochemical examinations and intraoperative complications were set as explanatory variables. The risk factors for anaesthesia-related death were evaluated using chi-square test or Fisher's exact test, followed by multivariable logistic regression analysis of the data. Significance was set at p < 0.05. RESULTS: Thirteen dogs that died from surgical error or euthanasia were excluded from statistical analysis. The total mortality rate in this study was 0.65% [28/4310 dogs; 95% confidence interval (CI), 0.41-0.89]. Furthermore, 75% (95% CI, 55.1-89.3) of anaesthesia-related deaths occurred in dogs with pre-existing diseases. Most of the deaths occurred postoperatively (23/28; 82.1%; 95% CI, 63.1-93.9). Preoperative serum glucose concentration <77 mg dL-1 (6/46; 13.0%; 95% CI, 4.9-26.3), disturbance of consciousness (6/50; 12.0%; 95% CI, 4.5-24.3), white cell count >15,200 µL-1 (16/499; 3.4%; 95% CI, 1.9-5.5) and American Society of Anesthesiologists grade III-V (19/1092; 1.7%; 95% CI, 1.1-2.7) were identified as risk factors for anaesthesia-related death. Intraoperative hypoxaemia (8/34; 23.5%; 95% CI, 10.7-41.2) and tachycardia (4/148; 2.7%; 95% CI, 0.7-6.8) were also risk factors for anaesthesia-related death. CONCLUSIONS AND CLINICAL RELEVANCE: The results revealed that certain preoperative characteristics were associated with increased odds of anaesthesia-related death, specifically low serum glucose concentration and disturbances of consciousness. Greater attention to correcting preanaesthetic patient abnormalities may reduce the risk of anaesthesia-related death.

Complete genome sequence of Streptococcus troglodytae TKU31 isolated from the oral cavity of a chimpanzee (Pan troglodytes).

Streptococcus troglodytae TKU31 was isolated from the oral cavity of a chimpanzee (Pan troglodytes) and was found to be the most closely related species of the mutans group streptococci to Streptococcus mutans. The complete sequence of TKU31 genome consists of a single circular chromosome that is 2,097,874 base pairs long and has a G + C content of 37.18%. It possesses 2082 coding sequences (CDSs), 65 tRNAs and five rRNA operons (15 rRNAs). Two clustered regularly interspaced short palindromic repeats, six insertion sequences and two predicted prophage elements were identified. The genome of TKU31 harbors some putative virulence associated genes, including gtfB, gtfC and gtfD genes encoding glucosyltransferase and gbpA, gbpB, gbpC and gbpD genes encoding glucan-binding cell wall-anchored protein. The deduced amino acid identity of the rhamnose-glucose polysaccharide F gene (rgpF), which is one of the serotype determinants, is 91% identical with that of S. mutans LJ23 (serotype k) strain. However, two other virulence-associated genes cnm and cbm, which encode the collagen-binding proteins, were not found in the TKU31 genome. The complete genome sequence of S. troglodytae TKU31 has been deposited at DDBJ/European Nucleotide Archive/GenBank under the accession no. AP014612.

Minor contributions of the maxillary sinus to the air-conditioning performance in macaque monkeys.

The nasal passages mainly adjust the temperature and humidity of inhaled air to reach the alveolar condition required in the lungs. By contrast to most other non-human primates, macaque monkeys are distributed widely among tropical, temperate and subarctic regions, and thus some species need to condition the inhaled air in cool and dry ambient atmospheric areas. The internal nasal anatomy is believed to have undergone adaptive modifications to improve the air-conditioning performance. Furthermore, the maxillary sinus (MS), an accessory hollow communicating with the nasal cavity, is found in macaques, whereas it is absent in most other extant Old World monkeys, including savanna monkeys. In this study, we used computational fluid dynamics simulations to simulate the airflow and heat and water exchange over the mucosal surface in the nasal passage. Using the topology models of the nasal cavity with and without the MS, we demonstrated that the MS makes little contribution to the airflow pattern and the air-conditioning performance within the nasal cavity in macaques. Instead, the inhaled air is conditioned well in the anterior portion of the nasal cavity before reaching the MS in both macaques and savanna monkeys. These findings suggest that the evolutionary modifications and coetaneous variations in the nasal anatomy are rather independent of transitions and variations in the climate and atmospheric environment found in the habitats of macaques.

Streptococcus panodentis sp. nov. from the oral cavities of chimpanzees.

Three strains TKU9, TKU49 and TKU50(T) , were isolated from the oral cavities of chimpanzees (Pan troglodytes). The isolates were all gram-positive, facultative anaerobic cocci that lacked catalase activity. Analysis of partial 16S rRNA gene sequences showed that the most closely related species was Streptococcus infantis (96.7%). The next most closely related species to the isolates were S. rubneri, S. mitis, S. peroris and S. australis (96.6 to 96.4%). Based on the rpoB and gyrB gene sequences, TKU50(T) was clustered with other member of the mitis group. Enzyme activity and sugar fermentation patterns differentiated this novel bacterium from other members of the mitis group streptococci. The DNA G + C content of strain TKU50(T) was 46.7 mol%, which is the highest reported value for members of the mitis group (40-46 mol%). On the basis of the phenotypic characterization, partial 16S rRNA gene and sequences data for two housekeeping gene (gyrB and rpoB), we propose a novel taxa, S. panodentis for TKU 50(T) (type strain = CM 30579(T) = DSM 29921(T) ), for these newly described isolates.

Endodontic Treatment of a Maxillary Incisor Tooth in a Chimpanzee (Pan troglodytes).

Chimpanzees (Pan troglodytes) with teeth severely damaged by dental caries and/or periodontal disease are often managed with medication and/or tooth extraction. A common endodontic treatment for severely decayed teeth in a 26-year-old female chimpanzee is reported. The left maxillary central incisor tooth had lost its crown, probably due to trauma that was not recent, and it had a fistula most likely due to chronic apical periodontitis. The diagnosis was confirmed radiographically before treatment. To treat the infected root canal, endodontic treatment used in humans was adapted for a chimpanzee. After the treatment, the tooth was sealed using an adhesive resin composite. At 11-years post-treatment, there were no signs of recurrence of the lesion or of failure of the tooth seal. The results of this case report suggest that common endodontic treatments used in humans are also effective in chimpanzees.

Deep Learning for Face Detection and Pain Assessment in Japanese macaques (Macaca fuscata).

Facial expressions have increasingly been used to assess emotional states in mammals. The recognition of pain in research animals is essential for their well-being and leads to more reliable research outcomes. Automating this process could contribute to early pain diagnosis and treatment. Artificial neural networks have become a popular option for image classification tasks in recent years due to the development of deep learning. In this study, we investigated the ability of a deep learning model to detect pain in Japanese macaques based on their facial expression. Thirty to 60 min of video footage from Japanese macaques undergoing laparotomy was used in the study. Macaques were recorded undisturbed in their cages before surgery (No Pain) and one day after the surgery before scheduled analgesia (Pain). Videos were processed for facial detection and image extraction with the algorithms RetinaFace (adding a bounding box around the face for image extraction) or Mask R-CNN (contouring the face for extraction). ResNet50 used 75% of the images to train systems; the other 25% were used for testing. Test accuracy varied from 48 to 54% after box extraction. The low accuracy of classification after box extraction was likely due to the incorporation of features that were not relevant for pain (for example, background, illumination, skin color, or objects in the enclosure). However, using contour extraction, preprocessing the images, and fine-tuning, the network resulted in 64% appropriate generalization. These results suggest that Mask R-CNN can be used for facial feature extractions and that the performance of the classifying model is relatively accurate for nonannotated single-frame images.

Systemic AL kappa chain amyloidosis in a captive Bornean orangutan (Pongo pygmaeus).

Systemic amyloid light-chain (AL) amyloidosis is an infrequent disease in which amyloid fibrils derived from the immunoglobulin light chain are deposited in systemic organs, resulting in functional impairment. This disease has been notably uncommon in animals, and nonhuman primates have not been reported to develop it. In this study, we identified the systemic AL kappa chain amyloidosis in a captive Bornean orangutan (Pongo pygmaeus) and analyzed its pathogenesis. Amyloid deposits were found severely in the submucosa of the large intestine, lung, mandibular lymph nodes, and mediastinal lymph nodes, with milder lesions in the liver and kidney. Mass spectrometry-based proteomic analysis revealed an abundant constant domain of the immunoglobulin kappa chain in the amyloid deposits. Immunohistochemistry further confirmed that the amyloid deposits were positive for immunoglobulin kappa chains. In this animal, AL amyloidosis resulted in severe involvement of the gastrointestinal submucosa and lymph nodes, which is consistent with the characteristics of AL amyloidosis in humans, suggesting that AL amyloid may have a similar deposition mechanism across species. This report enhances the pathological understanding of systemic AL amyloidosis in animals by providing a detailed characterization of this disease based on proteomic analysis.