Dynamic off-resonance correction improves functional image analysis in fMRI of awake behaving non-human primates.

Introduction: Use of functional MRI in awake non-human primate (NHPs) has recently increased. Scanning animals while awake makes data collection possible in the absence of anesthetic modulation and with an extended range of possible experimental designs. Robust awake NHP imaging however is challenging due to the strong artifacts caused by time-varying off-resonance changes introduced by the animal's body motion. In this study, we sought to thoroughly investigate the effect of a newly proposed dynamic off-resonance correction method on brain activation estimates using extended awake NHP data. Methods: We correct for dynamic B0 changes in reconstruction of highly accelerated simultaneous multi-slice EPI acquisitions by estimating and correcting for dynamic field perturbations. Functional MRI data were collected in four male rhesus monkeys performing a decision-making task in the scanner, and analyses of improvements in sensitivity and reliability were performed compared to conventional image reconstruction. Results: Applying the correction resulted in reduced bias and improved temporal stability in the reconstructed time-series data. We found increased sensitivity to functional activation at the individual and group levels, as well as improved reliability of statistical parameter estimates. Conclusions: Our results show significant improvements in image fidelity using our proposed correction strategy, as well as greatly enhanced and more reliable activation estimates in GLM analyses.

Initial and corrective submovement encoding differences within primary motor cortex during precision reaching.

Precision reaching often requires corrective submovements to obtain the desired goal. Most studies of reaching have focused on single initial movements, and implied the cortical encoding model was the same for all submovements. However, corrective submovements may show different encoding patterns from the initial submovement with distinct patterns of activation across the population. Two rhesus macaques performed a precision center-out-task with small targets. Neural activity from single units in primary motor cortex and associated behavioral data were recorded to evaluate movement characteristics. Neural population data and individual neuronal firing rates identified with a peak finding algorithm to identify peaks in hand speed were examined for encoding differences between initial and corrective submovements. Individual neurons were fitted with a regression model that included the reach vector, position, and speed to predict firing rate. For both initial and corrective submovements, the largest effect remained movement direction. We observed a large subset changed their preferred direction greater than 45° between initial and corrective submovements. Neuronal depth of modulation also showed considerable variation when adjusted for movement speed. By utilizing principal component analysis, neural trajectories of initial and corrective submovements progressed through different neural subspaces. These findings all suggest that different neural encoding patterns exist for initial and corrective submovements within the cortex. We hypothesize that this variation in how neurons change to encode small, corrective submovements might allow for a larger portion of the neural space being used to encode a greater range of movements with varying amplitudes and levels of precision.

Individual differences in sociocognitive traits in semi-free-ranging rhesus monkeys (Macaca mulatta).

Characterizing individual differences in cognition is crucial for understanding the evolution of cognition as well as to test the biological consequences of different cognitive traits. Here, we harnessed the strengths of a uniquely large, naturally-living primate population at the Cayo Santiago Biological Field Station to characterized individual differences in rhesus monkey performance across two social cognitive tasks. A total of n = 204 semi-free-ranging adult rhesus monkeys participated in a data collection procedure, where we aimed to test individuals on both tasks at two time-points that were one year apart. In the socioemotional responses task, we assessed monkeys' attention to conspecific photographs with neutral versus negative emotional expressions. We found that monkeys showed overall declines in interest in conspecific photographs with age, but relative increases in attention to threat stimuli specifically, and further that these responses exhibited long-term stability across repeated testing. In the gaze following task we assessed monkeys' propensity to co-orient with an experimenter. Here, we found no evidence for age-related change in responses, and responses showed only limited repeatability over time. Finally, we found some evidence for common individual variation for performance across the tasks: monkeys that showed greater interest in conspecific photographs were more likely to follow a human's gaze. These results show how studies of comparative cognitive development and aging can provide insights into the evolution of cognition, and identify core primate social cognitive traits that may be related across and within individuals.

Proteomic profiling of regenerated urinary bladder tissue in a non-human primate augmentation model.

Urinary bladder dysfunction can be caused by environmental, genetic, and developmental insults. Depending upon insult severity, the bladder may lose its ability to maintain volumetric capacity and intravesical pressure resulting in renal deterioration. Bladder augmentation enterocystoplasty (BAE) is utilized to increase bladder capacity to preserve renal function using autologous bowel tissue as a "patch." To avoid the clinical complications associated with this procedure, we have engineered composite grafts comprised of autologous bone marrow mesenchymal stem cells (MSCs) co-seeded with CD34+ hematopoietic stem/progenitor cells (HSPCs) onto a pliable synthetic scaffold [poly(1,8-octamethylene-citrate-co-octanol)(POCO)] or a biological scaffold (SIS; small intestinal submucosa) to regenerate bladder tissue in our baboon bladder augmentation model. We set out to determine the global protein expression profile of bladder tissue that has undergone regeneration with the aforementioned stem cell seeded scaffolds along with baboons that underwent BAE. Data demonstrate that POCO and SIS grafted animals share high protein homogeneity between native and regenerated tissues while BAE animals displayed heterogeneous protein expression between the tissues following long-term engraftment. We posit that stem cell-seeded scaffolds can recapitulate tissue that is nearly indistinguishable from native tissue at the protein level and may be used in lieu of procedures such as BAE.

Hue and Orientation Pinwheels in Macaque Area V4.

Area V4 is an intermediate-level area of the macaque visual cortical hierarchy that serves key functions in cortical visual processing by integrating feedforward inputs from multiple functional compartments in lower areas such as V1 and V2 and providing feedforward inputs to many areas in inferotemporal, parietal, and prefrontal cortex. While many previous imaging studies of V4 have analyzed the differential responses to color, orientation, disparity, and motion stimuli, many details of the spatial organization of significant hue and orientation tuning have not been fully described. The Support Vector Machine (SVM) decoding of intrinsic cortical single-condition responses was used to generate high-resolution maps of hue and orientation tuning in V4. Like V1 and V2, V4 contains maps of iso-orientation domains organized around pinwheel centers. V4 contains maps of hue that consist of iso-hue domains surrounding pinwheel centers. The circular organization of these pinwheels more closely represents the perception of hue than is observed in antecedent cortical areas. Domains significantly tuned for hue occupy roughly four times the surface of the orientation domains, are largely segregated from each other, and overlap by roughly 5%. The spatial organization of hue and orientation pinwheels and their domains are largely consistent with the largely segregated inputs arising from the thin and interstripe compartments of V2. This modular segregation of processing suggests that further integration of color and shape must occur in inferotemporal cortical areas that receive direct projections from V4.

Zoonotic pathogens in wild Asian primates: a systematic review highlighting research gaps.

Introduction: Ongoing global changes, including natural land conversion for agriculture and urbanization, modify the dynamics of human-primate contacts, resulting in increased zoonotic risks. Although Asia shelters high primate diversity and experiences rapid expansion of human-primate contact zones, there remains little documentation regarding zoonotic surveillance in the primates of this region. Methods: Using the PRISMA guidelines, we conducted a systematic review to compile an inventory of zoonotic pathogens detected in wild Asian primates, while highlighting the coverage of primate species, countries, and pathogen groups surveyed, as well as the diagnostic methods used across the studies. Moreover, we compared the species richness of pathogens harbored by primates across diverse types of habitats classified according to their degree of anthropization (i.e., urban vs. rural vs. forest habitats). Results and discussion: Searches of Scopus, PubMed, and the Global Mammal Parasite Database yielded 152 articles on 39 primate species. We inventoried 183 pathogens, including 63 helminthic gastrointestinal parasites, two blood-borne parasites, 42 protozoa, 45 viruses, 30 bacteria, and one fungus. Considering each study as a sample, species accumulation curves revealed no significant differences in specific richness between habitat types for any of the pathogen groups analyzed. This is likely due to the insufficient sampling effort (i.e., a limited number of studies), which prevents drawing conclusive findings. This systematic review identified several publication biases, particularly the uneven representation of host species and pathogen groups studied, as well as a lack of use of generic diagnostic methods. Addressing these gaps necessitates a multidisciplinary strategy framed in a One Health approach, which may facilitate a broader inventory of pathogens and ultimately limit the risk of cross-species transmission at the human-primate interface. Strengthening the zoonotic surveillance in primates of this region could be realized notably through the application of more comprehensive diagnostic techniques such as broad-spectrum analyses without a priori selection.

Protocol to record and analyze primate leaping in three-dimensional in the wild.

Several studies comparing primate locomotion under lab versus field conditions have shown the importance of implementing both types of studies, as each has their advantages and disadvantages. However, three-dimensional (3D) motion capture of primates has been challenging under natural conditions. In this study, we provide a detailed protocol on how to collect 3D biomechanical data on primate leaping in their natural habitat that can be widely implemented. To record primate locomotion in the dense forest we use modified GoPro Hero Black cameras with zoom lenses that can easily be carried around and set up on tripods. We outline details on how to obtain camera calibrations at greater heights and how to process the collected data using the MATLAB camera calibration app and the motion tracking software DLTdv8a. We further developed a new MATLAB application "WildLeap3D" to generate biomechanical performance metrics from the derived x, y, z coordinates of the leaps. We provide details on how to collect data on support diameter, compliance, and orientation, and combine these with the jumps to study locomotor performance in an ecological context. We successfully reconstructed leaps of wild primates in the 3D space under natural conditions and provided data on four representative leaps. We provide exemplar data on primate velocity and acceleration during a leap and show how our protocol can be used to analyze segmental kinematics. This study will help to make motion capture of freely moving animals more accessible and help further our knowledge about animal locomotion and movement.

Impact of diet change on the gut microbiome of common marmosets (Callithrix jacchus).

Gastrointestinal diseases are the most frequently reported clinical problems in captive common marmosets (Callithrix jacchus), often affecting the health and welfare of the animal and ultimately their use as a research subject. The microbiome has been shown to be intimately connected to diet and gastrointestinal health. Here, we use shotgun metagenomics and untargeted metabolomics in fecal samples of common marmosets collected before, during, and after a dietary transition from a biscuit to a gel diet. The overall health of marmosets, measured as weight recovery and reproductive outcome, improved after the diet transition. Moreover, each marmoset pair had significant shifts in the microbiome and metabolome after the diet transition. In general, we saw a decrease in Escherichia coli and Prevotella species and an increase in Bifidobacterium species. Untargeted metabolic profiles indicated that polyamine levels, specifically cadaverine and putrescine, were high after diet transition, suggesting either an increase in excretion or a decrease in intestinal reabsorption at the intestinal level. In conclusion, our data suggest that Bifidobacterium species could potentially be useful as probiotic supplements to the laboratory marmoset diet. Future studies with a larger sample size will be beneficial to show that this is consistent with the diet change. IMPORTANCE: Appropriate diet and health of the common marmoset in captivity are essential both for the welfare of the animal and to improve experimental outcomes. Our study shows that a gel diet compared to a biscuit diet improves the health of a marmoset colony, is linked to increases in Bifidobacterium species, and increases the removal of molecules associated with disease. The diet transition had an influence on the molecular changes at both the pair and time point group levels, but only at the pair level for the microbial changes. It appears to be more important which genes and functions present changed rather than specific microbes. Further studies are needed to identify specific components that should be considered when choosing an appropriate diet and additional supplementary foods, as well as to validate the benefits of providing probiotics. Probiotics containing Bifidobacterium species appear to be useful as probiotic supplements to the laboratory marmoset diet, but additional work is needed to validate these findings.

Ecological and genetic variables co-vary with social group identity to shape the gut microbiome of a pair-living primate.

Primates exhibit diverse social systems that are intricately linked to their biology, behavior, and evolution, all of which influence the acquisition and maintenance of their gut microbiomes (GMs). However, most studies of wild primate populations focus on taxa with relatively large group sizes, and few consider pair-living species. To address this gap, we investigate how a primate's social system interacts with key environmental, social, and genetic variables to shape the GM in pair-living, red-bellied lemurs (Eulemur rubriventer). Previous research on this species suggests that social interactions within groups influence interindividual microbiome similarity; however, the impacts of other nonsocial variables and their relative contributions to gut microbial variation remain unclear. We sequenced the 16S ribosomal RNA hypervariable V4-V5 region to characterize the GM from 26 genotyped individuals across 11 social groups residing in Ranomafana National Park, Madagascar. We estimated the degree to which sex, social group identity, genetic relatedness, dietary diversity, and home range proximity were associated with variation in the gut microbial communities residing in red-bellied lemurs. All variables except sex played a significant role in predicting GM composition. Our model had high levels of variance inflation, inhibiting our ability to determine which variables were most predictive of gut microbial composition. This inflation is likely due to red-bellied lemurs' pair-living, pair-bonded social system that leads to covariation among environmental, social, and genetic variables. Our findings highlight some of the factors that predict GM composition in a tightly bonded, pair-living species and identify variables that require further study. We propose that future primate microbiome studies should simultaneously consider environmental, social, and genetic factors to improve our understanding of the relationships among sociality, the microbiome, and primate ecology and evolution.

Comparative pathogenesis of three Mayaro virus genotypes in the cynomolgus macaque.

Mayaro virus (MAYV), a mosquito-borne alphavirus, is considered an emerging threat to public health with epidemic potential. Phylogenetic studies show the existence of three MAYV genotypes. In this study, we provide a preliminary analysis of the pathogenesis of all three MAYV genotypes in cynomolgus macaques (Macaca facicularis, Mauritian origin). Significant MAYV-specific RNAemia and viremia were detected during acute infection in animals challenged intravenously with the three MAYV genotypes, and strong neutralizing antibody responses were observed. MAYV RNA was detected at high levels in lymphoid tissues, joint muscle and synovia over 1 month after infection, suggesting that this model could serve as a promising tool in studying MAYV-induced chronic arthralgia, which can persist for years. Significant leucopenia was observed across all MAYV genotypes, peaking with RNAemia. Notable differences in the severity of acute RNAemia and composition of cytokine responses were observed among the three MAYV genotypes. Our model showed no outward signs of clinical disease, but several major endpoints for future MAYV pathology and intervention studies are described. Disruptions to normal blood cell counts and cytokine responses were markedly distinct from those observed in macaque models of CHIKV infection, underlining the importance of developing non-human primate models specific to MAYV infection.

Hematology and serum biochemistry of free-ranging mantled howler monkeys (Alouatta palliata) at La Pacifica, Costa Rica.

BACKGROUND: Hematologic and blood biochemical values are key tools for assessing primate health. A long-term behavioral study of howler monkeys at a single site (La Pacífica, Guanacaste, Costa Rica), afforded the opportunity to develop baseline values for a large group of animals, evaluating differences between adult males and females and comparing to a report in the same population two decades later. METHODS: In 1998, 64 free-ranging mantled howler monkeys were anesthetized and sampled for hematologic and biochemical analysis. RESULTS: Blood analysis is reported for 29 adult females, 9 juvenile females, 19 adult males and 3 juvenile males. Four adults were excluded due to external injury or disease. There were few significant differences between adult females, juvenile females, and adult males. CONCLUSIONS: Baseline blood parameters are useful for determining normal values for howler monkey populations. The values for total protein, blood urea nitrogen, glucose, liver enzymes and potassium differed from a later study in 2019 may indicate changes that are influencing howler monkey health.

Exploratory studies of ethanol drinking in the white-tufted marmoset (Callithrix jacchus).

The white-tufted marmoset is a small, nonhuman primate that is rapidly gaining popularity as a model organism, especially for neuroscience research. To date, little work in the alcohol research field has utilized the marmoset. As a step toward establishing the marmoset as a research model for alcohol experimentation, a series of exploratory studies were undertaken to characterize ethanol drinking behavior. A voluntary drinking paradigm was established whereby the common marmoset would consume pharmacologically relevant amounts of ethanol. To facilitate ethanol consumption, ethanol was mixed with a marshmallow flavored solution (hereafter called marshmallow juice) to mask the presumed adverse taste of ethanol. Using marshmallow juice flavored solutions, marmosets readily consumed ethanol up to 1 g/kg during 10 min binge-like drinking sessions or up to 5 g/kg during ∼4 h drinking sessions. Consumption of 1.0-1.5 g/kg during a 30 min session resulted in blood ethanol concentrations of 49-73 mg/dl, which are predicted to be pharmacologically relevant. In animals that were stably consuming ethanol in marshmallow juice, gradually reducing the concentration of the marshmallow juice flavoring resulted in markedly reduced ethanol consumption. Lastly, when offered a choice between ethanol in marshmallow juice and marshmallow juice alone, marmosets displayed a very strong preference for the marshmallow juice solution without ethanol. From these studies, it is concluded that marmosets will voluntarily consume ethanol if the taste is masked with a sweet solution such as marshmallow juice. These studies represent the first report of alcohol consumption and preference in the white-tufted marmoset.

Genetic barrier to resistance: a critical parameter for efficacy of neutralizing monoclonal antibodies against SARS-CoV-2 in a nonhuman primate model.

The potency of antibody neutralization in cell culture has been used as the key criterion for selection of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for clinical development. As other aspects may also influence the degree of protection in vivo, we compared the efficacy of two neutralizing monoclonal antibodies (TRES6 and 4C12) targeting different epitopes of the receptor binding domain (RBD) of SARS-CoV-2 in a prophylactic setting in rhesus monkeys. All four animals treated with TRES6 had reduced viral loads in the upper respiratory tract 2 days after naso-oropharyngeal challenge with the Alpha SARS-CoV-2 variant. Starting 2 days after challenge, mutations conferring resistance to TRES6 were dominant in two of the rhesus monkeys, with both animals failing to maintain reduced viral loads. Consistent with its lower serum neutralization titer at the day of challenge, prophylaxis with 4C12 tended to suppress viral load at day 2 less efficiently than TRES6. However, a week after challenge, mean viral loads in the lower respiratory tract in 4C12-treated animals were lower than in the TRES6 group and no mutations conferring resistance to 4C12 could be detected in viral isolates from nasal or throat swabs. Thus, genetic barrier to resistance seems to be a critical parameter for the efficacy of prophylaxis with monoclonal antibodies against SARS-CoV-2. Furthermore, comparison of antibody concentrations in respiratory secretions to those in serum shows reduced distribution of the 4C12 antibody into respiratory secretions and a delay in the appearance of antibodies in bronchoalveolar lavage fluid compared to their appearance in secretions of the upper respiratory tract.IMPORTANCEMonoclonal antibodies are a powerful tool for the prophylaxis and treatment of acute viral infections. Hence, they were one of the first therapeutic agents licensed for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Oftentimes, the main criterion for the selection of antibodies for clinical development is their potency of neutralization in cell culture. By comparing two antibodies targeting the Spike protein of SARS-CoV-2, we now observed that the antibody that neutralized SARS-CoV-2 more efficiently in cell culture suppressed viral load in challenged rhesus monkeys to a lesser extent. Extraordinary rapid emergence of mutants of the challenge virus, which had lost their sensitivity to the antibody, was identified as the major reason for the reduced efficacy of the antibody in rhesus monkeys. Therefore, the viral genetic barrier to resistance to antibodies also affects their efficacy.

Chimpanzees (Pan troglodytes) recognize that their guesses could be wrong and can pass a two-cup disjunctive syllogism task.

When chimpanzees search for hidden food, do they realize that their guesses may not be correct? We applied a post-decision wagering paradigm to a simple two-cup search task, varying whether we gave participants visual access to the baiting and then asking after they had chosen one of the cups whether they would prefer a smaller but certain reward instead of their original choice (experiment 1). Results showed that chimpanzees were more likely to accept the smaller reward in occluded than visible conditions. Experiment 2 found the same effect when we blocked visual access but manipulated the number of hiding locations for the food piece, showing that the effect is not owing to representation type. Experiments 3 and 4 showed that when given information about the contents of the unchosen cup, chimpanzees were able to flexibly update their choice behaviour accordingly. These results suggest that language is not a pre-requisite to solving the disjunctive syllogism and provides a valuable contribution to the debate on logical reasoning in non-human animals.

A simple accurate method for concentration-QTc analysis in preclinical animal models.

INTRODUCTION: In preclinical cardiovascular safety pharmacology studies, statistical analysis of the rate corrected QT interval (QTc) is the focus for predicting QTc interval changes in the clinic. Modeling of a concentration/QTc relationship, common clinically, is limited due to minimal pharmacokinetic (PK) data in nonclinical testing. It is possible, however, to relate the average drug plasma concentration from sparse PK samples over specific times to the mean corrected QTc. We hypothesize that averaging drug plasma concentration and the QTc-rate relationship over time provides a simple, accurate concentration-QTc relationship bridging statistical and concentration/QTc modeling. METHODS: Cardiovascular telemetry studies were conducted in non-human primates (NHP; n = 48) and canines (n = 8). Pharmacokinetic samples were collected on separate study days in both species. Average plasma concentrations for specific intervals (CAverage0-X) were calculated for moxifloxacin in canines and NHP using times corresponding to super-intervals for the QTc data statistical analysis. The QTc effect was calculated for each super-interval using a linear regression correction incorporating QT and HR data from the whole super-interval. The concentration QTc effects were then modeled. RESULTS: In NHP, a 10.9 ± 0.06 ms (mean ± 95% CI) change in QTc was detected at approximately 1.5× the moxifloxacin plasma concentration that causes a 10 ms QTc change in humans, based on a 0-24 h super-interval. When simulating a drug without QT effects, mock, no effect on QTc was detected at up to 3× the clinical concentration. Similarly, in canines, a 16.6 ± 0.1 ms change was detected at 1.7× critical clinical moxifloxacin concentration, and a 0.04 ± 0.1 ms change was seen for mock. CONCLUSIONS: While simultaneous PK and QTc data points are preferred, practical constraints and the need for QTc averaging did not prevent concentration-QTc analyses. Utilizing a 0-24 h super-interval method illustrates a simple and effective method to address cardiovascular questions when preclinical drug exposures exceed clinical concentrations.

Analysis of the aging-related biomarker in a nonhuman primate model using multilayer omics.

BACKGROUND: Aging is a prominent risk factor for diverse diseases; therefore, an in-depth understanding of its physiological mechanisms is required. Nonhuman primates, which share the closest genetic relationship with humans, serve as an ideal model for exploring the complex aging process. However, the potential of the nonhuman primate animal model in the screening of human aging markers is still not fully exploited. Multiomics analysis of nonhuman primate peripheral blood offers a promising approach to evaluate new therapies and biomarkers. This study explores aging-related biomarker through multilayer omics, including transcriptomics (mRNA, lncRNA, and circRNA) and proteomics (serum and serum-derived exosomes) in rhesus monkeys (Macaca mulatta). RESULTS: Our findings reveal that, unlike mRNAs and circRNAs, highly expressed lncRNAs are abundant during the key aging period and are associated with cancer pathways. Comparative analysis highlighted exosomal proteins contain more types of proteins than serum proteins, indicating that serum-derived exosomes primarily regulate aging through metabolic pathways. Finally, eight candidate aging biomarkers were identified, which may serve as blood-based indicators for detecting age-related brain changes. CONCLUSIONS: Our results provide a comprehensive understanding of nonhuman primate blood transcriptomes and proteomes, offering novel insights into the aging mechanisms for preventing or treating age-related diseases.

Electrical rejuvenation of chronically implanted macroelectrodes in nonhuman primates.

Objective.Electrodes chronically implanted in the brain undergo complex changes over time that can lower the signal to noise ratio (SNR) of recorded signals and reduce the amount of energy delivered to the tissue during therapeutic stimulation, both of which are relevant for the development of robust, closed-loop control systems. Several factors have been identified that link changes in the electrode-tissue interface (ETI) to increased impedance and degraded performance in micro- and macro-electrodes. Previous studies have demonstrated that brief pulses applied every few days can restore SNR to near baseline levels during microelectrode recordings in rodents, a process referred to as electrical rejuvenation. However, electrical rejuvenation has not been tested in clinically relevant macroelectrode designs in large animal models, which could serve as preliminary data for translation of this technique. Here, several variations of this approach were tested to characterize parameters for optimization.Approach. Alternating-current (AC) and direct-current (DC) electrical rejuvenation methods were explored in three electrode types, chronically implanted in two adult male nonhuman primates (NHP) (Macaca mulatta), which included epidural electrocorticography (ECoG) electrodes and penetrating deep-brain stimulation (DBS) electrodes. Electrochemical impedance spectroscopy (EIS) was performed before and after each rejuvenation paradigm as a gold standard measure of impedance, as well as at subsequent intervals to longitudinally track the evolution of the ETI. Stochastic error modeling was performed to assess the standard deviation of the impedance data, and consistency with the Kramers-Kronig relations was assessed to evaluate the stationarity of EIS measurement.Main results. AC and DC rejuvenation were found to quickly reduce impedance and minimize the tissue component of the ETI on all three electrode types, with DC and low-frequency AC producing the largest impedance drops and reduction of the tissue component in Nyquist plots. The effects of a single rejuvenation session were found to last from several days to over 1 week, and all rejuvenation pulses induced no observable changes to the animals' behavior.Significance. These results demonstrate the effectiveness of electrical rejuvenation for diminishing the impact of chronic ETI changes in NHP with clinically relevant macroelectrode designs.

Deforestation and non-human primate malarias will be a threat to malaria elimination in the future: Insights from Southeast Asia.

Malaria continues to be a global public health problem although it has been eliminated from many countries. Sri Lanka and China are two countries that recently achieved malaria elimination status, and many countries in Southeast Asia are currently in the pipeline for achieving the same goal by 2030. However, Plasmodium knowlesi, a non-human primate malaria parasite continues to pose a threat to public health in this region, infecting many humans in all countries in Southeast Asia except for Timor-Leste. Besides, other non-human primate malaria parasite such as Plasmodium cynomolgi and Plasmodium inui are infecting humans in the region. The non-human primates, the long-tailed and pig-tailed macaques which harbour these parasites are now increasingly prevalent in farms and forest fringes close by to the villages. Additionally, the Anopheles mosquitoes belonging to the Lecuosphyrus Group are also present in these areas which makes them ideal for transmitting the non-human primate malaria parasites. With changing landscape and deforestation, non-human primate malaria parasites will affect more humans in the coming years with the elimination of human malaria. Perhaps due to loss of immunity, more humans will be infected as currently being demonstrated in Malaysia. Thus, control measures need to be instituted rapidly to achieve the malaria elimination status by 2030. However, the zoonotic origin of the parasite and the changes of the vectors behaviour to early biting seems to be the stumbling block to the malaria elimination efforts in this region. In this review, we discuss the challenges faced in malaria elimination due to deforestation and the serious threat posed by non-human primate malaria parasites.

Oral cavity squamous cell carcinomas in zoo-managed Goeldi's monkeys (Callimico goeldii).

BACKGROUND: Oral cavity squamous cell carcinomas (OCSCCs) are relatively common in multiple non-human primate species but are poorly documented in Goeldi's monkeys. METHODS: Four Goeldi's monkeys with OCSCC, from three zoological collections, underwent necropsy with cytology, histopathology, immunohistochemistry, and pan-herpesvirus PCR analysis. RESULTS: All animals were euthanised and exhibited poor-to-emaciated body condition. Three OCSCCs arose from the maxillary oral mucosa and a single OCSCC was primarily mandibular, with bone invasion evident in three cases. Histologically, one OCSCC in situ was diagnosed, whilst the rest were typically invasive OCSCCs. Neoplastic cells were immunopositive for pancytokeratin and E-cadherin. All examined cases were negative for regional lymph node (RLN) and/or distant metastases, cyclooxygenase-2 (COX-2) immunoexpression, and panherpesvirus PCR expression. CONCLUSIONS: OCSCCs in Goeldi's monkeys may be deeply invasive, but not readily metastatic. No herpesvirus-association or COX-2 expression was evident; the latter suggesting that NSAIDs are unlikely to be a viable chemotherapeutic treatment.