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The availability of effective vaccines and a high vaccination rate allowed the recent mitigation, or even withdrawal, of many protective measures for containing the SARS CoV-2 pandemic. At the same time, new and highly mutated variants of the virus are found to have significantly higher transmissibility and reduced vaccine efficacy, thus causing high infection rates during the third year of the pandemic. The combination of reduced measures and increased infectivity poses a particular risk for unvaccinated individuals, including animals susceptible to the virus. Among the latter, non-human primates (NHPs) are particularly vulnerable. They serve as important models in various fields of biomedical research and because of their cognitive capabilities, they receive particular attention in animal welfare regulations around the world. Yet, although they played an extraordinarily important role for developing and testing vaccines against SARS-CoV-2, the protection of captive rhesus monkeys against Covid-19 has rarely been discussed. We here report upon twofold mRNA vaccination of a cohort of 19 elderly rhesus monkeys (Macaca mulatta) against infection by SARS-CoV-2. All animals were closely monitored on possible side effects of vaccination, and were tested for neutralising antibodies against the virus. The data show that vaccination of rhesus monkeys is a safe and reliable measure to protect these animals against SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Keeping rhesus monkeys as laboratory animals requires timely prevention and treatment of infections, including diseases of bacterial etiology. Based on our own studies of the microflora of healthy and sick monkeys, as well as analysis of published reports, we identified clinically significant representatives of pathogenic and opportunistic bacteria: E. coli, Staphylococcus aureus, Klebsiella spp., Proteus spp. The isolates of these bacterial species and genera circulating in monkeys kept in the enclosure were isolated, four virulent bacteriophage strains with a wide spectrum of lytic activity against these isolates were selected and newly isolated. The composition based on virulent bacteriophage strains was tested on monkeys with assessment of its safety and its dynamics of detection of phage-specific DNA. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) is an endocrine-disrupting chemical, and is predominantly metabolized into glucuronide in mammals. The present study was conducted in order to examine the hepatic and intestinal glucuronidation of BPA in humans and laboratory animals such as monkeys, dogs, rats, and mice in an in vitro system using microsomal fractions. Km, Vmax, and CLint values in human liver microsomes were 7.54 µM, 17.7 nmol/min/mg protein, and 2.36 mL/min/mg protein, respectively. CLint values in liver microsomes of monkey, dogs, rats, and mice were 1.5-, 2.4-, 1.7- and 8.2-fold that of humans, respectively. In intestinal microsomes, Km, Vmax, and CLint values in humans were 39.3 µM, 0.65 nmol/min/mg protein, and 0.02 mL/min/mg protein, respectively. The relative levels of CLint in monkey, dogs, rats, and mice to that of humans were 7.0-, 12-, 34-, and 29-fold, respectively. Although CLint values were higher in liver microsomes than in intestinal microsomes in all species, and marked species difference in the ratio of liver to intestinal microsomes was observed as follows: humans, 118; monkeys, 25; dogs, 23; rats, 5.9; mice, 33. These results suggest that the functional roles of UDP-glucuronosyltransferase (UGT) enzymes expressed in the liver and intestines in the metabolism of BPA extensively differ among humans, monkeys, dogs, rats, and mice. [ABSTRACT FROM AUTHOR]

Despite the prevalence of laboratory animals such as monkeys, rats, and mice in clinical drug trials, we know little regarding the oxidation of regorafenib in these test subjects. This study aimed to elucidate species differences in the kinetics of regorafenib oxidation into two metabolites: regorafenib N-oxide (M-2) and hydroxyregorafenib (M-3). M-2 formation best fitted the Hill equation and showed positive cooperativity in liver and small intestinal microsomes from all species. For all species, M-2 formation had a higher maximum velocity in microsomes from the liver than the small intestines. Maximum velocity was also higher in microsomes from humans and monkeys than those from rats and mice. M-3 formation was well-fitted to the Hill equation and showed positive cooperativity in all microsomes, except those from rat small intestines, where it exhibited biphasic kinetics. At half the maximum velocity, substrate concentration for M-2 and M-3 formation was lower in microsomes from humans than from other species. Moreover, M-2 was the major metabolite in microsomes from humans, monkeys, and mice, whereas M-2 and M-3 were the major metabolites in rat microsomes. M-2 and M-3 formation involving CYP3A4 and CYP3A5 fitted to the Hill equation. However, M-3 formation involving CYP2J2 fitted to the substrate inhibition model. Our study confirmed species differences in regorafenib oxidative metabolism. [ABSTRACT FROM AUTHOR]

This study was aimed at establishing the subcorticals substrates of the cognitive and visceromotor circuits of the A32 and A25 cortices of the medial prefrontal cortex and their projections and interactions with subcortical complexes in the common marmoset monkey (Callithrix jacchus). The study was primarily restricted to the nuclei of the diencephalon and amygdala. The common marmoset is a neotropical primate of the new world, and the absence of telencephalic gyrus favors the mapping of neuronal fibers. The biotinylated dextran amine was employed as an anterograde tracer. There was an evident pattern of rostrocaudal distribution of fibers within the subcortical nuclei, with medial orientation. Considering this distribution, fibers originating from the A25 cortex were found to be more clustered in the diencephalon and amygdala than those originating in the A32 cortex. Most areas of the amygdala received fibers from both cortices. In the diencephalon, all regions received projections from the A32, while the A25 fibers were restricted to the thalamus, hypothalamus, and epithalamus at different densities. Precise deposits of neuronal tracers provided here may significantly contribute to expand our understanding of specific connectivity among the medial prefrontal cortex with limbic regions and diencephalic areas, key elements to the viscerocognitive process. [ABSTRACT FROM AUTHOR]

The recent increase in reliable, simultaneous high channel count extracellular recordings is exciting for physiologists and theoreticians because it offers the possibility of reconstructing the underlying neuronal circuits. We recently presented a method of inferring this circuit connectivity from neuronal spike trains by applying the generalized linear model to cross-correlograms. Although the algorithm can do a good job of circuit reconstruction, the parameters need to be carefully tuned for each individual dataset. Here we present another method using a Convolutional Neural Network for Estimating synaptic Connectivity from spike trains. After adaptation to huge amounts of simulated data, this method robustly captures the specific feature of monosynaptic impact in a noisy cross-correlogram. There are no user-adjustable parameters. With this new method, we have constructed diagrams of neuronal circuits recorded in several cortical areas of monkeys. [ABSTRACT FROM AUTHOR]

Some monkeys housed in research facilities develop abnormal behavior ranging from stereotypic to the more serious condition of self‐injurious behavior (SIB). We initially sought to understand how and why monkeys engaged in SIB and more importantly why only a small percentage of laboratory monkeys, with seemingly similar housing and background, developed this disorder. Of particular importance was the recognition that different pathways might lead to SIB and that strong individual differences would affect the manifestation of this disorder and the response to treatment. We developed a comprehensive plan to identify effective treatment and prevention strategies. We started with characterizing the disorder in terms of prevalence and types of environments in which it was found. We then conducted observations on a cohort of SIB and control monkeys to identify conditions associated with SIB (e.g., disordered sleep) as well as clinical disease states and congenital defects that could be precipitating factors. We examined the environmental events that triggered episodes of SIB in monkeys with the disorder and evaluated three models that might explain the reinforcement contingencies associated with SIB, including tension reduction, self‐stimulation, and social communication. Possible treatments for SIB such as environmental enrichment, social housing, and pharmacotherapy were tested by our group and others. To date, no single treatment has been found to abolish SIB, and each of these treatments is impacted by individual differences. To develop possible prevention strategies, we examined colony management and health records to find risk factors for SIB. These risk factors generalized to other facilities, and considerable effort was expended by all behavioral managers at these facilities to reduce early life stress exposure, to minimize the length of individual cage housing by emphasizing pair housing, and to reduce the possible stressfulness of various veterinary/medical procedures by implementing positive reinforcement training. Research Highlights: Self‐injurious behavior (SIB) occurs in a small percentage of nonhuman primates found in laboratories, zoos, and natural settings.Multiple pathways can lead to SIB, such as clinical disease, stress by genotype interactions, and inadvertent reinforcement of SIB as a communication signal.SIB is often comorbid with heightened aggressiveness, stress dysregulation, and sleep disruption.No treatment is effective in abolishing SIB in all animals. Prevention includes reducing or eliminating the risk factors that have been associated with SIB (e.g., altered early rearing experiences and individual cage housing) and instituting positive reinforcement training for many basic husbandry and veterinary/medical procedures. [ABSTRACT FROM AUTHOR]

In post-stroke patients, a decreased adherence to antiplatelet drugs is a major challenge in the prevention of recurrent stroke. Previously, we reported an antiplatelet vaccine against S100A9 in mice, but the use of Freund's adjuvant and the difference in amino acid sequences in epitopes between mice and humans were problematic for clinical use. Here, we redesigned the S100A9 vaccine for the common sequence in both humans and monkeys and examined its effects in cynomolgus monkeys with Alum adjuvant. First, we assessed several candidate epitopes and selected 102 to 112 amino acids as the suitable epitope, which could produce antibodies. When this peptide vaccine was intradermally injected into 4 cynomolgus monkeys with Alum, the antibody against human S100A9 was successfully produced. Anti-thrombotic effects were shown in two monkeys in a mixture of vaccinated serum and fresh whole blood from another cynomolgus monkey. Additionally, the anti-thrombotic effects were partially inhibited by the epitope peptide, indicating the feasibility of neutralizing anti-thrombotic effects of produced antibodies. Prolongation of bleeding time was not observed in vaccinated monkeys. Although further studies on increasing the effect of vaccine and safety are necessary, this vaccine will be a promising approach to improve adherence to antiplatelet drugs in clinical settings. [ABSTRACT FROM AUTHOR]

Many groups are working to improve the results of clinical allogeneic islet transplantation in a primate model. However, few studies have focused on the optimal islet dose for achieving normal glycemia without exogenous insulin after transplantation in primate models or on the relationship between rejection and islet amyloid polypeptide (IAPP) expression. We evaluated the dose (10,000, 20,000, and > 25,000 islet equivalents (IEQ)/kg) needed to achieve normal glycemia without exogenous insulin after transplantation using eleven cynomolgus monkeys, and we analyzed the characteristics exhibited in the islets after transplantation. 10,000 IEQ/kg (N = 2) failed to control blood glucose level, despite injection with the highest dose of exogenous insulin, and 20,000 IEQ/kg group (N = 5) achieved unstable control, with a high insulin requirement. However, 25,000 IEQ/kg (N = 4) achieved normal glycemia without exogenous insulin and maintained it for more than 60 days. Immunohistochemistry results from staining islets found in liver biopsies indicated that as the number of transplanted islets decreased, the amount of IAPP accumulation within the islets increased, which accelerated CD3+ T cell infiltration. In conclusion, the optimal transplantation dose for achieving a normal glycemia without exogenous insulin in our cynomolgus monkey model was > 25,000 IEQ/kg, and the accumulation of IAPP early after transplantation, which depends on the transplanted islet dose, can be considered one factor in rejection. [ABSTRACT FROM AUTHOR]

The neural mechanisms underlying the effects of continuous Theta-Burst Stimulation (cTBS) in humans are poorly understood. Animal studies can clarify the effects of cTBS on individual neurons, but behavioral evidence is necessary to demonstrate the validity of the animal model. We investigated the behavioral effect of cTBS applied over parietal cortex in rhesus monkeys performing a visually-guided grasping task with two differently sized objects, which required either a power grip or a pad-to-side grip. We used Fitts' law, predicting shorter grasping times (GT) for large compared to small objects, to investigate cTBS effects on two different grip types. cTBS induced long-lasting object-specific and dose-dependent changes in GT that remained present for up to two hours. High-intensity cTBS increased GTs for a power grip, but shortened GTs for a pad-to-side grip. Thus, high-intensity stimulation strongly reduced the natural GT difference between objects (i.e. the Fitts' law effect). In contrast, low-intensity cTBS induced the opposite effects on GT. Modifying the coil orientation from the standard 45-degree to a 30-degree angle induced opposite cTBS effects on GT. These findings represent behavioral evidence for the validity of the nonhuman primate model to study the neural underpinnings of non-invasive brain stimulation. [ABSTRACT FROM AUTHOR]

This report describes a case of unintended importation of tropical baby jumping spiders to a laboratory monkey colony. The spiders were detected in a cocoon attached to a banana for monkey consumption. In identifying the family of spiders as jumping spiders (Salticidae), it turned out that these spiders would not have been venomous to humans and they most likely would not have had the potential to establish a new spider colony in the facility. [ABSTRACT FROM AUTHOR]

Moving objects are often occluded behind larger, stationary objects, but we can easily predict when and where they reappear. Here, we show that the prediction of object reappearance is subject to adaptive learning. When monkeys generated predictive saccades to the location of target reappearance, systematic changes in the location or timing of target reappearance independently altered the endpoint or latency of the saccades. Furthermore, spatial adaptation of predictive saccades did not alter visually triggered reactive saccades, whereas adaptation of reactive saccades altered the metrics of predictive saccades. Our results suggest that the extrapolation of motion trajectory may be subject to spatial and temporal recalibration mechanisms located upstream from the site of reactive saccade adaptation. Repetitive exposure of visual error for saccades induces qualitatively different adaptation, which might be attributable to different regions in the cerebellum that regulate learning of trajectory prediction and saccades. [ABSTRACT FROM AUTHOR]

Transverse expansion or proclination of the teeth are valid alternatives to extraction in cases of crowding, but lack of stability and development of bone dehiscences have been demonstrated as side effects subsequent to anterior displacement of the incisors. The aim of this study was to repair the osseous dehiscence associated with incisor proclination. The multiple adjacent bone dehiscences were treated with a titanium membrane and bone matrix. Exposed root surfaces were covered with newly formed tissues. The patients in this study are the first to demonstrate the treatment of bone dehiscences that may occur as a result of orthodontic proclination. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to describe the stress and strain fields around orthodontically loaded dental implants using the finite element method and to evaluate the relationship between the generated strain and the biologic reaction expressed through histomorphometric parameters. Finally, this study aimed to evaluate the interaction between the orthodontic loading and the deformation generated by normal occlusal function. Materials and Methods: Sixteen titanium dental implants were inserted in extraction sockets after the removal of the second premolars and first molars of 4 adult Macaca fascicularis monkeys. After 17 weeks of healing, the implants were loaded by a pair of Sentalloy springs (50 cN) for 16 weeks. After sacrifice, tissue blocks including the implants and surrounding bone were excised. Five tissue blocks were scanned with a synchrotron radiation-based microtomography (μCT) scanner and sample-specific finite element models were generated. Subsequently all samples were prepared for histomorphometric analysis. Results: All implants were osseointe grated, although the surrounding alveolar bone differed from sample to sample. As a consequence the finite element analyses showed that the stresses and strains in the peri-implant alveolar bone greatly varied among the samples. A high level of remodeling activity was found close to the implants. Discussion: Individual differences between the receptors (in this case, the monkeys) have a large effect on both the biologic and morphologic parameters. These variations were indeed found to have a substantial impact on the (re)modeling dynamics and the load transfer mechanisms around the implants. Conclusions: By integrating different analysis techniques to evaluate bone (re)modeling around orthodontically loaded implants, this study has demonstrated the complexity and case-specific character of alveolar adaptation to orthodontic loading. Furthermore, stresses generated by combined functional and orthodontic forces should not be neglected. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to evaluate the pulpal response of a fluoride-releasing one-step adhesive in nonexposed monkey teeth. Materials and Methods: Cervical Class V cavities were prepared in monkey teeth. The cavities were divided into three groups of different restorative materials. A one-step adhesive (SI-IB551, Shofu) was applied to the teeth, and the cavities were filled with a resin composite (Beautifil, Shofu). In the other two groups, a two-step adhesive (Imperva FluoroBond, Shofu) together with either a resin composite (Beautifil) or a glass-ionomer cement (Fuji II, GC) was placed in the cavities. The teeth were then extracted after 3, 30, and 90 days, fixed in 10% buffered formalin solution, and prepared according to routine histological techniques. Five-micrometer sections were stained with hematoxylin and eosin, or Brown & Brenn gram stain for bacterial observation. Four histological features, odontoblastic change, inflammatory cell infiltrate, reparative dentin formation, and the bacterial staining, were evaluated and compared. The results were compared statistically with significance defined as p < 0.05 (Kruskall- Wallis test). Results: Disarrangement of the odontoblasts and slight inflammatory cell infiltrations were the main initial reactions, while deposition of reparative dentin was the major long-term reaction in all groups. No statistically significant differences in the four histological features were seen among the restorative materials placed in the cavities (p > 0.05). No serious pulpal inflammatory reactions, such as necrosis or abscess formation, were observed in any of the experimental groups. Conclusion: The one-step adhesive showed acceptable biological compatibility with the monkey pulp, whereas the pulpal response to the system was minimally different from that of the glass-ionomer cement or the two-step self-etching adhesive. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the present study was to evaluate the histologic results of bone cavities that were surgically created in the mandibles of Cebus apella monkeys and filled with autogenous bone, PerioGlas, FillerBone, or Bone Source. Materials and Methods: Surgical cavities 5 mm in diameter were prepared through both mandibular cortices in the mandibular angle region. The cavities were randomly filled, and the animals were divided into groups according to the material employed: Group 1 cavities were filled with autogenous corticocancellous bone; group 2 cavities were filled with calcium phosphate cement (BoneSource); and group 3 and group 4 cavities were filled with bioactive glass (FillerBone and PerioGlas, respectively). After 180 days the animals were sacrificed, and specimens were prepared following routine laboratory procedures for hematoxylin/eosin staining and histologic evaluation. Results: The histologic analysis showed that autogenous bone allowed total repair of the bone defects; bioactive glasses (FillerBone and PerioGlas) allowed total repair of the defects with intimate contact of the remaining granules and newly formed bone; and the cavities filled with calcium phosphate cement (BoneSource) were generally filled by connective fibrous tissue, and the material was almost totally resorbed. Discussion: The autogenous bone, FillerBone, and PerioGlas provided results similar to those in the current literature, showing that autogenous bone is the best choice for filling critical-size defects. Synthetic implanted materials demonstrated biocompatibility, but the bioglasses demonstrated osteoconductive activity that did not occur with calcium phosphate (Bone-Source). Conclusion: According to the methodology used in this study, it can be concluded that the utilization of autogenous bone and bioactive glasses permitted the repair of surgically created critical-size defects by newly formed bone; the synthetic implanted materials demonstrated biocompatibility, and the bioactive glasses demonstrated osteoconductive activity. The PerioGlas was mostly resorbed and replaced by bone and the remaining granules were in close contact with bone; the Filler-Bone showed many granules in contact with the newly formed bone; BoneSource did not permit repair of the critical-size defects, and the defects were generally filled by connective fibrous tissue. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this work was to evaluate the in vivo long-term durability of bond strength and morphological appearance of interfaces between dentin and two adhesive systems. Materials and Methods: Class V cavities were prepared on the facial surfaces of 6 intact teeth of a monkey, and restored with Unifil Bond/Unifil F and Fuji Bond LC/Clearfil AP-X. One year later, 10 other teeth were restored with the same materials and the monkey was sacrificed after 24 hours. For in vitro examination, 6 more teeth were extracted from the monkey, restored in a similar manner with the two materials, and stored in 37°C water for 1 day. All specimens were subjected to the microtensile bond strength (μTBS) test. The debonded surfaces of specimens were morphologically observed with the FE-SEM. Results: There were no statistically significant differences among the mean μTBS obtained for Unifil Bond/Unifil F under the three conditions (1 day and 1 year in vivo, and 1 day in vitro), and most specimens showed cohesive failure within resin composite (Unifil F). However, FE-SEM observations showed that resinous material within the hybrid layer made by Unifil Bond seemed to increase in porosity after 1 year. For Fuji Bond LC/Clearfil AP-X, μTBS at 1 day in vitro was significantly higher than that at 1 year in vivo, and bond strengths in vivo tended to decrease over time, although a statistically significant difference was not observed. From FE-SEM observations, most specimens showed cohesive failure within the adhesive (Fuji Bond LC). Conclusion: Bond strengths of the two adhesive systems tended to decrease for 1 year in vivo. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to observe, after removing occlusal trauma and conducting plaque control, possible macroscopic and histologic changes in peri-implant tissue that had deteriorated resulting from experimental peri-implantitis, and to investigate the necessity for treatment procedures for peri-implantitis. Materials and Methods: Four monkeys (Macaca fascicularis) in good general health were used in this experiment. Three months after the second premolar and the first molar were extracted from the right mandible, 2 IMZ experimental implants were placed in each monkey. After a 3-month osseointegration period, a second surgery was conducted, followed by making an impression for fabrication of the prosthesis. Excessive occlusal height of the prosthesis was adjusted to 250 μm, and the experiment was continued for 8 weeks after placement of the prosthesis. Three models were created: (1) A superstructure with an excessive occlusal height was used for 8 weeks without any brushing (positive control, model P); (2) after the first 4 weeks with a prosthesis with excessive occlusal height and no brushing, the superstructure was removed and not used for the last 4 weeks while brushing was conducted (experimental model, model E); and (3) for 8 weeks, a prosthesis with an appropriate occlusal height was used with brushing (negative control, model N). Results: When these 3 models were compared with each other, macroscopic findings indicated inflammation only in model P. Mobility of implants was not seen in any model. Histopathologic observations revealed a slight difference between model E and model P in terms of the degree of inflammatory cell infiltration in the connective tissue. Discussion: No difference was found in the degree of bone resorption. Partial tearing was observed at the contact region between epithelial tissue and implant surfaces. Conclusions: (1) The contact between implants and epithelial or connective tissue is fragile; (2) inflammation and occlusion must be controlled more prudently than in the case of natural teeth; and (3) once peri-implantitis has progressed, the control of occlusion and inflammation is probably not sufficient to promote the healing mechanism. [ABSTRACT FROM AUTHOR]

The success of bone-inductive cytokines in surgical alveolar defects is greatly dependent upon the ability of carrier materials to effectively deliver the inductive protein to the surgical site. An evaluation of three types of carrier materials was undertaken in six monkeys using an osseous defect of 2.0 cm that was produced by partial resection of the maxilla and mandible and placement of titanium implants in each alveolar quadrant. After 5 months, abutments were placed on the implants, which were allowed to function for an additional 5 months. Intravital labeling with tetracycline was used to evaluate the late healing remodeling processes. The carriers were evaluated by studying (1) the amount of surface osseointegration on the root-form implants; (2) the bone density as related to trabecular pattern and cortex formation; and (3) the quantitative and qualitative thickness of the alveolar bone buccolingually at the implanted sites. Of the three materials, the calcium carbonate coral (BioCoral) produced a decreased amount of bone regeneration in comparison with both the poly(methylethyl methacrylate) material (HTR) and the porous bone mineral (Bio- Oss). Both the HTR and Bio-Oss with rhBMP-2 produced excellent thickness of the repaired alveolar ridge. All three materials produced the same amount of osseointegration with the titanium implant surfaces. Good bone quality, as reflected in thickening of the trabecular bone patterns, was seen with both Bio-Oss and HTR. While all three of these carrier materials appeared to produce good osseointegration with the titanium implants, BioCoral did not effect a quantitative or qualitative restoration of the alveolar bone comparable to that following the use of either HTR or Bio-Oss with rhBMP-2. [ABSTRACT FROM AUTHOR]

Objective: This study was undertaken to compare the healing response of permanent primate pulps to pulpotomy procedures following hemorrhage control and adhesive hybridization to their response after conventional treatments. Method and materials: Forty-two cavities were placed throughout the dentitions of 4 adult monkeys. In 24 teeth, following mechanical bur exposure and pulpotomy, hemorrhage was controlled with application of 3% sodium hypochlorite. The cavity was rinsed and the enamel-dentin-pulp surface was restored with an adhesive system tor 6 and 7 months. Calcium hydroxide, formocresol, and resin-modified glass-ionomer cement were placed as conventional treatments in 18 teeth for 70 days and cavities were sealed with resin-modified glass-ionomer cement. Following perfusion fixation, tissues were demineralized, sectioned, stained, and histologically graded using defined criteria. Results: Of 24 adhesive system pulps, 10 showed no or minimal pulpal response, 1 showed an acute response, 6 showed a chronic response, 2 showed a severe response, and 5 showed compartmentalized zones of localized necrosis. Only 8 adhesive system pulps showed stained bacteria associated with inflamed tissues. Thirteen adhesive system pulps showed dentin bridging directly at the adhesive system interface. Calcium hydroxide-treated specimens showed healing and dentin formation, while resin-modified glass-ionomer cement and formocresol treatments failed to result in any bridging. Apical tissues in all adhesive-treated specimens showed normal pulps and primary odontoblasts along their entire walls. Conclusion: Permanent pulps without periapical radiolucencies may survive pulpotomy, provided that hemorrhage is properly controlled and the pulp-restoration interface is hybridized to exclude all microleakage. [ABSTRACT FROM AUTHOR]

The influence of experimental occlusal overload on peri-implantitis in monkeys (Macaca fascicularis) has been examined to explain the pathology of the disease that develops in the tissue around osseointegrated implants. In the first article of this series, it was reported that bone resorption was not observed around implants when occlusal trauma was produced by a superstructure that was in supraocclusal contact with an excess occlusal height of approximately 100 μm, provided there was no inflammation in the peri-implant tissue. In the second part of the study, experimental inflammation was created in the peri-implant tissue, and occlusal overload was produced by a superstructure with an excess occlusal height of 100 μm. Notable bone resorption was observed around the implant with the passage of time. These results suggested that, in addition to the control of inflammation in peri-implant tissue, traumatic occlusion may play a role in bone breakdown around the implant. In the present study, while the peri-implant tissue was kept in an inflammation-free state, bone level changes around the implants were investigated when various levels of traumatic force were exerted. The supraoccluding prostheses were defined as excessively high by 100 μm, 180 μm, and 250 μm, respectively. The heights were determined with an image analysis device, and the bone responses around the implants induced by the traumatic forces were investigated. The results showed that bone resorption around implants tended to increase with 180 μm or more excessive height of the superstructure. This suggests that the threshold of excessive height of the superstructures at which peri-implant tissue breakdown may start is approximately 180 μm. It is also suggested that there is a possibility of bone resorption around the implants caused by excess occlusal trauma, even when there is no inflammation in peri-implant tissue. [ABSTRACT FROM AUTHOR]

The present study compares the biologic behavior of BioGran and Calcitite as fillers for surgical cavities in the mandibles of 4 adult monkeys (Cebus apella). The surgical cavities were prepared through both mandibular cortices, with a diameter of 5 mm, in the angle region. Two cavities were prepared on the right side and 1 on the left and divided into 3 groups: R1 sites were filled with bioglass (BioGran), R2 sites were not filled, and L sites were filled with hydroxyapatite (Calcitite). After 180 days the animals were sacrificed and the specimens were removed for histologic processing. Results showed no bone formation in group R2 (empty cavities). BioGran-treated sites showed bone formation and total repair of the bone defect, and the bioglass particles were almost totally resorbed and substituted by bone. The few remaining crystals were in intimate contact with newly formed bone. Calcitite did not allow bone formation, and granules inside the cavities were involved by connective tissue. Based upon those results, the authors concluded that bioglass resulted in total obliteration of the surgical cavity with bone and hydroxyapatite was present in a large amount and involved by connective tissue, without bone formation. [ABSTRACT FROM AUTHOR]

The effect of PerioGlas (synthetic bone particulate) on wound healing of experimental palatal periodontal defects in monkeys was evaluated. Chronic periodontal defects were created on the palatal aspects of maxillary, molars and premolors. Open-flop debridement was performed. Experimental sites received PerioGlas, while control sites received no further treatment. Histologic measurements were performed on new bone, new cementum, epithelial downgrowth, and recession. Results showed significantly more new cementum and less epithelial downgrowth in the sites that received PerioGlas (P<0.05). The present results indicate that PerioGlas may enhance periodontal wound healing outcomes. [ABSTRACT FROM AUTHOR]

Posterior parietal cortex (PPC) activity correlates with monkeys’ decisions during visual discrimination and categorization tasks. However, recent work has questioned whether decision-correlated PPC activity plays a causal role in such decisions. That study focused on PPC’s contribution to motor aspects of decisions (deciding where to move), but not sensory evaluation aspects (deciding what you are looking at). We employed reversible inactivation to compare PPC’s contributions to motor and sensory aspects of decisions. Inactivation affected both aspects of behavior, but preferentially impaired decisions when visual stimuli, rather than motor response targets, were in the inactivated visual field. This demonstrates a causal role for PPC in decision-making, with preferential involvement in evaluating attended task-relevant sensory stimuli compared with motor planning. [ABSTRACT FROM AUTHOR]

This study evaluated the long-term effects of the cathepsin K inhibitor ONO-5334 on bone mass and strength in ovariectomised (OVX) cynomolgus monkeys. Animals were assigned to one of the following six groups: Sham (non-OVX), OVX control treated with vehicle, ONO-5334 1.2, 6 or 30 mg/kg/day, p.o., or alendronate (ALN) 0.05 mg/kg/2 weeks, i.v. for 16 months. Peripheral quantitative computed tomography (pQCT) analysis revealed that ONO-5334 increased not only trabecular bone mineral density (BMD) but also cortical BMD in the distal radius and the lumbar vertebra. ONO-5334 and ALN suppressed the deterioration of trabecular architecture by micro-CT analysis in the distal radius. Assessments of bone strength showed that ONO-5334 increased maximum load at the distal and midshaft radius. The linear regression lines between bone mass and strength in the lumbar vertebra were tended to be shifted towards increasing bone strength in the ONO-5334 6 and 30 mg/kg groups compared with the ALN groups. This indicated that bone strength was higher in the ONO-5334 groups than the ALN group, even though bone mineral content (BMC) and BMD were comparable. Subpopulation analysis revealed that, at similar integral BMC or BMD level, cortical bone mass for ONO-5334 was higher than for ALN; the opposite effects were observed for trabecular bone. In conclusion, ONO-5334 preferentially increased cortical bone, which may provide a greater contribution to bone strength. Since these results support a different mode of action for ONO-5334 compared with that of ALN, ONO-5334 may offer new therapeutic options to patients with osteoporosis. [ABSTRACT FROM AUTHOR]

This essay is a meditation on the ways in which the scientific community and the arts community alike are feeling their way through the transdisciplinary subject of interspecies communication and how, in the absence of a single systematic program, both art and science can provide their own platforms to challenge how humans habitually think about communicating with animals.Creature Comforts begins with an exploration oflaboratory animals and their relationshipswith their handlers, and ends with a probing look at the use and inclusion of lab animals in contemporary art. [ABSTRACT FROM AUTHOR]

Microorganisms play important roles in obesity; however, the role of the gut microbiomes in obesity is controversial because of the inconsistent findings. This study investigated the gut microbiome communities in obese and lean groups of captive healthy cynomolgus monkeys reared under strict identical environmental conditions, including their diet. No significant differences in the relative abundance of Firmicutes, Bacteroidetes and Prevotella were observed between the obese and lean groups, but a significant difference in Spirochetes (p < 0.05) was noted. Microbial diversity and richness were similar, but highly variable results in microbial composition, diversity, and richness were observed in individuals, irrespective of their state of obesity. Distinct clustering between the groups was not observed by principal coordinate analysis using an unweighted pair group method. Higher sharedness values (95.81% ± 2.28% at the genus level, and 79.54% ± 5.88% at the species level) were identified among individual monkeys. This paper reports the association between the gut microbiome and obesity in captive non-human primate models reared under controlled environments. The relative proportion of Firmicutes and Bacteroidetes as well as the microbial diversity known to affect obesity were similar in the obese and lean groups of monkeys reared under identical conditions. Therefore, obesity-associated microbial changes reported previously appear to be associated directly with environmental factors, particularly diet, rather than obesity. [ABSTRACT FROM AUTHOR]

Understanding the principles by which agents interact with both complex environments and each other is a key goal of decision neuroscience. However, most previous studies have used experimental paradigms in which choices are discrete (and few), play is static, and optimal solutions are known. Yet in natural environments, interactions between agents typically involve continuous action spaces, ongoing dynamics, and no known optimal solution. Here, we seek to bridge this divide by using a “penalty shot” task in which pairs of monkeys competed against each other in a competitive, real-time video game. We modeled monkeys’ strategies as driven by stochastically evolving goals, onscreen positions that served as set points for a control model that produced observed joystick movements. We fit this goal-based dynamical system model using approximate Bayesian inference methods, using neural networks to parameterize players’ goals as a dynamic mixture of Gaussian components. Our model is conceptually simple, constructed of interpretable components, and capable of generating synthetic data that capture the complexity of real player dynamics. We further characterized players’ strategies using the number of change points on each trial. We found that this complexity varied more across sessions than within sessions, and that more complex strategies benefited offensive players but not defensive players. Together, our experimental paradigm and model offer a powerful combination of tools for the study of realistic social dynamics in the laboratory setting. [ABSTRACT FROM AUTHOR]

Neurons with histopathological changes consistent with granulovacuolar degeneration (GVD) were found in brain sections from aged cynomolgus monkeys (Macaca fascicularis) with clinical and pathological signs of cognitive aging. To our knowledge, this is the first reported description of GVD in non-human primates. GVD-like lesions were found also in age-matched cognitively healthy subjects, albeit in lower numbers, suggesting that they may relate to aging and the increase may have tendency to increase with the memory deficits. The increased incidence of GVD-like lesions in memory-impaired subjects with pahological backgrounds of senile plaques (SPs) and tauopathy is, however, an interesting observation of relevance to the characterization of pathologies in the spontaneous cynomolgus monkey model of human Alzheimer's type of brain pathology. [ABSTRACT FROM AUTHOR]

Highlights • We recorded in the brainstem of vocalizing marmoset monkeys with laminar probes. • The system enables flexible positioning of the probes within an implanted chamber. • Single-unit activity was simultaneously recorded from a high number of sites. • Single unit activity can be recorded with the implanted probe over several weeks. • Several probes can be consecutively implanted within a single animal. Abstract Background Chronic recordings with multi-electrode arrays are widely used to study neural networks underlying complex primate behaviors. Most of these systems are designed for studying neural activity in the cortical hemispheres resulting in a lack of devices being capable of simultaneously recording from ensembles of neurons in deep brainstem structures. However, to fully understand complex behavior, it is fundamental to also decipher the intrinsic mechanisms of the underlying motor pattern generating circuits in the brainstem. New method We report a light-weight system that simultaneously measures single-unit activity from a large number of recording sites in the brainstem of marmoset monkeys. It includes a base chamber fixed to the animal's skull and a removable upper chamber that can be semi-chronically mounted to the base chamber to flexibly position an embedded micro-drive containing a 32-channel laminar probe to record from various positions within the brainstem for several weeks. Results The current system is capable of simultaneously recording stable single-unit activity from a large number of recording sites in the brainstem of vocalizing marmoset monkeys. Comparison with existing methods To the best of our knowledge, chronic systems to record from deep brainstem structures with multi-site laminar probes in awake, behaving monkeys do not yet exist. Conclusions The semi-chronic implantation of laminar electrodes into the brainstem of behaving marmoset monkeys opens new research possibilities in fully understanding the neural mechanisms underlying complex behaviors in marmoset monkeys. [ABSTRACT FROM AUTHOR]

SMTP-7 (Stachybotrys microspora triprenyl phenol-7) is a small molecule that promotes thrombolysis and suppresses inflammation possibly through plasminogen modulation and soluble epoxide hydrolase (sEH) inhibition, respectively. Here, we demonstrate an efficacy of SMTP-7 in a severe embolic stroke model in monkeys. The middle cerebral artery was embolized by an autologous blood clot. Saline, SMTP-7, or tissue-type plasminogen activator (t-PA) (n = 5 in each group) was given after 3 hours, and neurologic deficit scoring and infarct characterization were performed after 24 hours. Hemorrhagic infarct-accompanied premature death was observed for two animals in t-PA group. SMTP-7 treatment significantly reduced the sizes of infarct by 65%, edema by 37%, and clot by 55% compared to saline treatment. Plasma levels of the products of plasminogen activation (plasmin-α2-antiplasmin complex) and sEH reaction (dihydroxyeicosatrienoic acid) in SMTP-7 group were 794% (P < 0.05) and 60% (P = 0.085) compared to saline group, respectively. No significant changes in the plasma levels of MMP-9, CRP, MCP-1, and S100B were found. There was an inverse correlation between plasmin-α2-antiplasmin complex level and infarct volume (r = 0.93, P < 0.05), suggesting a role of thrombolysis in the SMTP-7 action to limit infarct development. In conclusion, SMTP-7 is effective in treating severe embolic stroke in monkeys under conditions where t-PA treatment tends to cause hemorrhagic infarct-associated premature death. [ABSTRACT FROM AUTHOR]

Abstract Organophosphorus nerve agents still represent a serious risk to human health. In the French armed forces, the current emergency treatment against OP intoxications is a fully licensed wet-dry dual-chambered autoinjector (Ineurope ®), that contains pralidoxime methylsulfate (2-PAM) to reactivate inhibited acetylcholinesterase (AChE), atropine sulfate (AS) and avizafone chlorhydrate (AVZ). While this treatment is effective against several of the known nerve agents, it shows little efficacy against the Russian VX (VR), one of the most toxic compounds. HI-6 dimethanesulfonate (HI-6 DMS) is an oxime able to reactivate in vitro and in vivo VR-inhibited AChE. To confirm the superiority of HI-6 DMS towards 2-PAM prior to licensing, we compared the two 3-drug-combinations (HI-6 vs 2-PAM, 33 and 18 mg/kg respectively, equimolar doses; AS/AVZ 0.25/0.175 mg/kg respectively) in VR-poisoned cynomolgus macaques, the model required by the French drug regulatory agency. In parallel we performed HI-6 pharmacokinetics analysis using a one compartment model. A better efficacy of the HI-6 DMS combination was clearly observed: up to 5 LD 50 of VR (i.m.), a single administration of the HI-6 DMS combination, shortly after the onset of clinical signs, prevented death of the four intoxicated animals. Conversely 2-PAM only prevented death in one out of three subjects exposed to the same amount of VR. As expected with V agents, reinhibition of blood AChE was observed but without any apparent impact on the clinical recovery of the animals. A single administration of the HI-6 DMS combination was still but partially effective at 15 LD 50 of VR, allowing a 50% survival rate. [ABSTRACT FROM AUTHOR]

This study evaluated periodontal tissue response to a new bioresorbable guided tissue regeneration barrier material following guided tissue regeneration treatment of dehiscence-type defects at 45 teeth in 15 monkeys. The results were clinically and histologically evaluated 6 weeks and 3, 6, 12, and 24 months post-treatment. Healing was uneventful and without inflammation or other adverse tissue reactions. Following 6 weeks of healing, the matrix barrier was completely integrated with the surrounding tissues, preventing epithelial downgrowth along the device. There were no inflammatory cell infiltrates adjacent to the material. New attachment (ie. new cementum with inserting collagen fibers) and new supporting bone were found after 6 weeks of healing. The matrix barrier maintained its functional stability for a minimum of 6 weeks. The subsequent slow resorption process of the material occurred without detrimental effects on the surrounding tissues, demonstrating the biocompatibility of the material. The material was completely resorbed after 6 to 12 months. At the final stages of the resorption process, macrophages and multinuclear cells were present within the tissue that replaced the material. The design and the resorption pattern of the matrix barrier are discussed in relation to the regenerative wound healing process. [ABSTRACT FROM AUTHOR]

The potential for guided tissue regeneration was evaluated in one-walled interproximal sites in Macaca fascicularis. Histologic differences were evaluated at 1 and 3 months. Within the experimental (barrier) group, 100% of the root surfaces with potential for regeneration were covered with new cementum, whereas the control specimens had 20% or less new cementum. The amount of regeneration was determined by the position of the barrier membrane; the more coronal the barrier, the greater the regeneration. Observations indicated that the optimal time for barrier removal is between 1 and 3 months. [ABSTRACT FROM AUTHOR]

This article discusses a study which examined the effects of orthodontic movement of teeth into artificially produced infrabony lesions. The study used two female rhesus monkeys with adult dentitions as subjects in this study. Clinical signs of marginal gingivitis were observed in the animals during the first week of the experiment. Orthodontic bands were fitted on the maxillary first molars and canines of the animals after forty-two weeks. Histological analyses showed that there were great numbers of fibroblasts in the periodontal ligament spaces. It also found that the periodontal ligament fibers are under compression and that there is a loss of fiber orientation. Evidence of cementogenesis was also observed on the tension sides of the cemental surface.

This study evaluated the histoIogic responses of two different adhesive systems on the teeth of seven healthy adult monkeys. Class V cavities in 128 teeth were observed at 7, 21 to 27, and 90 to 97 days. Statistical data showed no significant differences in pulp inflammation between the Optibond (Kerr). XR-Bond (Kerr), and IRM (Caulk) groups in pulps at the three time intervals. Some odontoblastic disruption and inflammation was seen in pulps restored with XR-Primer at the three time intervals. Pulp healing was similar in teeth treated with both direct-capped Optibond and calcium hydroxide, and there was no significant increase in pulpal inflammation with time. No abscesses or necrotic pulps were seen in any teeth. Optibond and XR-Bond adhesive systems are biologically acceptable in nonhuman primate pulp tissues. [ABSTRACT FROM AUTHOR]

The purpose of this study was to compare the healing response of submerged implants with that of nonsubmerged implants and to determine the influence of oral hygiene procedures on the initial healing response adjacent to nonsubmerged implants. Radiographs demonstrated direct bone-implant contact of submerged and nonsubmerged implants. No significant differences in bone-implant scores were recorded between the submerged and nonsubmerged implants with oral hygiene. Oral hygiene procedures during healing had a positive influence on the gingival status and marginal bone height adjacent to nonsubmerged implants. [ABSTRACT FROM AUTHOR]

The article offers information on a dental research conducted in order to determine the natural occurrence of gingivitis in squirrel monkeys. Twelve middle-aged adult male squirrel monkeys were obtained for the research. The monkeys had been sedated with an intramuscular (IM) injection. On the 14th day, a new dietary regimen was begun for the animals. One of the groups continued on a diet of monkey chow pellets, whereas the other group received a soft diet in the form of cakes. Initial examination showed that all buccal surfaces anterior to the second premolars exhibited gingivitis. On the other hand, no sign of gingivitis was discovered in buccal surfaces distal to the maxillary second premolar or mandibular first premolar.

The article presents a research which examines the mode of healing after intentional extensive mucoperiosteal incisions, which were made with the help of electrosurgical electrodes on Rhesus monkeys. The researchers, as reported, placed four electrosurgical and four scalpel wounds on contralateral sides of opposite arches in each of two monkeys. The researchers, as reported, found that intentional bony contact with the electrosurgical electrode resulted in severely delayed soft tissue healing, disruption of the periosteum, and necrosis of the underlying bone. The researchers concluded that to treat inadvertent electrode and periosteal tissue contact, and to minimize patient discomfort, belated healing should be avoided.

Brain connectivity in non-human primates (NHPs) has been mainly investigated using tracer techniques and functional connectivity studies. Data on structural connections are scarce and come from diffusion tensor imaging (DTI), since gross anatomical white matter dissection studies in the NHP are lacking. The current study aims to illustrate the course and topography of the major white matter tracts in the macaque using Klingler’s fiber dissection. 10 hemispheres obtained from 5 primate brains (Macaca mulatta) were studied according to Klingler’s fiber dissection technique. Dissection was performed in a stepwise mesial and lateral fashion exposing the course and topography of the major white matter bundles. Major white matter tracts in the NHP include the corona radiata, tracts of the sagittal stratum, the uncinate fasciculus, the cingulum and the fornix. Callosal fiber topography was homologous to the human brain with leg motor fibers running in the posterior half of the corpus callosum. The relative size of the anterior commissure was larger in the NHP. NHPs and humans share striking homologies with regard to the course and topography of the major white matter tracts. [ABSTRACT FROM AUTHOR]

Caudal primary motor cortex (M1, area 4) is sensitive to cutaneous inputs, but the extent to which the physical details of complex stimuli are encoded is not known. We investigated the sensitivity of M1 neurons (4 Macaca mulatta monkeys) to textured stimuli (smooth/rough or rough/rougher) during the performance of a texture discrimination task and, for some cells, during a no-task condition (same surfaces; no response). The recordings were made from the hemisphere contralateral to the stimulated digits; the motor response (sensory decision) was made with the nonstimulated arm. Most M1 cells were modulated during surface scanning in the task (88%), but few of these were texture-related (24%). In contrast, 44% of M1 neurons were texture related in the no-task condition. Recordings from the neighboring primary somatosensory cortex (S1), the potential source of texture-related signals to M1, showed that S1 neurons were significantly more likely to be texture related during the task (57 vs 24%) than M1. No difference was observed in the no-task condition (52 vs. 44%). In these recordings, the details about surface texture were relevant for S1 but not for M1. We suggest that tactile inputs to M1 were selectively suppressed when the animals were engaged in the task. S1 was spared these controls, as the same inputs were task-relevant. Taken together, we suggest that the suppressive effects are most likely exerted directly at the level of M1, possibly through the activation of a top-down gating mechanism specific to motor set/intention. [ABSTRACT FROM AUTHOR]

Infantile strabismus is a common disorder characterized by a chronic misalignment of the eyes, impairment of binocular vision, and oculomotor abnormalities. Nonhuman primates with strabismus, induced in infancy, show a pattern of abnormalities similar to those of strabismic children. This allows strabismic nonhuman primates to serve as an ideal animal model to examine neural mechanisms associated with aberrant oculomotor behavior. Here, we test the hypothesis that impairment of disparity vergence and horizontal saccade disconjugacy in exotropia and esotropia are associated with disrupted tuning of near- and far-response neurons in the supraoculomotor area (SOA). In normal animals, these neurons carry signals related to vergence position and/or velocity. We hypothesized that, in strabismus, these neurons modulate inappropriately in association with saccades between equidistant targets. We recorded from 62 SOA neurons from 4 strabismic animals (2 esotropes and 2 exotropes) during visually guided saccades to a target that stepped to different locations on a tangent screen. Under these same conditions, SOA neurons in normal animals show no detectable modulation. In our strabismic subjects, we found that a subset of SOA neurons carry weak vergence velocity signals during saccades. In addition, a subset of SOA neurons showed clear modulation associated with slow fluctuations of horizontal strabismus angle in the absence of a saccade. We suggest that abnormal SOA activity contributes to fixation instability but plays only a minor role in the horizontal disconjugacy of saccades that do not switch fixation from one eye to the other. [ABSTRACT FROM AUTHOR]

A wide variety of methods, such as enzymatic methods, LC-MS, and LC-MS/MS, are currently available for the concentration determination of plasma glucose in studies of diabetes, obesity, exercise, etc. However, these methods rarely discriminate endogenous and exogenous glucose in plasma. A novel NMR strategy for discriminative quantification of the endogenous and exogenous glucose in plasma has been developed using an adapted isotope dilution 1H-13C heteronuclear single-quantum correlation (ID-HSQC) with uniformly 13C-labeled glucose as a tracer of exogenous glucose. This method takes advantage of the distinct 1H-13C chemical shifts of the hemiacetal group of the α-D-glucopyranose and makes use of the 13C-13C one-bond J-coupling (1JCC) in uniformly 13C-labeled glucose to differentiate the 1H-13C HSQC signal of labeled glucose from that of its natural counterpart when data are acquired in high-resolution mode. The molar ratio between the endogenous and exogenous plasma glucose can then be calculated from the peak intensities of the natural and labeled glucose. The accuracy and precision of the method were evaluated using a series of standard mixtures of natural and uniformly 13C-labeled glucose with varied but known concentrations. Application of this method is demonstrated for the quantification of endogenous and exogenous glucose in plasma derived from healthy and diabetic cynomolgus monkeys. The results nicely agree with our previous LC-MS/MS results. Considering the natural abundance of 13C isotope at the level of 1.1% in endogenous glucose, comparable peak intensities of quantitatively measurable signals derived from natural and labeled glucose imply that the ID-HSQC can tolerate a significantly high ratio of isotope dilution, with labeled/natural glucose at ~ 1%. We expect that the ID-HSQC method can serve as an alternative approach to the biomedical or clinical studies of glucose metabolism. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) transmission through infected blood and blood products has already been described. However, little is known about the bone marrow (BM) as source of HEV infection. Our study aimed to investigate the presence of HEV antigen (Ag) and histological changes in BM of cynomolgus monkeys (Macaca fascicularis) experimentally and naturally infected with HEV. Four cynomolgus monkeys with acute, and two with chronic hepatitis E ─ after immunosuppressive therapy with tacrolimus ─ were compared with one colony-bred animal naturally infected. Both, natural and experimental infections were characterized by anti-HEV IgG seroconversion detected by ELISA, and viral RNA isolation confirmed by RT-qPCR and qualitative nested RT-PCR. BM biopsies were collected from all animals, submitted to histology and indirect immunofluorescence techniques and observed, respectively, by light and confocal microscopy. The HEV Ag-fluorescent-labeled cells were detected from BM biopsies obtained from three monkeys with acute and one with chronic hepatitis E, and also from the naturally infected monkey. In the experimentally infected animals with acute hepatitis, HEV Ag detection occurred at 160 days post-infection, even after viral clearance in serum, feces, and liver. Double-stranded RNA, a replicative marker, was detected in BM cells from both acute and chronically infected animals. Major histological findings included vacuolization in mononuclear and endosteal cells, an absence of organized inflammatory infiltrates, and also some fields suggesting displasic focal BM disease. These findings support the hypothesis of BM cells as secondary target sites of HEV persistence. Further experimental studies should be carried out to confirm the assumption of HEV transmission through BM transplantation. [ABSTRACT FROM AUTHOR]

An effective HIV vaccine has yet to be developed and defining immune correlates of protection against HIV infection is of paramount importance to inform future vaccine design. The complement system is a component of innate immunity that can directly lyse pathogens and shape adaptive immunity. To determine if complement lysis of SIV and/or SIV-infected cells represents a protective immune correlate against SIV infection, sera from previously vaccinated and challenged Rhesus macaques were analyzed for the induction of antibody-dependent complement-mediated lysis (ADCML). Importantly, the vaccine regimen, consisting of a replication-competent adenovirus type 5 host-range mutant SIV recombinant prime followed by a monomeric gp120 or oligomeric gp140 boost, resulted in overall delayed SIV acquisition only in females. Here, sera from all vaccinated animals induced ADCML of SIV and SIV-infected cells efficiently, regardless of sex. A modest correlation of SIV lysis with reduced infection rate in males but not females, together with reduced peak viremia in all animals boosted with gp140 suggested a potential for influencing protective efficacy. Gag-specific IgG, and gp120-specific IgG and IgM, correlated with SIV lysis in females while Env-specific IgM correlated with SIV43 infected cell lysis in males indicating sex differences in vaccine-induced antibody characteristics and function. In fact, gp120-/gp140-specific antibody functional correlates between ADCC, ADCP, and ADCML as well as gp120-specific IgG glycan profiles and corresponding ADCML correlations varied depending on the sex of the vaccinees. Overall, these data suggest that sex influences vaccine-induced antibody function which should be considered in design of globally-effective HIV vaccines in the future. [ABSTRACT FROM AUTHOR]