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does mucosal b1 activation result in the accumulation of peak igm during chronic intrarectal sivmac239 exposure to protect chinese-origin rhesus macaques from disease progression?human immunodeficiency virus (hiv) infection is characterized by a dynamic process and highly variable progression. although extensive comparisons have been reported between the minority of non-progressors (npgs) and the majority of progressors (pgs), the underlying mechanism is still unclear. one reason for this is that the initial onset of infection is very difficult to track, particularly when men who have sex with men (msm) are predominantly responsible for the transmission of human hiv. to ...202032265850
nonhuman primate model of oculocutaneous albinism with tyr and oca2 mutations.human visual acuity is anatomically determined by the retinal fovea. the ontogenetic development of the fovea can be seriously hindered by oculocutaneous albinism (oca), which is characterized by a disorder of melanin synthesis. although people of all ethnic backgrounds can be affected, no efficient treatments for oca have been developed thus far, due partly to the lack of effective animal models. rhesus macaques are genetically homologous to humans and, most importantly, exhibit structures of t ...202032259106
experimental treatment of siv-infected macaques via autograft of ccr5-disrupted hematopoietic stem and progenitor cells.hematopoietic stem cell (hsc)-based gene therapy targeting ccr5 represents a promising way to cure human immunodeficiency virus type 1 (hiv-1) infection. yet the preclinical animal model with transplantation of autologous ccr5-ablated hscs remains to be optimized. in this study, four chinese rhesus macaques of simian immunodeficiency virus (siv) chronic infection were given long-term antiretroviral therapy (art), during which peripheral cd34+ hematopoietic stem and progenitor cells (hspcs) were ...202032258215
urinary supar: a non-invasive biomarker of infection and tissue inflammation for use in studies of large free-ranging mammals.studies of large free-ranging mammals incorporating physiological measurements typically require the collection of urine or faecal samples, due to ethical and practical concerns over trapping or darting animals. however, there is a dearth of validated biomarkers of immune activation and inflammation that can be measured non-invasively. we here evaluate the utility of urinary measurements of the soluble form of the urokinase plasminogen activator receptor (supar), for use as a health marker in st ...202032257339
long-term delivery of an anti-siv monoclonal antibody with aav.long-term delivery of anti-hiv monoclonal antibodies using adeno-associated virus (aav) holds promise for the prevention and treatment of hiv infection. we previously reported that after receiving a single administration of aav vector coding for anti-siv antibody 5l7, monkey 84-05 achieved high levels of aav-delivered 5l7 igg1 in vivo which conferred sterile protection against six successive, escalating dose, intravenous challenges with highly infectious, highly pathogenic sivmac239, including a ...202032256496
nanoparticle-based platform for activatable fluorescence imaging and photothermal ablation of endometriosis.endometriosis is a painful disorder where endometrium-like tissue forms lesions outside of the uterine cavity. intraoperative identification and removal of these lesions are difficult. this study presents a nanoplatform that concurrently delineates and ablates endometriosis tissues using real-time near-infrared (nir) fluorescence and photothermal therapy (ptt). the nanoplatform consists of a dye, silicon naphthalocyanine (sinc), capable of both nir fluorescence imaging and ptt, and a polymeric n ...202032250034
selective attention for affiliative and agonistic interactions of dominants and close affiliates in macaques.monitoring conspecifics is a crucial process in social learning and a building block of social cognition. selective attention to social stimuli results from interactions of subject and stimulus characteristics with dominance rank often emerging as an important predictor. we extend previous research by providing as stimuli naturally occurring affiliative interactions between group members instead of pictorial or auditory representations of conflicts, and by extending to the affiliative relationsh ...202032249792
treatment with mesenchymal-derived extracellular vesicles reduces injury-related pathology in pyramidal neurons of monkey perilesional ventral premotor cortex.functional recovery after cortical injury, such as stroke, is associated with neural circuit reorganization, but the underlying mechanisms and efficacy of therapeutic interventions promoting neural plasticity in primates are not well understood. bone marrow mesenchymal stem cell-derived extracellular vesicles (msc-evs), which mediate cell-to-cell inflammatory and trophic signaling, are thought be viable therapeutic targets. we recently showed, in aged female rhesus monkeys, that systemic adminis ...202032241837
obesogenic diet-associated c-reactive protein predicts reduced central dopamine and corticostriatal functional connectivity in female rhesus monkeys.alterations in dopamine (da) signaling and reductions in functional connectivity (fc; a measure of temporal correlations of activity between different brain regions) within dopaminergic reward pathways are implicated in the etiology of psychopathology and have been associated with increased concentrations of inflammatory markers, including c-reactive protein. peripheral and central inflammatory cytokines that have been shown to disrupt da signaling and corticostriatal fc are associated with c-re ...202032240763
targeting the oxe receptor as a potential novel therapy for asthma.5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ete) is an arachidonic acid metabolite formed by oxidation of the 5-lipoxygenase (5-lo) product 5s-hydroxy-6,8,11,14-eicosatetraenoic acid (5s-hete) by the nadp+-dependent enzyme 5-hydroxyeicosanoid dehydrogenase. it is the only 5-lo product with appreciable chemoattractant activity for human eosinophils. its actions are mediated by the selective oxe receptor, which is highly expressed on eosinophils, basophils, neutrophils and monocytes. orthologs of ...202032240653
rhesus macaque brain developmental trajectory: a longitudinal analysis using tensor-based structural morphometry and diffusion tensor imaging.the typical developmental trajectory of brain structure among nonhuman primates (nhps) remains poorly understood. in this study, we characterized the normative trajectory of developmental change among a cohort of rhesus monkeys (n = 28), ranging in age from 2 to 22 months, using structural mri datasets that were longitudinally acquired every 3-4 months. we hypothesized that nhp-specific transient intracranial volume decreases reported during late infancy would be part of the typical developmenta ...202032239147
a durable protective immune response to wild-type measles virus infection of macaques is due to viral replication and spread in lymphoid tissues.infection with wild-type (wt) measles virus (mev) is an important cause of childhood mortality that leads to lifelong protective immunity in survivors. wt mev and the live-attenuated mev used in the measles vaccine (lamv) are antigenically similar, but the determinants of attenuation are unknown, and protective immunity induced by lamv is less robust than that induced by wt mev. to identify factors that contribute to these differences, we compared virologic and immunologic responses after respir ...202032238577
irak1 is a critical mediator of inflammation-induced preterm birth.preterm birth (ptb) is a major cause of neonatal mortality and morbidity, often triggered by chorioamnionitis or intrauterine inflammation (iui) with or without infection. recently, there has been a strong association of il-1 with ptb. we hypothesized that il-1r-associated kinase 1 (irak1), a key signaling mediator in the tlr/il-1 pathway, plays a critical role in ptb. in human fetal membranes (fm) collected immediately after birth from women delivering preterm, p-irak1 was significantly increas ...202032238461
correction for mavigner et al., "simian immunodeficiency virus persistence in cellular and anatomic reservoirs in antiretroviral therapy-suppressed infant rhesus macaques". 202032234801
primate version of modified rankin scale for classifying dysfunction in rhesus monkeys.background and purpose- nonhuman primates are increasingly used in translational studies of ischemic stroke. however, current scoring systems in monkeys (eg, nonhuman primate stroke scale) do not focus on impairments in activities of daily living, so clinically relevant data are scarce for evaluating functional deficits in this model. methods- here, we referenced the modified rankin scale to provide a primate version of rankin scale (prs) for ranking neurological dysfunction in monkeys following ...202032233743
conditionally reprogrammed macaque endocervical cells retain steroid receptor expression and produce mucus.cervical mucus produced by the endocervix plays an essential role as a hormonally induced regulator of female fertility. cervical mucus fluctuates in both physical characteristics and in sperm penetrability in response to estrogens and progestogens. however, the mechanisms by which steroid hormones change mucus remains poorly understood. current in vitro models have limited capability to study these questions as primary endocervical cells possess limited expansion potential, and immortalized cel ...202032232331
a state-based probabilistic method for decoding hand position during movement from ecog signals in non-human primate.in this study, we proposed a state-based probabilistic method for decoding hand positions during unilateral and bilateral movements using the ecog signals recorded from the brain of rhesus monkey.202032224511
tuberculosis-associated ifn-i induces siglec-1 on tunneling nanotubes and favors hiv-1 spread in macrophages.while tuberculosis (tb) is a risk factor in hiv-1-infected individuals, the mechanisms by which mycobacterium tuberculosis (mtb) worsens hiv-1 pathogenesis remain scarce. we showed that hiv-1 infection is exacerbated in macrophages exposed to tb-associated microenvironments due to tunneling nanotube (tnt) formation. to identify molecular factors associated with tnt function, we performed a transcriptomic analysis in these macrophages, and revealed the up-regulation of siglec-1 receptor. siglec-1 ...202032223897
daily ethanol drinking followed by an abstinence period impairs bone marrow niche and mitochondrial function of hematopoietic stem/progenitor cells in rhesus macaques.unhealthy consumption of alcohol is a major public health crisis with strong associations between immunological dysfunctions, high vulnerability to infectious disease, anemia, and an increase in the risk of hematological malignancies. however, there is a lack of studies addressing alcohol-induced changes in bone marrow (bm) and hematopoiesis as fundamental aspects of immune system function.202032220015
immunohistochemical distribution of 10 gabaa receptor subunits in the forebrain of the rhesus monkey macaca mulatta.gabaa receptors are composed of five subunits arranged around a central chloride channel. their subunits originate from different genes or gene families. the majority of gabaa receptors in the mammalian brain consist of two α-, two β- and one γ- or δ-subunit. this subunit organization crucially determines the physiological and pharmacological properties of the gabaa receptors. using immunohistochemistry, we investigated the distribution of 10 gabaa receptor subunits (α1, α2, α3, α4, α5, β1, β2, ...202032220012
distinguishing between parallel and serial processing in visual attention from neurobiological data.serial and parallel processing in visual search have been long debated in psychology, but the processing mechanism remains an open issue. serial processing allows only one object at a time to be processed, whereas parallel processing assumes that various objects are processed simultaneously. here, we present novel neural models for the two types of processing mechanisms based on analysis of simultaneously recorded spike trains using electrophysiological data from prefrontal cortex of rhesus monk ...202032218974
characterisation of the gut microbial community of rhesus macaques in high-altitude environments.the mammal intestinal microbiota is involved in various physiological processes and plays a key role in host environment adaption. however, for non-human primates (nhps), little is known about their gut microbial community in high-altitude environments and even less about their adaption to such habitats. we characterised the gut microbial community of rhesus macaques from multiple high-altitude environments and compared it to those of low-altitude populations.202032216756
hiv env-specific igg antibodies induced by vaccination of neonatal rhesus macaques persist and can be augmented by a late booster immunization in infancy.the hiv epidemics in infants and adolescent women are linked. young women of childbearing age are at high risk for hiv infection and, due to poor hiv testing rates and low adherence to antiretroviral therapy, are at high risk for mother-to-infant transmission. we hypothesize that hiv vaccine regimens initiated in early life would provide the necessary time frame to induce mature and highly functional env-specific antibody responses that could potentially also protect against hiv acquisition late ...202032213623
a multiplex centrality metric for complex social networks: sex, social status, and family structure predict multiplex centrality in rhesus macaques.members of a society interact using a variety of social behaviors, giving rise to a multi-faceted and complex social life. for the study of animal behavior, quantifying this complexity is critical for understanding the impact of social life on animals' health and fitness. multilayer network approaches, where each interaction type represents a different layer of the social network, have the potential to better capture this complexity than single layer approaches. calculating individuals' centrali ...202032211232
a combination of two human monoclonal antibodies limits fetal damage by zika virus in macaques.human infection by zika virus (zikv) during pregnancy can lead to vertical transmission and fetal aberrations, including microcephaly. prophylactic administration of antibodies can diminish or prevent zikv infection in animal models, but whether passive immunization can protect nonhuman primates and their fetuses during pregnancy has not been determined. z004 and z021 are neutralizing monoclonal antibodies to domain iii of the envelope (ediii) of zikv. together the two antibodies protect nonpreg ...202032209664
route of vaccine administration alters antigen trafficking but not innate or adaptive immunity.although intramuscular (i.m.) administration is the most commonly used route for licensed vaccines, subcutaneous (s.c.) delivery is being explored for several new vaccines under development. here, we use rhesus macaques, physiologically relevant to humans, to identify the anatomical compartments and early immune processes engaged in the response to immunization via the two routes. administration of fluorescently labeled hiv-1 envelope glycoprotein trimers displayed on liposomes enables visualiza ...202032209459
cross-species cortical alignment identifies different types of anatomical reorganization in the primate temporal lobe.evolutionary adaptations of temporo-parietal cortex are considered to be a critical specialization of the human brain. cortical adaptations, however, can affect different aspects of brain architecture, including local expansion of the cortical sheet or changes in connectivity between cortical areas. we distinguish different types of changes in brain architecture using a computational neuroanatomy approach. we investigate the extent to which between-species alignment, based on cortical myelin, ca ...202032202497
evaluation of the immune response of a h7n9 candidate vaccine virus derived from the fifth wave a/guangdong/17sf003/2016.highly pathogenic influenza h7n9 viruses that emerged in the fifth wave of h7n9 outbreak pose a risk to human health. the world health organization has updated the candidate vaccine viruses for h7n9 viruses recently. in this study, we evaluated the immune response to an updated h7n9 candidate vaccine virus, which derived from the highly pathogenic a/guangdong/17sf003/2016 (gd/16) in mice and rhesus macaques. gd/16 vaccination elicited robust neutralizing, virus-specific immunoglobulin g antibodi ...202032201204
generation and functional assessment of nonhuman primate regulatory dendritic cells and their therapeutic efficacy in renal transplantation.nonhuman primates (nhp) are important pre-clinical models for evaluation of the safety and efficacy of the most promising potential therapeutic advances in organ transplantation based on rodent studies. although rare, dendritic cells (dc) play important roles in preservation of self tolerance and dc with immunoregulatory properties (regulatory dc; dcreg) can promote transplant tolerance in rodents when adoptively transferred to allograft recipients. nhp dcreg can be generated ex vivo from bone m ...202032197811
opioid receptors in immune and glial cells-implications for pain control.opioid receptors comprise μ (mop), δ (dop), κ (kop), and nociceptin/orphanin fq (nop) receptors. opioids are agonists of mop, dop, and kop receptors, whereas nociceptin/orphanin fq (n/ofq) is an agonist of nop receptors. activation of all four opioid receptors in neurons can induce analgesia in animal models, but the most clinically relevant are mop receptor agonists (e.g., morphine, fentanyl). opioids can also affect the function of immune cells, and their actions in relation to immunosuppressi ...202032194554
effect of chemogenetic actuator drugs on prefrontal cortex-dependent working memory in nonhuman primates.the most common chemogenetic neuromodulatory system, designer receptors exclusively activated by designer drugs (dreadds), uses a non-endogenous actuator ligand to activate a modified muscarinic acetylcholine receptor that is insensitive to acetylcholine. it is crucial in studies using these systems to test the potential effects of dreadd actuators prior to any dreadd transduction, so that effects of dreadds can be attributed to the chemogenetic system rather than the actuator drug, particularly ...202032193513
rhesus monkey rhadinovirus isolated from hemangioma tissue.we isolated a rhesus monkey rhadinovirus, isolate rrvmmu 209-07, from hemangioma tissue. the virion dna was sequenced by illumina-based sequencing. isolate rrvmmu 209-07 is highly similar overall to rrv 26-95, but considerable differences exist in the 3' region of the genome.202032193241
the effects of intramuscular naloxone dose on mu receptor displacement of carfentanil in rhesus monkeys.naloxone (nlx) is a mu receptor antagonist used to treat acute opioid overdoses. currently approved doses of naloxone to treat opioid overdoses are 4 mg intranasal (in) and 2 mg intramuscular (im). however, higher mu receptor occupancy (ro) may be required to treat overdoses due to more potent synthetic opioids such as fentanyl and carfentanil that have entered the illicit drug market recently. to address this need, a higher dose of nlx has been investigated in a 5 mg im formulation called zimhi ...202032192089
a new look at neurobehavioral development in rhesus monkey neonates (macaca mulatta).the brazelton neonatal behavioral assessment scale (nbas) evaluates a newborn infant's autonomic, motor, state, temperament, and social-attentional systems, which can help to identify infants at risk of developmental problems. given the prevalence of rhesus monkeys being used as an animal model for human development, here we aimed to validate a standardized test battery modeled after the nbas for use with nonhuman primates called the infant behavioral assessment scale (ibas), employing explorato ...202032187719
reproductive outcomes in rhesus macaques (macaca mulatta) with naturally-acquired trypanosoma cruzi infection.chagas disease is a zoonotic vector-borne disease caused by infection with the protozoan parasite trypanosoma cruzi. t. cruzi is found in latin america and the southern united states, where it infects many species, including humans and nonhuman primates (nhps). nhps are susceptible to natural infection and can develop clinical symptoms consistent with human disease, including chagasic cardiomyopathy, gastrointestinal disease and transplacental transmission, leading to congenital infection. due t ...202032183928
itr-seq, a next-generation sequencing assay, identifies genome-wide dna editing sites in vivo following adeno-associated viral vector-mediated genome editing.identifying nuclease-induced double-stranded breaks in dna on a genome-wide scale is critical for assessing the safety and efficacy of genome editing therapies. we previously demonstrated that after administering adeno-associated viral (aav) vector-mediated genome-editing strategies in vivo, vector sequences integrated into the host organism's genomic dna at double-stranded breaks. thus, identifying the genomic location of inserted aav sequences would enable us to identify dsb events, mainly der ...202032183699
is human-rhesus macaque (macaca mulatta) conflict in india a case of human-human conflict?the perceptions of wildlife managers regarding human-wildlife conflict (hwc) scenarios are likely to affect the outcomes of conflict mitigation measures. we studied the attitudes and perceptions of forest department personnel regarding the management of human-rhesus macaque conflict (hrmc) in himachal pradesh, northern india. we collected data through a questionnaire survey and used frameworks from organizational psychology to draw insights from our results. forest department personnel belonging ...202032180172
comparative ecological and behavioral study of macaca assamensis and m. mulatta in shivapuri nagarjun national park, nepal.resource partitioning reduces the competition between different species within the same habitat, promoting their coexistence. to understand how such species co-adapt to reduce conflicts, we examined the behavior of two primates, assamese macaque (macaca assamensis) and rhesus macaque (macaca mulatta), from april 2017 to march 2018 in sivapuri nagarjun national park (snnp), kathmandu valley, nepal. we performed 1580 and 1261 scan sessions on wild multi-male/multi-female groups of assamese and rhe ...202032180044
clinical and pathologic features of spontaneous klebsiella pneumoniae infection in 9 rhesus macaques (macaca mulatta).klebsiella pneumoniae is a gram-negative bacterium found in the environment and as a commensal in humans and animals. in humans, k. pneumoniae is one of the most serious nosocomial infections encountered currently and is characterized by liver abscesses, pneumonia, and bacteremia resulting in meningoencephalitis and endophthalmitis. k. pneumoniae in veterinary medicine is rarely reported in nhp, and recent literature describing this disease is sparse. in our colony of predominantly outdoor-house ...202032178759
emotional responses in monkeys differ depending on the stimulus type, sex, and neonatal amygdala lesion status.the amygdala plays an essential role in evaluating social information, threat detection, and learning fear associations. yet, most of that knowledge comes from studies in adult humans and animals with a fully developed amygdala. given the considerable protracted postnatal development of the amygdala, it is important to understand how early damage to this structure may impact the long-term development of behavior. the current study examined behavioral responses toward social, innate, or learned a ...202032175761
engagement of monocytes, nk cells, and cd4+ th1 cells by alvac-siv vaccination results in a decreased risk of sivmac251 vaginal acquisition.the recombinant canarypox alvac-hiv/gp120/alum vaccine regimen was the first to significantly decrease the risk of hiv acquisition in humans, with equal effectiveness in both males and females. similarly, an equivalent siv-based alvac vaccine regimen decreased the risk of virus acquisition in indian rhesus macaques of both sexes following intrarectal exposure to low doses of sivmac251. here, we demonstrate that the alvac-siv/gp120/alum vaccine is also efficacious in female chinese rhesus macaque ...202032163525
the human il-15 superagonist n-803 promotes migration of virus-specific cd8+ t and nk cells to b cell follicles but does not reverse latency in art-suppressed, shiv-infected macaques.despite the success of antiretroviral therapy (art) to halt viral replication and slow disease progression, this treatment is not curative and there remains an urgent need to develop approaches to clear the latent hiv reservoir. the human il-15 superagonist n-803 (formerly alt-803) is a promising anti-cancer biologic with potent immunostimulatory properties that has been extended into the field of hiv as a potential "shock and kill" therapeutic for hiv cure. however, the ability of n-803 to reac ...202032163523
intergenerational effects of mother's early rearing experience on offspring treatment and socioemotional development.this longitudinal study spans two generations of rhesus monkeys. first, the study investigates the effects of early rearing experiences on the maternal behavior of first-generation mothers (rates of premature infant rejection) and, second, the study investigates the effects of maternal rejection on the behavior of second-generation infants. rhesus macaque mother-infant dyads (macaca mulatta-n = 176) were observed twice weekly, with each session lasting 300 s. first-generation mothers were raised ...202032162325
mhc-e-restricted cd8+ t cells target hepatitis b virus-infected human hepatocytes.currently 247 million people are living with chronic hepatitis b virus infection (chb), and the development of novel curative treatments is urgently needed. immunotherapy is an attractive approach to treat chb, yet therapeutic approaches to augment the endogenous hepatitis b virus (hbv)-specific t cell response in chb patients have demonstrated little success. in this study, we show that strain 68-1 rhesus macaque (rm) cmv vaccine vectors expressing hbv ags engender hbv-specific cd8+ t cells unc ...202032161099
safety and immunogenicity of an experimental live combination vaccine against enterovirus 71 and coxsackievirus a16 in rhesus monkeys.enterovirus 71 (ev-a71) and coxsackievirus a16 (cv-a16) are the two most common pathogens causing hand, foot, and mouth disease (hfmd). previously, we obtained one candidate live attenuated strain each for ev-a71 and cv-a16; here, we evaluated the safety and immunogenicity of a combinedlive vaccine against ev-a71 and cv-a16 generated from these two candidate strains. rhesus monkeys were intramuscularly treated with a live combinationvaccine against both ev-a71 and cv-a16 or with either vaccine a ...202032159429
behavioural variability contributes to over-staying in patchy foraging.foragers often systematically deviate from rate-maximizing choices in two ways: accuracy and precision. that is, they use suboptimal threshold values and also show variability in their application of those thresholds. we hypothesized that these biases are related and, more specifically, that foragers' widely known accuracy bias--over-staying--could be explained, at least in part, by their imprecision. to test this hypothesis, we analysed choices made by three rhesus macaques in a computerized pa ...202032156171
monitoring compound-related effects on coagulability in rats and cynomolgus and rhesus monkeys by thrombin generation kinetic measurement.thrombin generation assay (tga) is a sensitive method for the assessment of the global clotting potential of plasma. this kinetic assay can detect both hypocoagulable and hypercoagulable conditions: delayed or reduced thrombin generation leading to a prolonged clotting time, or induced thrombin activity, shifting the coagulation cascade toward thrombosis. the purpose of this study is to qualify the tga in nonhuman primates (nhp) and rats for its use during nonclinical in vivo and in vitro studie ...202032153221
inference of nonlinear receptive field subunits with spike-triggered clustering.responses of sensory neurons are often modeled using a weighted combination of rectified linear subunits. since these subunits often cannot be measured directly, a flexible method is needed to infer their properties from the responses of downstream neurons. we present a method for maximum likelihood estimation of subunits by soft-clustering spike-triggered stimuli, and demonstrate its effectiveness in visual neurons. for parasol retinal ganglion cells in macaque retina, estimated subunits partit ...202032149600
native chemical ligation via n-acylurea thioester surrogates obtained by fmoc solid-phase peptide synthesis.native chemical ligation (ncl) enables the direct chemical synthesis and semisynthesis of proteins of different sizes and compositions, streamlining the access to proteins containing posttranslational modifications (ptms). ncl assembles peptide fragments through the chemoselective reaction of a c-terminal α-thioester peptide, prepared either by chemical synthesis or via intein-splicing technology, and a recombinant or synthetic peptide containing an n-terminal cys. whereas the generation of c-te ...202032144666
the lateral prefrontal cortex of primates encodes stimulus colors and their behavioral relevance during a match-to-sample task.the lateral prefrontal cortex of primates (lpfc) plays a central role in complex cognitive behavior, in decision-making as well as in guiding top-down attention. however, how and where in lpfc such behaviorally relevant signals are computed is poorly understood. we analyzed neural recordings from chronic microelectrode arrays implanted in lpfc region 8av/45 of two rhesus macaques. the animals performed a feature match-to-sample task requiring them to match both motion and color information in a ...202032144331
specific substitutions in region v2 of gp120 env confer shiv neutralisation resistance.a tier 2 shiv-mk38 strain was obtained after two in vivo passages of tier 1 shiv-mk1. shiv-mk38#818, cloned from the mk38 strain, was neutralisation-resistant, like the parental mk38 strain, to shiv-infected monkey plasma (mp), hiv-1-infected human pooled plasma (hpp), and kd247 monoclonal antibody (mab) (anti-v3 gp120 env). we investigated the mechanisms underlying the resistance of #818, specifically the amino acid substitutions that confer resistance to mk1. we introduced amino acid substitut ...202032138199
animal models of congenital cytomegalovirus transmission: implications for vaccine development.although cytomegaloviruses (cmvs) are species-specific, the study of nonhuman cmvs in animal models can help to inform and direct research aimed at developing a human cmv (hcmv) vaccine. because the driving force behind the development of hcmv vaccines is to prevent congenital infection, the animal model in question must be one in which vertical transmission of virus occurs to the fetus. fortunately, two such animal models-the rhesus macaque cmv and guinea pig cmv-are characterized by congenital ...202032134481
postnatal development of the entorhinal cortex: a stereological study in macaque monkeys.the entorhinal cortex is the main gateway for interactions between the neocortex and the hippocampus. distinct regions, layers, and cells of the hippocampal formation exhibit different profiles of structural and molecular maturation during postnatal development. here, we provide estimates of neuron number, neuronal soma size, and volume of the different layers and subdivisions of the monkey entorhinal cortex (eo, er, elr, ei, elc, ec, ecl) during postnatal development. we found different develop ...202032134112
differential outcomes following optimization of simian-human immunodeficiency viruses from clades ae, b, and c.simian-human immunodeficiency virus (shiv) infection of rhesus monkeys is an important preclinical model for human immunodeficiency virus type 1 (hiv-1) vaccines, therapeutics, and cure strategies. shivs have been optimized by incorporating hiv-1 env residue 375 mutations that mimic the bulky or hydrophobic residues typically found in simian immunodeficiency virus (siv) env to improve rhesus cd4 binding. we applied this strategy to three shiv challenge stocks (shiv-sf162p3, shiv-ae16, and shiv-3 ...202032132241
establishment and evaluation of a monkey acute cerebral ischemia model.cerebral ischemia seriously threatens human health and is characterized by high rates of incidence, disability and death. developing an ideal animal model of cerebral ischemia that reflects the human clinical features is critical for pathological studies and clinical research. the goal of this study is to establish a local cerebral ischemia model in rhesus macaque, thereby providing an optimal animal model to study cerebral ischemia.202032130353
immunotherapy with dna vaccine and live attenuated rubella/siv gag vectors plus early art can prevent sivmac251 viral rebound in acutely infected rhesus macaques.anti-retroviral therapy (art) has been highly successful in controlling hiv replication, reducing viral burden, and preventing both progression to aids and viral transmission. yet, art alone cannot cure the infection. even after years of successful therapy, art withdrawal leads inevitably to viral rebound within a few weeks or months. our hypothesis: effective therapy must control both the replicating virus pool and the reactivatable latent viral reservoir. to do this, we have combined art and i ...202032130229
passive immunization with an extended half-life monoclonal antibody protects rhesus macaques against aerosolized ricin toxin.inhalation of ricin toxin (rt), a category b biothreat agent, provokes an acute respiratory distress syndrome marked by pro-inflammatory cytokine and chemokine production, neutrophilic exudate, and pulmonary edema. the severity of rt exposure is attributed to the tropism of the toxin's b subunit (rtb) for alveolar macrophages and airway epithelial cells, coupled with the extraordinarily potent ribosome-inactivating properties of the toxin's enzymatic subunit (rta). while there are currently no v ...202032128254
interspecies comparison of simultaneous thrombin and plasmin generation.animal models of hemostasis are often extrapolated to humans; however, only a few studies have compared coagulation and fibrinolysis across species. simultaneous thrombin (tg) and plasmin (pg) generation is useful to assessing coagulation and fibrinolysis within the same sample. in this study, we performed simultaneous tg and pg analysis in blood plasma samples from humans and 6 species commonly evaluated in pre-clinical research. tg and pg were investigated in male and female donor platelet-poo ...202032127577
selective intra-arterial brain cooling improves long-term outcomes in a non-human primate model of embolic stroke: efficacy depending on reperfusion status.nearly all stroke neuroprotection modalities, including selective intra-arterial cooling (si-ac), have failed to be translated from bench to bed side. potentially overlooked reasons may be biological gaps, inadequate attention to reperfusion states and mismatched attention to neurological benefits. to advance stroke translation, we describe a novel thrombus-based stroke model in adult rhesus macaques. intra-arterial thrombolysis with tissue plasminogen activator leads to three clinically relevan ...202032126876
characterization of two neutralizing antibodies against rift valley fever virus gn protein.the rift valley fever virus (rvfv) is an arthropod-borne virus that can not only cause severe disease in domestic animals but also in humans. however, the licensed vaccines or available therapeutics for humans do not exist. here, we report two gn-specific neutralizing antibodies (nabs), isolated from a rhesus monkey immunized with recombinant human adenoviruses type 4 expressing rift valley fever virus gn and gc protein (rhadv4-gngcopt). the two nabs were both able to protect host cells from rvf ...202032120864
potential effects of antibiotic-induced gut microbiome alteration on blood-brain barrier permeability compromise in rhesus monkeys.the blood-brain barrier (bbb) contributes to the maintenance of brain homeostasis. gut microbiome composition affects bbb development and expression of tight junction proteins in rodents. however, we still do not know if there is any direct effect of gut microbial composition on bbb permeability and function in normal adult animals. in the current study, we determined temporal and spatial changes in bbb permeability of rhesus monkeys receiving amoxicillin-clavulanic acid (ac) by monitoring the c ...202032112442
anti-pd-1 treatment disrupts the painkilling effects of morphine.pd-1 depletion or nivolumab treatment dampened morphine antinociception in mice and rhesus macaques.202032111598
mapping the epitopes of schistosoma japonicum esophageal gland proteins for incorporation into vaccine constructs.the development of a schistosome vaccine has proved challenging but we have suggested that characterisation of the self-cure mechanism in rhesus macaques might provide a route to an effective product. the schistosome esophagus is a complex structure where blood processing is initiated by secretions from anterior and posterior glands, achieved by a mixture of ~40 unique proteins. the mechanism of self-cure in macaques involves cessation of feeding, after which worms slowly starve to death. antibo ...202032107503
chloroquine and rapamycin augment interleukin-37 expression via the lc3, erk, and ap-1 axis in the presence of lipopolysaccharides.il-37 is a cytokine that plays critical protective roles in many metabolic inflammatory diseases, and its therapeutic potential has been confirmed by exogenous il-37 administration. however, its regulatory mechanisms remain unclear. u937 cells were treated with autophagy-modifying reagents (3-ma, chloroquine, and rapamycin) with or without lps stimulation. thereafter, il-37 expression and autophagic markers (beclin1, p62/sqstm1, and lc3) were determined. for regulatory signal pathways, phosphory ...202032104716
complete protection in macaques conferred by purified inactivated zika vaccine: defining a correlate of protection.a critical global health need exists for a zika vaccine capable of mitigating the effects of future zika epidemics. in this study we evaluated the antibody responses and efficacy of an aluminum hydroxide adjuvanted purified inactivated zika vaccine (pizv) against challenge with zika virus (zikv) strain prvabc59. indian rhesus macaques received two doses of pizv at varying concentrations ranging from 0.016 µg - 10 µg and were subsequently challenged with zikv six weeks or one year following the s ...202032103097
effects of opioid/cannabinoid mixtures on impulsivity and memory in rhesus monkeys.the opioid epidemic underscores the need for safer and more effective treatments for pain. combining opioid receptor agonists with drugs that relieve pain through nonopioid mechanisms could be a useful strategy for reducing the dose of opioid needed to treat pain, thereby reducing risks associated with opioids alone. opioid/cannabinoid mixtures might be useful in this context; individually, opioids and cannabinoids have modest effects on cognition, and it is important to determine whether those ...202032101988
a neural network for online spike classification that improves decoding accuracy.separating neural signals from noise can improve brain-computer interface performance and stability. however, most algorithms for separating neural action potentials from noise are not suitable for use in real time and have shown mixed effects on decoding performance. with the goal of removing noise that impedes online decoding, we sought to automate the intuition of human spike-sorters to operate in real time with an easily tunable parameter governing the stringency with which spike waveforms a ...202032101491
discovery of [11c]mk-6884: a positron emission tomography (pet) imaging agent for the study of m4muscarinic receptor positive allosteric modulators (pams) in neurodegenerative diseases.the measurement of receptor occupancy (ro) using positron emission tomography (pet) has been instrumental in guiding discovery and development of cns directed therapeutics. we and others have investigated muscarinic acetylcholine receptor 4 (m4) positive allosteric modulators (pams) for the treatment of symptoms associated with neuropsychiatric disorders. in this article, we describe the synthesis, in vitro, and in vivo characterization of a series of central pyridine-related m4 pams that can be ...202032101422
mineralized trichobezoars in a rhesus macaque (macaca mulatta).a five-year-old female rhesus macaque (macaca mulatta) presented with a thin body condition and multiple palpable mid-abdominal masses. mineralized cecal trichobezoars were removed surgically. thirteen months later, similar masses recurred and were confirmed with radiographs. this is the first case report of a mineralized cecal trichobezoar in a rhesus macaque.202032100304
neural correlates of strategy switching in the macaque orbital prefrontal cortex.we can adapt flexibly to environment changes and search for the most appropriate rule to a context. the orbital prefrontal cortex (pfo) has been associated with decision making, rule generation and maintenance, and more generally has been considered important for behavioral flexibility. to better understand the neural mechanisms underlying the flexible behavior, we studied the ability to generate a switching signal in monkey pfo when a strategy is changed. in the strategy task, we used a visual ...202032098903
identification of hiv-1 envelope mutations that enhance entry using macaque cd4 and ccr5.although rhesus macaques are an important animal model for hiv-1 vaccine development research, most transmitted hiv-1 strains replicate poorly in macaque cells. a major genetic determinant of this species-specific restriction is a non-synonymous mutation in macaque cd4 that results in reduced hiv-1 envelope (env)-mediated viral entry compared to human cd4. recent research efforts employing either laboratory evolution or structure-guided design strategies have uncovered several mutations in env's ...202032098152
spontaneous krt5 gene mutation in rhesus macaques (macaca mulatta): a novel nonhuman primate model of epidermolysis bullosa simplex.epidermolysis bullosa simplex (ebs) is an inherited skin disorder characterized by increased skin and mucous membrane fragility. most cases are caused by mutations in keratin 5 (krt5) and keratin 14 (krt14). mutations of these genes result in cytoskeletal disruption of the basal keratinocytes. gross and histopathologic findings of 2 clinically affected homozygous rhesus macaques with an insertion variant mutation in krt5 are described and compared with 6 deceased phenotypically normal animals th ...202032096448
myocardial changes in diabetic and nondiabetic nonhuman primates.diabetic human patients have increased risk of heart failure compared to healthy subjects. the underlying mechanisms for this are not fully understood, and to help develop improved treatment strategies, well-characterized animal models are essential. to investigate cardiac dysfunction in diabetes, this study evaluated myocardial changes in 10 aging rhesus monkeys with and without diabetes. based on evaluation of plasma glycosylated hemoglobin and glucose, 7 of 10 rhesus macaques had diabetes for ...202032096447
correction: antibiotic-induced microbiome perturbations are associated with significant alterations to colonic mucosal immunity in rhesus macaques.an amendment to this paper has been published and can be accessed via a link at the top of the paper.202032094503
variations in the expression of terminal oligosaccharide units and glycosylation of poly(n-acetyllactosamine) chain in the helicobacter pylori lipopolysaccharide upon colonization of rhesus macaques.helicobacter pylori is an important human pathogen that causes gastritis, gastric and duodenal ulcers, and gastric cancer. o-polysaccharides of h. pylori lipopolysaccharide (lps) are composed of (β1→3)-poly(n-acetyllactosamine) (polylacnac) decorated with multiple α-l-fucose residues. in many strains, their terminal lacnac units are mono- or di-fucosylated to mimic lewis x (lex) and/or lewis y (ley) oligosaccharides. the studies in rhesus macaques as a model of human infection by h. pylori showe ...202032093599
selectivity to approaching motion in retinal inputs to the dorsal visual pathway.to efficiently navigate through the environment and avoid potential threats, an animal must quickly detect the motion of approaching objects. current models of primate vision place the origins of this complex computation in the visual cortex. here, we report that detection of approaching motion begins in the retina. several ganglion cell types, the retinal output neurons, show selectivity to approaching motion. synaptic current recordings from these cells further reveal that this preference for ...202032091390
oxldl enhances choroidal neovascularization lesion through inducing vascular endothelium to mesenchymal transition process and angiogenic factor expression.oxidized lowdensity lipoprotein (oxldl) can impact the formation of choroidal neovascularization (cnv) via regulating endothelial cell proliferation and secretion of inflammatory and angiogenic factors, but the specific molecular mechanism is not clear. in this study, we evaluated the role of molecular pathways that affect angiogenesis at different stages. in vivo, we found that intravitreal injection of oxldl following the laser photocoagulation significantly enhanced the cnv size. in vitro exp ...202032087305
extraretinal spike normalization in retinal ganglion cell axons.spike conduction velocity characteristically differs between myelinated and unmyelinated axons. here we test whether spikes of myelinated and unmyelinated paths differ in other respects by measuring rat retinal ganglion cell (rgc) spike duration in the intraretinal, unmyelinated nerve fiber layer and the extraretinal, myelinated optic nerve and optic chiasm. we find that rapid spike firing and illumination broaden spikes in intraretinal axons but not in extraretinal axons. rgc axons thus initiat ...202032086286
short-term caloric restriction attenuates obesity-induced pro-inflammatory response in male rhesus macaques.white adipose tissue (wat) hypertrophy is an essential hallmark of obesity and is associated with the activation of resident immune cells. while the benefits of caloric restriction (cr) on health span are generally accepted, its effects on wat physiology are not well understood. we previously demonstrated that short-term cr reverses obesity in male rhesus macaques exposed to a high-fat western-style diet (wsd). here, we analyzed subcutaneous wat biopsies collected from this cohort of animals bef ...202032085416
long-term evolution and remodeling of soft drusen in rhesus macaques.to characterize the evolution and structure of soft drusen in aged rhesus macaques using in vivo multimodal retinal imaging and ex vivo histologic and ultrastructural analyses as a nonhuman primate model of early age-related macular degeneration (amd).202032084273
induction of transient virus replication facilitates antigen-independent isolation of siv-specific monoclonal antibodies.structural characterization of the hiv-1 envelope (env) glycoprotein has facilitated the development of env probes to isolate hiv-specific monoclonal antibodies (mabs). however, preclinical studies have largely evaluated these virus-specific mabs against chimeric viruses, which do not naturally infect non-human primates, in contrast to the unconstrained simian immunodeficiency virus (siv)mac239 clone. given the paucity of native-like reagents for the isolation of siv-specific b cells, we examine ...202032083148
mechanisms that allow cortical preparatory activity without inappropriate movement.we reveal a novel mechanism that explains how preparatory activity can evolve in motor-related cortical areas without prematurely inducing movement. the smooth eye movement region of the frontal eye fields (fefsem) is a critical node in the neural circuit controlling smooth pursuit eye movement. preparatory activity evolves in the monkey fefsem during fixation in parallel with an objective measure of visual-motor gain. we propose that the use of fefsem output as a gain signal rather than a movem ...202032081130
immune correlates of postexposure vaccine protection against marburg virus.postexposure immunization can prevent disease and reduce transmission following pathogen exposure. the rapid immunostimulatory properties of recombinant vesicular stomatitis virus (rvsv)-based vaccines make them suitable postexposure treatments against the filoviruses ebola virus and marburg virus (marv); however, the mechanisms that drive this protection are undefined. previously, we reported 60-75% survival of rhesus macaques treated with rvsv vectors expressing marv glycoprotein (gp) 20-30 mi ...202032080323
comparison of shortened mosaic hiv-1 vaccine schedules: a randomised, double-blind, placebo-controlled phase 1 trial (ipcavd010/hpx1002) and a preclinical study in rhesus monkeys (nhp 17-22).current efficacy studies of a mosaic hiv-1 prophylactic vaccine require four vaccination visits over one year, which is a complex regimen that could prove challenging for vaccine delivery at the community level, both for recipients and clinics. in this study, we evaluated the safety, tolerability, and immunogenicity of shorter, simpler regimens of trivalent ad26.mos.hiv expressing mosaic hiv-1 env/gag/pol antigens combined with aluminium phosphate-adjuvanted clade c gp140 protein.202032078815
nf-κb duplications in the promoter-variant hiv-1c ltr impact inflammation without altering viral replication in the context of simian human immunodeficiency viruses and opioid-exposure.recent spread of the promoter variant (4-κb) human immunodeficiency virus-1 clade c (hiv-1c) strain is attributed to duplication of the nuclear factor kappa b (nf-κb) binding sites and potential increased heroin consumption in india. to study the underlying biology of 4-κb hiv-1c in rhesus macaques, we engineered a promoter-chimera variant (4nf-κb) simian human immunodeficiency virus (shiv) by substituting the hiv-1c long terminal repeat (ltr) region consisting of 4 nf-κb and 3 sp-1 sites with t ...202032076422
immune checkpoint modulation enhances hiv-1 antibody induction.eliciting protective titers of hiv-1 broadly neutralizing antibodies (bnabs) is a goal of hiv-1 vaccine development, but current vaccine strategies have yet to induce bnabs in humans. many bnabs isolated from hiv-1-infected individuals are encoded by immunoglobulin gene rearrangments with infrequent naive b cell precursors and with unusual genetic features that may be subject to host regulatory control. here, we administer antibodies targeting immune cell regulatory receptors ctla-4, pd-1 or ox4 ...202032075963
a bivalent, spherical virus-like particle vaccine enhances breadth of immune responses against pathogenic ebola viruses in rhesus macaques.the 2013-2016 ebola outbreak in west africa led to accelerated efforts to develop vaccines against these highly virulent viruses. a live, recombinant vesicular stomatitis virus-based vaccine has been deployed in outbreak settings and appears highly effective. vaccines based on replication-deficient adenovirus vectors either alone or in combination with a multivalent modified vaccinia ankara (mva) ebola vaccine also appear promising and are progressing in clinical evaluation. however, the ability ...202032075939
nef-mediated cd3-tcr downmodulation dampens acute inflammation and promotes siv immune evasion.the inability of nef to downmodulate the cd3-t cell receptor (tcr) complex distinguishes hiv-1 from other primate lentiviruses and may contribute to its high virulence. however, the role of this nef function in virus-mediated immune activation and pathogenicity remains speculative. here, we selectively disrupted this nef activity in sivmac239 and analyzed the consequences for the virological, immunological, and clinical outcome of infection in rhesus macaques. the inability to downmodulate cd3-t ...202032075764
oral microbiome and gingival transcriptome profiles of ligature-induced periodontitis.this investigation evaluated the relationship of the oral microbiome and gingival transcriptome in health and periodontitis in nonhuman primates (macaca mulatta). subgingival plaque samples and gingival biopsies were collected from healthy sites and at sites undergoing ligature-induced periodontitis. microbial samples were analyzed with 16s amplicon sequencing to identify bacterial profiles in young (3 to 7 y) and adult (12 to 23 y) animals. the gingival transcriptome was determined with a micro ...202032075482
spatial neuronal integration supports a global representation of visual numerosity in primate association cortices.our sense of number rests on the activity of neurons that are tuned to the number of items and show great invariance across display formats and modalities. whether numerosity coding becomes abstracted from local spatial representations characteristic of visual input is not known. we mapped the visual receptive fields (rfs) of numerosity-selective neurons in the pfc and ventral intraparietal area in rhesus monkeys. we found numerosity selectivity in pfc and ventral intraparietal neurons irrespect ...202032073351
rearing condition may alter neonatal development of captive bolivian squirrel monkeys (saimiri boliviensis boliviensis).nursery rearing has well-known consequences for primate species. relative to some other primate species, research has indicated a reduced impact of nursery rearing on squirrel monkeys, particularly in terms of rates, severity, and persistence of abnormal behavior. we administered the primate neonatal neurobehavioral assessment to 29 dam-reared and 13 nursery-reared squirrel monkeys (saimiri boliviensis boliviensis) at 2 and 6 weeks of age. mixed-model anovas comparing composite scores and indivi ...202032072635
methylphenidate affects task-switching and neural signaling in non-human primates.low doses of psychostimulants such as methylphenidate (mph), which increase extracellular dopamine and norepinephrine by inhibiting their reuptake, are the most commonly used treatment for attention deficit hyperactivity disorder (adhd). therapeutic doses of these drugs may improve focused attention at the expense of hindering other cognitive functions, including the ability to adapt behavior in response to changing circumstances-cognitive flexibility. cognitive flexibility is thought to depend ...202032067136
the role of the posterior parietal cortex in saccadic error processing.ocular saccades rapidly displace the fovea from one point of interest to another, thus minimizing the loss of visual information and ensuring the seamless continuity of visual perception. however, because of intrinsic variability in sensory-motor processing, saccades often miss their intended target, necessitating a secondary corrective saccade. behavioral evidence suggests that the oculomotor system estimates saccadic error by relying on two sources of information: the retinal feedback obtained ...202032065255
spontaneous color preferences in rhesus monkeys: what is the advantage of primate trichromacy?color perception and color signaling play an important role in various aspects of animal behavior. however, in mammals, trichromatic vision characterized by three retinal photopigments tuned to peak short, middle and long wavelengths is limited only to some primate species. in old and new world primates a second photopigment has appeared repeatedly during phylogeny, allowing red colors to be distinguished from yellows and greens. several hypotheses aspire to explain the adaptive benefits of tric ...202032061913
high-throughput identification of mhc class i binding peptides using an ultradense peptide array.rational vaccine development and evaluation requires identifying and measuring the magnitude of epitope-specific cd8 t cell responses. however, conventional cd8 t cell epitope discovery methods are labor intensive and do not scale well. in this study, we accelerate this process by using an ultradense peptide array as a high-throughput tool for screening peptides to identify putative novel epitopes. in a single experiment, we directly assess the binding of four common indian rhesus macaque mhc cl ...202032060132
suprachoroidal and subretinal injections of aav using transscleral microneedles for retinal gene delivery in nonhuman primates.retinal gene therapy using adeno-associated viruses (aavs) is constrained by the mode of viral vector delivery. intravitreal aav injections are impeded by the internal limiting membrane barrier, while subretinal injections require invasive surgery and produce a limited region of therapeutic effect. in this study, we introduce a novel mode of ocular gene delivery in rhesus macaques using transscleral microneedles to inject aav8 into the subretinal or suprachoroidal space, a potential space betwee ...202032055646
prophylactic and therapeutic remdesivir (gs-5734) treatment in the rhesus macaque model of mers-cov infection.the continued emergence of middle east respiratory syndrome (mers) cases with a high case fatality rate stresses the need for the availability of effective antiviral treatments. remdesivir (gs-5734) effectively inhibited mers coronavirus (mers-cov) replication in vitro, and showed efficacy against severe acute respiratory syndrome (sars)-cov in a mouse model. here, we tested the efficacy of prophylactic and therapeutic remdesivir treatment in a nonhuman primate model of mers-cov infection, the r ...202032054787
age-related differences in the gut microbiome of rhesus macaques.aging is a multifactorial process characterized by progressive changes in gut physiology and the intestinal mucosal immune system. these changes, along with alterations in lifestyle, diet, nutrition, inflammation and immune function alter both composition and stability of the gut microbiota. given the impact of environmental influences on the gut microbiota, animal models are particularly useful in this field. to understand the relationship between the gut microbiota and aging in nonhuman primat ...202032052009
presence of inflammatory group i and iii innate lymphoid cells in the colon of simian immunodeficiency virus-infected rhesus macaques.chronic, low-grade, systemic, and mucosal inflammation correlates with increased morbidity and poor clinical outcomes among patients living with human immunodeficiency virus (hiv). these long-term complications are linked to the disruption of gastrointestinal (gi) tract epithelial barrier integrity and subsequent microbial translocation. however, the mechanisms responsible for these downstream effects of infection are unknown. here, we demonstrate that during the disruption of the gi tract and i ...202032051277
effects of corneal crosslinking on corneal shape stabilization after orthokeratology.orthokeratology (ortho-k) works to reshape cornea and is the only non-surgical way to enable vision without corrective aids. however, its effect is only temporary, and successful stabilization requires ongoing ortho-k wear to maintain the reshaping effect. corneal crosslinking (cxl) is a commonly-used technique in clinical practice to stabilize corneal shape in keratoconic eyes. however, whether or not cxl can stabilize corneal shape after ortho-k in normal cornea has not been reported. therefor ...202032047218
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