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Sample records for preterm primate model

  1. Use of nonhuman primate models to investigate mechanisms of infection-associated preterm birth

    Science.gov (United States)

    Adams Waldorf, Kristina M.; Rubens, Craig E.; Gravett, Michael G.

    2010-01-01

    Preterm birth is the most important direct cause of neonatal mortality and remains a major challenge for obstetrics and global health. Intrauterine infection causes approximately 50% of early preterm births. Animal models using pregnant mice, rabbits, or sheep, demonstrate the key link between infection and premature birth, but differ in mechanisms of parturition and placental structure from humans. The nonhuman primate (NHP) is a powerful model which emulates many features of human placentation and parturition. The contributions of the NHP model to preterm birth research are reviewed emphasizing the role of infections, and potential development of preventative and therapeutic strategies. PMID:21040390

  2. Uterine overdistention induces preterm labor mediated by inflammation: observations in pregnant women and nonhuman primates.

    Science.gov (United States)

    Adams Waldorf, Kristina M; Singh, Natasha; Mohan, Aarthi R; Young, Roger C; Ngo, Lisa; Das, Ananya; Tsai, Jesse; Bansal, Aasthaa; Paolella, Louis; Herbert, Bronwen R; Sooranna, Suren R; Gough, G Michael; Astley, Cliff; Vogel, Keith; Baldessari, Audrey E; Bammler, Theodor K; MacDonald, James; Gravett, Michael G; Rajagopal, Lakshmi; Johnson, Mark R

    2015-12-01

    Uterine overdistention is thought to induce preterm labor in women with twin and multiple pregnancies, but the pathophysiology remains unclear. We investigated for the first time the pathogenesis of preterm birth associated with rapid uterine distention in a pregnant nonhuman primate model. A nonhuman primate model of uterine overdistention was created using preterm chronically catheterized pregnant pigtail macaques (Macaca nemestrina) by inflation of intraamniotic balloons (N = 6), which were compared to saline controls (N = 5). Cesarean delivery was performed due to preterm labor or at experimental end. Microarray, quantitative reverse transcriptase polymerase chain reaction, Luminex (Austin, TX), and enzyme-linked immunosorbent assay were used to measure messenger RNA (mRNA) and/or protein levels from monkey (amniotic fluid, myometrium, maternal plasma) and human (amniocytes, amnion, myometrium) tissues. Statistical analysis employed analysis of covariance and Wilcoxon rank sum. Biomechanical forces were calculated using the law of Laplace. Preterm labor occurred in 3 of 6 animals after balloon inflation and correlated with greater balloon volume and uterine wall stress. Significant elevations of inflammatory cytokines and prostaglandins occurred following uterine overdistention in an "inflammatory pulse" that correlated with preterm labor (interleukin [IL]-1β, tumor necrosis factor [TNF]-α, IL-6, IL-8, CCL2, prostaglandin E2, prostaglandin F2α, all P labor (IL6, IL8, CCL2, all P labor. Our results indicate that inflammation is an early event after a mechanical stress on the uterus and leads to preterm labor when the stress is sufficiently great. Further, we find evidence of uterine tissue remodeling and muscle growth as a common, perhaps compensatory, response to uterine distension. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Uterine overdistention induces preterm labor mediated by inflammation: observations in pregnant women and nonhuman primates

    Science.gov (United States)

    Waldorf, Kristina M. Adams; Singh, Natasha; Mohan, Aarthi R.; Young, Roger C.; Ngo, Lisa; Das, Ananya; Tsai, Jesse; Bansal, Aasthaa; Paolella, Louis; Herbert, Bronwen R.; Sooranna, Suren R.; Gough, G. Michael; Astley, Cliff; Vogel, Keith; Baldessari, Audrey E.; Bammler, Theodor K.; MacDonald, James; Gravett, Michael G.; Rajagopal, Lakshmi; Johnson, Mark R.

    2015-01-01

    OBJECTIVE Uterine overdistention is thought to induce preterm labor in women with twin and multiple pregnancies, but the pathophysiology remains unclear. We investigated for the first time the pathogenesis of preterm birth associated with rapid uterine distention in a pregnant nonhuman primate model. STUDY DESIGN A nonhuman primate model of uterine overdistention was created using preterm chronically catheterized pregnant pigtail macaques (Macaca nemestrina) by inflation of intraamniotic balloons (N = 6), which were compared to saline controls (N = 5). Cesarean delivery was performed due to preterm labor or at experimental end. Microarray, quantitative reverse transcriptase polymerase chain reaction, Luminex (Austin, TX), and enzyme-linked immunosorbent assay were used to measure messenger RNA (mRNA) and/or protein levels from monkey (amniotic fluid, myometrium, maternal plasma) and human (amniocytes, amnion, myometrium) tissues. Statistical analysis employed analysis of covariance and Wilcoxon rank sum. Biomechanical forces were calculated using the law of Laplace. RESULTS Preterm labor occurred in 3 of 6 animals after balloon inflation and correlated with greater balloon volume and uterine wall stress. Significant elevations of inflammatory cytokines and prostaglandins occurred following uterine overdistention in an “inflammatory pulse” that correlated with preterm labor (interleukin [IL]-1β, tumor necrosis factor [TNF]-α, IL-6, IL-8, CCL2, prostaglandin E2, prostaglandin F2α, all P < .05). A similar inflammatory response was observed in amniocytes in vitro following mechanical stretch (IL1β, IL6, and IL8 mRNA multiple time points, P < .05), in amnion of women with polyhydramnios (IL6 and TNF mRNA, P < .05) and in amnion (TNF-α) and myometrium of women with twins in early labor (IL6, IL8, CCL2, all P < .05). Genes differentially expressed in the nonhuman primate after balloon inflation and in women with polyhydramnios and twins are involved in tissue

  4. Primate-specific evolution of noncoding element insertion into PLA2G4C and human preterm birth

    Directory of Open Access Journals (Sweden)

    Fellman Vineta

    2010-12-01

    Full Text Available Abstract Background The onset of birth in humans, like other apes, differs from non-primate mammals in its endocrine physiology. We hypothesize that higher primate-specific gene evolution may lead to these differences and target genes involved in human preterm birth, an area of global health significance. Methods We performed a comparative genomics screen of highly conserved noncoding elements and identified PLA2G4C, a phospholipase A isoform involved in prostaglandin biosynthesis as human accelerated. To examine whether this gene demonstrating primate-specific evolution was associated with birth timing, we genotyped and analyzed 8 common single nucleotide polymorphisms (SNPs in PLA2G4C in US Hispanic (n = 73 preterm, 292 control, US White (n = 147 preterm, 157 control and US Black (n = 79 preterm, 166 control mothers. Results Detailed structural and phylogenic analysis of PLA2G4C suggested a short genomic element within the gene duplicated from a paralogous highly conserved element on chromosome 1 specifically in primates. SNPs rs8110925 and rs2307276 in US Hispanics and rs11564620 in US Whites were significant after correcting for multiple tests (p PLA2G4C activity. Conclusions Our findings suggest that variation in PLA2G4C may influence preterm birth risk by increasing levels of prostaglandins, which are known to regulate labor.

  5. Nonhuman primate models in translational regenerative medicine.

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    Daadi, Marcel M; Barberi, Tiziano; Shi, Qiang; Lanford, Robert E

    2014-12-01

    Humans and nonhuman primates (NHPs) are similar in size, behavior, physiology, biochemistry, structure and function of organs, and complexity of the immune system. Research on NHPs generates complementary data that bridge translational research from small animal models to humans. NHP models of human disease offer unique opportunities to develop stem cell-based therapeutic interventions that directly address relevant and challenging translational aspects of cell transplantation therapy. These include the use of autologous induced pluripotent stem cell-derived cellular products, issues related to the immune response in autologous and allogeneic setting, pros and cons of delivery techniques in a clinical setting, as well as the safety and efficacy of candidate cell lines. The NHP model allows the assessment of complex physiological, biochemical, behavioral, and imaging end points, with direct relevance to human conditions. At the same time, the value of using primates in scientific research must be carefully evaluated and timed due to expense and the necessity for specialized equipment and highly trained personnel. Often it is more efficient and useful to perform initial proof-of-concept studies for new therapeutics in rodents and/or other species before the pivotal studies in NHPs that may eventually lead to first-in-human trials. In this report, we present how the Southwest National Primate Research Center, one of seven NIH-funded National Primate Research Centers, may help the global community in translating promising technologies to the clinical arena.

  6. Nonhuman primate models of polycystic ovary syndrome

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    Abbott, David H; Nicol, Lindsey E; Levine, Jon E; Xu, Ning; Goodarzi, Mark O; Dumesic, Daniel A

    2013-01-01

    With close genomic and phenotypic similarity to humans, nonhuman primate models provide comprehensive epigenetic mimics of polycystic ovary syndrome (PCOS), suggesting early life targeting for prevention. Fetal exposure to testosterone (T), of all nonhuman primate emulations, provides the closest PCOS-like phenotypes, with early-to-mid gestation T-exposed female rhesus monkeys exhibiting adult reproductive, endocrinological and metabolic dysfunctional traits that are co-pathologies of PCOS. Late gestational T exposure, while inducing adult ovarian hyperandrogenism and menstrual abnormalities, has less dysfunctional metabolic accompaniment. Fetal exposures to dihydrotestosterone (DHT) or diethylstilbestrol (DES) suggest androgenic and estrogenic aspects of fetal programming. Neonatal exposure to T produces no PCOS-like outcome, while continuous T treatment of juvenile females causes precocious weight gain and early menarche (high T), or high LH and weight gain (moderate T). Acute T exposure of adult females generates polyfollicular ovaries, while chronic T exposure induces subtle menstrual irregularities without metabolic dysfunction. PMID:23370180

  7. Perinatal asphyxia in a nonhuman primate model.

    Science.gov (United States)

    Jacobson Misbe, Elizabeth N; Richards, Todd L; McPherson, Ronald J; Burbacher, Thomas M; Juul, Sandra E

    2011-01-01

    Perinatal asphyxia is a leading cause of brain injury in neonates, occurring in 2-4 per 1,000 live births, and there are limited treatment options. Because of their similarity to humans, nonhuman primates are ideal for performing preclinical tests of safety and efficacy for neurotherapeutic interventions. We previously developed a primate model of acute perinatal asphyxia using 12-15 min of umbilical cord occlusion. Continuing this research, we have increased cord occlusion time from 15 to 18 min and extended neurodevelopmental follow-up to 9 months. The purpose of this report is to evaluate the increase in morbidity associated with 18 min of asphyxia by comparing indices obtained from colony controls, nonasphyxiated controls and asphyxiated animals. Pigtail macaques were delivered by hysterotomy after 0, 15 or 18 min of cord occlusion, then resuscitated. Over the ensuing 9 months, for each biochemical and physiologic parameters, behavioral and developmental evaluations, and structural and spectroscopic MRI were recorded. At birth, all asphyxiated animals required resuscitation with positive pressure ventilation and exhibited biochemical and clinical characteristics diagnostic of hypoxic-ischemic encephalopathy, including metabolic acidosis and attenuated brain activity. Compared with controls, asphyxiated animals developed long-term physical and cognitive deficits. This preliminary report characterizes the acute and chronic consequences of perinatal asphyxia in a nonhuman primate model, and describes diagnostic imaging tools for quantifying correlates of neonatal brain injury as well as neurodevelopmental tests for evaluating early motor and cognitive outcomes. Copyright © 2011 S. Karger AG, Basel.

  8. PET imaging using parkinsonian primate model

    International Nuclear Information System (INIS)

    Nagai, Yuji

    2004-01-01

    Many animal models have been for studying neutrodegenerative diseases in humans. Among them, Parkinson's disease (PD) model in primates treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is expected to be valid and useful in the field of regenerative medicine. MPTP-treated monkeys demonstrate parkinsonian syndrome, such as tremor, dyskinesia, rigidity, immobility, caused by the degeneration of dopamine neurons at the nigrostriatal pathway. In this model, investigation of cognitive impairment that is one of the important aspects of PD could be possible. We evaluated the degeneration process of nigrostriatal dopamine neurons with positron emission tomography (PET) using unanesthetized MPTP-treated two cynomolgus monkeys (Macaca fascicularis). The tracers used were [11C]PE2I, [11C]DOPA, [11C]raclopride for monitoring dopamine transporter (DAT) densities, dopamine (DA) turnover, dopamine D2-receptor (D2R) densities, respectively. The gross behavioral observation was also performed referring to the criteria of the PD symptoms. The motor dysfunction was not clearly observed up to the cumulative doses of 3 mg/kg MPTP. This period was called 'asymptomatic period'. As a result of PET scans in the asymptomatic period, DAT densities and DA turnover had already decreased greatly, but D2R densities had not changed clearly. These findings suggest that PET imaging can delineate the dopaminergic dysfunction in vivo even in the asymptomatic period. In human study of PD, it is reported that parkinsonism is shown after great loss of dopaminergic neutrons as well as pre-synaptic dysfunction. MPTP-treated monkeys demonstrate the parkinsonian syndrome with the similar mechanism as human PD. It can be expected that PET study with MPTP-monkeys would provide important clues relevant to the underlying cause of PD and be useful for preclinical study of regenerative medicine in this disease. (author)

  9. Delayed development of systemic immunity in preterm pigs as a model for preterm infants

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    Nguyen, Duc Ninh; Jiang, Pingping; Frøkiær, Hanne; Heegaard, Peter M. H.; Thymann, Thomas; Sangild, Per T.

    2016-01-01

    Preterm neonates are highly sensitive to systemic infections in early life but little is known about systemic immune development following preterm birth. We hypothesized that preterm neonates have immature systemic immunity with distinct developmental trajectory for the first several weeks of life, relative to those born at near-term or term. Using pigs as a model, we characterized blood leukocyte subsets, antimicrobial activities and TLR-mediated cytokine production during the first weeks after preterm birth. Relative to near-term and term pigs, newborn preterm pigs had low blood leukocyte counts, poor neutrophil phagocytic rate, and limited cytokine responses to TLR1/2/5/7/9 and NOD1/2 agonists. The preterm systemic responses remained immature during the first postnatal week, but thereafter showed increased blood leukocyte numbers, NK cell proportion, neutrophil phagocytic rate and TLR2-mediated IL-6 and TNF-α production. These immune parameters remained different between preterm and near-term pigs at 2–3 weeks, even when adjusted for post-conceptional age. Our data suggest that systemic immunity follows a distinct developmental trajectory following preterm birth that may be influenced by postnatal age, complications of prematurity and environmental factors. Consequently, the immediate postnatal period may represent a window of opportunity to improve innate immunity in preterm neonates by medical, antimicrobial or dietary interventions. PMID:27830761

  10. Analog VLSI-based modeling of the primate oculomotor system.

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    Horiuchi, T K; Koch, C

    1999-01-01

    One way to understand a neurobiological system is by building a simulacrum that replicates its behavior in real time using similar constraints. Analog very large-scale integrated (VLSI) electronic circuit technology provides such an enabling technology. We here describe a neuromorphic system that is part of a long-term effort to understand the primate oculomotor system. It requires both fast sensory processing and fast motor control to interact with the world. A one-dimensional hardware model of the primate eye has been built that simulates the physical dynamics of the biological system. It is driven by two different analog VLSI chips, one mimicking cortical visual processing for target selection and tracking and another modeling brain stem circuits that drive the eye muscles. Our oculomotor plant demonstrates both smooth pursuit movements, driven by a retinal velocity error signal, and saccadic eye movements, controlled by retinal position error, and can reproduce several behavioral, stimulation, lesion, and adaptation experiments performed on primates.

  11. Modelling primate control of grasping for robotics applications

    CSIR Research Space (South Africa)

    Kleinhans, A

    2014-09-01

    Full Text Available -1 European Conference on Computer Vision (ECCV) Workshops, Zurich, Switzerland, 7 September 2014 Modelling primate control of grasping for robotics applications Ashley Kleinhans1, Serge Thill2, Benjamin Rosman1, Renaud Detry3 & Bryan Tripp4 1 CSIR...

  12. Reproductive/developmental toxicity and immunotoxicity assessment in the nonhuman primate model

    International Nuclear Information System (INIS)

    Buse, Eberhard; Habermann, Gunnar; Osterburg, Ingrid; Korte, Rainhart; Weinbauer, Gerhard F.

    2003-01-01

    Nonhuman primates are being used increasingly as a non-rodent animal model during preclinical toxicology and safety assessment on the basis of proven similarity and comparability between nonhuman primates and humans. The validity of the nonhuman primate models applies to many aspects of toxicological testing and holds particularly true for the evaluation of reproductive toxicology and developmental toxicology. More recently, the advent of humanized antibodies and vaccines imposed further demand on nonhuman primate models since many immunotherapeutics do not interact with rodent receptors but frequently only cross-react with primate tissue. In this paper we discuss the suitability of primate models for reproductive, developmental and immunotoxicology testing, and present our initial data on the development of lymphatic organs and immune system in a nonhuman primate model

  13. Non-Human Primate Models of Orthopoxvirus Infections

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    Anne Schmitt

    2014-06-01

    Full Text Available Smallpox, one of the most destructive diseases, has been successfully eradicated through a worldwide vaccination campaign. Since immunization programs have been stopped, the number of people with vaccinia virus induced immunity is declining. This leads to an increase in orthopoxvirus (OPXV infections in humans, as well as in animals. Additionally, potential abuse of Variola virus (VARV, the causative agent of smallpox, or monkeypox virus, as agents of bioterrorism, has renewed interest in development of antiviral therapeutics and of safer vaccines. Due to its high risk potential, research with VARV is restricted to two laboratories worldwide. Therefore, numerous animal models of other OPXV infections have been developed in the last decades. Non-human primates are especially suitable due to their close relationship to humans. This article provides a review about on non-human primate models of orthopoxvirus infections.

  14. [Primate models of human viral hepatitis].

    Science.gov (United States)

    Poleshchuk, V F; Mikhaĭlov, M I; Zamiatina, N A

    2006-01-01

    The paper summarizes the updates available in the literature and the authors' own data on the etiology of hepatitis, its models, and experimental studies on susceptible simian types. A comparative analysis of the etiological agents--the causative agents of simian and human hepatitis will give a better insight into the evolution of its viruses.

  15. Pain Relief in Nonhuman Primate Models of Arthritis.

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    Vierboom, Michel P M; Breedveld, Elia; Keehnen, Merei; Klomp, Rianne; Bakker, Jaco

    2017-01-01

    Animal models of rheumatoid arthritis are important in the elucidation of etiopathogenic mechanisms of the disease and for the development of promising new therapies. Species specificity of new biological compounds and their mode of action preclude safety and efficacy testing in rodent models of disease. Nonhuman primates (NHP) can fill this niche and provide the only relevant model. Over the last two decades models of collagen-induced arthritis (CIA) were developed in the rhesus monkey and the common marmoset. However, NHP are higher-order animals and complex sentient beings. So especially in models where pain is an intricate part of the disease, analgesia needs to be addressed because of ethical considerations. In our model, a morphine-based pain relief was used that does not interfere with the normal development of disease allowing us to evaluate important mechanistic aspects of the arthritis.

  16. Emergent patterns of social affiliation in primates, a model.

    Directory of Open Access Journals (Sweden)

    Ivan Puga-Gonzalez

    2009-12-01

    Full Text Available Many patterns of affiliative behaviour have been described for primates, for instance: reciprocation and exchange of grooming, grooming others of similar rank, reconciliation of fights, and preferential reconciliation with more valuable partners. For these patterns several functions and underlying cognitive processes have been suggested. It is, however, difficult to imagine how animals may combine these diverse considerations in their mind. Although the co-variation hypothesis, by limiting the social possibilities an individual has, constrains the number of cognitive considerations an individual has to take, it does not present an integrated theory of affiliative patterns either. In the present paper, after surveying patterns of affiliation in egalitarian and despotic macaques, we use an individual-based model with a high potential for self-organisation as a starting point for such an integrative approach. In our model, called GrooFiWorld, individuals group and, upon meeting each other, may perform a dominance interaction of which the outcomes of winning and losing are self-reinforcing. Besides, if individuals think they will be defeated, they consider grooming others. Here, the greater their anxiety is, the greater their "motivation" to groom others. Our model generates patterns similar to many affiliative patterns of empirical data. By merely increasing the intensity of aggression, affiliative patterns in the model change from those resembling egalitarian macaques to those resembling despotic ones. Our model produces such patterns without assuming in the mind of the individual the specific cognitive processes that are usually thought to underlie these patterns (such as recordkeeping of the acts given and received, a tendency to exchange, memory of the former fight, selective attraction to the former opponent, and estimation of the value of a relationship. Our model can be used as a null model to increase our understanding of affiliative

  17. Immunology studies in non-human primate models of tuberculosis.

    Science.gov (United States)

    Flynn, JoAnne L; Gideon, Hannah P; Mattila, Joshua T; Lin, Philana Ling

    2015-03-01

    Non-human primates, primarily macaques, have been used to study tuberculosis for decades. However, in the last 15 years, this model has been refined substantially to allow careful investigations of the immune response and host-pathogen interactions in Mycobacterium tuberculosis infection. Low-dose challenge with fully virulent strains in cynomolgus macaques result in the full clinical spectrum seen in humans, including latent and active infection. Reagents from humans are usually cross-reactive with macaques, further facilitating the use of this model system to study tuberculosis. Finally, macaques develop the spectrum of granuloma types seen in humans, providing a unique opportunity to investigate bacterial and host factors at the local (lung and lymph node) level. Here, we review the past decade of immunology and pathology studies in macaque models of tuberculosis. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. A Non-Human Primate Model of Severe Pneumococcal Pneumonia

    Science.gov (United States)

    Reyes, Luis F.; Restrepo, Marcos I.; Hinojosa, Cecilia A.; Soni, Nilam J.; Shenoy, Anukul T.; Gilley, Ryan P.; Gonzalez-Juarbe, Norberto; Noda, Julio R.; Winter, Vicki T.; de la Garza, Melissa A.; Shade, Robert E.; Coalson, Jacqueline J.; Giavedoni, Luis D.; Anzueto, Antonio; Orihuela, Carlos J.

    2016-01-01

    Rationale Streptococcus pneumoniae is the leading cause of community-acquired pneumonia and infectious death in adults worldwide. A non-human primate model is needed to study the molecular mechanisms that underlie the development of severe pneumonia, identify diagnostic tools, explore potential therapeutic targets, and test clinical interventions during pneumococcal pneumonia. Objective To develop a non-human primate model of pneumococcal pneumonia. Methods Seven adult baboons (Papio cynocephalus) were surgically tethered to a continuous monitoring system that recorded heart rate, temperature, and electrocardiography. Animals were inoculated with 109 colony-forming units of S. pneumoniae using bronchoscopy. Three baboons were rescued with intravenous ampicillin therapy. Pneumonia was diagnosed using lung ultrasonography and ex vivo confirmation by histopathology and immunodetection of pneumococcal capsule. Organ failure, using serum biomarkers and quantification of bacteremia, was assessed daily. Results Challenged animals developed signs and symptoms of pneumonia 4 days after infection. Infection was characterized by the presence of cough, tachypnea, dyspnea, tachycardia and fever. All animals developed leukocytosis and bacteremia 24 hours after infection. A severe inflammatory reaction was detected by elevation of serum cytokines, including Interleukin (IL)1Ra, IL-6, and IL-8, after infection. Lung ultrasonography precisely detected the lobes with pneumonia that were later confirmed by pathological analysis. Lung pathology positively correlated with disease severity. Antimicrobial therapy rapidly reversed symptomology and reduced serum cytokines. Conclusions We have developed a novel animal model for severe pneumococcal pneumonia that mimics the clinical presentation, inflammatory response, and infection kinetics seen in humans. This is a novel model to test vaccines and treatments, measure biomarkers to diagnose pneumonia, and predict outcomes. PMID:27855182

  19. The Non-Human Primate Experimental Glaucoma Model

    Science.gov (United States)

    Burgoyne, Claude F.

    2015-01-01

    The purpose of this report is to summarize the current strengths and weaknesses of the non-human primate (NHP) experimental glaucoma (EG) model through sections devoted to its history, methods, important findings, alternative optic neuropathy models and future directions. NHP EG has become well established for studying human glaucoma in part because the NHP optic nerve head (ONH) shares a close anatomic association with the human ONH and because it provides the only means of systematically studying the very earliest visual system responses to chronic IOP elevation, i.e. the conversion from ocular hypertension to glaucomatous damage. However, NHPs are impractical for studies that require large animal numbers, demonstrate spontaneous glaucoma only rarely, do not currently provide a model of the neuropathy at normal levels of IOP, and cannot easily be genetically manipulated, except through tissue-specific, viral vectors. The goal of this summary is to direct NHP EG and non-NHP EG investigators to the previous, current and future accomplishment of clinically relevant knowledge in this model. PMID:26070984

  20. Non-human Primate Models for Brain Disorders - Towards Genetic Manipulations via Innovative Technology.

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    Qiu, Zilong; Li, Xiao

    2017-04-01

    Modeling brain disorders has always been one of the key tasks in neurobiological studies. A wide range of organisms including worms, fruit flies, zebrafish, and rodents have been used for modeling brain disorders. However, whether complicated neurological and psychiatric symptoms can be faithfully mimicked in animals is still debatable. In this review, we discuss key findings using non-human primates to address the neural mechanisms underlying stress and anxiety behaviors, as well as technical advances for establishing genetically-engineered non-human primate models of autism spectrum disorders and other disorders. Considering the close evolutionary connections and similarity of brain structures between non-human primates and humans, together with the rapid progress in genome-editing technology, non-human primates will be indispensable for pathophysiological studies and exploring potential therapeutic methods for treating brain disorders.

  1. Delayed development of systemic immunity in preterm pigs as a model for preterm infants

    DEFF Research Database (Denmark)

    Nguyen, Duc Ninh; Jiang, Pingping; Frøkiær, Hanne

    2016-01-01

    Preterm neonates are highly sensitive to systemic infections in early life but little is known about systemic immune development following preterm birth. We hypothesized that preterm neonates have immature systemic immunity with distinct developmental trajectory for the first several weeks of life......-mediated IL-6 and TNF-α production. These immune parameters remained different between preterm and near-term pigs at 2-3 weeks, even when adjusted for post-conceptional age. Our data suggest that systemic immunity follows a distinct developmental trajectory following preterm birth that may be influenced......, poor neutrophil phagocytic rate, and limited cytokine responses to TLR1/2/5/7/9 and NOD1/2 agonists. The preterm systemic responses remained immature during the first postnatal week, but thereafter showed increased blood leukocyte numbers, NK cell proportion, neutrophil phagocytic rate and TLR2...

  2. A novel nonhuman primate model for influenza transmission.

    Directory of Open Access Journals (Sweden)

    Louise H Moncla

    Full Text Available Studies of influenza transmission are necessary to predict the pandemic potential of emerging influenza viruses. Currently, both ferrets and guinea pigs are used in such studies, but these species are distantly related to humans. Nonhuman primates (NHP share a close phylogenetic relationship with humans and may provide an enhanced means to model the virological and immunological events in influenza virus transmission. Here, for the first time, it was demonstrated that a human influenza virus isolate can productively infect and be transmitted between common marmosets (Callithrix jacchus, a New World monkey species. We inoculated four marmosets with the 2009 pandemic virus A/California/07/2009 (H1N1pdm and housed each together with a naïve cage mate. We collected bronchoalveolar lavage and nasal wash samples from all animals at regular intervals for three weeks post-inoculation to track virus replication and sequence evolution. The unadapted 2009 H1N1pdm virus replicated to high titers in all four index animals by 1 day post-infection. Infected animals seroconverted and presented human-like symptoms including sneezing, nasal discharge, labored breathing, and lung damage. Transmission occurred in one cohabitating pair. Deep sequencing detected relatively few genetic changes in H1N1pdm viruses replicating in any infected animal. Together our data suggest that human H1N1pdm viruses require little adaptation to replicate and cause disease in marmosets, and that these viruses can be transmitted between animals. Marmosets may therefore be a viable model for studying influenza virus transmission.

  3. Utility of large-animal models of BPD: chronically ventilated preterm lambs.

    Science.gov (United States)

    Albertine, Kurt H

    2015-05-15

    This paper is focused on unique insights provided by the preterm lamb physiological model of bronchopulmonary dysplasia (BPD). Connections are also made to insights provided by the former preterm baboon model of BPD, as well as to rodent models of lung injury to the immature, postnatal lung. The preterm lamb and baboon models recapitulate the clinical setting of preterm birth and respiratory failure that require prolonged ventilation support for days or weeks with oxygen-rich gas. An advantage of the preterm lamb model is the large size of preterm lambs, which facilitates physiological studies for days or weeks during the evolution of neonatal chronic lung disease (CLD). To this advantage is linked an integrated array of morphological, biochemical, and molecular analyses that are identifying the role of individual genes in the pathogenesis of neonatal CLD. Results indicate that the mode of ventilation, invasive mechanical ventilation vs. less invasive high-frequency nasal ventilation, is related to outcomes. Our approach also includes pharmacological interventions that test causality of specific molecular players, such as vitamin A supplementation in the pathogenesis of neonatal CLD. The new insights that are being gained from our preterm lamb model may have important translational implications about the pathogenesis and treatment of BPD in preterm human infants. Copyright © 2015 the American Physiological Society.

  4. Experimental and Numerical Modeling of Aerosol Delivery for Preterm Infants

    Directory of Open Access Journals (Sweden)

    Iñigo Aramendia

    2018-02-01

    Full Text Available Respiratory distress syndrome (RDS represents one of the major causes of mortality among preterm infants, and the best approach to treat it is an open research issue. The use of perfluorocarbons (PFC along with non-invasive respiratory support techniques has proven the usefulness of PFC as a complementary substance to achieve a more homogeneous surfactant distribution. The aim of this work was to study the inhaled particles generated by means of an intracorporeal inhalation catheter, evaluating the size and mass distribution of different PFC aerosols. In this article, we discuss different experiments with the PFC perfluorodecalin (PFD and FC75 with a driving pressure of 4–5 bar, evaluating properties such as the aerodynamic diameter (Da, since its value is directly linked to particle deposition in the lung. Furthermore, we develop a numerical model with computational fluid dynamics (CFD techniques. The computational results showed an accurate prediction of the airflow axial velocity at different downstream positions when compared with the data gathered from the real experiments. The numerical validation of the cumulative mass distribution for PFD particles also confirmed a closer match with the experimental data measured at the optimal distance of 60 mm from the catheter tip. In the case of FC75, the cumulative mass fraction for particles above 10 µm was considerable higher with a driving pressure of 5 bar. These numerical models could be a helpful tool to assist parametric studies of new non-invasive devices for the treatment of RDS in preterm infants.

  5. Large animal and primate models of spinal cord injury for the testing of novel therapies.

    Science.gov (United States)

    Kwon, Brian K; Streijger, Femke; Hill, Caitlin E; Anderson, Aileen J; Bacon, Mark; Beattie, Michael S; Blesch, Armin; Bradbury, Elizabeth J; Brown, Arthur; Bresnahan, Jacqueline C; Case, Casey C; Colburn, Raymond W; David, Samuel; Fawcett, James W; Ferguson, Adam R; Fischer, Itzhak; Floyd, Candace L; Gensel, John C; Houle, John D; Jakeman, Lyn B; Jeffery, Nick D; Jones, Linda Ann Truett; Kleitman, Naomi; Kocsis, Jeffery; Lu, Paul; Magnuson, David S K; Marsala, Martin; Moore, Simon W; Mothe, Andrea J; Oudega, Martin; Plant, Giles W; Rabchevsky, Alexander Sasha; Schwab, Jan M; Silver, Jerry; Steward, Oswald; Xu, Xiao-Ming; Guest, James D; Tetzlaff, Wolfram

    2015-07-01

    Large animal and primate models of spinal cord injury (SCI) are being increasingly utilized for the testing of novel therapies. While these represent intermediary animal species between rodents and humans and offer the opportunity to pose unique research questions prior to clinical trials, the role that such large animal and primate models should play in the translational pipeline is unclear. In this initiative we engaged members of the SCI research community in a questionnaire and round-table focus group discussion around the use of such models. Forty-one SCI researchers from academia, industry, and granting agencies were asked to complete a questionnaire about their opinion regarding the use of large animal and primate models in the context of testing novel therapeutics. The questions centered around how large animal and primate models of SCI would be best utilized in the spectrum of preclinical testing, and how much testing in rodent models was warranted before employing these models. Further questions were posed at a focus group meeting attended by the respondents. The group generally felt that large animal and primate models of SCI serve a potentially useful role in the translational pipeline for novel therapies, and that the rational use of these models would depend on the type of therapy and specific research question being addressed. While testing within these models should not be mandatory, the detection of beneficial effects using these models lends additional support for translating a therapy to humans. These models provides an opportunity to evaluate and refine surgical procedures prior to use in humans, and safety and bio-distribution in a spinal cord more similar in size and anatomy to that of humans. Our results reveal that while many feel that these models are valuable in the testing of novel therapies, important questions remain unanswered about how they should be used and how data derived from them should be interpreted. Copyright © 2015 Elsevier

  6. A cellular and molecular model of response kinetics and adaptation in primate cones and horizontal cells

    NARCIS (Netherlands)

    Hateren, Hans van

    2005-01-01

    A model for the sensitivity regulation in the primate outer retina is developed and validated using horizontal cell measurements from the literature. The main conclusion is that the phototransduction of the cones is the key factor regulating sensitivity. The model consists of a nonlinearity cascaded

  7. Genome sequencing and comparison of two nonhuman primate animal models, the cynomolgus and Chinese rhesus macaques

    DEFF Research Database (Denmark)

    Yan, Guangmei; Zhang, Guojie; Fang, Xiaodong

    2011-01-01

    The nonhuman primates most commonly used in medical research are from the genus Macaca. To better understand the genetic differences between these animal models, we present high-quality draft genome sequences from two macaque species, the cynomolgus/crab-eating macaque and the Chinese rhesus...

  8. A new conservation strategy for China-A model starting with primates.

    Science.gov (United States)

    Pan, Ruliang; Oxnard, Charles; Grueter, Cyril C; Li, Baoguo; Qi, Xiaoguang; He, Gang; Guo, Songtao; Garber, Paul A

    2016-11-01

    Although the evolutionary history of primates in China dates to the Eocene, and includes major radiations of lorisids, hominoids, cercopithecines, and colobines during the Miocene, Pliocene, and Pleistocene, extensive human-induced habitat change and deforestation over the past few centuries has resulted in 22 of 25 extant species listed as threatened or endangered, and two species of gibbons extirpated in the last few years. This commentary briefly reviews factors that have contributed to the decline of primates in China over the past 400 years, and in particular how major social events and economic development in modern China have resulted in unsustainable environmental change. In response, we describe our efforts to develop a strategic scientific, educational and conservation partnership in China, focusing on primates, in which GIS technology will be used to integrate geographical profiles, climatic information, and changes in land use patterns and human and nonhuman primate distributions to highlight issues of immediate concern and to develop priority-based conservation solutions. Our goal is to evaluate how human-induced environmental change has impacted primates over time and to predict the likelihood of primate population extinctions in the near future. This model represents an early warning system that will be widely available to the Chinese government, public, educational institutions, researchers, and NGOs through social media and educational videos in order to arouse public awareness and promote wildlife conservation. We encourage colleagues across a broad range of academic disciplines, political ideologies, and the public to help move this strategy into reality, the sooner the better. Am. J. Primatol. 78:1137-1148, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  9. Common marmoset (Callithrix jacchus) as a primate model for behavioral neuroscience studies.

    Science.gov (United States)

    Prins, Noeline W; Pohlmeyer, Eric A; Debnath, Shubham; Mylavarapu, Ramanamurthy; Geng, Shijia; Sanchez, Justin C; Rothen, Daniel; Prasad, Abhishek

    2017-06-01

    The common marmoset (Callithrix jacchus) has been proposed as a suitable bridge between rodents and larger primates. They have been used in several types of research including auditory, vocal, visual, pharmacological and genetics studies. However, marmosets have not been used as much for behavioral studies. Here we present data from training 12 adult marmosets for behavioral neuroscience studies. We discuss the husbandry, food preferences, handling, acclimation to laboratory environments and neurosurgical techniques. In this paper, we also present a custom built "scoop" and a monkey chair suitable for training of these animals. The animals were trained for three tasks: 4 target center-out reaching task, reaching tasks that involved controlling robot actions, and touch screen task. All animals learned the center-out reaching task within 1-2 weeks whereas learning reaching tasks controlling robot actions task took several months of behavioral training where the monkeys learned to associate robot actions with food rewards. We propose the marmoset as a novel model for behavioral neuroscience research as an alternate for larger primate models. This is due to the ease of handling, quick reproduction, available neuroanatomy, sensorimotor system similar to larger primates and humans, and a lissencephalic brain that can enable implantation of microelectrode arrays relatively easier at various cortical locations compared to larger primates. All animals were able to learn behavioral tasks well and we present the marmosets as an alternate model for simple behavioral neuroscience tasks. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Modelling bronchopulmonary dysplasia in animals: arguments for the preterm rabbit model.

    Science.gov (United States)

    Salaets, Thomas; Gie, Andre; Tack, Bieke; Deprest, Jan; Toelen, Jaan

    2017-09-26

    Bronchopulmonary dysplasia (BPD) remains a frequent and disabling consequence of preterm birth, despite the recent advances in neonatal intensive care. There is a need to further improve outcomes and many novel therapeutic or preventive strategies are therefore investigated in animal models. We discuss in this review the aspects of human BPD pathophysiology and phenotype, which ideally should be mimicked by an animal model for this disease. Prematurity remains the common denominator in the heterogeneous spectrum of human BPD, and preterm animal models thus have a clear translational advantage. Additional factors, like excessive oxygen, mechanical ventilation and infection, which frequently have been studied in animal models, can contribute to preterm lung injury however are not indispensable to develop BPD. The phenotype of human BPD is characterized by alveolar developmental arrest with extracellular matrix remodeling, signs of obstructive airway disease and pulmonary vascular disease. Many animal models mimic this phenotype and have their place in BPD research, but results should be interpreted bearing in mind the specific advantages and disadvantages of the model. Term mice and rats are well suited for basic explorative research on specific disease mechanisms, essential for the generation of new hypotheses, while the larger ventilated preterm baboons and lambs provide a good platform for the ultimate translation of these strategies towards clinical application. The preterm rabbit model seems a promising model as it the smallest model that includes a factor of prematurity and has a unique position between the small and large animal models. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. The Mouse Lemur, a Genetic Model Organism for Primate Biology, Behavior, and Health.

    Science.gov (United States)

    Ezran, Camille; Karanewsky, Caitlin J; Pendleton, Jozeph L; Sholtz, Alex; Krasnow, Maya R; Willick, Jason; Razafindrakoto, Andriamahery; Zohdy, Sarah; Albertelli, Megan A; Krasnow, Mark A

    2017-06-01

    Systematic genetic studies of a handful of diverse organisms over the past 50 years have transformed our understanding of biology. However, many aspects of primate biology, behavior, and disease are absent or poorly modeled in any of the current genetic model organisms including mice. We surveyed the animal kingdom to find other animals with advantages similar to mice that might better exemplify primate biology, and identified mouse lemurs ( Microcebus spp.) as the outstanding candidate. Mouse lemurs are prosimian primates, roughly half the genetic distance between mice and humans. They are the smallest, fastest developing, and among the most prolific and abundant primates in the world, distributed throughout the island of Madagascar, many in separate breeding populations due to habitat destruction. Their physiology, behavior, and phylogeny have been studied for decades in laboratory colonies in Europe and in field studies in Malagasy rainforests, and a high quality reference genome sequence has recently been completed. To initiate a classical genetic approach, we developed a deep phenotyping protocol and have screened hundreds of laboratory and wild mouse lemurs for interesting phenotypes and begun mapping the underlying mutations, in collaboration with leading mouse lemur biologists. We also seek to establish a mouse lemur gene "knockout" library by sequencing the genomes of thousands of mouse lemurs to identify null alleles in most genes from the large pool of natural genetic variants. As part of this effort, we have begun a citizen science project in which students across Madagascar explore the remarkable biology around their schools, including longitudinal studies of the local mouse lemurs. We hope this work spawns a new model organism and cultivates a deep genetic understanding of primate biology and health. We also hope it establishes a new and ethical method of genetics that bridges biological, behavioral, medical, and conservation disciplines, while

  12. Connections Matter: Social Networks and Lifespan Health in Primate Translational Models

    Science.gov (United States)

    McCowan, Brenda; Beisner, Brianne; Bliss-Moreau, Eliza; Vandeleest, Jessica; Jin, Jian; Hannibal, Darcy; Hsieh, Fushing

    2016-01-01

    Humans live in societies full of rich and complex relationships that influence health. The ability to improve human health requires a detailed understanding of the complex interplay of biological systems that contribute to disease processes, including the mechanisms underlying the influence of social contexts on these biological systems. A longitudinal computational systems science approach provides methods uniquely suited to elucidate the mechanisms by which social systems influence health and well-being by investigating how they modulate the interplay among biological systems across the lifespan. In the present report, we argue that nonhuman primate social systems are sufficiently complex to serve as model systems allowing for the development and refinement of both analytical and theoretical frameworks linking social life to health. Ultimately, developing systems science frameworks in nonhuman primate models will speed discovery of the mechanisms that subserve the relationship between social life and human health. PMID:27148103

  13. Testing the priority-of-access model in a seasonally breeding primate species

    OpenAIRE

    Dubuc, Constance; Muniz, Laura; Heistermann, Michael; Engelhardt, Antje; Widdig, Anja

    2011-01-01

    In mammals, when females are clumped in space, male access to receptive females is usually determined by a dominance hierarchy based on fighting ability. In polygynandrous primates, as opposed to most mammalian species, the strength of the relationship between male social status and reproductive success varies greatly. It has been proposed that the degree to which paternity is determined by male rank decreases with increasing female reproductive synchrony. The priority-of-access model (PoA) p...

  14. Regulation of EGF and Prostaglandin Expression during Neonatal Gastrointestinal Injury in a Non-Human Primate Explant Model

    Science.gov (United States)

    2017-05-05

    Neonatal Gastrointestinal Injury in a Non- Human Primate Explant Model presented at/published to Pediatric Academic Societies Meeting, San Francisco CA...Prostaglandin Expression During Neonatal Gastrointestinal Injury in a Non- Human Primate Explant Model AUTHORS: Steven J. Acevedo, MOl, Nicholas B. Alana2...Medical Center, San Antonio, Texas’ 2Department of Biology , Trinity University, San Antonio, Texas’ JDepartment of Pediatrics/Division of Neonatology

  15. Human iPS cell-derived dopaminergic neurons function in a primate Parkinson's disease model.

    Science.gov (United States)

    Kikuchi, Tetsuhiro; Morizane, Asuka; Doi, Daisuke; Magotani, Hiroaki; Onoe, Hirotaka; Hayashi, Takuya; Mizuma, Hiroshi; Takara, Sayuki; Takahashi, Ryosuke; Inoue, Haruhisa; Morita, Satoshi; Yamamoto, Michio; Okita, Keisuke; Nakagawa, Masato; Parmar, Malin; Takahashi, Jun

    2017-08-30

    Induced pluripotent stem cells (iPS cells) are a promising source for a cell-based therapy to treat Parkinson's disease (PD), in which midbrain dopaminergic neurons progressively degenerate. However, long-term analysis of human iPS cell-derived dopaminergic neurons in primate PD models has never been performed to our knowledge. Here we show that human iPS cell-derived dopaminergic progenitor cells survived and functioned as midbrain dopaminergic neurons in a primate model of PD (Macaca fascicularis) treated with the neurotoxin MPTP. Score-based and video-recording analyses revealed an increase in spontaneous movement of the monkeys after transplantation. Histological studies showed that the mature dopaminergic neurons extended dense neurites into the host striatum; this effect was consistent regardless of whether the cells were derived from patients with PD or from healthy individuals. Cells sorted by the floor plate marker CORIN did not form any tumours in the brains for at least two years. Finally, magnetic resonance imaging and positron emission tomography were used to monitor the survival, expansion and function of the grafted cells as well as the immune response in the host brain. Thus, this preclinical study using a primate model indicates that human iPS cell-derived dopaminergic progenitors are clinically applicable for the treatment of patients with PD.

  16. A Novel Translational Model of Spinal Cord Injury in Nonhuman Primate.

    Science.gov (United States)

    Le Corre, Marine; Noristani, Harun N; Mestre-Frances, Nadine; Saint-Martin, Guillaume P; Coillot, Christophe; Goze-Bac, Christophe; Lonjon, Nicolas; Perrin, Florence E

    2017-11-27

    Spinal cord injuries (SCI) lead to major disabilities affecting > 2.5 million people worldwide. Major shortcomings in clinical translation result from multiple factors, including species differences, development of moderately predictive animal models, and differences in methodologies between preclinical and clinical studies. To overcome these obstacles, we first conducted a comparative neuroanatomical analysis of the spinal cord between mice, Microcebus murinus (a nonhuman primate), and humans. Next, we developed and characterized a new model of lateral spinal cord hemisection in M. murinus. Over a 3-month period after SCI, we carried out a detailed, longitudinal, behavioral follow-up associated with in vivo magnetic resonance imaging ( 1 H-MRI) monitoring. Then, we compared lesion extension and tissue alteration using 3 methods: in vivo 1 H-MRI, ex vivo 1 H-MRI, and classical histology. The general organization and glial cell distribution/morphology in the spinal cord of M. murinus closely resembles that of humans. Animals assessed at different stages following lateral hemisection of the spinal cord presented specific motor deficits and spinal cord tissue alterations. We also found a close correlation between 1 H-MRI signal and microglia reactivity and/or associated post-trauma phenomena. Spinal cord hemisection in M. murinus provides a reliable new nonhuman primate model that can be used to promote translational research on SCI and represents a novel and more affordable alternative to larger primates.

  17. French research program on the physiological problems caused by weightlessness. Use of the primate model

    Science.gov (United States)

    Pesquies, P. C.; Milhaud, C.; Nogues, C.; Klein, M.; Cailler, B.; Bost, R.

    The need to acquire a better knowledge of the main biological problems induced by microgravity implies—in addition to human experimentation—the use of animal models, and primates seem to be particularly well adapted to this type of research. The major areas of investigation to be considered are the phospho-calcium metabolism and the metabolism of supporting tissues, the hydroelectrolytic metabolism, the cardiovascular function, awakeness, sleep-awakeness cycles, the physiology of equilibrium and the pathophysiology of space sickness. Considering this program, the Centre d'Etudes et de Recherches de Medecine Aerospatiale, under the sponsorship of the Centre National d'Etudes Spatiales, developed both a program of research on restrained primates for the French-U.S. space cooperation (Spacelab program) and for the French-Soviet space cooperation (Bio-cosmos program), and simulation of the effects of microgravity by head-down bedrest. Its major characteristics are discussed in the study.

  18. Interspecific perspective on mechanical and nonmechanical models of primate circumorbital morphology.

    Science.gov (United States)

    Ravosa, M J

    1991-11-01

    Linear dimensions and angular orientations of the browridge, postorbital bar, and postorbital septum were obtained from a representative series of primates and compared with variables associated with several nonmechanical and biomechanical/mechanical models put forward to explain the form and function of the circumorbital region. Analyses of the results indicate that face size is the primary determinant of variation in primate circumorbital morphology. Anteroposterior browridge thickness is correlated with neural-orbital disjunction among anthropoid primates, but not among prosimians. This difference appears related to differences in the construction of the upper face and anterior cranial fossa between prosimians and anthropoids. Little support is demonstrated for the anterior dental loading model of browridge development. Mediolateral postorbital bar width and (to a lesser degree) browridge height are correlated with neurofacial torsion during mastication and variation in masticatory muscle size. These analyses further suggest that since circumorbital structures (especially the browridges) are located the farthest away from the chewing apparatus, they are least affected by masticatory stresses.

  19. PET studies in nonhuman primate models of cocaine abuse: translational research related to vulnerability and neuroadaptations.

    Science.gov (United States)

    Gould, Robert W; Duke, Angela N; Nader, Michael A

    2014-09-01

    The current review highlights the utility of positron emission tomography (PET) imaging to study the neurobiological substrates underlying vulnerability to cocaine addiction and subsequent adaptations following chronic cocaine self-administration in nonhuman primate models of cocaine abuse. Environmental (e.g., social rank) and sex-specific influences on dopaminergic function and sensitivity to the reinforcing effects of cocaine are discussed. Cocaine-related cognitive deficits have been hypothesized to contribute to high rates of relapse and are described in nonhuman primate models. Lastly, the long-term consequences of cocaine on neurobiology are discussed. PET imaging and longitudinal, within-subject behavioral studies in nonhuman primates have provided a strong framework for designing pharmacological and behavioral treatment strategies to aid drug-dependent treatment seekers. Non-invasive PET imaging will allow for individualized treatment strategies. Recent advances in radiochemistry of novel PET ligands and other imaging modalities can further advance our understanding of stimulant use on the brain. This article is part of the Special Issue Section entitled 'Neuroimaging in Neuropharmacology'. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Gene therapy in nonhuman primate models of human autoimmune disease

    NARCIS (Netherlands)

    t'Hart, B. A.; Vervoordeldonk, M.; Heeney, J. L.; Tak, P. P.

    2003-01-01

    Before autoimmune diseases in humans can be treated with gene therapy, the safety and efficacy of the used vectors must be tested in valid experimental models. Monkeys, such as the rhesus macaque or the common marmoset, provide such models. This publication reviews the state of the art in monkey

  1. Incorporating the gut microbiota into models of human and non-human primate ecology and evolution.

    Science.gov (United States)

    Amato, Katherine R

    2016-01-01

    The mammalian gut is home to a diverse community of microbes. Advances in technology over the past two decades have allowed us to examine this community, the gut microbiota, in more detail, revealing a wide range of influences on host nutrition, health, and behavior. These host-gut microbe interactions appear to shape host plasticity and fitness in a variety of contexts, and therefore represent a key factor missing from existing models of human and non-human primate ecology and evolution. However, current studies of the gut microbiota tend to include limited contextual data or are clinical, making it difficult to directly test broad anthropological hypotheses. Here, I review what is known about the animal gut microbiota and provide examples of how gut microbiota research can be integrated into the study of human and non-human primate ecology and evolution with targeted data collection. Specifically, I examine how the gut microbiota may impact primate diet, energetics, disease resistance, and cognition. While gut microbiota research is proliferating rapidly, especially in the context of humans, there remain important gaps in our understanding of host-gut microbe interactions that will require an anthropological perspective to fill. Likewise, gut microbiota research will be an important tool for filling remaining gaps in anthropological research. © 2016 Wiley Periodicals, Inc.

  2. Born early and born poor: An eco-bio-developmental model for poverty and preterm birth.

    Science.gov (United States)

    Brumberg, H L; Shah, S I

    2015-01-01

    Poverty is associated with adverse long-term cognitive outcomes in children. Poverty is also linked with preterm delivery which, in turn, is associated with adverse cognitive outcomes. However, the extent of the effect of poverty on preterm delivery, as well as proposed mechanisms by which they occur, have not been well described. Further, the impact of poverty on preterm school readiness has not been reviewed. As the childhood poverty level continues to increase in the U.S., we examine the evidence around physiological, neurological, cognitive and learning outcomes associated with prematurity in the context of poverty. We use the evidence gathered to suggest an Eco-Bio-Developmental model, emphasizing poverty as a toxic stress which predisposes preterm birth and which, via epigenetic forces, can continue into the next generation. Continued postnatal social disadvantage for these developmentally high-risk preterm infants is strongly linked with poor neurodevelopmental outcomes, decreased school readiness, and decreased educational attainment which can perpetuate the poverty cycle. We suggest social remedies aimed at decreasing the impact of poverty on mothers, fathers, and children which may be effective in reducing the burden of preterm birth.

  3. A mouse model of spontaneous preterm birth based on the genetic ablation of biglycan and decorin

    Science.gov (United States)

    Calmus, Megan L.; Macksoud, Elyse E.; Tucker, Richard; Iozzo, Renato V.; Lechner, Beatrice E.

    2011-01-01

    Preterm premature rupture of membranes is responsible for one third of preterm births. Ehlers-Danlos syndrome (EDS) is associated with preterm premature rupture of membranes in humans. Notably, an EDS variant is caused by a genetic mutation resulting in abnormal secretion of biglycan and decorin, two small leucine-rich proteoglycans highly expressed in reproductive tissues. Because biglycan/decorin null mutant (Bgn−/−Dcn−/−) mice demonstrate phenotypic changes similar to EDS, we utilized this model to test whether either or both biglycan and decorin play a role in the attainment of successful term gestation. Wild-type, biglycan null mutant, decorin null mutant and biglycan/decorin null mutant pregnancies were assessed for length of gestation, pup and placenta weight and litter size. Quantitative real-time polymerase chain reaction was performed to measure biglycan and decorin gene expression and immunohistochemistry was performed to assess protein expression in placenta and fetal membranes at embryonic day E12, E15 and E18. Bgn−/−Dcn−/− dams displayed preterm birth, whereas the possession of at least two biglycan or decorin wild-type alleles was protective of preterm birth. Bgn−/−Dcn−/− pups were decreased at postnatal day P1 but not at E18. Biglycan and decorin were upregulated in the placenta in each other’s absence and were developmentally regulated in fetal membranes, suggesting that these two proteoglycans demonstrate genetic complementation and contribute to gestational success in a dose dependent manner. Thus, the biglycan/decorin null mutant mouse is a model of genetically induced preterm birth and perinatal loss. This model presents novel targets for preventive or therapeutic manipulation of preterm birth. PMID:21502335

  4. Nonhuman Primate Models of Chikungunya Virus Infection and Disease (CHIKV NHP Model

    Directory of Open Access Journals (Sweden)

    Rebecca Broeckel

    2015-09-01

    Full Text Available Chikungunya virus (CHIKV is a positive-sense RNA virus transmitted by Aedes mosquitoes. CHIKV is a reemerging Alphavirus that causes acute febrile illness and severe and debilitating polyarthralgia of the peripheral joints. Huge epidemics and the rapid spread of CHIKV seen in India and the Indian Ocean region established CHIKV as a global health concern. This concern was further solidified by the recent incursion of the virus into the Western hemisphere, a region without pre-existing immunity. Nonhuman primates (NHPs serve as excellent animal models for understanding CHIKV pathogenesis and pre-clinical assessment of vaccines and therapeutics. NHPs present advantages over rodent models because they are a natural amplification host for CHIKV and they share significant genetic and physiological homology with humans. CHIKV infection in NHPs results in acute fever, rash, viremia and production of type I interferon. NHPs develop CHIKV-specific B and T-cells, generating neutralizing antibodies and CHIKV-specific CD4+ and CD8+ T-cells. CHIKV establishes a persistent infection in NHPs, particularly in cynomolgus macaques, because infectious virus could be recovered from spleen, liver, and muscle as late as 44 days post infection. NHPs are valuable models that are useful in preclinical testing of vaccines and therapeutics and uncovering the details of CHIKV pathogenesis.

  5. In vivo biological effects of stereotactic radiosurgery: A primate model

    Energy Technology Data Exchange (ETDEWEB)

    Lunsford, L.D.; Altschuler, E.M.; Flickinger, J.C.; Wu, A.; Martinez, A.J. (Univ. of Pittsburgh School of Medicine, PA (USA))

    1990-09-01

    Single-fraction, closed skull, small-volume irradiation (radiosurgery) of intact intracranial structures requires accurate knowledge of radiation tolerance. We have developed a baboon model to assess the in vivo destructive radiobiological effects of stereotactic radiosurgery. Three baboons received a single-fraction, 150-Gy lesion of the caudate nucleus, the thalamus, or the pons using the 8-mm diameter collimator of the gamma unit. Serial standard neurodiagnostic tests (neurological examination, computed tomographic scan, magnetic resonance imaging, stable xenon-enhanced computed tomographic scan of cerebral blood flow, somatosensory and brain stem evoked potentials, and myelin basic protein levels of cerebrospinal fluid) were compared with preoperative studies. Magnetic resonance imaging revealed the development of a lesion at the target site between 45 and 60 days after irradiation. Deterioration of the brain stem evoked potentials preceded imaging changes when the lesion encroached on auditory pathways. Myelin basic protein levels increased subsequent to imaging changes. Postmortem neuropathological examination confirmed a well-demarcated radionecrosis of the target volume. The baboon model appears to be an excellent method to study the in vivo biological effects of radiosurgery.

  6. A non-human primate model for gluten sensitivity.

    Directory of Open Access Journals (Sweden)

    Michael T Bethune

    2008-02-01

    Full Text Available Gluten sensitivity is widespread among humans. For example, in celiac disease patients, an inflammatory response to dietary gluten leads to enteropathy, malabsorption, circulating antibodies against gluten and transglutaminase 2, and clinical symptoms such as diarrhea. There is a growing need in fundamental and translational research for animal models that exhibit aspects of human gluten sensitivity.Using ELISA-based antibody assays, we screened a population of captive rhesus macaques with chronic diarrhea of non-infectious origin to estimate the incidence of gluten sensitivity. A selected animal with elevated anti-gliadin antibodies and a matched control were extensively studied through alternating periods of gluten-free diet and gluten challenge. Blinded clinical and histological evaluations were conducted to seek evidence for gluten sensitivity.When fed with a gluten-containing diet, gluten-sensitive macaques showed signs and symptoms of celiac disease including chronic diarrhea, malabsorptive steatorrhea, intestinal lesions and anti-gliadin antibodies. A gluten-free diet reversed these clinical, histological and serological features, while reintroduction of dietary gluten caused rapid relapse.Gluten-sensitive rhesus macaques may be an attractive resource for investigating both the pathogenesis and the treatment of celiac disease.

  7. Life history of the most complete fossil primate skeleton: exploring growth models for Darwinius

    Science.gov (United States)

    López-Torres, Sergi; Schillaci, Michael A.; Silcox, Mary T.

    2015-01-01

    Darwinius is an adapoid primate from the Eocene of Germany, and its only known specimen represents the most complete fossil primate ever found. Its describers hypothesized a close relationship to Anthropoidea, and using a Saimiri model estimated its age at death. This study reconstructs the ancestral permanent dental eruption sequences for basal Euprimates, Haplorhini, Anthropoidea, and stem and crown Strepsirrhini. The results show that the ancestral sequences for the basal euprimate, haplorhine and stem strepsirrhine are identical, and similar to that of Darwinius. However, Darwinius differs from anthropoids by exhibiting early development of the lower third molars relative to the lower third and fourth premolars. The eruption of the lower second premolar marks the point of interruption of the sequence in Darwinius. The anthropoid Saimiri as a model is therefore problematic because it exhibits a delayed eruption of P2. Here, an alternative strepsirrhine model based on Eulemur and Varecia is presented. Our proposed model shows an older age at death than previously suggested (1.05–1.14 years), while the range for adult weight is entirely below the range proposed previously. This alternative model is more consistent with hypotheses supporting a stronger relationship between adapoids and strepsirrhines. PMID:26473056

  8. A Unilateral Cervical Spinal Cord Contusion Injury Model in Non-Human Primates (Macaca mulatta)

    Science.gov (United States)

    Salegio, Ernesto A.; Sparrey, Carolyn J.; Camisa, William; Fischer, Jason; Leasure, Jeremi; Buckley, Jennifer; Nout-Lomas, Yvette S.; Rosenzweig, Ephron S.; Moseanko, Rod; Strand, Sarah; Hawbecker, Stephanie; Lemoy, Marie-Josee; Haefeli, Jenny; Ma, Xiaokui; Nielson, Jessica L.; Edgerton, V.R.; Ferguson, Adam R.; Tuszynski, Mark H.

    2016-01-01

    Abstract The development of a non-human primate (NHP) model of spinal cord injury (SCI) based on mechanical and computational modeling is described. We scaled up from a rodent model to a larger primate model using a highly controllable, friction-free, electronically-driven actuator to generate unilateral C6-C7 spinal cord injuries. Graded contusion lesions with varying degrees of functional recovery, depending upon pre-set impact parameters, were produced in nine NHPs. Protocols and pre-operative magnetic resonance imaging (MRI) were used to optimize the predictability of outcomes by matching impact protocols to the size of each animal's spinal canal, cord, and cerebrospinal fluid space. Post-operative MRI confirmed lesion placement and provided information on lesion volume and spread for comparison with histological measures. We evaluated the relationships between impact parameters, lesion measures, and behavioral outcomes, and confirmed that these relationships were consistent with our previous studies in the rat. In addition to providing multiple univariate outcome measures, we also developed an integrated outcome metric describing the multivariate cervical SCI syndrome. Impacts at the higher ranges of peak force produced highly lateralized and enduring deficits in multiple measures of forelimb and hand function, while lower energy impacts produced early weakness followed by substantial recovery but enduring deficits in fine digital control (e.g., pincer grasp). This model provides a clinically relevant system in which to evaluate the safety and, potentially, the efficacy of candidate translational therapies. PMID:26788611

  9. Models of Stress in Nonhuman Primates and Their Relevance for Human Psychopathology and Endocrine Dysfunction

    Science.gov (United States)

    Meyer, Jerrold S.; Hamel, Amanda F.

    2014-01-01

    Stressful life events have been linked to the onset of severe psychopathology and endocrine dysfunction in many patients. Moreover, vulnerability to the later development of such disorders can be increased by stress or adversity during development (e.g., childhood neglect, abuse, or trauma). This review discusses the methodological features and results of various models of stress in nonhuman primates in the context of their potential relevance for human psychopathology and endocrine dysfunction, particularly mood disorders and dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) system. Such models have typically examined the effects of stress on the animals' behavior, endocrine function (primarily the HPA and hypothalamic-pituitary-gonadal systems), and, in some cases, immune status. Manipulations such as relocation and/or removal of an animal from its current social group or, alternatively, formation of a new social group can have adverse effects on all of these outcome measures that may be either transient or more persistent depending on the species, sex, and other experimental conditions. Social primates may also experience significant stress associated with their rank in the group's dominance hierarchy. Finally, stress during prenatal development or during the early postnatal period may have long-lasting neurobiological and endocrine effects that manifest in an altered ability to cope behaviorally and physiologically with later challenges. Whereas early exposure to severe stress usually results in deficient coping abilities, certain kinds of milder stressors can promote subsequent resilience in the animal. We conclude that studies of stress in nonhuman primates can model many features of stress exposure in human populations and that such studies can play a valuable role in helping to elucidate the mechanisms underlying the role of stress in human psychopathology and endocrine dysfunction. PMID:25225311

  10. Models of stress in nonhuman primates and their relevance for human psychopathology and endocrine dysfunction.

    Science.gov (United States)

    Meyer, Jerrold S; Hamel, Amanda F

    2014-01-01

    Stressful life events have been linked to the onset of severe psychopathology and endocrine dysfunction in many patients. Moreover, vulnerability to the later development of such disorders can be increased by stress or adversity during development (e.g., childhood neglect, abuse, or trauma). This review discusses the methodological features and results of various models of stress in nonhuman primates in the context of their potential relevance for human psychopathology and endocrine dysfunction, particularly mood disorders and dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) system. Such models have typically examined the effects of stress on the animals' behavior, endocrine function (primarily the HPA and hypothalamic-pituitary-gonadal systems), and, in some cases, immune status. Manipulations such as relocation and/or removal of an animal from its current social group or, alternatively, formation of a new social group can have adverse effects on all of these outcome measures that may be either transient or more persistent depending on the species, sex, and other experimental conditions. Social primates may also experience significant stress associated with their rank in the group's dominance hierarchy. Finally, stress during prenatal development or during the early postnatal period may have long-lasting neurobiological and endocrine effects that manifest in an altered ability to cope behaviorally and physiologically with later challenges. Whereas early exposure to severe stress usually results in deficient coping abilities, certain kinds of milder stressors can promote subsequent resilience in the animal. We conclude that studies of stress in nonhuman primates can model many features of stress exposure in human populations and that such studies can play a valuable role in helping to elucidate the mechanisms underlying the role of stress in human psychopathology and endocrine dysfunction. © The Author 2014. Published by Oxford University Press on

  11. Titi Monkeys as a Novel Non-Human Primate Model for the Neurobiology of Pair Bonding
.

    Science.gov (United States)

    Bales, Karen L; Arias Del Razo, Rocío; Conklin, Quinn A; Hartman, Sarah; Mayer, Heather S; Rogers, Forrest D; Simmons, Trenton C; Smith, Leigh K; Williams, Alexia; Williams, Donald R; Witczak, Lynea R; Wright, Emily C

    2017-09-01

    It is now widely recognized that social bonds are critical to human health and well-being. One of the most important social bonds is the attachment relationship between two adults, known as the pair bond . The pair bond involves many characteristics that are inextricably linked to quality of health, including providing a secure psychological base and acting as a social buffer against stress. The majority of our knowledge about the neurobiology of pair bonding comes from studies of a socially monogamous rodent, the prairie vole ( Microtus ochrogaster ), and from human imaging studies, which inherently lack control. Here, we first review what is known of the neurobiology of pair bonding from humans and prairie voles. We then present a summary of the studies we have conducted in titi monkeys ( Callicebus cupreus )-a species of socially monogamous New World primates. Finally, we construct a neural model based on the location of neuropeptide receptors in the titi monkey brain, as well as the location of neural changes in our imaging studies, with some basic assumptions based on the prairie vole model. In this model, we emphasize the role of visual mating stimuli as well as contributions of the dopaminergic reward system and a strong role for the lateral septum. This model represents an important step in understanding the neurobiology of social bonds in non-human primates, which will in turn facilitate a better understanding of these mechanisms in humans.

  12. An authentic animal model of the very preterm infant on nasal continuous positive airway pressure.

    Science.gov (United States)

    Dargaville, Peter A; Lavizzari, Anna; Padoin, Priscila; Black, Don; Zonneveld, Elroy; Perkins, Elizabeth; Sourial, Magdy; Rajapaksa, Anushi E; Davis, Peter G; Hooper, Stuart B; Moss, Timothy Jm; Polglase, Graeme R; Tingay, David G

    2015-12-01

    The surge in uptake of nasal continuous positive airway pressure (CPAP) for respiratory support in preterm infants has occurred in the absence of an authentic animal model. Such a model would allow investigation of research questions of physiological and therapeutic importance. We therefore aimed to develop a preterm lamb model of the non-intubated very preterm infant on CPAP. After staged exteriorisation and instrumentation, preterm lambs were delivered from anaesthetised ewes at 131 to 133 days gestation. Via a single nasal prong (4-mm internal diameter, 6- to 7-cm depth), positive pressure was delivered from the outset, with nasal intermittent positive pressure ventilation (NIPPV) used until transition to nasal CPAP was attempted, and periodically thereafter for hypoventilation. Caffeine and doxapram were used as respiratory stimulants. Gastric distension was prevented with an oesophageal balloon. Cardiorespiratory parameters and results of arterial blood gas analyses were monitored throughout the study period, which continued for 150 min after first transition to CPAP. Ten preterm lambs were studied, at gestation 132 ± 1 days (mean ± SD) and birth weight 3.6 ± 0.45 kg. After stabilisation on NIPPV, transition to nasal CPAP was first attempted at 28 ± 11 min. There was transient respiratory acidosis, with gradual resolution as spontaneous respiratory activity increased. In the final hour, 79% ± 33% of time was spent on CPAP alone, with typical respiratory rates around 60 breaths per minute. PaCO2 at end-experiment was 58 ± 36 mmHg. Non-intubated preterm lambs can be effectively transitioned to nasal CPAP soon after birth. This animal model will be valuable for further research.

  13. Nonhuman Primate Models of Type 1 Diabetes Mellitus for Islet Transplantation

    Directory of Open Access Journals (Sweden)

    Haitao Zhu

    2014-01-01

    Full Text Available Islet transplantation is an attractive treatment of type 1 diabetes mellitus (T1DM. Animal models of diabetes mellitus (DM contribute a lot to the experimental studies of islet transplantation and to evaluations of isolated islet grafts for future clinical applications. Diabetic nonhuman primates (NHPs represent the suitable models of DMs to better evaluate the effectiveness of islet transplantation, to assess new strategies for controlling blood glucose (BG, relieving immune rejection, or prolonging islet survival, and eventually to translate the preclinical data into tangible clinical practice. This review introduces some NHP models of DM, clarifies why and how the models should be used, and elucidates the usefulness and limitations of the models in islet transplantation.

  14. Preterm Birth

    Science.gov (United States)

    ... After hours (404) 639-2888 Contact Media Preterm Birth Recommend on Facebook Tweet Share Compartir Preterm birth ... Can anything be done to prevent a preterm birth? Preventing preterm birth remains a challenge because there ...

  15. Group size, grooming and fission in primates: a modeling approach based on group structure.

    Science.gov (United States)

    Sueur, Cédric; Deneubourg, Jean-Louis; Petit, Odile; Couzin, Iain D

    2011-03-21

    In social animals, fission is a common mode of group proliferation and dispersion and may be affected by genetic or other social factors. Sociality implies preserving relationships between group members. An increase in group size and/or in competition for food within the group can result in decrease certain social interactions between members, and the group may split irreversibly as a consequence. One individual may try to maintain bonds with a maximum of group members in order to keep group cohesion, i.e. proximity and stable relationships. However, this strategy needs time and time is often limited. In addition, previous studies have shown that whatever the group size, an individual interacts only with certain grooming partners. There, we develop a computational model to assess how dynamics of group cohesion are related to group size and to the structure of grooming relationships. Groups' sizes after simulated fission are compared to observed sizes of 40 groups of primates. Results showed that the relationship between grooming time and group size is dependent on how each individual attributes grooming time to its social partners, i.e. grooming a few number of preferred partners or grooming equally or not all partners. The number of partners seemed to be more important for the group cohesion than the grooming time itself. This structural constraint has important consequences on group sociality, as it gives the possibility of competition for grooming partners, attraction for high-ranking individuals as found in primates' groups. It could, however, also have implications when considering the cognitive capacities of primates. Copyright © 2010 Elsevier Ltd. All rights reserved.

  16. Technical note: Modeling primate occlusal topography using geographic information systems technology.

    Science.gov (United States)

    Zuccotti, L F; Williamson, M D; Limp, W F; Ungar, P S

    1998-09-01

    Most functional analyses of primate tooth form have been limited to linear or area measurements. Such studies have offered but a limited glimpse at differences in occlusal relief among taxa. Such differences in dental topography may relate to tooth function and, so, have considerable implications for the inference of diet from fossil teeth. In this article, we describe a technique to model and compare primate molars in three dimensions using Geographic Resources Analysis Support System (GRASS) software. We examine unworn lower second molars of three extant hominoids with known differences in diet (Gorilla gorilla, Pan troglodytes, and Pongo pygmaeus), and two fossil forms, (Afropithecus turkanesis and Dryopithecus laietanus). First, we obtained approximately 400 landmarks on the occlusal surfaces of each tooth using an electromagnetic digitizer. Raster "terrain models" of occlusal surfaces were then created by interpolation of the coordinate data. We used GRASS terrain analysis automated techniques to quantify the volumes and slopes of individual cusps. We also used the GRASS watershed technique to identify the volume of liquid that would accumulate in each tooth's basin (a measure of basin area), and the directions and intensity of drainage over the occlusal surface. In sum, GRASS shows considerable potential for the characterization and comparison of tooth surfaces. Furthermore, techniques described here are not limited to the study of teeth, but may be broadly applicable to studies of skulls, joints, and other biological structures.

  17. Protective efficacy of neutralizing monoclonal antibodies in a nonhuman primate model of Ebola hemorrhagic fever.

    Science.gov (United States)

    Marzi, Andrea; Yoshida, Reiko; Miyamoto, Hiroko; Ishijima, Mari; Suzuki, Yasuhiko; Higuchi, Megumi; Matsuyama, Yukie; Igarashi, Manabu; Nakayama, Eri; Kuroda, Makoto; Saijo, Masayuki; Feldmann, Friederike; Brining, Douglas; Feldmann, Heinz; Takada, Ayato

    2012-01-01

    Ebola virus (EBOV) is the causative agent of severe hemorrhagic fever in primates, with human case fatality rates up to 90%. Today, there is neither a licensed vaccine nor a treatment available for Ebola hemorrhagic fever (EHF). Single monoclonal antibodies (MAbs) specific for Zaire ebolavirus (ZEBOV) have been successfully used in passive immunization experiments in rodent models, but have failed to protect nonhuman primates from lethal disease. In this study, we used two clones of human-mouse chimeric MAbs (ch133 and ch226) with strong neutralizing activity against ZEBOV and evaluated their protective potential in a rhesus macaque model of EHF. Reduced viral loads and partial protection were observed in animals given MAbs ch133 and ch226 combined intravenously at 24 hours before and 24 and 72 hours after challenge. MAbs circulated in the blood of a surviving animal until virus-induced IgG responses were detected. In contrast, serum MAb concentrations decreased to undetectable levels at terminal stages of disease in animals that succumbed to infection, indicating substantial consumption of these antibodies due to virus replication. Accordingly, the rapid decrease of serum MAbs was clearly associated with increased viremia in non-survivors. Our results indicate that EBOV neutralizing antibodies, particularly in combination with other therapeutic strategies, might be beneficial in reducing viral loads and prolonging disease progression during EHF.

  18. Prospects for genetically modified non-human primate models, including the common marmoset.

    Science.gov (United States)

    Sasaki, Erika

    2015-04-01

    Genetically modified mice have contributed much to studies in the life sciences. In some research fields, however, mouse models are insufficient for analyzing the molecular mechanisms of pathology or as disease models. Often, genetically modified non-human primate (NHP) models are desired, as they are more similar to human physiology, morphology, and anatomy. Recent progress in studies of the reproductive biology in NHPs has enabled the introduction of exogenous genes into NHP genomes or the alteration of endogenous NHP genes. This review summarizes recent progress in the production of genetically modified NHPs, including the common marmoset, and future perspectives for realizing genetically modified NHP models for use in life sciences research. Copyright © 2015 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  19. Hydrogen and oxygen isotope ratios in body water and hair: modeling isotope dynamics in nonhuman primates.

    Science.gov (United States)

    O'Grady, Shannon P; Valenzuela, Luciano O; Remien, Christopher H; Enright, Lindsey E; Jorgensen, Matthew J; Kaplan, Jay R; Wagner, Janice D; Cerling, Thure E; Ehleringer, James R

    2012-07-01

    The stable isotopic composition of drinking water, diet, and atmospheric oxygen influence the isotopic composition of body water ((2)H/(1)H, (18)O/(16)O expressed as δ(2) H and δ(18)O). In turn, body water influences the isotopic composition of organic matter in tissues, such as hair and teeth, which are often used to reconstruct historical dietary and movement patterns of animals and humans. Here, we used a nonhuman primate system (Macaca fascicularis) to test the robustness of two different mechanistic stable isotope models: a model to predict the δ(2)H and δ(18)O values of body water and a second model to predict the δ(2)H and δ(18)O values of hair. In contrast to previous human-based studies, use of nonhuman primates fed controlled diets allowed us to further constrain model parameter values and evaluate model predictions. Both models reliably predicted the δ(2)H and δ(18)O values of body water and of hair. Moreover, the isotope data allowed us to better quantify values for two critical variables in the models: the δ(2)H and δ(18)O values of gut water and the (18)O isotope fractionation associated with a carbonyl oxygen-water interaction in the gut (α(ow)). Our modeling efforts indicated that better predictions for body water and hair isotope values were achieved by making the isotopic composition of gut water approached that of body water. Additionally, the value of α(ow) was 1.0164, in close agreement with the only other previously measured observation (microbial spore cell walls), suggesting robustness of this fractionation factor across different biological systems. © 2012 Wiley Periodicals, Inc.

  20. A novel highly reproducible and lethal nonhuman primate model for orthopox virus infection.

    Directory of Open Access Journals (Sweden)

    Marit Kramski

    Full Text Available The intentional re-introduction of Variola virus (VARV, the agent of smallpox, into the human population is of great concern due its bio-terroristic potential. Moreover, zoonotic infections with Cowpox (CPXV and Monkeypox virus (MPXV cause severe diseases in humans. Smallpox vaccines presently available can have severe adverse effects that are no longer acceptable. The efficacy and safety of new vaccines and antiviral drugs for use in humans can only be demonstrated in animal models. The existing nonhuman primate models, using VARV and MPXV, need very high viral doses that have to be applied intravenously or intratracheally to induce a lethal infection in macaques. To overcome these drawbacks, the infectivity and pathogenicity of a particular CPXV was evaluated in the common marmoset (Callithrix jacchus.A CPXV named calpox virus was isolated from a lethal orthopox virus (OPV outbreak in New World monkeys. We demonstrated that marmosets infected with calpox virus, not only via the intravenous but also the intranasal route, reproducibly develop symptoms resembling smallpox in humans. Infected animals died within 1-3 days after onset of symptoms, even when very low infectious viral doses of 5x10(2 pfu were applied intranasally. Infectious virus was demonstrated in blood, saliva and all organs analyzed.We present the first characterization of a new OPV infection model inducing a disease in common marmosets comparable to smallpox in humans. Intranasal virus inoculation mimicking the natural route of smallpox infection led to reproducible infection. In vivo titration resulted in an MID(50 (minimal monkey infectious dose 50% of 8.3x10(2 pfu of calpox virus which is approximately 10,000-fold lower than MPXV and VARV doses applied in the macaque models. Therefore, the calpox virus/marmoset model is a suitable nonhuman primate model for the validation of vaccines and antiviral drugs. Furthermore, this model can help study mechanisms of OPV pathogenesis.

  1. Olive baboons: a non-human primate model for testing dengue virus type 2 replication.

    Science.gov (United States)

    Valdés, Iris; Gil, Lázaro; Castro, Jorge; Odoyo, Damián; Hitler, Rikoi; Munene, Elephas; Romero, Yaremis; Ochola, Lucy; Cosme, Karelia; Kariuki, Thomas; Guillén, Gerardo; Hermida, Lisset

    2013-12-01

    This study evaluated the use of a non-human primate, the olive baboon (Papio anubis), as a model of dengue infection. Olive baboons closely resemble humans genetically and physiologically and have been used extensively for assessing novel vaccine formulations. Two doses of dengue virus type 2 (DENV-2) were tested in baboons: 10(3) and 10(4) pfu. Similarly, African green monkeys received the same quantity of virus and acted as positive controls. Following exposure, high levels of viremia were detected in both animal species. There was a trend to detect more days of viremia and more homogeneous viral titers in animals receiving the low viral dose. In addition, baboons infected with the virus generally exhibited positive virus isolation 1 day later than African green monkeys. Humoral responses consisting of antiviral and neutralizing antibodies were detected in all animals after infection. We conclude that baboons provide an alternative non-human primate species for experimental DENV-2 infection and we recommend their use for further tests of vaccines, administering the lowest dose assayed: 10(3) pfu. Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  2. Bioinformatic and statistical analysis of the optic nerve head in a primate model of ocular hypertension

    Directory of Open Access Journals (Sweden)

    Rasmussen Carol A

    2008-09-01

    Full Text Available Abstract Background The nonhuman primate model of glaucomatous optic neuropathy most faithfully reproduces the human disease. We used high-density oligonucleotide arrays to investigate whole genome transcriptional changes occurring at the optic nerve head during primate experimental glaucoma. Results Laser scarification of the trabecular meshwork of cynomolgus macaques produced elevated intraocular pressure that was monitored over time and led to varying degrees of damage in different samples. The macaques were examined clinically before enucleation and the myelinated optic nerves were processed post-mortem to determine the degree of neuronal loss. Global gene expression was examined in dissected optic nerve heads with Affymetrix GeneChip microarrays. We validated a subset of differentially expressed genes using qRT-PCR, immunohistochemistry, and immuno-enriched astrocytes from healthy and glaucomatous human donors. These genes have previously defined roles in axonal outgrowth, immune response, cell motility, neuroprotection, and extracellular matrix remodeling. Conclusion Our findings show that glaucoma is associated with increased expression of genes that mediate axonal outgrowth, immune response, cell motility, neuroprotection, and ECM remodeling. These studies also reveal that, as glaucoma progresses, retinal ganglion cell axons may make a regenerative attempt to restore lost nerve cell contact.

  3. Development of a Nonhuman Primate (Rhesus Macaque) Model of Uncontrolled Traumatic Liver Hemorrhage.

    Science.gov (United States)

    Sheppard, Forest R; Macko, Antoni; Fryer, Darren M; Ozuna, Kassandra M; Brown, Alexander K; Crossland, Randy F; Tadaki, Douglas K

    2015-08-01

    Hemorrhage is the leading cause of potentially survivable trauma mortality, necessitating the development of improved therapeutic interventions. The objective of this study was to develop and characterize a reproducible clinically translatable nonhuman primate model of uncontrolled severe hemorrhage. Such a model is required to facilitate the development and meaningful evaluation of human-derived therapeutics. In Rhesus macaques, a laparoscopic left-lobe hepatectomy of 25% (n = 2), 50% (n = 4), or 60% (n = 6) was performed at T = 0 min, with no attempt at hemorrhage control until T = 120 min. A constant-rate infusion of normal saline was administered between T = 15 and 120 min to a total volume of 20 mL/kg. At T = 120 min, a laparotomy was performed to gain surgical hemostasis and quantify blood loss. Physiological parameters were recorded, and blood samples were collected at defined intervals until termination of the study at T = 480 min. Statistical analyses used Student t tests, with P < 0.05 considered statistically significant. Results are reported as mean ± SEM. The calculated percent blood loss for the 25% hepatectomy group was negligible (2.3% ± 0.2%), whereas the 50% and 60% hepatectomy groups exhibited 26.6% ± 7.1% and 24.9% ± 3.8% blood loss, respectively. At T = 5 min, blood pressure for the 25%, 50%, and 60% hepatectomy groups was reduced by 13.8%, 60.8%, and 63.2% from the respective baseline values (P < 0.05). In the 60% hepatectomy group, alterations in thromboelastometry parameters and systemic inflammatory markers were observed. The development of a translatable nonhuman primate model of uncontrolled hemorrhage is an ongoing process. This study demonstrates that 60% hepatectomy offers a significant reproducible injury applicable for the evaluation of human-derived therapeutics.

  4. Modeling Zika plasma viral dynamics in non-human primates: insights into viral pathogenesis and antiviral strategies

    Energy Technology Data Exchange (ETDEWEB)

    Best, Katharine [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Guedj, Jeremie [Univ. of Paris (France). IAME; Madelain, Vincent [Univ. of Paris (France); de Lamballerie, Xavier [Aix-Marseille Univ. (France); L, So-Yonim [Harvard Univ., Cambridge, MA (United States). Center for Virology and Vaccine Research; Osuna, Christa E [Harvard Univ., Cambridge, MA (United States). Center for Virology and Vaccine Research; Whitney, James [Harvard Univ., Cambridge, MA (United States). Center for Virology and Vaccine Research; Perelson, Alan S. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-10-24

    The recent outbreak of Zika virus (ZIKV) has been associated with fetal abnormalities and neurological complications, prompting global concern. Here we present the first mathematical analysis of the within-host dynamics of plasma ZiKV burden in a non-human primate model, allowing for characterization of the growth and clearance of ZIKV within an individual macaque.

  5. Genome editing in nonhuman primates: approach to generating human disease models.

    Science.gov (United States)

    Chen, Y; Niu, Y; Ji, W

    2016-09-01

    Nonhuman primates (NHPs) are superior than rodents to be animal models for the study of human diseases, due to their similarities in terms of genetics, physiology, developmental biology, social behaviour and cognition. Transgenic animals have become a key tool in functional genomics to generate models for human diseases and validate new drugs. However, until now, progress in the field of transgenic NHPs has been slow because of technological limitations. Many human diseases, including neurodegenerative disorders, are caused by mutations in endogenous genes. Fortunately, recent developments in precision gene editing have led to the generation of NHP models for human diseases. Since 2014, there have been several reports of the generation of monkey models using transcription activator-like endonucleases (TALENs) or clustered regularly interspaced short palindromic repeats (CRISPR/Cas9); some of these NHP models showed symptoms that were much closer to those of human diseases than have been seen previously in mouse models. No off-targeting was observed in the NHP models, and multiple gene knockout and biallelic mutants were feasible with low efficiency. These findings suggest that there are many possibilities to establish NHP models for human diseases that can mimic human diseases more faithfully than rodent models. © 2016 The Association for the Publication of the Journal of Internal Medicine.

  6. Understanding primate brain evolution

    OpenAIRE

    Dunbar, R.I.M; Shultz, Susanne

    2007-01-01

    We present a detailed reanalysis of the comparative brain data for primates, and develop a model using path analysis that seeks to present the coevolution of primate brain (neocortex) and sociality within a broader ecological and life-history framework. We show that body size, basal metabolic rate and life history act as constraints on brain evolution and through this influence the coevolution of neocortex size and group size. However, they do not determine either of these variables, which ap...

  7. Antibody-Mediated Rejection in Sensitized Nonhuman Primates: Modeling Human Biology.

    Science.gov (United States)

    Burghuber, C K; Kwun, J; Page, E J; Manook, M; Gibby, A C; Leopardi, F V; Song, M; Farris, A B; Hong, J J; Villinger, F; Adams, A B; Iwakoshi, N N; Knechtle, S J

    2016-06-01

    We have established a model of sensitization in nonhuman primates and tested two immunosuppressive regimens. Animals underwent fully mismatched skin transplantation, and donor-specific antibody (DSA) response was monitored by flow cross-match. Sensitized animals subsequently underwent kidney transplantation from their skin donor. Immunosuppression included tacrolimus, mycophenolate, and methylprednisolone. Three animals received basiliximab induction; compared with nonsensitized animals, they showed a shorter mean survival time (4.7 ± 3.1 vs. 187 ± 88 days). Six animals were treated with T cell depletion (anti-CD4/CD8 mAbs), which prolonged survival (mean survival time 21.6 ± 19.0 days). All presensitized animals showed antibody-mediated rejection (AMR). In two of three basiliximab-injected animals, cellular rejection (ACR) was prominent. After T cell depletion, three of six monkeys experienced early acute rejection within 8 days with histological evidence of thrombotic microangiopathy and AMR. The remaining three monkeys survived 27-44 days, with mixed AMR and ACR. Most T cell-depleted animals experienced a rebound of DSA that correlated with deteriorating kidney function. We also found an increase in proliferating memory B cells (CD20(+) CD27(+) IgD(-) Ki67(+) ), lymph node follicular helper T cells (ICOS(+) PD-1(hi) CXCR5(+) CD4(+) ), and germinal center (GC) response. Depletion controlled cell-mediated rejection in sensitized nonhuman primates better than basiliximab, yet grafts were rejected with concomitant DSA rise. This model provides an opportunity to test novel desensitization strategies. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  8. Preterm infant gut microbiota affects intestinal epithelial development in a humanized microbiome gnotobiotic mouse model.

    Science.gov (United States)

    Yu, Yueyue; Lu, Lei; Sun, Jun; Petrof, Elaine O; Claud, Erika C

    2016-09-01

    Development of the infant small intestine is influenced by bacterial colonization. To promote establishment of optimal microbial communities in preterm infants, knowledge of the beneficial functions of the early gut microbiota on intestinal development is needed. The purpose of this study was to investigate the impact of early preterm infant microbiota on host gut development using a gnotobiotic mouse model. Histological assessment of intestinal development was performed. The differentiation of four epithelial cell lineages (enterocytes, goblet cells, Paneth cells, enteroendocrine cells) and tight junction (TJ) formation was examined. Using weight gain as a surrogate marker for health, we found that early microbiota from a preterm infant with normal weight gain (MPI-H) induced increased villus height and crypt depth, increased cell proliferation, increased numbers of goblet cells and Paneth cells, and enhanced TJs compared with the changes induced by early microbiota from a poor weight gain preterm infant (MPI-L). Laser capture microdissection (LCM) plus qRT-PCR further revealed, in MPI-H mice, a higher expression of stem cell marker Lgr5 and Paneth cell markers Lyz1 and Cryptdin5 in crypt populations, along with higher expression of the goblet cell and mature enterocyte marker Muc3 in villus populations. In contrast, MPI-L microbiota failed to induce the aforementioned changes and presented intestinal characteristics comparable to a germ-free host. Our data demonstrate that microbial communities have differential effects on intestinal development. Future studies to identify pioneer settlers in neonatal microbial communities necessary to induce maturation may provide new insights for preterm infant microbial ecosystem therapeutics. Copyright © 2016 the American Physiological Society.

  9. A computational model of the development of separate representations of facial identity and expression in the primate visual system.

    Science.gov (United States)

    Tromans, James Matthew; Harris, Mitchell; Stringer, Simon Maitland

    2011-01-01

    Experimental studies have provided evidence that the visual processing areas of the primate brain represent facial identity and facial expression within different subpopulations of neurons. For example, in non-human primates there is evidence that cells within the inferior temporal gyrus (TE) respond primarily to facial identity, while cells within the superior temporal sulcus (STS) respond to facial expression. More recently, it has been found that the orbitofrontal cortex (OFC) of non-human primates contains some cells that respond exclusively to changes in facial identity, while other cells respond exclusively to facial expression. How might the primate visual system develop physically separate representations of facial identity and expression given that the visual system is always exposed to simultaneous combinations of facial identity and expression during learning? In this paper, a biologically plausible neural network model, VisNet, of the ventral visual pathway is trained on a set of carefully-designed cartoon faces with different identities and expressions. The VisNet model architecture is composed of a hierarchical series of four Self-Organising Maps (SOMs), with associative learning in the feedforward synaptic connections between successive layers. During learning, the network develops separate clusters of cells that respond exclusively to either facial identity or facial expression. We interpret the performance of the network in terms of the learning properties of SOMs, which are able to exploit the statistical indendependence between facial identity and expression.

  10. A computational model of the development of separate representations of facial identity and expression in the primate visual system.

    Directory of Open Access Journals (Sweden)

    James Matthew Tromans

    Full Text Available Experimental studies have provided evidence that the visual processing areas of the primate brain represent facial identity and facial expression within different subpopulations of neurons. For example, in non-human primates there is evidence that cells within the inferior temporal gyrus (TE respond primarily to facial identity, while cells within the superior temporal sulcus (STS respond to facial expression. More recently, it has been found that the orbitofrontal cortex (OFC of non-human primates contains some cells that respond exclusively to changes in facial identity, while other cells respond exclusively to facial expression. How might the primate visual system develop physically separate representations of facial identity and expression given that the visual system is always exposed to simultaneous combinations of facial identity and expression during learning? In this paper, a biologically plausible neural network model, VisNet, of the ventral visual pathway is trained on a set of carefully-designed cartoon faces with different identities and expressions. The VisNet model architecture is composed of a hierarchical series of four Self-Organising Maps (SOMs, with associative learning in the feedforward synaptic connections between successive layers. During learning, the network develops separate clusters of cells that respond exclusively to either facial identity or facial expression. We interpret the performance of the network in terms of the learning properties of SOMs, which are able to exploit the statistical indendependence between facial identity and expression.

  11. ICRP 67 Biokinetic Models for AM-241 Applied to Nonhuman Primates.

    Science.gov (United States)

    Alomairy, Nada A; Brey, Richard R; Guilmette, Raymond A

    2017-05-01

    Between 1960 and 1985, Patricia Durbin and colleagues performed studies on the distribution of intravenously and intramuscularly injected Am citrate with dosages ranging from 16 to 32 kBq kg in 30 male and female non-human primates (NHP). Dr. Durbin died unexpectedly in March of 2009, leaving much of the extensive serial blood, bioassay, and autopsy data from these NHP studies unanalyzed. As part of the experimental design, serial blood samples were taken, and urine and feces samples were collected separately for the duration of the study. The measurements of urine, fecal excretion, blood samples, and organ burden data obtained from the animals were used to evaluate the transfer rates of the ICRP 67 biokinetic model for Am. Seven cases, in which the primates were administered Am citrate by intravenous injection, were evaluated using the ICRP 67 systemic model. There were differences ranging from 51.4% underestimated to 102.7% overestimated activity between the predicted intake, which was calculated using IMBA Professional Plus software and based upon the urine bioassay data and the actual activity. The difference between the predicted activity at the time of death in the liver and skeleton using IMBA professional software and the value of the measured activity at the time of death were also compared. Generally, the ratios of predicted activity in the liver and skeleton at the time of death to the measured activity were consistently more than 1. However, the ratios were less than 1 in the skeleton for animals that were sacrificed 2,199 and 973 d post injection. The posterior probability distributions for model parameters derived using WeLMoS method were inconsistent with the ICRP 67 default parameters. The prediction made based on the posterior probability distributions for model parameters derived using WeLMoS gave the best fit to these data; however, the modified parameters overestimated the activity in almost all cases. The difference between the predicted Am

  12. Advances in nonhuman primate models of autism: Integrating neuroscience and behavior.

    Science.gov (United States)

    Bauman, M D; Schumann, C M

    2018-01-01

    Given the prevalence and societal impact of autism spectrum disorders (ASD), there is an urgent need to develop innovative preventative strategies and treatments to reduce the alarming number of cases and improve core symptoms for afflicted individuals. Translational efforts between clinical and preclinical research are needed to (i) identify and evaluate putative causes of ASD, (ii) determine the underlying neurobiological mechanisms, (iii) develop and test novel therapeutic approaches and (iv) ultimately translate basic research into safe and effective clinical practices. However, modeling a uniquely human brain disorder, such as ASD, will require sophisticated animal models that capitalize on unique advantages of diverse species including drosophila, zebra fish, mice, rats, and ultimately, species more closely related to humans, such as the nonhuman primate. Here we discuss the unique contributions of the rhesus monkey (Macaca mulatta) model to ongoing efforts to understand the neurobiology of the disorder, focusing on the convergence of brain and behavior outcome measures that parallel features of human ASD. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Non human primate models for Alzheimer's disease-related research and drug discovery

    NARCIS (Netherlands)

    Van Dam, Debby; De Deyn, Peter Paul

    2017-01-01

    Introduction: Pathophysiological mechanisms underlying Alzheimer's disease (AD) remain insufficiently documented for the identification of accurate diagnostic markers and purposeful target discovery and development. Nonhuman primates (NHPs) have important translational value given their close

  14. A Nonhuman Primate Model of Human Radiation-Induced Venocclusive Liver Disease and Hepatocyte Injury

    Energy Technology Data Exchange (ETDEWEB)

    Yannam, Govardhana Rao [Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska (United States); Han, Bing [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi' an Jiaotong University, Xi' an, Shaanxi (China); Setoyama, Kentaro [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Yamamoto, Toshiyuki [Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska (United States); Ito, Ryotaro; Brooks, Jenna M. [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Guzman-Lepe, Jorge [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Department of Pathology, Children' s Hospital of Pittsburgh, Pittsburgh, Pennsylvania (United States); Galambos, Csaba [Department of Pathology, Children' s Hospital of Pittsburgh, Pittsburgh, Pennsylvania (United States); Fong, Jason V. [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Deutsch, Melvin; Quader, Mubina A. [Department of Radiation Oncology, Children' s Hospital of Pittsburgh, Pittsburgh, Pennsylvania (United States); Yamanouchi, Kosho [Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York (United States); Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, New York (United States); Kabarriti, Rafi; Mehta, Keyur [Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York (United States); Soto-Gutierrez, Alejandro [Department of Pathology, Children' s Hospital of Pittsburgh, Pittsburgh, Pennsylvania (United States); McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); and others

    2014-02-01

    Background: Human liver has an unusual sensitivity to radiation that limits its use in cancer therapy or in preconditioning for hepatocyte transplantation. Because the characteristic veno-occlusive lesions of radiation-induced liver disease do not occur in rodents, there has been no experimental model to investigate the limits of safe radiation therapy or explore the pathogenesis of hepatic veno-occlusive disease. Methods and Materials: We performed a dose-escalation study in a primate, the cynomolgus monkey, using hypofractionated stereotactic body radiotherapy in 13 animals. Results: At doses ≥40 Gy, animals developed a systemic syndrome resembling human radiation-induced liver disease, consisting of decreased albumin, elevated alkaline phosphatase, loss of appetite, ascites, and normal bilirubin. Higher radiation doses were lethal, causing severe disease that required euthanasia approximately 10 weeks after radiation. Even at lower doses in which radiation-induced liver disease was mild or nonexistent, latent and significant injury to hepatocytes was demonstrated by asialoglycoprotein-mediated functional imaging. These monkeys developed hepatic failure with encephalopathy when they received parenteral nutrition containing high concentrations of glucose. Histologically, livers showed central obstruction via an unusual intimal swelling that progressed to central fibrosis. Conclusions: The cynomolgus monkey, as the first animal model of human veno-occlusive radiation-induced liver disease, provides a resource for characterizing the early changes and pathogenesis of venocclusion, for establishing nonlethal therapeutic dosages, and for examining experimental therapies to minimize radiation injury.

  15. A Nonhuman Primate Model of Human Radiation-Induced Venocclusive Liver Disease and Hepatocyte Injury

    International Nuclear Information System (INIS)

    Yannam, Govardhana Rao; Han, Bing; Setoyama, Kentaro; Yamamoto, Toshiyuki; Ito, Ryotaro; Brooks, Jenna M.; Guzman-Lepe, Jorge; Galambos, Csaba; Fong, Jason V.; Deutsch, Melvin; Quader, Mubina A.; Yamanouchi, Kosho; Kabarriti, Rafi; Mehta, Keyur; Soto-Gutierrez, Alejandro

    2014-01-01

    Background: Human liver has an unusual sensitivity to radiation that limits its use in cancer therapy or in preconditioning for hepatocyte transplantation. Because the characteristic veno-occlusive lesions of radiation-induced liver disease do not occur in rodents, there has been no experimental model to investigate the limits of safe radiation therapy or explore the pathogenesis of hepatic veno-occlusive disease. Methods and Materials: We performed a dose-escalation study in a primate, the cynomolgus monkey, using hypofractionated stereotactic body radiotherapy in 13 animals. Results: At doses ≥40 Gy, animals developed a systemic syndrome resembling human radiation-induced liver disease, consisting of decreased albumin, elevated alkaline phosphatase, loss of appetite, ascites, and normal bilirubin. Higher radiation doses were lethal, causing severe disease that required euthanasia approximately 10 weeks after radiation. Even at lower doses in which radiation-induced liver disease was mild or nonexistent, latent and significant injury to hepatocytes was demonstrated by asialoglycoprotein-mediated functional imaging. These monkeys developed hepatic failure with encephalopathy when they received parenteral nutrition containing high concentrations of glucose. Histologically, livers showed central obstruction via an unusual intimal swelling that progressed to central fibrosis. Conclusions: The cynomolgus monkey, as the first animal model of human veno-occlusive radiation-induced liver disease, provides a resource for characterizing the early changes and pathogenesis of venocclusion, for establishing nonlethal therapeutic dosages, and for examining experimental therapies to minimize radiation injury

  16. Monitoring and Counteracting Functional Deterioration in Parkinson’s Disease: A Multilevel Integrative Approach in a Primate Model System

    Science.gov (United States)

    2007-09-01

    Philippens CONTRACTING ORGANIZATION: TNO Defense Safety and Security RYSWYK 2288GJ REPORT DATE: September 2007...approach in a primate model system 5b. GRANT NUMBER W81XWH-05-1-0517 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Philippens , Ingrid, H.; Verhave... Philippens , 2006) it has generally accepted to have a well tolerated profile in human users (Bensimon et al., 1994). The ‘drowsiness’ does seem to have

  17. Does body posture influence hand preference in an ancestral primate model?

    Directory of Open Access Journals (Sweden)

    Leliveld Lisette

    2011-02-01

    Full Text Available Abstract Background The origin of human handedness and its evolution in primates is presently under debate. Current hypotheses suggest that body posture (postural origin hypothesis and bipedalism hypothesis have an important impact on the evolution of handedness in primates. To gain insight into the origin of manual lateralization in primates, we studied gray mouse lemurs, suggested to represent the most ancestral primate condition. First, we investigated hand preference in a simple food grasping task to explore the importance of hand usage in a natural foraging situation. Second, we explored the influence of body posture by applying a forced food grasping task with varying postural demands (sit, biped, cling, triped. Results The tested mouse lemur population did not prefer to use their hands alone to grasp for food items. Instead, they preferred to pick them up using a mouth-hand combination or the mouth alone. If mouth usage was inhibited, they showed an individual but no population level handedness for all four postural forced food grasping tasks. Additionally, we found no influence of body posture on hand preference in gray mouse lemurs. Conclusion Our results do not support the current theories of primate handedness. Rather, they propose that ecological adaptation indicated by postural habit and body size of a given species has an important impact on hand preference in primates. Our findings suggest that small-bodied, quadrupedal primates, adapted to the fine branch niche of dense forests, prefer mouth retrieval of food and are less manually lateralized than large-bodied species which consume food in a more upright, and less stable body posture.

  18. Hyperopic refractive correction by LASIK, SMILE or lenticule reimplantation in a non-human primate model.

    Science.gov (United States)

    Williams, Geraint P; Wu, Benjamin; Liu, Yu Chi; Teo, Ericia; Nyein, Chan L; Peh, Gary; Tan, Donald T; Mehta, Jodhbir S

    2018-01-01

    Hyperopia is a common refractive error, apparent in 25% of Europeans. Treatments include spectacles, contact lenses, laser interventions and surgery including implantable contact lenses and lens extraction. Laser treatment offers an expedient and reliable means of correcting ametropia. LASIK is well-established however SMILE (small-incision lenticule extraction) or lenticule implantation (derived from myopic laser-correction) are newer options. In this study we compared the outcomes of hyperopic LASIK, SMILE and lenticule re-implantation in a primate model at +2D/+4D treatment. While re-implantation showed the greatest regression, broadly comparable refractive results were seen at 3-months with SMILE and LASIK (<1.4D of intended), but a greater tendency to regression in +2D lenticule reimplantation. Central corneal thickness showed greater variation at +2D treatment, but central thickening during lenticule reimplantation at +4D treatment was seen (-17± 27μm LASIK, -45 ± 18μm SMILE and 28 ± 17μm Re-implantation; p <0.01) with expected paracentral thinning following SMILE. Although in vivo confocal microscopy appeared to show higher reflectivity in all +4D treatment groups, there were minimal and inconsistent changes in inflammatory responses between modalities. SMILE and lenticule re-implantation may represent a safe and viable method for treating hyperopia, but further optimization for lower hyperopic treatments is warranted.

  19. Environmental modulation of drug taking: Nonhuman primate models of cocaine abuse and PET neuroimaging.

    Science.gov (United States)

    Nader, Michael A; Banks, Matthew L

    2014-01-01

    The current review highlights the importance of environmental variables on cocaine self-administration in nonhuman primate models of drug abuse. In addition to describing the behavioral consequences, potential mechanisms of action are discussed, based on imaging results using the non-invasive and translational technique of positron emission tomography (PET). In this review, the role of three environmental variables - both positive and negative - are described: alternative non-drug reinforcers; social rank (as an independent variable) and punishment of cocaine self-administration. These environmental stimuli can profoundly influence brain function and drug self-administration. We focus on environmental manipulations involving non-drug alternatives (e.g., food reinforcement) using choice paradigms. Manipulations such as response cost and social variables (e.g., social rank, social stress) also influence the behavioral effects of drugs. Importantly, these manipulations are amenable to brain imaging studies. Taken together, these studies emphasize the profound impact environmental variables can have on drug taking, which should provide important information related to individual-subject variability in treatment responsiveness, and the imaging work may highlight pharmacological targets for medications related to treating drug abuse. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Perceptual learning in a non-human primate model of artificial vision.

    Science.gov (United States)

    Killian, Nathaniel J; Vurro, Milena; Keith, Sarah B; Kyada, Margee J; Pezaris, John S

    2016-11-22

    Visual perceptual grouping, the process of forming global percepts from discrete elements, is experience-dependent. Here we show that the learning time course in an animal model of artificial vision is predicted primarily from the density of visual elements. Three naïve adult non-human primates were tasked with recognizing the letters of the Roman alphabet presented at variable size and visualized through patterns of discrete visual elements, specifically, simulated phosphenes mimicking a thalamic visual prosthesis. The animals viewed a spatially static letter using a gaze-contingent pattern and then chose, by gaze fixation, between a matching letter and a non-matching distractor. Months of learning were required for the animals to recognize letters using simulated phosphene vision. Learning rates increased in proportion to the mean density of the phosphenes in each pattern. Furthermore, skill acquisition transferred from trained to untrained patterns, not depending on the precise retinal layout of the simulated phosphenes. Taken together, the findings suggest that learning of perceptual grouping in a gaze-contingent visual prosthesis can be described simply by the density of visual activation.

  1. Primates in Human-Modified and Fragmented Landscapes: The Conservation Relevance of Modelling Habitat and Disturbance Factors in Density Estimation.

    Directory of Open Access Journals (Sweden)

    Nathalie Cavada

    Full Text Available Accurate density estimations of threatened animal populations is essential for management and conservation. This is particularly critical for species living in patchy and altered landscapes, as is the case for most tropical forest primates. In this study, we used a hierarchical modelling approach that incorporates the effect of environmental covariates on both the detection (i.e. observation and the state (i.e. abundance processes of distance sampling. We applied this method to already published data on three arboreal primates of the Udzungwa Mountains of Tanzania, including the endangered and endemic Udzungwa red colobus (Procolobus gordonorum. The area is a primate hotspot at continental level. Compared to previous, 'canonical' density estimates, we found that the inclusion of covariates in the modelling makes the inference process more informative, as it takes in full account the contrasting habitat and protection levels among forest blocks. The correction of density estimates for imperfect detection was especially critical where animal detectability was low. Relative to our approach, density was underestimated by the canonical distance sampling, particularly in the less protected forest. Group size had an effect on detectability, determining how the observation process varies depending on the socio-ecology of the target species. Lastly, as the inference on density is spatially-explicit to the scale of the covariates used in the modelling, we could confirm that primate densities are highest in low-to-mid elevations, where human disturbance tend to be greater, indicating a considerable resilience by target monkeys in disturbed habitats. However, the marked trend of lower densities in unprotected forests urgently calls for effective forest protection.

  2. The primate community of Cachoeira (Brazilian Amazonia): a model to decipher ecological partitioning among extinct species.

    Science.gov (United States)

    Ramdarshan, Anusha; Alloing-Séguier, Thomas; Merceron, Gildas; Marivaux, Laurent

    2011-01-01

    Dental microwear analysis is conducted on a community of platyrrhine primates from South America. This analysis focuses on the primate community of Cachoeira Porteira (Para, Brazil), in which seven sympatric species occur: Alouatta seniculus, Ateles paniscus, Cebus apella, Chiropotes satanas, Pithecia Pithecia, Saguinus midas, and Saimiri sciureus. Shearing quotients are also calculated for each taxon of this primate community. Dental microwear results indicate significant differences between taxa, but are somewhat insufficient when it comes to discriminating between ecologically similar taxa. The primates of Cachoeira Porteira all incorporate a certain amount of fruit in their diet, entailing a definite amount of inter-specific competition as they must share food resources. Alouatta is the most folivorous taxon of this community, which is corroborated by dental microwear analysis. Ateles, although of a similar size to Alouatta, limits inter-specific competition by incorporating more fruit in its diet. Cebus has a very diverse omnivorous diet, which is highlighted in this study, as it compares to both fruit and leaf eating taxa. In some cases, microwear results need to be supplemented by other methods. For example, dental microwear seems insufficient to distinguish between Pithecia and Chiropotes, which eat foods with similar physical properties. However, other methods (i.e. shearing quotients and body mass) provide enough complimentary information to be able to highlight differences between the two taxa. On the other hand, dental microwear can highlight differences between primates which have similar diets, such as Saimiri and Saguinus. In this case, differences could be due to other exogenous factors.

  3. Evolutionary modeling and correcting for observation error support a 3/5 brain-body allometry for primates.

    Science.gov (United States)

    Grabowski, Mark; Voje, Kjetil L; Hansen, Thomas F

    2016-05-01

    The tight brain-body allometry across mammals and primates has motivated and informed many hypotheses about brain evolution in humans and other taxa. While a 2/3 or a 3/4 scaling is often at the core of such research, such exponents are derived from estimates based on particular statistical and evolutionary assumptions without careful consideration of how either may influence findings. Here we quantify primate brain-body allometry using phylogenetic comparative methods based on models of both adaptive and constrained evolution, and estimate and account for observational error in both response and predictor variables. Our results supported an evolutionary model in which brain size is directly constrained to evolve in unison with body size, rather than adapting to changes in the latter. The effects of controlling for phylogeny and observation error were substantial, and our analysis yielded a novel 3/5 scaling exponent for primate brain-body evolutionary allometry. Using this exponent with the latest brain- and body-size estimates to calculate new encephalization quotients for apes, humans, and fossil hominins, we found early hominins were substantially more encephalized than previously thought. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. The use of non-human primates as animal models for the study of hepatitis viruses

    Directory of Open Access Journals (Sweden)

    C.L. Vitral

    1998-08-01

    Full Text Available Hepatitis viruses belong to different families and have in common a striking hepatotropism and restrictions for propagation in cell culture. The transmissibility of hepatitis is in great part limited to non-human primates. Enterically transmitted hepatitis viruses (hepatitis A virus and hepatitis E virus can induce hepatitis in a number of Old World and New World monkey species, while the host range of non-human primates susceptible to hepatitis viruses transmitted by the parenteral route (hepatitis B virus, hepatitis C virus and hepatitis delta virus is restricted to few species of Old World monkeys, especially the chimpanzee. Experimental studies on non-human primates have provided an invaluable source of information regarding the biology and pathogenesis of these viruses, and represent a still indispensable tool for vaccine and drug testing.

  5. Biodistribution of Yttrium-90-Labeled Anti-CD45 Antibody in a Nonhuman Primate Model

    Energy Technology Data Exchange (ETDEWEB)

    Nemecek, Eneida; Hamlin, Donald K.; Fisher, Darrell R.; Krohn, Kenneth A.; Pagel, John M.; Applebaum, F. R.; Press, Oliver W.; Matthews, Dana C.

    2005-01-15

    Radioimmunotherapy may improve the outcome of hematopoietic cell transplantation for hematologic malignancies by delivering targeted radiation to hematopoietic organs while relatively sparing nontarget organs. We evaluated the organ localization of yttrium-90-labeled anti-CD45 (90Y-anti-CD45) antibody in macaques, a model that had previously predicted iodine-131-labeled anti-CD-45 (131I-anti-CD45) antibody biodistribution in humans. Experimental Design: Twelve Macaca nemestrina primates received anti-CD45 antibody labeled with 1 to 2 mCi of 90Y followed by serial blood sampling and marrow and lymph node biopsies, and necropsy. The content of 90Y per gram of tissue was determined by liquid scintillation spectrometry. Time-activity curves were constructed using average isotope concentrations in each tissue at measured time points to yield the fractional residence time and estimate radiation absorbed doses for each organ per unit of administered activity. The biodistribution of 90Y-anti-CD45 antibody was then compared with that previously obtained with 131I-anti-CD45 antibody in macaques. Results: The spleen received 2,120, marrow 1,060, and lymph nodes 315 cGy/mCi of 90Y injected. The liver and lungs were the nontarget organs receiving the highest radiation absorbed doses (440 and 285 cGy/mCi, respectively). Ytrrium-90-labeled anti-CD45 antibody delivered 2.5- and 3.7-fold more radiation to marrow than to liver and lungs, respectively. The ratios previously observed with 131I-antiCD45 antibody were 2.5-and 2.2-fold more radiation to marrow than to liver and lungs, respectively. Conclusions: This study shows that 90Y-anti-CD45 antibody can deliver relatively selective radiation to hematopoietic tissues, with similar ratios of radiation delivered to target versus nontarget organs, as compared with the 131I immunoconjugate in the same animal model.

  6. 3D printing and modelling of customized implants and surgical guides for non-human primates.

    Science.gov (United States)

    Chen, Xing; Possel, Jessy K; Wacongne, Catherine; van Ham, Anne F; Klink, P Christiaan; Roelfsema, Pieter R

    2017-07-15

    Primate neurobiologists use chronically implanted devices such as pedestals for head stabilization and chambers to gain access to the brain and study its activity. Such implants are skull-mounted, and made from a hard, durable material, such as titanium. Here, we present a low-cost method of creating customized 3D-printed cranial implants that are tailored to the anatomy of individual animals. We performed pre-surgical computed tomography (CT) and magnetic resonance (MR) scans to generate three-dimensional (3D) models of the skull and brain. We then used 3D modelling software to design implantable head posts, chambers, and a pedestal anchorage base, as well as craniotomy guides to aid us during surgery. Prototypes were made from plastic or resin, while implants were 3D-printed in titanium. The implants underwent post-processing and received a coating of osteocompatible material to promote bone integration. Their tailored fit greatly facilitated surgical implantation, and eliminated the gap between the implant and the bone. To date, our implants remain robust and well-integrated with the skull. Commercial-off-the-shelf solutions typically come with a uniform, flat base, preventing them from sitting flush against the curved surface of the skull. This leaves gaps for fluid and tissue ingress, increasing the risk of microbial infection and tissue inflammation, as well as implant loss. The use of 3D printing technology enabled us to quickly and affordably create unique, complex designs, avoiding the constraints levied by traditional production methods, thereby boosting experimental success and improving the wellbeing of the animals. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

  7. GROUP B STREPTOCOCCUS CIRCUMVENTS NEUTROPHILS AND NEUTROPHIL EXTRACELLULAR TRAPS DURING AMNIOTIC CAVITY INVASION AND PRETERM LABOR

    Science.gov (United States)

    Boldenow, Erica; Gendrin, Claire; Ngo, Lisa; Bierle, Craig; Vornhagen, Jay; Coleman, Michelle; Merillat, Sean; Armistead, Blair; Whidbey, Christopher; Alishetti, Varchita; Santana-Ufret, Veronica; Ogle, Jason; Gough, Michael; Srinouanprachanh, Sengkeo; MacDonald, James W; Bammler, Theo K; Bansal, Aasthaa; Liggitt, H. Denny; Rajagopal, Lakshmi; Waldorf, Kristina M Adams

    2016-01-01

    Preterm birth is a leading cause of neonatal morbidity and mortality. Although microbial invasion of the amniotic cavity (MIAC) is associated with the majority of early preterm births, the temporal events that occur during MIAC and preterm labor are not known. Group B Streptococci (GBS) are β-hemolytic, gram-positive bacteria, which commonly colonize the vagina but have been recovered from the amniotic fluid in preterm birth cases. To understand temporal events that occur during MIAC, we utilized a unique chronically catheterized nonhuman primate model that closely emulates human pregnancy. This model allows monitoring of uterine contractions, timing of MIAC and immune responses during pregnancy-associated infections. Here, we show that adverse outcomes such as preterm labor, MIAC, and fetal sepsis were observed more frequently during infection with hemolytic GBS when compared to nonhemolytic GBS. Although MIAC was associated with systematic progression in chorioamnionitis beginning with chorionic vasculitis and progressing to neutrophilic infiltration, the ability of the GBS hemolytic pigment toxin to induce neutrophil cell death and subvert killing by neutrophil extracellular traps (NETs) in placental membranes in vivo facilitated MIAC and fetal injury. Furthermore, compared to maternal neutrophils, fetal neutrophils exhibit decreased neutrophil elastase activity and impaired phagocytic functions to GBS. Collectively, our studies demonstrate how a unique bacterial hemolytic lipid toxin enables GBS to circumvent neutrophils and NETs in placental membranes to induce fetal injury and preterm labor. PMID:27819066

  8. Stochastic modeling of central apnea events in preterm infants

    Science.gov (United States)

    Clark, Matthew T.; Delos, John B.; Lake, Douglas E.; Lee, Hoshik; Fairchild, Karen D.; Kattwinkel, John; Moorman, J. Randall

    2016-01-01

    Summary A near-ubiquitous pathology in very low birth weight infants is neonatal apnea, breathing pauses with slowing of the heart and falling blood oxygen. Events of substantial duration occasionally occur after an infant is discharged from the NICU. It is not known whether apneas result from a predictable process or from a stochastic process, but the observation that they occur in seemingly random clusters justifies the use of stochastic models. We use a hidden-Markov model to analyze the distribution of durations of apneas and the distribution of times between apneas. The model suggests the presence of four breathing states, ranging from very stable (with an average lifetime of 12 hours) to very unstable (with an average lifetime of 10 seconds). Although the states themselves are not visible, the mathematical analysis gives estimates of the transition rates among these states. We have obtained these transition rates, and shown how they change with post-menstrual age; as expected, the residence time in the more stable breathing states increases with age. We also extrapolated the model to predict the frequency of very prolonged apnea during the first year of life. This paradigm – stochastic modeling of cardiorespiratory control in neonatal infants to estimate risk for severe clinical events – may be a first step toward personalized risk assessment for life threatening apnea events after NICU discharge. PMID:26963049

  9. Stochastic modeling of central apnea events in preterm infants

    International Nuclear Information System (INIS)

    Clark, Matthew T; Lake, Douglas E; Randall Moorman, J; Delos, John B; Lee, Hoshik; Fairchild, Karen D; Kattwinkel, John

    2016-01-01

    A near-ubiquitous pathology in very low birth weight infants is neonatal apnea, breathing pauses with slowing of the heart and falling blood oxygen. Events of substantial duration occasionally occur after an infant is discharged from the neonatal intensive care unit (NICU). It is not known whether apneas result from a predictable process or from a stochastic process, but the observation that they occur in seemingly random clusters justifies the use of stochastic models. We use a hidden-Markov model to analyze the distribution of durations of apneas and the distribution of times between apneas. The model suggests the presence of four breathing states, ranging from very stable (with an average lifetime of 12 h) to very unstable (with an average lifetime of 10 s). Although the states themselves are not visible, the mathematical analysis gives estimates of the transition rates among these states. We have obtained these transition rates, and shown how they change with post-menstrual age; as expected, the residence time in the more stable breathing states increases with age. We also extrapolated the model to predict the frequency of very prolonged apnea during the first year of life. This paradigm—stochastic modeling of cardiorespiratory control in neonatal infants to estimate risk for severe clinical events—may be a first step toward personalized risk assessment for life threatening apnea events after NICU discharge. (paper)

  10. Stochastic modeling of central apnea events in preterm infants.

    Science.gov (United States)

    Clark, Matthew T; Delos, John B; Lake, Douglas E; Lee, Hoshik; Fairchild, Karen D; Kattwinkel, John; Moorman, J Randall

    2016-04-01

    A near-ubiquitous pathology in very low birth weight infants is neonatal apnea, breathing pauses with slowing of the heart and falling blood oxygen. Events of substantial duration occasionally occur after an infant is discharged from the neonatal intensive care unit (NICU). It is not known whether apneas result from a predictable process or from a stochastic process, but the observation that they occur in seemingly random clusters justifies the use of stochastic models. We use a hidden-Markov model to analyze the distribution of durations of apneas and the distribution of times between apneas. The model suggests the presence of four breathing states, ranging from very stable (with an average lifetime of 12 h) to very unstable (with an average lifetime of 10 s). Although the states themselves are not visible, the mathematical analysis gives estimates of the transition rates among these states. We have obtained these transition rates, and shown how they change with post-menstrual age; as expected, the residence time in the more stable breathing states increases with age. We also extrapolated the model to predict the frequency of very prolonged apnea during the first year of life. This paradigm-stochastic modeling of cardiorespiratory control in neonatal infants to estimate risk for severe clinical events-may be a first step toward personalized risk assessment for life threatening apnea events after NICU discharge.

  11. Systemic Biodistribution and Intravitreal Pharmacokinetic Properties of Bevacizumab, Ranibizumab, and Aflibercept in a Nonhuman Primate Model.

    Science.gov (United States)

    Christoforidis, John Byron; Briley, Karen; Binzel, Katherine; Bhatia, Prayna; Wei, Lai; Kumar, Krishan; Knopp, Michael Vinzenz

    2017-11-01

    To determine the intravitreal pharmacokinetic properties and to study the systemic biodistribution characteristics of I-124-labeled bevacizumab, ranibizumab, and aflibercept with positron emission tomography-computed tomography (PET/CT) imaging in a nonhuman primate model. Three groups with four owl monkeys per group underwent intravitreal injection with 1.25 mg/0.05 mL I-124 bevacizumab, 0.5 mg/0.05 mL I-124 ranibizumab, or 2.0 mg/0.05 mL I-124 aflibercept in the right eye of each subject. All subjects were imaged using PET/CT on days 0, 1, 2, 4, 8, 14, 21, 28, and 35. Serum blood draws were performed at hours 1, 2, 4, 8, 12 and days 1, 2, 4, 8, 14, 21, 28, and 35. Radioactivity emission measurements were used to determine the intravitreal half-lives of each agent and to study the differences of radioactivity uptake in nonocular organs. The intravitreal half-lives were 3.60 days for I-124 bevacizumab, 2.73 days for I-124 ranibizumab, and 2.44 days for I-124 aflibercept. Serum levels were highest and most prolonged for bevacizumab as compared to both ranibizumab and aflibercept. All agents were primarily excreted through the renal and mononuclear phagocyte systems. However, bevacizumab was also found in significantly higher levels in the liver, heart, and distal femur bones. Among the three anti-VEGF agents used in clinical practice, bevacizumab demonstrated the longest intravitreal retention time and aflibercept the shortest. Significantly higher and prolonged levels of bevacizumab were found in the serum as well as in the heart, liver, and distal bones. These differences may be considered by clinicians when formulating treatment algorithms for intravitreal therapies with these agents.

  12. 3D printing and modelling of customized implants and surgical guides for non-human primates

    NARCIS (Netherlands)

    Chen, Xing; Possel, Jessy K.; Wacongne, Catherine; van Ham, Anne F.; Klink, P. Christiaan; Roelfsema, Pieter R.

    2017-01-01

    Background: Primate neurobiologists use chronically implanted devices such as pedestals for head stabilization and chambers to gain access to the brain and study its activity. Such implants are skull-mounted, and made from a hard, durable material, such as titanium. New method: Here, we present a

  13. 3D printing and modelling of customized implants and surgical guides for non-human primates

    NARCIS (Netherlands)

    Chen, Xing; Possel, Jessy K.; Wacongne, Catherine; van Ham, Anne F.; Klink, P. Christiaan; Roelfsema, Pieter R.

    2017-01-01

    Background Primate neurobiologists use chronically implanted devices such as pedestals for head stabilization and chambers to gain access to the brain and study its activity. Such implants are skull-mounted, and made from a hard, durable material, such as titanium. New method Here, we present a

  14. 3D printing and modelling of customized implants and surgical guides for non-human primates

    NARCIS (Netherlands)

    Chen, Xing; Possel, Jessy K; Wacongne, Catherine; van Ham, Anne F; Klink, P Christiaan; Roelfsema, Pieter R

    2017-01-01

    BACKGROUND: Primate neurobiologists use chronically implanted devices such as pedestals for head stabilization and chambers to gain access to the brain and study its activity. Such implants are skull-mounted, and made from a hard, durable material, such as titanium. NEW METHOD: Here, we present a

  15. Measles: What we have learned from non-human primate models

    NARCIS (Netherlands)

    R.L. de Swart (Rik)

    2018-01-01

    textabstractStudies in non-human primates (NHPs) have been crucial for our understanding of measles as a high impact viral disease of humans. Over a century ago, inoculations of NHPs with filtered secretions from measles patients first identified a virus as the causative agent of this disease. In

  16. Protection against Cutaneous Leishmaniasis Induced by Recombinant Antigens in Murine and Nonhuman Primate Models of the Human Disease

    Science.gov (United States)

    Campos-Neto, Antonio; Porrozzi, Renato; Greeson, Kay; Coler, Rhea N.; Webb, John R.; Seiky, Yasir A. W.; Reed, Steven G.; Grimaldi, Gabriel

    2001-01-01

    Leishmaniasis affects approximately 2 million people each year throughout the world. This high incidence is due in part to the lack of an efficacious vaccine. We present evidence that the recombinant leishmanial antigens LmSTI1 and TSA, which we identified and characterized previously, induce excellent protection in both murine and nonhuman primate (rhesus monkey) models of human cutaneous leishmaniasis. The remarkable protection induced by LmSTI1 and TSA in an animal model that is evolutionarily close to humans qualifies this antigen combination as a promising candidate subunit vaccine against human leishmaniasis. PMID:11349082

  17. Transcriptional modulation of intestinal innate defense/inflammation genes by preterm infant microbiota in a humanized gnotobiotic mouse model.

    Science.gov (United States)

    Lu, Lei; Yu, Yueyue; Guo, Yuee; Wang, Yunwei; Chang, Eugene B; Claud, Erika C

    2015-01-01

    It is known that postnatal functional maturation of the small intestine is facilitated by microbial colonization of the gut. Preterm infants exhibit defects in gut maturation, weak innate immunity against intestinal infection and increased susceptibility to inflammatory disorders, all of which may be related to the inappropriate microbial colonization of their immature intestines. The earliest microbes to colonize the preterm infant gut encounter a naïve, immature intestine. Thus this earliest microbiota potentially has the greatest opportunity to fundamentally influence intestinal development and immune function. The aim of this study was to characterize the effect of early microbial colonization on global gene expression in the distal small intestine during postnatal gut development. Gnotobiotic mouse models with experimental colonization by early (prior to two weeks of life) intestinal microbiota from preterm human infants were utilized. Microarray analysis was used to assess global gene expression in the intestinal epithelium. Multiple intestinal genes involved in metabolism, cell cycle regulation, cell-cell or cell-extracellular matrix communication, and immune function are developmental- and intestinal microbiota- regulated. Using a humanized gnotobiotic mouse model, we demonstrate that certain early preterm infant microbiota from prior to 2 weeks of life specifically induce increased NF-κB activation and a phenotype of increased inflammation whereas other preterm microbiota specifically induce decreased NF-κB activation. These fundamental differences correlate with altered clinical outcomes and suggest the existence of optimal early microbial communities to improve health outcomes.

  18. A semi-Markov chain approach to modeling respiratory patterns prior to extubation in preterm infants.

    Science.gov (United States)

    Onu, Charles C; Kanbar, Lara J; Shalish, Wissam; Brown, Karen A; Sant'Anna, Guilherme M; Kearney, Robert E; Precup, Doina

    2017-07-01

    After birth, extremely preterm infants often require specialized respiratory management in the form of invasive mechanical ventilation (IMV). Protracted IMV is associated with detrimental outcomes and morbidities. Premature extubation, on the other hand, would necessitate reintubation which is risky, technically challenging and could further lead to lung injury or disease. We present an approach to modeling respiratory patterns of infants who succeeded extubation and those who required reintubation which relies on Markov models. We compare the use of traditional Markov chains to semi-Markov models which emphasize cross-pattern transitions and timing information, and to multi-chain Markov models which can concisely represent non-stationarity in respiratory behavior over time. The models we developed expose specific, unique similarities as well as vital differences between the two populations.

  19. Preterm Labor

    Science.gov (United States)

    Preterm labor is labor that starts before 37 completed weeks of pregnancy. It can lead to premature birth. Premature babies may face serious health risks. Symptoms of preterm labor include Contractions every 10 minutes or more often ...

  20. The effect of bovine colostrum products on intestinal dysfunction and inflammation in a preterm pig model of necrotizing enterocolitis

    DEFF Research Database (Denmark)

    Støy, Ann Cathrine Findal

    and spray dried BC. The study showed that even though spray drying and pasteurization affected BC proteins, pasteurized and/or spray dried BC decreased the severity of NEC in pigs compared with milk formula, while a tendency towards lower NEC severity was observed in pig fed raw BC compared with milk......Necrotizing enterocolitis (NEC), primarily seen in preterm infants, is associated with high morbidity and mortality. The pathogenesis is not fully understood but risk factors include prematurity, enteral feeding (especially with milk formula), and the intestinal microbiota. Mother’s milk, rich...... in bioactive factors, has a protective effect against NEC, but not all preterm infants are able to receive mother’s milk. The overall aim of this thesis was to investigate if bovine colostrum (BC), also rich in bioactive factors, could serve as an alternative to mother’s milk. A preterm pig model of NEC...

  1. A model analysis of arterial oxygen desaturation during apnea in preterm infants.

    Science.gov (United States)

    Sands, Scott A; Edwards, Bradley A; Kelly, Vanessa J; Davidson, Malcolm R; Wilkinson, Malcolm H; Berger, Philip J

    2009-12-01

    Rapid arterial O(2) desaturation during apnea in the preterm infant has obvious clinical implications but to date no adequate explanation for why it exists. Understanding the factors influencing the rate of arterial O(2) desaturation during apnea (Sa(O)₂) is complicated by the non-linear O(2) dissociation curve, falling pulmonary O(2) uptake, and by the fact that O(2) desaturation is biphasic, exhibiting a rapid phase (stage 1) followed by a slower phase when severe desaturation develops (stage 2). Using a mathematical model incorporating pulmonary uptake dynamics, we found that elevated metabolic O(2) consumption accelerates Sa(O)₂throughout the entire desaturation process. By contrast, the remaining factors have a restricted temporal influence: low pre-apneic alveolar P(O)₂causes an early onset of desaturation, but thereafter has little impact; reduced lung volume, hemoglobin content or cardiac output, accelerates Sa(O)₂during stage 1, and finally, total blood O(2) capacity (blood volume and hemoglobin content) alone determines Sa(O)₂during stage 2. Preterm infants with elevated metabolic rate, respiratory depression, low lung volume, impaired cardiac reserve, anemia, or hypovolemia, are at risk for rapid and profound apneic hypoxemia. Our insights provide a basic physiological framework that may guide clinical interpretation and design of interventions for preventing sudden apneic hypoxemia.

  2. A model analysis of arterial oxygen desaturation during apnea in preterm infants.

    Directory of Open Access Journals (Sweden)

    Scott A Sands

    2009-12-01

    Full Text Available Rapid arterial O(2 desaturation during apnea in the preterm infant has obvious clinical implications but to date no adequate explanation for why it exists. Understanding the factors influencing the rate of arterial O(2 desaturation during apnea (Sa(O₂ is complicated by the non-linear O(2 dissociation curve, falling pulmonary O(2 uptake, and by the fact that O(2 desaturation is biphasic, exhibiting a rapid phase (stage 1 followed by a slower phase when severe desaturation develops (stage 2. Using a mathematical model incorporating pulmonary uptake dynamics, we found that elevated metabolic O(2 consumption accelerates Sa(O₂throughout the entire desaturation process. By contrast, the remaining factors have a restricted temporal influence: low pre-apneic alveolar P(O₂causes an early onset of desaturation, but thereafter has little impact; reduced lung volume, hemoglobin content or cardiac output, accelerates Sa(O₂during stage 1, and finally, total blood O(2 capacity (blood volume and hemoglobin content alone determines Sa(O₂during stage 2. Preterm infants with elevated metabolic rate, respiratory depression, low lung volume, impaired cardiac reserve, anemia, or hypovolemia, are at risk for rapid and profound apneic hypoxemia. Our insights provide a basic physiological framework that may guide clinical interpretation and design of interventions for preventing sudden apneic hypoxemia.

  3. Patient-specific induced pluripotent stem cells in neurological disease modeling: the importance of nonhuman primate models

    Directory of Open Access Journals (Sweden)

    Qiu Z

    2013-07-01

    Full Text Available Zhifang Qiu,1,2 Steven L Farnsworth,2 Anuja Mishra,1,2 Peter J Hornsby1,21Geriatric Research Education and Clinical Center, South Texas Veterans Health Care System, San Antonio, TX, USA; 2Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, TX, USAAbstract: The development of the technology for derivation of induced pluripotent stem (iPS cells from human patients and animal models has opened up new pathways to the better understanding of many human diseases, and has created new opportunities for therapeutic approaches. Here, we consider one important neurological disease, Parkinson's, the development of relevant neural cell lines for studying this disease, and the animal models that are available for testing the survival and function of the cells, following transplantation into the central nervous system. Rapid progress has been made recently in the application of protocols for neuroectoderm differentiation and neural patterning of pluripotent stem cells. These developments have resulted in the ability to produce large numbers of dopaminergic neurons with midbrain characteristics for further study. These cells have been shown to be functional in both rodent and nonhuman primate (NHP models of Parkinson's disease. Patient-specific iPS cells and derived dopaminergic neurons have been developed, in particular from patients with genetic causes of Parkinson's disease. For complete modeling of the disease, it is proposed that the introduction of genetic changes into NHP iPS cells, followed by studying the phenotype of the genetic change in cells transplanted into the NHP as host animal, will yield new insights into disease processes not possible with rodent models alone.Keywords: Parkinson's disease, pluripotent cell differentiation, neural cell lines, dopaminergic neurons, cell transplantation, animal models

  4. Efficacy of Intravenous Mannitol in the Management of Orbital Compartment Syndrome: A Nonhuman Primate Model.

    Science.gov (United States)

    Johnson, Davin; Winterborn, Andrew; Kratky, Vladimir

    2016-01-01

    To report the efficacy of intravenous mannitol in the treatment of orbital compartment syndrome. An experimental study was conducted on 4 nonhuman primates (8 orbits). Orbital compartment syndrome was simulated by injecting autologous blood into both orbits of each nonhuman primate until a pressure of 80 mm Hg was reached (time 0). After 10 minutes, nonhuman primates were randomized to receive an infusion of either mannitol or saline, given over 15 minutes. Five minutes after the infusion was complete, lateral canthotomy and cantholysis was performed on both orbits in isolated steps every 5 minutes. During the study protocol, orbital and intraocular pressures were recorded every 5 minutes, with a final set of measurements at 60 minutes. The primary outcome measures were the mean change in pressure from time 0 to 60 minutes, as well as the mean change in pressure during the infusion period. There was no statistically significant difference in the mean changes in orbital or intraocular pressure from time 0 to 60 minutes of the protocol. However, during the infusion period there was significantly greater decrease in both orbital and intraocular pressure in the mannitol compared with saline group (-34.0 vs. -9.3 mm Hg for orbital pressure [p = 0.03]; -34.8 vs. -9.7 mm Hg for intraocular pressure [p = 0.04]). While the definitive treatment of orbital compartment syndrome is lateral canthotomy and cantholysis, mannitol results in a rapid and clinically meaningful drop in orbital and intraocular pressure. The authors believe that their data support the routine use of mannitol in orbital compartment syndrome, especially when there is a delay in timely surgical management.

  5. Psychobiobehavioral Model for Preterm Birth in Pregnant Women in Low- and Middle-Income Countries

    Directory of Open Access Journals (Sweden)

    Shahirose S. Premji

    2015-01-01

    Full Text Available Preterm birth (PTB is a final common outcome resulting from many interrelated etiological pathways; of particular interest is antenatal psychosocial distress (i.e., stress, anxiety, and depression. In LMI countries, both exposure to severe life stressors and rate of PTB are on average greater when compared with high-income countries. In LMI countries women are exposed to some of the most extreme psychosocial stress worldwide (e.g., absolute poverty, limited social resources. High prevalence of antenatal stress and depression have been observed in some studies from LMI countries. We propose a psychosocial, biological, and behavioral model for investigating the complex multisystem interactions in stress responses leading to PTB and explain the basis of this approach. We discuss ethical considerations for a psychosocial, biological, and behavioral screening tool to predict PTB from a LMI country perspective.

  6. The preterm pig as a model of premature infant gait ataxia

    DEFF Research Database (Denmark)

    Bergström, A.; Ryom, K.; Vanden Hole, C.

    group has over many years refined a pig model of premature birth focusing on gut and immune system development. Phenotypically, we have observed distinct motoric problems e.g. falls, tiptoe walking and swaying in preterm pigs relative to term born counterparts, indicating compromised brain function......Aims/background Compromised gait, balance and motor coordination (ataxia) as observed in cases of cerebral palsy is a serious complication to premature birth. The cerebellum is a central region with regards to these brain functions and its development shows high sensitivity to premature birth. Our...... delays relative to terms, yet the limited cerebellar gene expression differences (mainly related to angiogenesis) suggest other brain regions e.g. motor cortex and basal ganglia to also be involved in compromised gait....

  7. Assisted Reproductive Technologies (ART) with Baboons Generate Live Offspring: A Nonhuman Primate Model for ART and Reproductive Sciences

    Science.gov (United States)

    Simerly, Calvin R.; Castro, Carlos A.; Jacoby, Ethan; Grund, Kevin; Turpin, Janet; McFarland, Dave; Champagne, Jamie; Jimenez, Joe B.; Frost, Pat; Bauer, Cassandra; Hewitson, Laura; Schatten, Gerald

    2012-01-01

    Human reproduction has benefited significantly by investigating non-human primate (NHP) models, especially rhesus macaques. To expand the Old World monkey species available for human reproductive studies, we present protocols in baboons, our closest Old World primate relatives, for Assisted Reproductive Technologies (ART) leading to live-born offspring. Baboons complement rhesus by confirming or modifying observations generated in humans often obtained by the study of clinically-discarded specimens donated by anonymous infertility patient-couples. Here, baboon ART protocols, including oocyte collection, in vitro fertilization, intracytoplasmic sperm injection (ICSI), preimplantation development to blastocyst stage and embryo transfer techniques are described. With baboon ART methodologies in place, motility during baboon fertilization was investigated by time-lapse video microscopy. The first ART baboons produced by ICSI, a pair of male twins, were delivered naturally at 165 days post-gestation. Genetic testing of these twins confirmed their ART parental origins and demonstrated that they are unrelated fraternal twins, not identicals. These results have implications for ART outcomes, embryonic stem cell derivation, and reproductive sciences. PMID:20631291

  8. Magnetic resonance imaging and tensor-based morphometry in the MPTP non-human primate model of Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Michel Modo

    Full Text Available Parkinson's disease (PD is the second most common neurodegenerative disorder producing a variety of motor and cognitive deficits with the causes remaining largely unknown. The gradual loss of the nigrostriatal pathway is currently considered the pivotal pathological event. To better understand the progression of PD and improve treatment management, defining the disease on a structural basis and expanding brain analysis to extra-nigral structures is indispensable. The anatomical complexity and the presence of neuromelanin, make the use of non-human primates an essential element in developing putative imaging biomarkers of PD. To this end, ex vivo T2-weighted magnetic resonance images were acquired from control and 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine (MPTP-treated marmosets. Volume measurements of the caudate, putamen, and substantia nigra indicated significant atrophy and cortical thinning. Tensor-based morphometry provided a more extensive and hypothesis free assessment of widespread changes caused by the toxin insult to the brain, especially highlighting regional cortical atrophy. The results highlight the importance of developing imaging biomarkers of PD in non-human primate models considering their distinct neuroanatomy. It is essential to further develop these biomarkers in vivo to provide non-invasive tools to detect pre-symptomatic PD and to monitor potential disease altering therapeutics.

  9. Magnetic resonance imaging and tensor-based morphometry in the MPTP non-human primate model of Parkinson's disease.

    Science.gov (United States)

    Modo, Michel; Crum, William R; Gerwig, Madeline; Vernon, Anthony C; Patel, Priya; Jackson, Michael J; Rose, Sarah; Jenner, Peter; Iravani, Mahmoud M

    2017-01-01

    Parkinson's disease (PD) is the second most common neurodegenerative disorder producing a variety of motor and cognitive deficits with the causes remaining largely unknown. The gradual loss of the nigrostriatal pathway is currently considered the pivotal pathological event. To better understand the progression of PD and improve treatment management, defining the disease on a structural basis and expanding brain analysis to extra-nigral structures is indispensable. The anatomical complexity and the presence of neuromelanin, make the use of non-human primates an essential element in developing putative imaging biomarkers of PD. To this end, ex vivo T2-weighted magnetic resonance images were acquired from control and 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated marmosets. Volume measurements of the caudate, putamen, and substantia nigra indicated significant atrophy and cortical thinning. Tensor-based morphometry provided a more extensive and hypothesis free assessment of widespread changes caused by the toxin insult to the brain, especially highlighting regional cortical atrophy. The results highlight the importance of developing imaging biomarkers of PD in non-human primate models considering their distinct neuroanatomy. It is essential to further develop these biomarkers in vivo to provide non-invasive tools to detect pre-symptomatic PD and to monitor potential disease altering therapeutics.

  10. Factors associated with preterm, early preterm and late preterm birth in Malawi.

    Directory of Open Access Journals (Sweden)

    Nynke R van den Broek

    Full Text Available Assessment of risk factors for preterm birth in a population with high incidence of preterm birth and HIV infection.Secondary analysis of data for 2,149 women included in a community based randomized placebo controlled trial for the prevention of preterm birth (APPLe trial (ISRCTN84023116 with gestational age at birth determined through ultrasound measurement in early pregnancy. Multivariate Logistic Regression analyses to obtain models for three outcome variables: all preterm, early preterm, and late preterm birth.No statistical differences were noted for the prevalence of HIV infection (p = 0.30 or syphilis (p = 0.12 between women who delivered preterm versus term. BMI (Adjusted OR 0.91 (0.85-0.97; p = 0.005 and weight gain (Adjusted OR 0.89 (0.82-0.97; p = 0.006 had an independent, protective effect. Previous preterm birth doubled the odds of preterm birth (Adjusted OR 2.13 (1.198-3.80; p = 0.01. Persistent malaria (despite malaria prophylaxis increased the risk of late preterm birth (Adjusted OR 1.99 (1.05-3.79; p = 0.04. Age <20 (Adjusted OR 1.73 (1.03-2.90; p = 0.04 and anemia (Adjusted OR 1.95 (1.08-3.52; p = 0.03 were associated with early preterm birth (<34 weeks.Despite claims that HIV infection is an important cause of preterm birth in Africa, we found no evidence of an association in this population (unexposed to anti-retroviral treatment. Persistent malaria was associated with late preterm birth. Maternal undernourishment and anemia were independently associated with early preterm birth. The study did not assess whether the link was direct or whether a common precursor such as chronic infection was responsible for both maternal effects and early labour.

  11. A model investigation of the impact of ventilation-perfusion mismatch on oxygenation during apnea in preterm infants.

    Science.gov (United States)

    Sands, Scott A; Edwards, Bradley A; Kelly, Vanessa J; Davidson, Malcolm R; Wilkinson, Malcolm H; Berger, Philip J

    2010-06-07

    Ventilation-perfusion (V/Q) mismatch is a prominent feature of preterm infants and adults with lung disease. V/Q mismatch is known to cause arterial hypoxemia under steady-state conditions, and has been proposed as the cause of rapid arterial oxygen desaturation during apnea. However, there is little evidence to support a role for V/Q mismatch in the dynamic changes in arterial oxygenation that occur during apnea. Using a mathematical model, we quantified the effect of V/Q mismatch on the rate of desaturation during apnea to ascertain whether it could lead to rates of up to 10%s(-1) as observed in preterm infants. We used a lung-body model for the preterm infant that incorporated 50 parallel alveolar-capillary units that were ventilated and perfused with the severity of V/Q mismatch (sigma) defined conventionally according to sigma=S.D. of the distribution of V/Q ratios. Average desaturation rate 10s from apnea onset was strongly elevated with worsening V/Q mismatch as a result of an earlier desaturation of low V/Q units compared with high V/Q units. However, V/Q mismatch had little impact after apnea onset, with peak desaturation rate only substantially increased if mismatching caused a lowered resting arterial O(2) saturation. In conclusion, V/Q mismatch causes a more immediate onset of desaturation during apnea, and therefore places preterm infants and adults with lung disease at risk of hypoxemic dips. However, V/Q mismatch does not accelerate desaturation rate beyond apnea onset and cannot, therefore, explain the rapid desaturation observed during recurrent apnea in preterm infants. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  12. Hebbian learning of hand-centred representations in a hierarchical neural network model of the primate visual system

    Science.gov (United States)

    Born, Jannis; Stringer, Simon M.

    2017-01-01

    A subset of neurons in the posterior parietal and premotor areas of the primate brain respond to the locations of visual targets in a hand-centred frame of reference. Such hand-centred visual representations are thought to play an important role in visually-guided reaching to target locations in space. In this paper we show how a biologically plausible, Hebbian learning mechanism may account for the development of localized hand-centred representations in a hierarchical neural network model of the primate visual system, VisNet. The hand-centered neurons developed in the model use an invariance learning mechanism known as continuous transformation (CT) learning. In contrast to previous theoretical proposals for the development of hand-centered visual representations, CT learning does not need a memory trace of recent neuronal activity to be incorporated in the synaptic learning rule. Instead, CT learning relies solely on a Hebbian learning rule, which is able to exploit the spatial overlap that naturally occurs between successive images of a hand-object configuration as it is shifted across different retinal locations due to saccades. Our simulations show how individual neurons in the network model can learn to respond selectively to target objects in particular locations with respect to the hand, irrespective of where the hand-object configuration occurs on the retina. The response properties of these hand-centred neurons further generalise to localised receptive fields in the hand-centred space when tested on novel hand-object configurations that have not been explored during training. Indeed, even when the network is trained with target objects presented across a near continuum of locations around the hand during training, the model continues to develop hand-centred neurons with localised receptive fields in hand-centred space. With the help of principal component analysis, we provide the first theoretical framework that explains the behavior of Hebbian learning

  13. Hebbian learning of hand-centred representations in a hierarchical neural network model of the primate visual system.

    Directory of Open Access Journals (Sweden)

    Jannis Born

    Full Text Available A subset of neurons in the posterior parietal and premotor areas of the primate brain respond to the locations of visual targets in a hand-centred frame of reference. Such hand-centred visual representations are thought to play an important role in visually-guided reaching to target locations in space. In this paper we show how a biologically plausible, Hebbian learning mechanism may account for the development of localized hand-centred representations in a hierarchical neural network model of the primate visual system, VisNet. The hand-centered neurons developed in the model use an invariance learning mechanism known as continuous transformation (CT learning. In contrast to previous theoretical proposals for the development of hand-centered visual representations, CT learning does not need a memory trace of recent neuronal activity to be incorporated in the synaptic learning rule. Instead, CT learning relies solely on a Hebbian learning rule, which is able to exploit the spatial overlap that naturally occurs between successive images of a hand-object configuration as it is shifted across different retinal locations due to saccades. Our simulations show how individual neurons in the network model can learn to respond selectively to target objects in particular locations with respect to the hand, irrespective of where the hand-object configuration occurs on the retina. The response properties of these hand-centred neurons further generalise to localised receptive fields in the hand-centred space when tested on novel hand-object configurations that have not been explored during training. Indeed, even when the network is trained with target objects presented across a near continuum of locations around the hand during training, the model continues to develop hand-centred neurons with localised receptive fields in hand-centred space. With the help of principal component analysis, we provide the first theoretical framework that explains the behavior

  14. Prediction of Human Glomerular Filtration Rate from Preterm Neonates to Adults: Evaluation of Predictive Performance of Several Empirical Models.

    Science.gov (United States)

    Mahmood, Iftekhar; Staschen, Carl-Michael

    2016-03-01

    The objective of this study was to evaluate the predictive performance of several allometric empirical models (body weight dependent, age dependent, fixed exponent 0.75, a data-dependent single exponent, and maturation models) to predict glomerular filtration rate (GFR) in preterm and term neonates, infants, children, and adults without any renal disease. In this analysis, the models were developed from GFR data obtained from inulin clearance (preterm neonates to adults; n = 93) and the predictive performance of these models were evaluated in 335 subjects (preterm neonates to adults). The primary end point was the prediction of GFR from the empirical allometric models and the comparison of the predicted GFR with measured GFR. A prediction error within ±30% was considered acceptable. Overall, the predictive performance of the four models (BDE, ADE, and two maturation models) for the prediction of mean GFR was good across all age groups but the prediction of GFR in individual healthy subjects especially in neonates and infants was erratic and may be clinically unacceptable.

  15. Estimating recurrence and incidence of preterm birth subject to measurement error in gestational age: A hidden Markov modeling approach.

    Science.gov (United States)

    Albert, Paul S

    2018-02-21

    Prediction of preterm birth as well as characterizing the etiological factors affecting both the recurrence and incidence of preterm birth (defined as gestational age at birth ≤ 37 wk) are important problems in obstetrics. The National Institute of Child Health and Human Development (NICHD) consecutive pregnancy study recently examined this question by collecting data on a cohort of women with at least 2 pregnancies over a fixed time interval. Unfortunately, measurement error due to the dating of conception may induce sizable error in computing gestational age at birth. This article proposes a flexible approach that accounts for measurement error in gestational age when making inference. The proposed approach is a hidden Markov model that accounts for measurement error in gestational age by exploiting the relationship between gestational age at birth and birth weight. We initially model the measurement error as being normally distributed, followed by a mixture of normals that has been proposed on the basis of biological considerations. We examine the asymptotic bias of the proposed approach when measurement error is ignored and also compare the efficiency of this approach to a simpler hidden Markov model formulation where only gestational age and not birth weight is incorporated. The proposed model is compared with alternative models for estimating important covariate effects on the risk of subsequent preterm birth using a unique set of data from the NICHD consecutive pregnancy study. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.

  16. Prefrontal cortical α2A-adrenoceptors and a possible primate model of attention deficit and hyperactivity disorder.

    Science.gov (United States)

    Ma, Chao-Lin; Sun, Xuan; Luo, Fei; Li, Bao-Ming

    2015-04-01

    Attention deficit and hyperactivity disorder (ADHD), a prevalent syndrome in children worldwide, is characterized by impulsivity, inappropriate inattention, and/or hyperactivity. It seriously afflicts cognitive development in childhood, and may lead to chronic under-achievement, academic failure, problematic peer relationships, and low self-esteem. There are at least three challenges for the treatment of ADHD. First, the neurobiological bases of its symptoms are still not clear. Second, the commonly prescribed medications, most showing short-term therapeutic efficacy but with a high risk of serious side-effects, are mainly based on a dopamine mechanism. Third, more novel and efficient animal models, especially in nonhuman primates, are required to accelerate the development of new medications. In this article, we review research progress in the related fields, focusing on our previous studies showing that blockade of prefrontal cortical α2A-adrenoceptors in monkeys produces almost all the typical behavioral symptoms of ADHD.

  17. The Development of Hand-Centered Visual Representations in the Primate Brain: A Computer Modeling Study Using Natural Visual Scenes.

    Science.gov (United States)

    Galeazzi, Juan M; Minini, Loredana; Stringer, Simon M

    2015-01-01

    Neurons that respond to visual targets in a hand-centered frame of reference have been found within various areas of the primate brain. We investigate how hand-centered visual representations may develop in a neural network model of the primate visual system called VisNet, when the model is trained on images of the hand seen against natural visual scenes. The simulations show how such neurons may develop through a biologically plausible process of unsupervised competitive learning and self-organization. In an advance on our previous work, the visual scenes consisted of multiple targets presented simultaneously with respect to the hand. Three experiments are presented. First, VisNet was trained with computerized images consisting of a realistic image of a hand and a variety of natural objects, presented in different textured backgrounds during training. The network was then tested with just one textured object near the hand in order to verify if the output cells were capable of building hand-centered representations with a single localized receptive field. We explain the underlying principles of the statistical decoupling that allows the output cells of the network to develop single localized receptive fields even when the network is trained with multiple objects. In a second simulation we examined how some of the cells with hand-centered receptive fields decreased their shape selectivity and started responding to a localized region of hand-centered space as the number of objects presented in overlapping locations during training increases. Lastly, we explored the same learning principles training the network with natural visual scenes collected by volunteers. These results provide an important step in showing how single, localized, hand-centered receptive fields could emerge under more ecologically realistic visual training conditions.

  18. Primate polonium metabolic models and their use in estimation of systemic radiation doses from bioassay data. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Cohen, N. [New York Univ. Medical Center, Tuxedo, NY (United States). Dept. of Environmental Medicine

    1989-03-15

    A Polonium metabolic model was derived and incorporated into a Fortran algorithm which estimates the systemic radiation dose from {sup 210}Po when applied to occupational urine bioassay data. The significance of the doses estimated are examined by defining the degree of uncertainty attached to them through comprehensive statistical testing procedures. Many parameters necessary for dosimetry calculations (such as organ partition coefficients and excretion fractions), were evaluated from metabolic studies of {sup 210}Po in non-human primates. Two tamarins and six baboons were injected intravenously with {sup 210}Po citrate. Excreta and blood samples were collected. Five of the baboons were sacrificed at times ranging from 1 day to 3 months post exposure. Complete necropsies were performed and all excreta and the majority of all skeletal and tissue samples were analyzed radiochemically for their {sup 210}Po content. The {sup 210}Po excretion rate in the baboon was more rapid than in the tamarin. The biological half-time of {sup 210}Po excretion in the baboon was approximately 15 days while in the tamarin, the {sup 210}Po excretion rate was in close agreement with the 50 day biological half-time predicted by ICRP 30. Excretion fractions of {sup 210}Po in the non-human primates were found to be markedly different from data reported elsewhere in other species, including man. A thorough review of the Po urinalysis procedure showed that significant recovery losses resulted when metabolized {sup 210}Po was deposited out of raw urine. Polonium-210 was found throughout the soft tissues of the baboon but not with the partition coefficients for liver, kidneys, and spleen that are predicted by the ICRP 30 metabolic model. A fractional distribution of 0.29 for liver, 0.07 for kidneys, and 0.006 for spleen was determined. Retention times for {sup 210}Po in tissues are described by single exponential functions with biological half-times ranging from 15 to 50 days.

  19. The development of hand-centred visual representations in the primate brain: a computer modelling study using natural visual scenes.

    Directory of Open Access Journals (Sweden)

    Juan Manuel Galeazzi

    2015-12-01

    Full Text Available Neurons that respond to visual targets in a hand-centred frame of reference have been found within various areas of the primate brain. We investigate how hand-centred visual representations may develop in a neural network model of the primate visual system called VisNet, when the model is trained on images of the hand seen against natural visual scenes. The simulations show how such neurons may develop through a biologically plausible process of unsupervised competitive learning and self-organisation. In an advance on our previous work, the visual scenes consisted of multiple targets presented simultaneously with respect to the hand. Three experiments are presented. First, VisNet was trained with computerized images consisting of a realistic image of a hand and and a variety of natural objects, presented in different textured backgrounds during training. The network was then tested with just one textured object near the hand in order to verify if the output cells were capable of building hand-centered representations with a single localised receptive field. We explain the underlying principles of the statistical decoupling that allows the output cells of the network to develop single localised receptive fields even when the network is trained with multiple objects. In a second simulation we examined how some of the cells with hand-centred receptive fields decreased their shape selectivity and started responding to a localised region of hand-centred space as the number of objects presented in overlapping locations during training increases. Lastly, we explored the same learning principles training the network with natural visual scenes collected by volunteers. These results provide an important step in showing how single, localised, hand-centered receptive fields could emerge under more ecologically realistic visual training conditions.

  20. Prediction of preterm birth in multiple pregnancies: development of a multivariable model including cervical length measurement at 16 to 21 weeks' gestation.

    Science.gov (United States)

    van de Mheen, Lidewij; Schuit, Ewoud; Lim, Arianne C; Porath, Martina M; Papatsonis, Dimitri; Erwich, Jan J; van Eyck, Jim; van Oirschot, Charlotte M; Hummel, Piet; Duvekot, Johannes J; Hasaart, Tom H M; Groenwold, Rolf H H; Moons, Karl G M; de Groot, Christianne J M; Bruinse, Hein W; van Pampus, Maria G; Mol, Ben W J

    2014-04-01

    To develop a multivariable prognostic model for the risk of preterm delivery in women with multiple pregnancy that includes cervical length measurement at 16 to 21 weeks' gestation and other variables. We used data from a previous randomized trial. We assessed the association between maternal and pregnancy characteristics including cervical length measurement at 16 to 21 weeks' gestation and time to delivery using multivariable Cox regression modelling. Performance of the final model was assessed for the outcomes of preterm and very preterm delivery using calibration and discrimination measures. We studied 507 women, of whom 270 (53%) delivered models for preterm and very preterm delivery had a c-index of 0.68 (95% CI 0.63 to 0.72) and 0.68 (95% CI 0.62 to 0.75), respectively, and showed good calibration. In women with a multiple pregnancy, the risk of preterm delivery can be assessed with a multivariable model incorporating cervical length and other predictors.

  1. A PAF receptor antagonist inhibits acute airway inflammation and late-phase responses but not chronic airway inflammation and hyperresponsiveness in a primate model of asthma

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    R. H. Gundel

    1992-01-01

    Full Text Available We have examined the effects of a PAF receptor antagonist, WEB 2170, on several indices of acute and chronic airway inflammation and associated changes in lung function in a primate model of allergic asthma. A single oral administration WEB 2170 provided dose related inhibition of the release of leukotriene C4 (LTC4 and prostaglandin D2 (PGD2 recovered and quantified in bronchoalveolar lavage (BAL fluid obtained during the acute phase response to inhaled antigen. In addition, oral WEB 2170 treatment in dual responder primates blocked the acute influx of neutrophils into the airways as well as the associated late-phase airway obstruction occurring 6 h after antigen inhalation. In contrast, a multiple dosing regime with WEB 2170 (once a day for 7 consecutive days failed to reduce the chronic airway inflammation (eosinophilic and associated airway hyperresponsiveness to inhaled methacholine that is characteristic of dual responder monkeys. Thus, we conclude that the generation of PAF following antigen inhalation contributes to the development of lipid mediators, acute airway inflammation and associated late-phase airway obstruction in dual responder primates; however, PAF does not play a significant role in the maintenance of chronic airway inflammation and associated airway hyperresponsiveness in this primate model.

  2. Comparison of Bayesian and frequentist approaches in modelling risk of preterm birth near the Sydney Tar Ponds, Nova Scotia, Canada

    Directory of Open Access Journals (Sweden)

    Canty Angelo

    2007-09-01

    Full Text Available Abstract Background This study compares the Bayesian and frequentist (non-Bayesian approaches in the modelling of the association between the risk of preterm birth and maternal proximity to hazardous waste and pollution from the Sydney Tar Pond site in Nova Scotia, Canada. Methods The data includes 1604 observed cases of preterm birth out of a total population of 17559 at risk of preterm birth from 144 enumeration districts in the Cape Breton Regional Municipality. Other covariates include the distance from the Tar Pond; the rate of unemployment to population; the proportion of persons who are separated, divorced or widowed; the proportion of persons who have no high school diploma; the proportion of persons living alone; the proportion of single parent families and average income. Bayesian hierarchical Poisson regression, quasi-likelihood Poisson regression and weighted linear regression models were fitted to the data. Results The results of the analyses were compared together with their limitations. Conclusion The results of the weighted linear regression and the quasi-likelihood Poisson regression agrees with the result from the Bayesian hierarchical modelling which incorporates the spatial effects.

  3. Behavioral and neuroanatomical outcomes in a rat model of preterm hypoxic-ischemic brain Injury: Effects of caffeine and hypothermia.

    Science.gov (United States)

    Potter, Molly; Rosenkrantz, Ted; Fitch, R Holly

    2018-02-21

    The current study investigated behavioral and post mortem neuroanatomical outcomes in Wistar rats with a neonatal hypoxic-ischemic (HI) brain injury induced on postnatal day 6 (P6; Rice-Vannucci HI method; Rice et al., 1981). This preparation models brain injury seen in premature infants (gestational age (GA) 32-35 weeks) based on shared neurodevelopmental markers at time of insult, coupled with similar neuropathologic sequelae (Rice et al., 1981; Workman et al., 2013). Clinically, HI insult during this window is associated with poor outcomes that include attention deficit hyperactivity disorder (ADHD), motor coordination deficits, spatial memory deficits, and language/learning disabilities. To assess therapies that might offer translational potential for improved outcomes, we used a P6 HI rat model to measure the behavioral and neuroanatomical effects of two prospective preterm neuroprotective treatments - hypothermia and caffeine. Hypothermia (aka "cooling") is an approved and moderately efficacious intervention therapy for fullterm infants with perinatal hypoxic-ischemic (HI) injury, but is not currently approved for preterm use. Caffeine is a respiratory stimulant used during removal of infants from ventilation but has shown surprising long-term benefits, leading to consideration as a therapy for HI of prematurity. Current findings support caffeine as a preterm neuroprotectant; treatment significantly improved some behavioral outcomes in a P6 HI rat model and partially rescued neuropathology. Hypothermia treatment (involving core temperature reduction by 4 °C over 5 hours), conversely, was found to be largely ineffective and even deleterious for some measures in both HI and sham rats. These results have important implications for therapeutic intervention in at-risk preterm populations, and promote caution in the application of hypothermia protocols to at-risk premature infants without further research. Copyright © 2018 ISDN. Published by Elsevier Ltd. All

  4. Combined oral contraceptives and body weight: do oral contraceptives cause weight gain? A primate model.

    Science.gov (United States)

    Edelman, A; Jensen, J T; Bulechowsky, M; Cameron, J

    2011-02-01

    The aim of this study was to determine if oral contraceptive (OC) use affects body weight, body composition and metabolism in primates. Reproductive-age female rhesus monkeys of normal and obese BMI were studied to document baseline weight stability, then treated continuously with an OC (dosed to achieve equivalent human serum levels for a 30 µg ethinyl estradiol/150 µg levonorgestrel preparation) for 237 days. Monkeys were monitored for changes in body weight, levels of physical activity (measured by a triaxial Actical accelerometer), food/caloric intake, percent body fat (dual energy X-ray absorptiometry, DEXA) and metabolism (24 h metabolic rate and serum metabolic substrate and hormone concentrations). All 10 monkeys completed the study protocol with no adverse events. While body weight (-0.73% change) and percent body fat (-1.78% change) of the normal BMI group did not significantly decrease from baseline, obese monkeys showed a significant decrease in body weight (-8.58% change, P body fat (-12.13% change P = 0.02) with OC treatment. In both the obese (P = 0.03) and the normal BMI (P = 0.01) groups, there was a significant increase in basal metabolic rate with OC use. No changes were seen in food intake, activity level or % lean muscle mass with OC use for either BMI-based group. Overall, OC use appears to cause a slight increase in basal metabolic rate in female monkeys, leading to a decrease in body weight and percent body fat in obese individuals.

  5. Protective potential of antioxidant enzymes as vaccines for schistosomiasis in a non-human primate model

    Directory of Open Access Journals (Sweden)

    Claudia eCarvalho-Queiroz

    2015-06-01

    Full Text Available Schistosomiasis remains a major cause of morbidity in the world. The challenge today is not so much in the clinical management of individual patients, but rather in population-based control of transmission in endemic areas. Recent large-scale efforts aimed at limiting schistosomiasis have produced limited success. There is an urgent need for complementary approaches, such as vaccines. We demonstrated previously that anti-oxidant enzymes such as Cu-Zn superoxide dismutase (SOD and glutathione S peroxidase (GPX, when administered as DNA-based vaccines induced significant levels of protection in inbred mice, greater than the target 40% reduction in worm burden compared to controls set as a minimum by the WHO. These results led us to investigate if immunization of non-human primates with antioxidants would stimulate an immune response that could confer protection, as a prelude for human trials. Issues of vaccine toxicity and safety that were difficult to address in mice were also investigated. All baboons in the study were examined clinically throughout the study and no adverse reactions occurred to the immunization. When our outbred baboons were vaccinated with two different formulations of SOD (SmCT-SOD and SmEC-SOD or one of GPX (SmGPX, they showed a reduction in worm number to varying degrees, when compared with the control group. More pronounced, vaccinated animals showed decreased bloody diarrhea, days of diarrhea and egg excretion (transmission, as well as reduction of eggs in the liver tissue and in the large intestine (pathology compared to controls. Specific IgG antibodies were present in sera after immunizations and 10 weeks after challenge infection compared to controls. PBMC, mesenteric and inguinal node cells from vaccinated animals proliferated and produced high levels of cytokines and chemokines in response to crude and recombinant antigens compared with controls. These data demonstrate the potential of antioxidants as vaccine

  6. Exploring the Innate Immunological Response of an Alternative Nonhuman Primate Model of Infectious Disease; the Common Marmoset

    Directory of Open Access Journals (Sweden)

    M. Nelson

    2014-01-01

    Full Text Available The common marmoset (Callithrix jacchus is increasingly being utilised as a nonhuman primate model for human disease, ranging from autoimmune to infectious disease. In order to fully exploit these models, meaningful comparison to the human host response is necessary. Commercially available reagents, primarily targeted to human cells, were utilised to assess the phenotype and activation status of key immune cell types and cytokines in naive and infected animals. Single cell suspensions of blood, spleen, and lung were examined. Generally, the phenotype of cells was comparable between humans and marmosets, with approximately 63% of all lymphocytes in the blood of marmosets being T cells, 25% B-cells, and 12% NK cells. The percentage of neutrophils in marmoset blood were more similar to human values than mouse values. Comparison of the activation status of cells following experimental systemic or inhalational infection exhibited different trends in different tissues, most obvious in cell types active in the innate immune response. This work significantly enhances the ability to understand the immune response in these animals and fortifies their use as models of infectious disease.

  7. Computational model of a primate arm: from hand position to joint angles, joint torques and muscle forces

    Science.gov (United States)

    Chan, Sherwin S.; Moran, Daniel W.

    2006-12-01

    Three-dimensional reaching by non-human primates is an important behavioral paradigm for investigating representations existing in motor control areas of the brain. Most studies to date have correlated neural activity to a few of the many arm motion parameters including: global hand position or velocity, joint angles, joint angular velocities, joint torques or muscle activations. So far, no single study has been able to incorporate all these parameters in a meaningful way that would allow separation of these often highly correlated variables. This paper introduces a three-dimensional, seven degree-of-freedom computational musculoskeletal model of the macaque arm that translates the coordinates of eight tracking markers placed on the arm into joint angles, joint torques, musculotendon lengths and finally into an optimized prediction of muscle forces. This paper uses this model to illustrate how the classic center-out reaching task used by many researchers over the last 20 years is not optimal in separating out intrinsic, extrinsic, kinematic and kinetic variables. However, by using the musculoskeletal model to design and test novel behavioral movement tasks, a priori, it is possible to disassociate the myriad of movement parameters in motor neurophysiological reaching studies.

  8. Long-term altered immune responses following fetal priming in a non-human primate model of maternal immune activation.

    Science.gov (United States)

    Rose, Destanie R; Careaga, Milo; Van de Water, Judy; McAllister, Kim; Bauman, Melissa D; Ashwood, Paul

    2017-07-01

    Infection during pregnancy can lead to activation of the maternal immune system and has been associated with an increased risk of having an offspring later diagnosed with a neurodevelopmental disorders (NDD) such as autism spectrum disorder (ASD) or schizophrenia (SZ). Most maternal immune activation (MIA) studies to date have been in rodents and usually involve the use of lipopolysaccharide (LPS) or polyinosinic:polycytidylic acid (poly I:C). However, since NDD are based on behavioral changes, a model of MIA in non-human primates could potentially provide data that helps illuminate complex behavioral and immune outputs in human NDD. In this study twenty-one pregnant rhesus macaques were either given three injections over 72 hours of poly I:C-LC, a double stranded RNA analog (viral mimic), or saline as a control. Injections were given near the end of the first trimester or near the end of the second trimester to determine if there were differences in immune output due to the timing of MIA.An additional three non-treated animals were used as controls. The offspring were followed until 4 years of age, with blood collected at the end of their first (year 1) and fourth (year 4) years to assess dynamic cellular immune function. Induced responses from peripheral immune cells were measured using multiplex assays.At one year of age, MIA exposed offspring displayed elevated production of innate inflammatory cytokines including: interleukin (IL)-1β, IL-6, IL-12p40, and tumor necrosis factor (TNF)α at baseline and following stimulation. At four years of age, the MIA exposed offspring continued to display elevated IL-1β, and there was also a pattern of an increased production of T-cell helper type (T H )-2 cytokines, IL-4 and IL-13. Throughout this time period, the offspring of MIA treated dams exhibited altered behavioral phenotypes including increased stereotyped behaviors. During the first two years, stereotyped behaviors were associated with innate cytokine production

  9. Exploration of preterm birth rates associated with different models of antenatal midwifery care in Scotland: Unmatched retrospective cohort analysis.

    Science.gov (United States)

    Symon, Andrew; Winter, Clare; Cochrane, Lynda

    2015-06-01

    preterm birth represents a significant personal, clinical, organisational and financial burden. Strategies to reduce the preterm birth rate have had limited success. Limited evidence indicates that certain antenatal care models may offer some protection, although the causal mechanism is not understood. We sought to compare preterm birth rates for mixed-risk pregnant women accessing antenatal care organised at a freestanding midwifery unit (FMU) and mixed-risk pregnant women attending an obstetric unit (OU) with related community-based antenatal care. unmatched retrospective 4-year Scottish cohort analysis (2008-2011) of mixed-risk pregnant women accessing (i) FMU antenatal care (n=1107); (ii) combined community-based and OU antenatal care (n=7567). Data were accessed via the Information and Statistics Division of the NHS in Scotland. Aggregates analysis and binary logistic regression were used to compare the cohorts׳ rates of preterm birth; and of spontaneous labour onset, use of pharmacological analgesia, unassisted vertex birth, and low birth weight. Odds ratios were adjusted for age, parity, deprivation score and smoking status in pregnancy. after adjustment the 'mixed risk' FMU cohort had a statistically significantly reduced risk of preterm birth (5.1% [n=57] versus 7.7% [n=583]; AOR 0.73 [95% CI 0.55-0.98]; p=0.034). Differences in these secondary outcome measures were also statistically significant: spontaneous labour onset (FMU 83.9% versus OU 74.6%; AOR 1.74 [95% CI 1.46-2.08]; p<0.001); minimal intrapartum analgesia (FMU 53.7% versus OU 34.4%; AOR 2.17 [95% CI 1.90-2.49]; p<0.001); spontaneous vertex delivery (FMU 71.9% versus OU 63.5%; AOR 1.46 [95% CI 1.32-1.78]; p<0.001). Incidence of low birth weight was not statistically significant after adjustment for other variables. There was no significant difference in the rate of perinatal or neonatal death. given this study׳s methodological limitations, we can only claim associations between the care model

  10. Eye growth in term- and preterm-born eyes modeled from magnetic resonance images.

    Science.gov (United States)

    Munro, Robert J; Fulton, Anne B; Chui, Toco Y P; Moskowitz, Anne; Ramamirtham, Ramkumar; Hansen, Ronald M; Prabhu, Sanjay P; Akula, James D

    2015-05-01

    We generated a model of eye growth and tested it against an eye known to develop abnormally, one with a history of retinopathy of prematurity (ROP). We reviewed extant magnetic resonance images (MRIs) from term and preterm-born patients for suitable images (n = 129). We binned subjects for analysis based upon postmenstrual age at birth (in weeks) and ROP history ("Term" ≥ 37, "Premature" ≤ 32 with no ROP, "ROP" ≤ 32 with ROP). We measured the axial positions and curvatures of the cornea, anterior and posterior lens, and inner retinal surface. We fit anterior chamber depth (ACD), posterior segment depth (PSD), axial length (AL), and corneal and lenticular curvatures with logistic growth curves that we then evaluated for significant differences. We also measured the length of rays from the centroid to the surface of the eye at 5° intervals, and described the length versus age relationship of each ray, L(ray)(x), using the same logistic growth curve. We determined the rate of ray elongation, E(ray)(x), from L(ray)dy/dx. Then, we estimated the scleral growth that accounted for E(ray)(x), G(x), at every age and position. Relative to Term, development of ACD, PSD, AL, and corneal and lenticular curvatures was delayed in ROP eyes, but not Premature eyes. In Term infants, G(x) was fast and predominantly equatorial; in age-matched ROP eyes, maximal G(x) was offset by approximately 90°. We produced a model of normal eye growth in term-born subjects. Relative to normal, the ROP eye is characterized by delayed, abnormal growth.

  11. Can neonatal sepsis be predicted in late preterm premature rupture of membranes? Development of a prediction model.

    Science.gov (United States)

    van der Ham, David P; van Kuijk, Sander; Opmeer, Brent C; Willekes, Christine; van Beek, Johannes J; Mulder, Antonius L M; van Loon, Aren J; Groenewout, Martiët; Mantel, Gerald D; Bloemenkamp, Kitty W M; Porath, Martina; Kwee, Anneke; Akerboom, Bettina M C; Papatsonis, Dimitri N M; Metz, Godfried C H; Nijhuis, Jan G; Mol, Ben W J

    2014-05-01

    Women with late preterm premature rupture of membranes (PROM) have an increased risk that their child will develop neonatal sepsis. We evaluated whether neonatal sepsis can be predicted from antepartum parameters in these women. We used multivariable logistic regression to develop a prediction model. Data were obtained from two recent randomized controlled trials on induction of labor versus expectant management in late preterm PROM (PPROMEXIL trials, (ISRCTN29313500 and ISRCTN05689407). Data from randomized as well as non-randomized women, who consented to the use of their medical data, were used. We evaluated 13 potential antepartum predictors for neonatal sepsis. Missing data were imputed. Discriminative ability of the model was expressed as the area under the receiver operating characteristic (ROC) curve and a calibration with both a calibration plot and the Hosmer and Lemeshow goodness-of-fit test. Overall performance of the prediction model was quantified as the scaled Brier score. We studied 970 women. Thirty-three (3.4%) neonates suffered neonatal sepsis. Maternal age (OR 1.09 per year), maternal CRP level (OR 1.01 per mmol/l), maternal temperature (OR 1.80 per °C) and positive GBS culture (OR 2.20) were associated with an increased risk of neonatal sepsis. The model had an area under the ROC-curve of 0.71. The model had both a good calibration and accuracy. Antepartum parameters aid in the more precise prediction of the risk of neonatal sepsis in women with late preterm PPROM. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  12. A computational model of lipopolysaccharide-induced nuclear factor kappa B activation: a key signalling pathway in infection-induced preterm labour.

    Directory of Open Access Journals (Sweden)

    Gemma C Sharp

    Full Text Available Preterm birth is the single biggest cause of significant neonatal morbidity and mortality, and the incidence is rising. Development of new therapies to treat and prevent preterm labour is seriously hampered by incomplete understanding of the molecular mechanisms that initiate labour at term and preterm. Computational modelling provides a new opportunity to improve this understanding. It is a useful tool in (i identifying gaps in knowledge and informing future research, and (ii providing the basis for an in silico model of parturition in which novel drugs to prevent or treat preterm labour can be "tested". Despite their merits, computational models are rarely used to study the molecular events initiating labour. Here, we present the first attempt to generate a dynamic kinetic model that has relevance to the molecular mechanisms of preterm labour. Using published data, we model an important candidate signalling pathway in infection-induced preterm labour: that of lipopolysaccharide (LPS -induced activation of Nuclear Factor kappa B. This is the first model of this pathway to explicitly include molecular interactions upstream of Nuclear Factor kappa B activation. We produced a formalised graphical depiction of the pathway and built a kinetic model based on ordinary differential equations. The kinetic model accurately reproduced published in vitro time course plots of Lipopolysaccharide-induced Nuclear Factor kappa B activation in mouse embryo fibroblasts. In this preliminary work we have provided proof of concept that it is possible to build computational models of signalling pathways that are relevant to the regulation of labour, and suggest that models that are validated with wet-lab experiments have the potential to greatly benefit the field.

  13. A computational model of lipopolysaccharide-induced nuclear factor kappa B activation: a key signalling pathway in infection-induced preterm labour.

    Science.gov (United States)

    Sharp, Gemma C; Ma, Hongwu; Saunders, Philippa T K; Norman, Jane E

    2013-01-01

    Preterm birth is the single biggest cause of significant neonatal morbidity and mortality, and the incidence is rising. Development of new therapies to treat and prevent preterm labour is seriously hampered by incomplete understanding of the molecular mechanisms that initiate labour at term and preterm. Computational modelling provides a new opportunity to improve this understanding. It is a useful tool in (i) identifying gaps in knowledge and informing future research, and (ii) providing the basis for an in silico model of parturition in which novel drugs to prevent or treat preterm labour can be "tested". Despite their merits, computational models are rarely used to study the molecular events initiating labour. Here, we present the first attempt to generate a dynamic kinetic model that has relevance to the molecular mechanisms of preterm labour. Using published data, we model an important candidate signalling pathway in infection-induced preterm labour: that of lipopolysaccharide (LPS) -induced activation of Nuclear Factor kappa B. This is the first model of this pathway to explicitly include molecular interactions upstream of Nuclear Factor kappa B activation. We produced a formalised graphical depiction of the pathway and built a kinetic model based on ordinary differential equations. The kinetic model accurately reproduced published in vitro time course plots of Lipopolysaccharide-induced Nuclear Factor kappa B activation in mouse embryo fibroblasts. In this preliminary work we have provided proof of concept that it is possible to build computational models of signalling pathways that are relevant to the regulation of labour, and suggest that models that are validated with wet-lab experiments have the potential to greatly benefit the field.

  14. Between the primate and 'reptilian' brain: Rodent models demonstrate the role of corticostriatal circuits in decision making.

    Science.gov (United States)

    Lee, A Moses; Tai, Lung-Hao; Zador, Anthony; Wilbrecht, Linda

    2015-06-18

    Decision making can be defined as the flexible integration and transformation of information from the external world into action. Recently, the development of novel genetic tools and new behavioral paradigms has made it attractive to study behavior of all kinds in rodents. By some perspectives, rodents are not an acceptable model for the study of decision making due to their simpler behavior often attributed to their less extensive cortical development when compared to non-human primates. We argue that decision making can be approached with a common framework across species. We review insights from comparative anatomy that suggest the expansion of cortical-striatal connectivity is a key development in evolutionary increases in behavioral flexibility. We briefly review studies that establish a role for corticostriatal circuits in integrative decision making. Finally, we provide an overview of a few recent, highly complementary rodent decision making studies using genetic tools, revealing with new cellular and temporal resolution how, when and where information can be integrated and compared in striatal circuits to influence choice. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  15. Operant conditioning of a multiple degree-of-freedom brain-machine interface in a primate model of amputation.

    Science.gov (United States)

    Balasubramanian, Karthikeyan; Southerland, Joshua; Vaidya, Mukta; Qian, Kai; Eleryan, Ahmed; Fagg, Andrew H; Sluzky, Marc; Oweiss, Karim; Hatsopoulos, Nicholas

    2013-01-01

    Operant conditioning with biofeedback has been shown to be an effective method to modify neural activity to generate goal-directed actions in a brain-machine interface. It is particularly useful when neural activity cannot be mathematically mapped to motor actions of the actual body such as in the case of amputation. Here, we implement an operant conditioning approach with visual feedback in which an amputated monkey is trained to control a multiple degree-of-freedom robot to perform a reach-to-grasp behavior. A key innovation is that each controlled dimension represents a behaviorally relevant synergy among a set of joint degrees-of-freedom. We present a number of behavioral metrics by which to assess improvements in BMI control with exposure to the system. The use of non-human primates with chronic amputation is arguably the most clinically-relevant model of human amputation that could have direct implications for developing a neural prosthesis to treat humans with missing upper limbs.

  16. Off-the-shelf human decellularized tissue-engineered heart valves in a non-human primate model.

    Science.gov (United States)

    Weber, Benedikt; Dijkman, Petra E; Scherman, Jacques; Sanders, Bart; Emmert, Maximilian Y; Grünenfelder, Jürg; Verbeek, Renier; Bracher, Mona; Black, Melanie; Franz, Thomas; Kortsmit, Jeroen; Modregger, Peter; Peter, Silvia; Stampanoni, Marco; Robert, Jérôme; Kehl, Debora; van Doeselaar, Marina; Schweiger, Martin; Brokopp, Chad E; Wälchli, Thomas; Falk, Volkmar; Zilla, Peter; Driessen-Mol, Anita; Baaijens, Frank P T; Hoerstrup, Simon P

    2013-10-01

    Heart valve tissue engineering based on decellularized xenogenic or allogenic starter matrices has shown promising first clinical results. However, the availability of healthy homologous donor valves is limited and xenogenic materials are associated with infectious and immunologic risks. To address such limitations, biodegradable synthetic materials have been successfully used for the creation of living autologous tissue-engineered heart valves (TEHVs) in vitro. Since these classical tissue engineering technologies necessitate substantial infrastructure and logistics, we recently introduced decellularized TEHVs (dTEHVs), based on biodegradable synthetic materials and vascular-derived cells, and successfully created a potential off-the-shelf starter matrix for guided tissue regeneration. Here, we investigate the host repopulation capacity of such dTEHVs in a non-human primate model with up to 8 weeks follow-up. After minimally invasive delivery into the orthotopic pulmonary position, dTEHVs revealed mobile and thin leaflets after 8 weeks of follow-up. Furthermore, mild-moderate valvular insufficiency and relative leaflet shortening were detected. However, in comparison to the decellularized human native heart valve control - representing currently used homografts - dTEHVs showed remarkable rapid cellular repopulation. Given this substantial in situ remodeling capacity, these results suggest that human cell-derived bioengineered decellularized materials represent a promising and clinically relevant starter matrix for heart valve tissue engineering. These biomaterials may ultimately overcome the limitations of currently used valve replacements by providing homologous, non-immunogenic, off-the-shelf replacement constructs. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Preterm labor

    DEFF Research Database (Denmark)

    Jørgensen, Jan Stener; Weile, Louise Katrine Kjær; Lamont, Ronald Francis

    2014-01-01

    While tocolytic therapy may not be indicated in all cases of spontaneous preterm labor (SPTL), the evidence that they are superior to placebo is robust. The perfect tocolytic that is 100% efficacious and 100% safe does not exist and efforts should continue to develop and introduce safer and more...... and arrange in utero transfer to a center with neonatal intensive care facilities, both of which reduce neonatal mortality and morbidity. Few tocolytics (β₂-agonists and atosiban) are licensed for use as tocolytics and only one was developed specifically to treat preterm labor (atosiban). Accordingly, most...

  18. Mechanical Design and Analysis of a Unilateral Cervical Spinal Cord Contusion Injury Model in Non-Human Primates.

    Science.gov (United States)

    Sparrey, Carolyn J; Salegio, Ernesto A; Camisa, William; Tam, Horace; Beattie, Michael S; Bresnahan, Jacqueline C

    2016-06-15

    Non-human primate (NHP) models of spinal cord injury better reflect human injury and provide a better foundation to evaluate potential treatments and functional outcomes. We combined finite element (FE) and surrogate models with impact data derived from in vivo experiments to define the impact mechanics needed to generate a moderate severity unilateral cervical contusion injury in NHPs (Macaca mulatta). Three independent variables (impactor displacement, alignment, and pre-load) were examined to determine their effects on tissue level stresses and strains. Mechanical measures of peak force, peak displacement, peak energy, and tissue stiffness were analyzed as potential determinants of injury severity. Data generated from FE simulations predicted a lateral shift of the spinal cord at high levels of compression (>64%) during impact. Submillimeter changes in mediolateral impactor position over the midline increased peak impact forces (>50%). Surrogate cords established a 0.5 N pre-load protocol for positioning the impactor tip onto the dural surface to define a consistent dorsoventral baseline position before impact, which corresponded with cerebrospinal fluid displacement and entrapment of the spinal cord against the vertebral canal. Based on our simulations, impactor alignment and pre-load were strong contributors to the variable mechanical and functional outcomes observed in in vivo experiments. Peak displacement of 4 mm after a 0.5N pre-load aligned 0.5-1.0 mm over the midline should result in a moderate severity injury; however, the observed peak force and calculated peak energy and tissue stiffness are required to properly characterize the severity and variability of in vivo NHP contusion injuries.

  19. Anti-factor IXa/X bispecific antibody ACE910 prevents joint bleeds in a long-term primate model of acquired hemophilia A

    Science.gov (United States)

    Yoshihashi, Kazutaka; Takeda, Minako; Kitazawa, Takehisa; Soeda, Tetsuhiro; Igawa, Tomoyuki; Sampei, Zenjiro; Kuramochi, Taichi; Sakamoto, Akihisa; Haraya, Kenta; Adachi, Kenji; Kawabe, Yoshiki; Nogami, Keiji; Shima, Midori; Hattori, Kunihiro

    2014-01-01

    ACE910 is a humanized anti-factor IXa/X bispecific antibody mimicking the function of factor VIII (FVIII). We previously demonstrated in nonhuman primates that a single IV dose of ACE910 exerted hemostatic activity against hemophilic bleeds artificially induced in muscles and subcutis, and that a subcutaneous (SC) dose of ACE910 showed a 3-week half-life and nearly 100% bioavailability, offering support for effective prophylaxis for hemophilia A by user-friendly SC dosing. However, there was no direct evidence that such SC dosing of ACE910 would prevent spontaneous bleeds occurring in daily life. In this study, we newly established a long-term primate model of acquired hemophilia A by multiple IV injections of an anti-primate FVIII neutralizing antibody engineered in mouse-monkey chimeric form to reduce its antigenicity. The monkeys in the control group exhibited various spontaneous bleeding symptoms as well as continuous prolongation of activated partial thromboplastin time; notably, all exhibited joint bleeds, which are a hallmark of hemophilia. Weekly SC doses of ACE910 (initial 3.97 mg/kg followed by 1 mg/kg) significantly prevented these bleeding symptoms; notably, no joint bleeding symptoms were observed. ACE910 is expected to prevent spontaneous bleeds and joint damage in hemophilia A patients even with weekly SC dosing, although appropriate clinical investigation is required. PMID:25274508

  20. Modeling a cascade of effects: the role of speed and executive functioning in preterm/full-term differences in academic achievement.

    Science.gov (United States)

    Rose, Susan A; Feldman, Judith F; Jankowski, Jeffery J

    2011-09-01

    This study identified deficits in executive functioning in pre-adolescent preterms and modeled their role, along with processing speed, in explaining preterm/full-term differences in reading and mathematics. Preterms (working memory, inhibition, and shifting. Confirmatory factor analysis showed that these executive functions, though correlated, were distinct from one another and from processing speed, which later proved to account for much of the intercorrelation among executive functions. In the best-fitting structural equation model, the negative effects of prematurity on achievement were completely mediated by the three executive functions and speed in a cascade of effects: prematurity → slower processing speed → poorer executive functioning (working memory) → lower achievement in math and reading. © 2011 Blackwell Publishing Ltd.

  1. The Importance of Understanding MHC-I Diversity in Nonhuman Primate Models of Human Infectious Diseases.

    Science.gov (United States)

    Maness, Nicholas J

    2017-01-01

    Decades of research, including the 1996 Nobel Prize in Medicine, confirm the evolutionary and immunological importance of CD8 T lymphocytes (TCD8+) that target peptides bound by the highly variable major histocompatibility complex class I (MHC-I) proteins. However, their perceived importance has varied dramatically over the past decade. Regardless, there remains myriad reasons to consider the diversity of MHC-I alleles and the TCD8+ that target them as enormously important in infectious disease research. Thus, understanding these molecules in the best animal models of human disease could be a necessity for optimizing the translational potential of these models. Knowledge of macaque MHC has substantially improved their utility for modeling HIV and could aid in modeling other viruses as well, both in the context of distribution of alleles across treatment groups in vaccine trials and in deciphering mechanisms of immune control of pathogens for which specific MHC alleles demonstrate differential impacts on disease.

  2. Reward optimization in the primate brain: a probabilistic model of decision making under uncertainty.

    Directory of Open Access Journals (Sweden)

    Yanping Huang

    Full Text Available A key problem in neuroscience is understanding how the brain makes decisions under uncertainty. Important insights have been gained using tasks such as the random dots motion discrimination task in which the subject makes decisions based on noisy stimuli. A descriptive model known as the drift diffusion model has previously been used to explain psychometric and reaction time data from such tasks but to fully explain the data, one is forced to make ad-hoc assumptions such as a time-dependent collapsing decision boundary. We show that such assumptions are unnecessary when decision making is viewed within the framework of partially observable Markov decision processes (POMDPs. We propose an alternative model for decision making based on POMDPs. We show that the motion discrimination task reduces to the problems of (1 computing beliefs (posterior distributions over the unknown direction and motion strength from noisy observations in a bayesian manner, and (2 selecting actions based on these beliefs to maximize the expected sum of future rewards. The resulting optimal policy (belief-to-action mapping is shown to be equivalent to a collapsing decision threshold that governs the switch from evidence accumulation to a discrimination decision. We show that the model accounts for both accuracy and reaction time as a function of stimulus strength as well as different speed-accuracy conditions in the random dots task.

  3. Collagen-induced arthritis in common marmosets: A new nonhuman primate model for chronic arthritis

    NARCIS (Netherlands)

    M.P.M. Vierboom (Michel); E. Breedveld (Elly); I. Kondova (Ivanela); B.A. 't Hart (Bert)

    2010-01-01

    textabstractIntroduction: There is an ever-increasing need for animal models to evaluate efficacy and safety of new therapeutics in the field of rheumatoid arthritis (RA). Particularly for the early preclinical evaluation of human-specific biologicals targeting the progressive phase of the disease,

  4. Reward optimization in the primate brain: a probabilistic model of decision making under uncertainty.

    Science.gov (United States)

    Huang, Yanping; Rao, Rajesh P N

    2013-01-01

    A key problem in neuroscience is understanding how the brain makes decisions under uncertainty. Important insights have been gained using tasks such as the random dots motion discrimination task in which the subject makes decisions based on noisy stimuli. A descriptive model known as the drift diffusion model has previously been used to explain psychometric and reaction time data from such tasks but to fully explain the data, one is forced to make ad-hoc assumptions such as a time-dependent collapsing decision boundary. We show that such assumptions are unnecessary when decision making is viewed within the framework of partially observable Markov decision processes (POMDPs). We propose an alternative model for decision making based on POMDPs. We show that the motion discrimination task reduces to the problems of (1) computing beliefs (posterior distributions) over the unknown direction and motion strength from noisy observations in a bayesian manner, and (2) selecting actions based on these beliefs to maximize the expected sum of future rewards. The resulting optimal policy (belief-to-action mapping) is shown to be equivalent to a collapsing decision threshold that governs the switch from evidence accumulation to a discrimination decision. We show that the model accounts for both accuracy and reaction time as a function of stimulus strength as well as different speed-accuracy conditions in the random dots task.

  5. Pathogenic Events in a Nonhuman Primate Model of Oral Poliovirus Infection Leading to Paralytic Poliomyelitis.

    Science.gov (United States)

    Shen, Ling; Chen, Crystal Y; Huang, Dan; Wang, Richard; Zhang, Meihong; Qian, Lixia; Zhu, Yanfen; Zhang, Alvin Zhuoran; Yang, Enzhuo; Qaqish, Arwa; Chumakov, Konstantin; Kouiavskaia, Diana; Vignuzzi, Marco; Nathanson, Neal; Macadam, Andrew J; Andino, Raul; Kew, Olen; Xu, Junfa; Chen, Zheng W

    2017-07-15

    Despite a great deal of prior research, the early pathogenic events in natural oral poliovirus infection remain poorly defined. To establish a model for study, we infected 39 macaques by feeding them single high doses of the virulent Mahoney strain of wild type 1 poliovirus. Doses ranging from 10 7 to 10 9 50% tissue culture infective doses (TCID 50 ) consistently infected all the animals, and many monkeys receiving 10 8 or 10 9 TCID 50 developed paralysis. There was no apparent difference in the susceptibilities of the three macaque species (rhesus, cynomolgus, and bonnet) used. Virus excretion in stool and nasopharynges was consistently observed, with occasional viremia, and virus was isolated from tonsils, gut mucosa, and draining lymph nodes. Viral replication proteins were detected in both epithelial and lymphoid cell populations expressing CD155 in the tonsil and intestine, as well as in spinal cord neurons. Necrosis was observed in these three cell types, and viral replication in the tonsil/gut was associated with histopathologic destruction and inflammation. The sustained response of neutralizing antibody correlated temporally with resolution of viremia and termination of virus shedding in oropharynges and feces. For the first time, this model demonstrates that early in the infectious process, poliovirus replication occurs in both epithelial cells (explaining virus shedding in the gastrointestinal tract) and lymphoid/monocytic cells in tonsils and Peyer's patches (explaining viremia), extending previous studies of poliovirus pathogenesis in humans. Because the model recapitulates human poliovirus infection and poliomyelitis, it can be used to study polio pathogenesis and to assess the efficacy of candidate antiviral drugs and new vaccines. IMPORTANCE Early pathogenic events of poliovirus infection remain largely undefined, and there is a lack of animal models mimicking natural oral human infection leading to paralytic poliomyelitis. All 39 macaques fed with

  6. Positron emission tomography imaging studies of dopamine receptors in primate models of addiction

    OpenAIRE

    Nader, Michael A; Czoty, Paul W; Gould, Robert W; Riddick, Natallia V

    2008-01-01

    Animal models have provided valuable information related to trait and state variables associated with vulnerability to drug addiction. Our brain imaging studies in monkeys have implicated D2 receptors in cocaine addiction. For example, an inverse relationship between D2 receptor availability and rates of cocaine self-administration has been documented. Moreover, environmental variables, such as those associated with formation of the social hierarchy, can impact receptor availability and sensi...

  7. Property in Nonhuman Primates

    Science.gov (United States)

    Brosnan, Sarah F.

    2011-01-01

    Property is rare in most nonhuman primates, most likely because their lifestyles are not conducive to it. Nonetheless, just because these species do not frequently maintain property does not mean that they lack the propensity to do so. Primates show respect for possession, as well as behaviors related to property, such as irrational decision…

  8. A model of primate visual cortex based on category-specific redundancies in natural images

    Science.gov (United States)

    Malmir, Mohsen; Shiry Ghidary, S.

    2010-12-01

    Neurophysiological and computational studies have proposed that properties of natural images have a prominent role in shaping selectivity of neurons in the visual cortex. An important property of natural images that has been studied extensively is the inherent redundancy in these images. In this paper, the concept of category-specific redundancies is introduced to describe the complex pattern of dependencies between responses of linear filters to natural images. It is proposed that structural similarities between images of different object categories result in dependencies between responses of linear filters in different spatial scales. It is also proposed that the brain gradually removes these dependencies in different areas of the ventral visual hierarchy to provide a more efficient representation of its sensory input. The authors proposed a model to remove these redundancies and trained it with a set of natural images using general learning rules that are developed to remove dependencies between responses of neighbouring neurons. Results of experiments demonstrate the close resemblance of neuronal selectivity between different layers of the model and their corresponding visual areas.

  9. Raptors and primate evolution.

    Science.gov (United States)

    McGraw, W Scott; Berger, Lee R

    2013-01-01

    Most scholars agree that avoiding predators is a central concern of lemurs, monkeys, and apes. However, given uncertainties about the frequency with which primates actually become prey, the selective importance of predation in primate evolution continues to be debated. Some argue that primates are often killed by predators, while others maintain that such events are relatively rare. Some authors have contended that predation's influence on primate sociality has been trivial; others counter that predation need not occur often to be a powerful selective force. Given the challenges of documenting events that can be ephemeral and irregular, we are unlikely ever to amass the volume of systematic, comparative data we have on such topics as feeding, social dynamics, or locomotor behavior. Nevertheless, a steady accumulation of field observations, insight gained from natural experiments, and novel taphonomic analyses have enhanced understanding of how primates interact with several predators, especially raptors, the subject of this review. Copyright © 2013 Wiley Periodicals, Inc.

  10. New primate model for the study of intravenous thrombotic potential and its modification

    International Nuclear Information System (INIS)

    Shoenfeld, N.A.; Yeager, A.; Connolly, R.; Ramberg, K.; Forgione, L.; Giorgio, A.; Valeri, C.R.; Callow, A.D.

    1988-01-01

    Advances in venous reconstruction have been limited by inherent venous thrombogenicity and the absence of a suitable prosthetic material for use in the venous system. We have designed an in vivo experimental model to evaluate early blood-material interactions within the venous system and to quantitate drug efficacy in the alteration of platelet function and fibrin deposition in the baboon. An 8F catheter was placed percutaneously in the femoral vein of an adult male baboon. Indium 111-labeled autogenous platelets or iodine 125-labeled human fibrinogen was infused before the introduction, into the inferior vena cava, of a linear array of 5 x 15 mm alternating Dacron and polytetrafluoroethylene samples attached to a benzalkonium-heparin-treated guide wire. At 60 or 120 minutes the samples were removed and a 1 ml aliquot of blood was drawn. The materials and blood samples were counted in a gamma well counter, and the material counts were normalized to the circulating label present in the 1 ml blood sample. The experiment was repeated after pretreatment with heparin, aspirin, or dextran. Whole blood clotting times and bleeding times were monitored. The results showed decreased platelet and fibrin deposition on polytetrafluoroethylene when compared with Dacron in the venous system. Aspirin, heparin, and dextran were all found to decrease platelet and fibrin deposition onto intravenously placed graft material samples (p less than 0.05, Student's t test). The data confirm the ability of the model to evaluate quantitatively anticoagulants, antiplatelet agents, and prospective graft materials for use in venous reconstructions

  11. Multisensory Integration and Internal Models for Sensing Gravity Effects in Primates

    Directory of Open Access Journals (Sweden)

    Francesco Lacquaniti

    2014-01-01

    Full Text Available Gravity is crucial for spatial perception, postural equilibrium, and movement generation. The vestibular apparatus is the main sensory system involved in monitoring gravity. Hair cells in the vestibular maculae respond to gravitoinertial forces, but they cannot distinguish between linear accelerations and changes of head orientation relative to gravity. The brain deals with this sensory ambiguity (which can cause some lethal airplane accidents by combining several cues with the otolith signals: angular velocity signals provided by the semicircular canals, proprioceptive signals from muscles and tendons, visceral signals related to gravity, and visual signals. In particular, vision provides both static and dynamic signals about body orientation relative to the vertical, but it poorly discriminates arbitrary accelerations of moving objects. However, we are able to visually detect the specific acceleration of gravity since early infancy. This ability depends on the fact that gravity effects are stored in brain regions which integrate visual, vestibular, and neck proprioceptive signals and combine this information with an internal model of gravity effects.

  12. Of mice and monkeys: using non-human primate models to bridge mouse- and human-based investigations of autism spectrum disorders

    Directory of Open Access Journals (Sweden)

    Watson Karli K

    2012-07-01

    Full Text Available Abstract The autism spectrum disorders (ASDs arise from a diverse array of genetic and environmental origins that disrupt the typical developmental trajectory of neural connectivity and synaptogenesis. ASDs are marked by dysfunctional social behavior and cognition, among other deficits. Greater understanding of the biological substrates of typical social behavior in animal models will further our understanding of the etiology of ASDs. Despite the precision and tractability of molecular genetics models of ASDs in rodents, these organisms lack the complexity of human social behavior, thus limiting their impact on understanding ASDs to basic mechanisms. Non-human primates (NHPs provide an attractive, complementary model for ASDs, due in part to the complexity and dynamics of social structures, reliance on vision for social signaling, and deep homology in brain circuitry mediating social behavior and reward. This knowledge is based on a rich literature, compiled over 50 years of observing primate behavior in the wild, which, in the case of rhesus macaques, is complemented by a large body of research characterizing neuronal activity during cognitive behavior. Several recent developments in this field are directly relevant to ASDs, including how the brain represents the perceptual features of social stimuli, how social information influences attention processes in the brain, and how the value of social interaction is computed. Because the symptoms of ASDs may represent extreme manifestations of traits that vary in intensity within the general population, we will additionally discuss ways in which nonhuman primates also show variation in social behavior and reward sensitivity. In cases where variation in species-typical behavior is analogous to similar variations in human behavior, we believe that study of the neural circuitry underlying this variation will provide important insights into the systems-level mechanisms contributing to ASD pathology.

  13. Understanding fetal factors that contribute to preterm birth: Sjögren-Larsson syndrome as a model.

    Science.gov (United States)

    Staps, Pippa; Hogeveen, Marije; Fuijkschot, Joris; van Drongelen, Joris; Willemsen, Michèl A A P

    2017-09-15

    Preterm birth is the world's leading cause of neonatal death. Unfortunately, the pathophysiology of preterm birth remains poorly understood. Sjögren-Larsson syndrome is a rare, neurometabolic disorder caused by a fatty aldehyde dehydrogenase deficiency. A majority of patients with Sjögren-Larsson syndrome is born preterm. Data of all known Dutch patients with Sjögren-Larsson syndrome and all cases reported in literature were analyzed to learn from preterm birth in context of this rare disease. Exact gestational age was known in 33 Dutch patients; 24 (73%) of them were born preterm, with a median gestational age of 36 weeks. The literature search confirmed our findings: 13 (59%) of 22 cases was born preterm. Preterm birth is a hallmark of Sjögren-Larsson syndrome, presumably caused by the abnormal lipid metabolism of the fetus. At least five additional rare genetic disorders (namely Ehlers-Danlos syndrome, ichthyosis prematurity syndrome, congenital analbuminemia, osteogenesis imperfecta type II and restrictive dermopathy) were found in literature that lead to preterm birth of the affected fetus. These disorders are in fact "experiments of nature" and as such they shed new lights on the mechanisms causing preterm birth.

  14. Deep Hierarchies in the Primate Visual Cortex

    DEFF Research Database (Denmark)

    Krüger, Norbert; Jannsen, Per; Kalkan, S.

    2013-01-01

    of the processing hierarchies present in the primate visual system considering recent discoveries in neurophysiology. The hierarchal processing in the primate visual system is characterized by a sequence of different levels of processing (in the order of ten) that constitute a deep hierarchy in contrast to the flat...... vision architectures predominantly used in today's mainstream computer vision. We hope that the functional description of the deep hierarchies realized in the primate visual system provides valuable insights for the design of computer vision algorithms, fostering increasingly productive interaction......Computational modeling of the primate visual system yields insights of potential relevance to some of the challenges that computer vision is facing, such as object recognition and categorization, motion detection and activity recognition or vision-based navigation and manipulation. This article...

  15. Examination of the safety of pediatric vaccine schedules in a non-human primate model: assessments of neurodevelopment, learning, and social behavior.

    Science.gov (United States)

    Curtis, Britni; Liberato, Noelle; Rulien, Megan; Morrisroe, Kelly; Kenney, Caroline; Yutuc, Vernon; Ferrier, Clayton; Marti, C Nathan; Mandell, Dorothy; Burbacher, Thomas M; Sackett, Gene P; Hewitson, Laura

    2015-06-01

    In the 1990s, the mercury-based preservative thimerosal was used in most pediatric vaccines. Although there are currently only two thimerosal-containing vaccines (TCVs) recommended for pediatric use, parental perceptions that vaccines pose safety concerns are affecting vaccination rates, particularly in light of the much expanded and more complex schedule in place today. The objective of this study was to examine the safety of pediatric vaccine schedules in a non-human primate model. We administered vaccines to six groups of infant male rhesus macaques (n = 12-16/group) using a standardized thimerosal dose where appropriate. Study groups included the recommended 1990s Pediatric vaccine schedule, an accelerated 1990s Primate schedule with or without the measles-mumps-rubella (MMR) vaccine, the MMR vaccine only, and the expanded 2008 schedule. We administered saline injections to age-matched control animals (n = 16). Infant development was assessed from birth to 12 months of age by examining the acquisition of neonatal reflexes, the development of object concept permanence (OCP), computerized tests of discrimination learning, and infant social behavior. Data were analyzed using analysis of variance, multilevel modeling, and survival analyses, where appropriate. We observed no group differences in the acquisition of OCP. During discrimination learning, animals receiving TCVs had improved performance on reversal testing, although some of these same animals showed poorer performance in subsequent learning-set testing. Analysis of social and nonsocial behaviors identified few instances of negative behaviors across the entire infancy period. Although some group differences in specific behaviors were reported at 2 months of age, by 12 months all infants, irrespective of vaccination status, had developed the typical repertoire of macaque behaviors. This comprehensive 5-year case-control study, which closely examined the effects of pediatric vaccines on early primate

  16. The visual development of hand-centered receptive fields in a neural network model of the primate visual system trained with experimentally recorded human gaze changes.

    Science.gov (United States)

    Galeazzi, Juan M; Navajas, Joaquín; Mender, Bedeho M W; Quian Quiroga, Rodrigo; Minini, Loredana; Stringer, Simon M

    2016-01-01

    Neurons have been found in the primate brain that respond to objects in specific locations in hand-centered coordinates. A key theoretical challenge is to explain how such hand-centered neuronal responses may develop through visual experience. In this paper we show how hand-centered visual receptive fields can develop using an artificial neural network model, VisNet, of the primate visual system when driven by gaze changes recorded from human test subjects as they completed a jigsaw. A camera mounted on the head captured images of the hand and jigsaw, while eye movements were recorded using an eye-tracking device. This combination of data allowed us to reconstruct the retinal images seen as humans undertook the jigsaw task. These retinal images were then fed into the neural network model during self-organization of its synaptic connectivity using a biologically plausible trace learning rule. A trace learning mechanism encourages neurons in the model to learn to respond to input images that tend to occur in close temporal proximity. In the data recorded from human subjects, we found that the participant's gaze often shifted through a sequence of locations around a fixed spatial configuration of the hand and one of the jigsaw pieces. In this case, trace learning should bind these retinal images together onto the same subset of output neurons. The simulation results consequently confirmed that some cells learned to respond selectively to the hand and a jigsaw piece in a fixed spatial configuration across different retinal views.

  17. Nonhuman primate models for cell-associated simian immunodeficiency virus transmission: the need to better understand the complexity of HIV mucosal transmission.

    Science.gov (United States)

    Bernard-Stoecklin, Sibylle; Gommet, Céline; Cavarelli, Mariangela; Le Grand, Roger

    2014-12-15

    Nonhuman primates are extensively used to assess strategies to prevent infection from sexual exposure to human immunodeficiency virus (HIV) and to study mechanisms of mucosal transmission. However, although semen represents one of the most important vehicles for the virus, the vast majority of preclinical challenge studies have used cell-free simian immunodeficiency virus (SIV) or simian/human immunodeficiency virus (SHIV) viral particles inoculated as diluted culture supernatants. Semen is a complex body fluid containing many factors that may facilitate or decrease HIV infectiousness. The virus in semen is present in different forms: as free virus particles or as cell-associated virus (ie, within infected leukocytes). Although cell-to-cell transmission of HIV is highly efficient, the role of cell-associated virus in semen has been surprisingly poorly investigated in nonhuman primate models. Mucosal exposure of macaques to cell-associated SIV by using infected peripheral blood mononuclear cells or spleen cells has been shown to be an efficient means of infection; however, it has yet to be shown that SIV- or SHIV-infected seminal leukocytes can transmit infection in vivo. Improvement of animal models to better recapitulate the complex microenvironment at portals of HIV entry is needed for testing candidate antiretrovirals, microbicides, and vaccines. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. A brief history of primate research: Global health improvements and ...

    African Journals Online (AJOL)

    Scientists rapidly realized the value of primates as research models – their evolutionary proximity to humans making them better predictors, or models, of human biology. Systematic studies using primates began in the last century and massive demand for research subjects almost caused the extinction of some important ...

  19. Use of metabolomics for the identification and validation of clinical biomarkers for preterm birth: Preterm SAMBA.

    Science.gov (United States)

    Cecatti, Jose G; Souza, Renato T; Sulek, Karolina; Costa, Maria L; Kenny, Louise C; McCowan, Lesley M; Pacagnella, Rodolfo C; Villas-Boas, Silas G; Mayrink, Jussara; Passini, Renato; Franchini, Kleber G; Baker, Philip N

    2016-08-08

    Spontaneous preterm birth is a complex syndrome with multiple pathways interactions determining its occurrence, including genetic, immunological, physiologic, biochemical and environmental factors. Despite great worldwide efforts in preterm birth prevention, there are no recent effective therapeutic strategies able to decrease spontaneous preterm birth rates or their consequent neonatal morbidity/mortality. The Preterm SAMBA study will associate metabolomics technologies to identify clinical and metabolite predictors for preterm birth. These innovative and unbiased techniques might be a strategic key to advance spontaneous preterm birth prediction. Preterm SAMBA study consists of a discovery phase to identify biophysical and untargeted metabolomics from blood and hair samples associated with preterm birth, plus a validation phase to evaluate the performance of the predictive modelling. The first phase, a case-control study, will randomly select 100 women who had a spontaneous preterm birth (before 37 weeks) and 100 women who had term birth in the Cork Ireland and Auckland New Zealand cohorts within the SCOPE study, an international consortium aimed to identify potential metabolomic predictors using biophysical data and blood samples collected at 20 weeks of gestation. The validation phase will recruit 1150 Brazilian pregnant women from five participant centres and will collect blood and hair samples at 20 weeks of gestation to evaluate the performance of the algorithm model (sensitivity, specificity, predictive values and likelihood ratios) in predicting spontaneous preterm birth (before 34 weeks, with a secondary analysis of delivery before 37 weeks). The Preterm SAMBA study intends to step forward on preterm birth prediction using metabolomics techniques, and accurate protocols for sample collection among multi-ethnic populations. The use of metabolomics in medical science research is innovative and promises to provide solutions for disorders with multiple

  20. Total Retinal Blood Flow in a Nonhuman Primate Optic Nerve Transection Model Using Dual-Beam Bidirectional Doppler FD-OCT and Microsphere Method.

    Science.gov (United States)

    Told, Reinhard; Wang, Lin; Cull, Grant; Thompson, Simon J; Burgoyne, Claude F; Aschinger, Gerold C; Schmetterer, Leopold; Werkmeister, René M

    2016-03-01

    We validated noninvasive Doppler-optical coherence tomography (OCT) blood flow measurements against the terminal microsphere method in a surgical induced optic nerve transection nonhuman primate model. In 6 nonhuman primates, total retinal blood flow (TRBF) was measured with a custom-built dual-beam bidirectional Doppler Fourier Domain (FD)-OCT. Peripapillary retinal nerve fiber layer thickness (RNFLT) was measured by Spectralis spectral-domain (SD)-OCT. Measurements were performed every 10 to 15 days before and after unilateral optic nerve transection (ONT) until RNFLT was reduced by more than 40% from baseline. Before the animals were killed, TRBF was measured using the microsphere technique. A significant correlation between all arterial and venous Doppler OCT TRBF measurements was found in ONT and contralateral control eyes (both P FD-OCT and the microsphere method. It also was possible to monitor changes over time in TRBF after ONT with Doppler OCT. These findings highlight the accuracy and potential of noninvasive Doppler OCT to provide valuable information for detecting early changes in ocular disease in future.

  1. Intraarterial reteplase and intravenous abciximab for treatment of acute ischemic stroke. A preliminary feasibility and safety study in a non-human primate model

    International Nuclear Information System (INIS)

    Qureshi, Adnan I.; Suri, M. Fareed K.; Ali, Zulfiqar; Ringer, Andrew J.; Boulos, Alan S.; Guterman, Lee R.; Hopkins, L. Nelson; Nakada, Marian T.; Alberico, Ronald A.; Martin, Lisa B.E.

    2005-01-01

    We performed a preliminary feasibility and safety study using intravenous (IV) administration of a platelet glycoprotein IIb/IIIa inhibitor (abciximab) in conjunction with intraarterial (IA) administration of a thrombolytic agent (reteplase) in a primate model of intracranial thrombosis. We introduced thrombus through superselective catheterization of the intracranial segment of the internal carotid artery in 16 primates. The animals were randomly assigned to receive IA reteplase and IV abciximab (n =4), IA reteplase and IV placebo (n =4), IA placebo and IV abciximab (n =4) or IA and IV placebo (n =4). Recanalization was assessed by serial angiography during the 6-h period after initiation of treatment. Postmortem magnetic resonance (MR) imaging was performed to determine the presence of cerebral infarction or intracranial hemorrhage. Partial or complete recanalization at 6 h after initiation of treatment (decrease of two or more points in pre-treatment angiographic occlusion grade) was observed in two animals treated with IA reteplase and IV abciximab, three animals treated with IA reteplase alone and one animal treated with IV abciximab alone. No improvement in perfusion was observed in animals that received IV and IA placebo. Cerebral infarction was demonstrated on postmortem MR imaging in three animals that received IA and IV placebo and in one animal each from the groups that received IA reteplase and IV abciximab or IV abciximab alone. One animal that received IV abciximab alone had a small intracerebral hemorrhage on MR imaging. (orig.)

  2. Magnetic resonance imaging and tensor-based morphometry in the MPTP non-human primate model of Parkinson’s disease

    Science.gov (United States)

    Crum, William R.; Gerwig, Madeline; Vernon, Anthony C.; Patel, Priya; Jackson, Michael J.; Rose, Sarah; Jenner, Peter; Iravani, Mahmoud M.

    2017-01-01

    Parkinson’s disease (PD) is the second most common neurodegenerative disorder producing a variety of motor and cognitive deficits with the causes remaining largely unknown. The gradual loss of the nigrostriatal pathway is currently considered the pivotal pathological event. To better understand the progression of PD and improve treatment management, defining the disease on a structural basis and expanding brain analysis to extra-nigral structures is indispensable. The anatomical complexity and the presence of neuromelanin, make the use of non-human primates an essential element in developing putative imaging biomarkers of PD. To this end, ex vivo T2-weighted magnetic resonance images were acquired from control and 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated marmosets. Volume measurements of the caudate, putamen, and substantia nigra indicated significant atrophy and cortical thinning. Tensor-based morphometry provided a more extensive and hypothesis free assessment of widespread changes caused by the toxin insult to the brain, especially highlighting regional cortical atrophy. The results highlight the importance of developing imaging biomarkers of PD in non-human primate models considering their distinct neuroanatomy. It is essential to further develop these biomarkers in vivo to provide non-invasive tools to detect pre-symptomatic PD and to monitor potential disease altering therapeutics. PMID:28738061

  3. Gene transfer in rodents and primates as a new tool for modeling diseases in animals and assessing functions by in vivo imaging

    International Nuclear Information System (INIS)

    Deglon, N.

    2006-01-01

    The identification of disease-causing genes in familial forms of neuro-degenerative disorders and the development of genetic models closely replicating human CNS pathologies have drastically changed our understanding of the molecular events leading to neuronal cell death. If these achievements open new opportunities of therapeutic interventions efficient delivery systems taking into account the specificity of the central nervous system are required to administer therapeutic candidates. In addition, there is a need to develop 1) genetic models in large animals that replicate late stages of the diseases and 2) imaging techniques suitable for longitudinal, quantitative and non-invasive evaluation of disease progression and the evaluation of new therapeutic strategies. Over the last few years, we have investigated the potential of lentiviral vectors as tool to model and treat CNS disorders. The use of lentiviral vectors to create animal model of these pathologies holds various advantages compared to classical transgenic approaches. Viral vectors are versatile, highly flexible tools to perform in vivo studies. Multiple genetic models can be created in a short period of time. High transduction efficiencies as well as robust and sustained trans-gene expression lead to the rapid appearance of functional and behavioral abnormalities and severe neuro-degeneration. Targeted injections in different brain areas can be used to investigate the regional specificity of the neuro-pathology and eliminate potential side effects associated with a widespread over-expression of the trans-gene. Finally, models can be established in different mammalian species including non-human primates, thereby providing an opportunity to assess complex behavioral changes and perform longitudinal follow-up of neuro-pathological alterations by imaging. We have demonstrated the proof of principle of this approach for Huntington's disease. We have shown that the intratriatal injection of lentiviral vector

  4. The adaptive value of primate color vision for predator detection.

    Science.gov (United States)

    Pessoa, Daniel Marques Almeida; Maia, Rafael; de Albuquerque Ajuz, Rafael Cavalcanti; De Moraes, Pedro Zurvaino Palmeira Melo Rosa; Spyrides, Maria Helena Constantino; Pessoa, Valdir Filgueiras

    2014-08-01

    The complex evolution of primate color vision has puzzled biologists for decades. Primates are the only eutherian mammals that evolved an enhanced capacity for discriminating colors in the green-red part of the spectrum (trichromatism). However, while Old World primates present three types of cone pigments and are routinely trichromatic, most New World primates exhibit a color vision polymorphism, characterized by the occurrence of trichromatic and dichromatic females and obligatory dichromatic males. Even though this has stimulated a prolific line of inquiry, the selective forces and relative benefits influencing color vision evolution in primates are still under debate, with current explanations focusing almost exclusively at the advantages in finding food and detecting socio-sexual signals. Here, we evaluate a previously untested possibility, the adaptive value of primate color vision for predator detection. By combining color vision modeling data on New World and Old World primates, as well as behavioral information from human subjects, we demonstrate that primates exhibiting better color discrimination (trichromats) excel those displaying poorer color visions (dichromats) at detecting carnivoran predators against the green foliage background. The distribution of color vision found in extant anthropoid primates agrees with our results, and may be explained by the advantages of trichromats and dichromats in detecting predators and insects, respectively. © 2014 Wiley Periodicals, Inc.

  5. The MPTP marmoset model of parkinsonism: a multi-purpose non-human primate model for neurodegenerative diseases.

    Science.gov (United States)

    Philippens, Ingrid H C H M; 't Hart, Bert A; Torres, German

    2010-12-01

    Aging societies face an increasing prevalence of neurodegenerative disorders for which no cure exists. The paucity of relevant animal models that faithfully reproduce clinical and pathogenic features of neurodegenerative diseases is a major cause for the lack of effective therapies. Clinically distinct disorders, such as Alzheimer's and Parkinson's disease, are driven by overlapping pathogenic mechanisms that converge onto vulnerable neurons to ultimately cause abnormal clinical outcomes. These similarities, particularly in the early phases of neurodegeneration, might help identify appropriate animal model systems for studying of cell pathology. While reviewing some of the cellular mechanisms of disease progression, we discuss the MPTP-induced model of Parkinsonism in marmoset monkeys as a model system for construct, face and predictive validity in neurodegenerative studies. Copyright © 2010 Elsevier Ltd. All rights reserved.

  6. Spatial-temporal modeling of the association between air pollution exposure and preterm birth: identifying critical windows of exposure.

    Science.gov (United States)

    Warren, Joshua; Fuentes, Montserrat; Herring, Amy; Langlois, Peter

    2012-12-01

    Exposure to high levels of air pollution during the pregnancy is associated with increased probability of preterm birth (PTB), a major cause of infant morbidity and mortality. New statistical methodology is required to specifically determine when a particular pollutant impacts the PTB outcome, to determine the role of different pollutants, and to characterize the spatial variability in these results. We develop a new Bayesian spatial model for PTB which identifies susceptible windows throughout the pregnancy jointly for multiple pollutants (PM(2.5) , ozone) while allowing these windows to vary continuously across space and time. We geo-code vital record birth data from Texas (2002-2004) and link them with standard pollution monitoring data and a newly introduced EPA product of calibrated air pollution model output. We apply the fully spatial model to a region of 13 counties in eastern Texas consisting of highly urban as well as rural areas. Our results indicate significant signal in the first two trimesters of pregnancy with different pollutants leading to different critical windows. Introducing the spatial aspect uncovers critical windows previously unidentified when space is ignored. A proper inference procedure is introduced to correctly analyze these windows. © 2012, The International Biometric Society.

  7. Behavioral and histological outcomes following neonatal HI injury in a preterm (P3) and term (P7) rodent model.

    Science.gov (United States)

    Alexander, M; Garbus, H; Smith, A L; Rosenkrantz, T S; Fitch, R H

    2014-02-01

    Hypoxia-ischemia (HI) occurs when blood and/or oxygen delivery to the brain is compromised. HI injuries can occur in infants born prematurely (well as in term infants with birth complications. In both preterm and term HI populations, brain injury is associated with subsequent behavioral deficits. Neonatal HI injury can be modeled in rodents (e.g., the Rice-Vannucci method, via cautery of right carotid followed by hypoxia). When this injury is induced early in life (between postnatal day (P)1-5), neuropathologies typical of human preterm HI are modeled. When injury is induced later (P7-12), neuropathologies typical of those seen in HI term infants are modeled. The current study sought to characterize the similarities/differences between outcomes following early (P3) and late (P7) HI injury in rats. Male rats with HI injury on P3 or P7, as well as sham controls, were tested on a variety of behavioral tasks in both juvenile and adult periods. Results showed that P7 HI rats displayed deficits on motor learning, rapid auditory processing (RAP), and other learning/memory tasks, as well as a reduction in volume in various neuroanatomical structures. P3 HI animals showed only transient deficits on RAP tasks in the juvenile period (but not in adulthood), yet robust deficits on a visual attention task in adulthood. P3 HI animals did not show any significant reductions in brain volume that we could detect. These data suggest that: (1) behavioral deficits following neonatal HI are task-specific depending on timing of injury; (2) P3 HI rats showed transient deficits on RAP tasks; (3) the more pervasive behavioral deficits seen following P7 HI injury were associated with substantial global tissue loss; and (4) persistent deficits in attention in P3 HI subjects might be linked to neural connectivity disturbances rather than a global loss of brain volume, given that no such pathology was found. These combined findings can be applied to our understanding of differing long

  8. A mobile, high-throughput semi-automated system for testing cognition in large non-primate animal models of Huntington disease.

    Science.gov (United States)

    McBride, Sebastian D; Perentos, Nicholas; Morton, A Jennifer

    2016-05-30

    For reasons of cost and ethical concerns, models of neurodegenerative disorders such as Huntington disease (HD) are currently being developed in farm animals, as an alternative to non-human primates. Developing reliable methods of testing cognitive function is essential to determining the usefulness of such models. Nevertheless, cognitive testing of farm animal species presents a unique set of challenges. The primary aims of this study were to develop and validate a mobile operant system suitable for high throughput cognitive testing of sheep. We designed a semi-automated testing system with the capability of presenting stimuli (visual, auditory) and reward at six spatial locations. Fourteen normal sheep were used to validate the system using a two-choice visual discrimination task. Four stages of training devised to acclimatise animals to the system are also presented. All sheep progressed rapidly through the training stages, over eight sessions. All sheep learned the 2CVDT and performed at least one reversal stage. The mean number of trials the sheep took to reach criterion in the first acquisition learning was 13.9±1.5 and for the reversal learning was 19.1±1.8. This is the first mobile semi-automated operant system developed for testing cognitive function in sheep. We have designed and validated an automated operant behavioural testing system suitable for high throughput cognitive testing in sheep and other medium-sized quadrupeds, such as pigs and dogs. Sheep performance in the two-choice visual discrimination task was very similar to that reported for non-human primates and strongly supports the use of farm animals as pre-clinical models for the study of neurodegenerative diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Hands of early primates.

    Science.gov (United States)

    Boyer, Doug M; Yapuncich, Gabriel S; Chester, Stephen G B; Bloch, Jonathan I; Godinot, Marc

    2013-12-01

    Questions surrounding the origin and early evolution of primates continue to be the subject of debate. Though anatomy of the skull and inferred dietary shifts are often the focus, detailed studies of postcrania and inferred locomotor capabilities can also provide crucial data that advance understanding of transitions in early primate evolution. In particular, the hand skeleton includes characteristics thought to reflect foraging, locomotion, and posture. Here we review what is known about the early evolution of primate hands from a comparative perspective that incorporates data from the fossil record. Additionally, we provide new comparative data and documentation of skeletal morphology for Paleogene plesiadapiforms, notharctines, cercamoniines, adapines, and omomyiforms. Finally, we discuss implications of these data for understanding locomotor transitions during the origin and early evolutionary history of primates. Known plesiadapiform species cannot be differentiated from extant primates based on either intrinsic hand proportions or hand-to-body size proportions. Nonetheless, the presence of claws and a different metacarpophalangeal [corrected] joint form in plesiadapiforms indicate different grasping mechanics. Notharctines and cercamoniines have intrinsic hand proportions with extremely elongated proximal phalanges and digit rays relative to metacarpals, resembling tarsiers and galagos. But their hand-to-body size proportions are typical of many extant primates (unlike those of tarsiers, and possibly Teilhardina, which have extremely large hands). Non-adapine adapiforms and omomyids exhibit additional carpal features suggesting more limited dorsiflexion, greater ulnar deviation, and a more habitually divergent pollex than observed plesiadapiforms. Together, features differentiating adapiforms and omomyiforms from plesiadapiforms indicate increased reliance on vertical prehensile-clinging and grasp-leaping, possibly in combination with predatory behaviors in

  10. Preterm dietary study

    DEFF Research Database (Denmark)

    Zachariassen, G; Fenger-Gron, J

    2014-01-01

    To describe eating habits and possible feeding intolerance among preterm infants based on type of nutrition.......To describe eating habits and possible feeding intolerance among preterm infants based on type of nutrition....

  11. Preterm Labor and Birth

    Science.gov (United States)

    ... Facebook Twitter Pinterest Email Print Preterm Labor and Birth In general, a normal human pregnancy lasts about ... is called preterm labor (or premature labor). A birth that occurs before 37 weeks is considered a ...

  12. Importance of Achromatic Contrast in Short-Range Fruit Foraging of Primates

    OpenAIRE

    Hiramatsu, Chihiro; Melin, Amanda D.; Aureli, Filippo; Schaffner, Colleen M.; Vorobyev, Misha; Matsumoto, Yoshifumi; Kawamura, Shoji

    2008-01-01

    Trichromatic primates have a 'red-green' chromatic channel in addition to luminance and 'blue-yellow' channels. It has been argued that the red-green channel evolved in primates as an adaptation for detecting reddish or yellowish objects, such as ripe fruits, against a background of foliage. However, foraging advantages to trichromatic primates remain unverified by behavioral observation of primates in their natural habitats. New World monkeys (platyrrhines) are an excellent model for this ev...

  13. Preclinical Testing of Antihuman CD28 Fab' Antibody in a Novel Nonhuman Primate Small Animal Rodent Model of Xenogenic Graft-Versus-Host Disease.

    Science.gov (United States)

    Hippen, Keli L; Watkins, Benjamin; Tkachev, Victor; Lemire, Amanda M; Lehnen, Charles; Riddle, Megan J; Singh, Karnail; Panoskaltsis-Mortari, Angela; Vanhove, Bernard; Tolar, Jakub; Kean, Leslie S; Blazar, Bruce R

    2016-12-01

    Graft-versus-host disease (GVHD) is a severe complication of hematopoietic stem cell transplantation. Current therapies to prevent alloreactive T cell activation largely cause generalized immunosuppression and may result in adverse drug, antileukemia and antipathogen responses. Recently, several immunomodulatory therapeutics have been developed that show efficacy in maintaining antileukemia responses while inhibiting GVHD in murine models. To analyze efficacy and better understand immunological tolerance, escape mechanisms, and side effects of clinical reagents, testing of species cross-reactive human agents in large animal GVHD models is critical. We have previously developed and refined a nonhuman primate (NHP) large animal GVHD model. However, this model is not readily amenable to semi-high throughput screening of candidate clinical reagents. Here, we report a novel, optimized NHP xenogeneic GVHD (xeno-GVHD) small animal model that recapitulates many aspects of NHP and human GVHD. This model was validated using a clinically available blocking, monovalent anti-CD28 antibody (FR104) whose effects in a human xeno-GVHD rodent model are known. Because human-reactive reagents may not be fully cross-reactive or effective in vivo on NHP immune cells, this NHP xeno-GVHD model provides immunological insights and direct testing on NHP-induced GVHD before committing to the intensive NHP studies that are being increasingly used for detailed evaluation of new immune therapeutic strategies before human trials.

  14. Prediction of preterm delivery

    NARCIS (Netherlands)

    Wilms, F.F.

    2014-01-01

    Preterm delivery is in quantity and in severity an important issue in the obstetric care in the Western world. There is considerable knowledge on maternal and obstetric risk factors of preterm delivery. Of the women presenting with preterm labor, the majority is pregnant with a male fetus and in

  15. Risk factors for cognitive impairment in school-age children born preterm: application of a hierarchical model

    Directory of Open Access Journals (Sweden)

    Maura Calixto Cecherelli de Rodrigues

    2012-08-01

    Full Text Available The purpose was to analyze factors associated with cognitive impairment in very low birth weight (VLBW children born preterm. A prospective cohort of 65 VLBW children was assessed at the age of eight years using the Wechsler Intelligence Scale for Children. A model for the relationship of variables with the cognitive impairment outcome attributed hierarchical levels: distal (socioeconomic variables, intermediate I and II (perinatal and neonatal variables, post-neonatal variables and proximal (child health and psychosocial stimulation. A multivariate logistic regression was performed. In the multivariate hierarchical logistic regression, the maternal education (OR=0.77, 95%CI 0.63-0.94 and number of prenatal visits (OR=0.73, 95%CI 0.54-0.99 showed a protective association, but the male (OR=7.3, 95%CI 1.54-35.3 was associated with worse results. The VLBW children cognitive performance in the age of eight years benefits from more educated mothers, better prenatal care, and the baby gender as female.

  16. Omega-3 polyunsaturated fatty acids enhance cytokine production and oxidative stress in a mouse model of preterm labor.

    Science.gov (United States)

    Boulis, Tharwat Stewart; Rochelson, Burton; Novick, Olivia; Xue, Xiangying; Chatterjee, Prodyot K; Gupta, Madhu; Solanki, Malvika H; Akerman, Meredith; Metz, Christine N

    2014-11-01

    Omega-3 polyunsaturated fatty acid (ω-3 PUFA) supplementation during pregnancy remains controversial. We sought to examine the effects of ω-3 PUFA on inflammation and oxidative stress in vitro and in vivo using a model of preterm labor. In vivo. Female Swiss Webster mice were fed a normal diet or a 5% fish oil (FO) diet for 3 weeks then mated with normal-fed males. On gestational day 15, dams were injected with either saline (n=10 per group) or lipopolysaccharide (LPS, intrauterine) (n=10 per group). Maternal plasma, amniotic fluid, placentas, and uteri were collected 4 h later and assessed for cytokines; maternal plasma and amniotic fluids were analyzed for oxidative stress. In vitro. RAW264.7 mouse macrophage-like cells were treated with either: vehicle, H2O2, docosahexaenoic acid (DHA), or eicosapentaenoic acid (EPA) (0, 0.1-100 μM) and analyzed for oxidative stress. In vivo. Administration of the 5% FO diet enhanced LPS-induced cytokines in the placenta (Pstress than control-fed animals (Pstress were observed in the amniotic fluid. In vitro. Treatment of macrophage-like cells with ω-3 PUFA significantly and dose-dependently increased oxidative stress (Pstress in vivo. Likewise, DHA and EPA induced oxidative stress in macrophage-like cells in vitro.

  17. Scaling of rotational inertia of primate mandibles.

    Science.gov (United States)

    Ross, Callum F; Iriarte-Diaz, Jose; Platts, Ellen; Walsh, Treva; Heins, Liam; Gerstner, Geoffrey E; Taylor, Andrea B

    2017-05-01

    The relative importance of pendulum mechanics and muscle mechanics in chewing dynamics has implications for understanding the optimality criteria driving the evolution of primate feeding systems. The Spring Model (Ross et al., 2009b), which modeled the primate chewing system as a forced mass-spring system, predicted that chew cycle time would increase faster than was actually observed. We hypothesized that if mandibular momentum plays an important role in chewing dynamics, more accurate estimates of the rotational inertia of the mandible would improve the accuracy with which the Spring Model predicts the scaling of primate chew cycle period. However, if mass-related momentum effects are of negligible importance in the scaling of primate chew cycle period, this hypothesis would be falsified. We also predicted that greater "robusticity" of anthropoid mandibles compared with prosimians would be associated with higher moments of inertia. From computed tomography scans, we estimated the scaling of the moment of inertia (I j ) of the mandibles of thirty-one species of primates, including 22 anthropoid and nine prosimian species, separating I j into the moment about a transverse axis through the center of mass (I xx ) and the moment of the center of mass about plausible axes of rotation. We found that across primates I j increases with positive allometry relative to jaw length, primarily due to positive allometry of jaw mass and I xx , and that anthropoid mandibles have greater rotational inertia compared with prosimian mandibles of similar length. Positive allometry of I j of primate mandibles actually lowers the predictive ability of the Spring Model, suggesting that scaling of primate chew cycle period, and chewing dynamics in general, are more strongly influenced by factors other than scaling of inertial properties of the mandible, such as the dynamic properties of the jaw muscles and neural control. Differences in cycle period scaling between chewing and locomotion

  18. Allostatic Load and Preterm Birth

    Directory of Open Access Journals (Sweden)

    David M. Olson

    2015-12-01

    Full Text Available Preterm birth is a universal health problem that is one of the largest unmet medical needs contributing to the global burden of disease. Adding to its complexity is that there are no means to predict who is at risk when pregnancy begins or when women will actually deliver. Until these problems are addressed, there will be no interventions to reduce the risk because those who should be treated will not be known. Considerable evidence now exists that chronic life, generational or accumulated stress is a risk factor for preterm delivery in animal models and in women. This wear and tear on the body and mind is called allostatic load. This review explores the evidence that chronic stress contributes to preterm birth and other adverse pregnancy outcomes in animal and human studies. It explores how allostatic load can be used to, firstly, model stress and preterm birth in animal models and, secondly, how it can be used to develop a predictive model to assess relative risk among women in early pregnancy. Once care providers know who is in the highest risk group, interventions can be developed and applied to mitigate their risk.

  19. Epidemiology of preterm birth.

    Science.gov (United States)

    Purisch, Stephanie E; Gyamfi-Bannerman, Cynthia

    2017-11-01

    Preterm birth is a worldwide epidemic with a global incidence of 15 million per year. Though rates of preterm birth in the United States have declined over the last decade, nearly 1 in 10 babies is still born preterm. The incidence, gestational age, and underlying etiology of preterm birth is highly variable across different racial and ethnic groups and geographic boundaries. In this article, we review the epidemiology of preterm birth in the United States and globally, with a focus on temporal trends and racial, ethnic, and geographic disparities. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. The role of genetic background in susceptibility to chemical warfare nerve agents across rodent and non-human primate models.

    Science.gov (United States)

    Matson, Liana M; McCarren, Hilary S; Cadieux, C Linn; Cerasoli, Douglas M; McDonough, John H

    2018-01-15

    Genetics likely play a role in various responses to nerve agent exposure, as genetic background plays an important role in behavioral, neurological, and physiological responses to environmental stimuli. Mouse strains or selected lines can be used to identify susceptibility based on background genetic features to nerve agent exposure. Additional genetic techniques can then be used to identify mechanisms underlying resistance and sensitivity, with the ultimate goal of developing more effective and targeted therapies. Here, we discuss the available literature on strain and selected line differences in cholinesterase activity levels and response to nerve agent-induced toxicity and seizures. We also discuss the available cholinesterase and toxicity literature across different non-human primate species. The available data suggest that robust genetic differences exist in cholinesterase activity, nerve agent-induced toxicity, and chemical-induced seizures. Available cholinesterase data suggest that acetylcholinesterase activity differs across strains, but are limited by the paucity of carboxylesterase data in strains and selected lines. Toxicity and seizures, two outcomes of nerve agent exposure, have not been fully evaluated for genetic differences, and thus further studies are required to understand baseline strain and selected line differences. Published by Elsevier B.V.

  1. Safety and Efficacy of the Complement Inhibitor AMY-101 in a Natural Model of Periodontitis in Non-human Primates

    Directory of Open Access Journals (Sweden)

    Tetsuhiro Kajikawa

    2017-09-01

    Full Text Available Periodontitis is a chronic inflammatory disease associated with overactivation of the complement system. Recent preclinical studies suggest that host-modulation therapies may contribute to effective treatment of human periodontitis, which may lead to loss of teeth and function if untreated. We previously showed that locally administered AMY-101 (Cp40, a peptidic inhibitor of the central complement component C3, can inhibit naturally occurring periodontitis in non-human primates (NHPs when given once a week. This study was undertaken to determine the local safety of increasing doses of the drug as well as its efficacy when given at a reduced frequency or after systemic administration. Our findings have determined a local dose of AMY-101 (0.1 mg/site that is free of local irritation and effective when given once every 3 weeks. Moreover, a daily subcutaneous dose of AMY-101 (4 mg/kg bodyweight was protective against NHP periodontitis, suggesting that patients treated for systemic disorders (e.g., paroxysmal nocturnal hemoglobinuria can additionally benefit in terms of improved periodontal condition. In summary, AMY-101 appears to be a promising candidate drug for the adjunctive treatment of human periodontitis, a notion that merits investigation in human clinical trials.

  2. HIV vaccine research and discovery in the nonhuman primates model: a unified theory in acquisition prevention and control of SIV infection.

    Science.gov (United States)

    Lynch, Rebecca M; Yamamoto, Takuya; McDermott, Adrian B

    2013-07-01

    Here we highlight the latest advances in HIV vaccine concepts that will expand our knowledge on how to elicit effective acquisition-prevention and/or control of simian immunodeficiency virus (SIV) replication in the nonhuman primate (NHP) model. In the context of the promising analyses from the RV144 Thai Trial and the effective control of SIV replication exerted by rhCMV-(SIV) elicited EM CD8 T cells, the HIV field has recently shifted toward vaccine concepts that combine protection from acquisition with effective control of SIV replication. Current studies in the NHP model have demonstrated the efficacy of HIV-neutralizing antibodies via passive transfer, the potential importance of the CD4 Tfh subset, the ability to effectively model the RV144 vaccine trial and the capacity of an Ad26 prime and modified vaccinia Ankara virus boost to elicit Env-specific antibody and cellular responses that both limit acquisition and control heterologous SIVmac251 challenge. The latest work in the NHP model suggests that the next generation HIV-1 vaccines should aim to provoke a comprehensive adaptive immune response for both prevention of SIV acquisition as well as control of replication in breakthrough infection.

  3. Emotional bookkeeping and high partner selectivity are necessary for the emergence of partner-specific reciprocal affiliation in an agent-based model of primate groups.

    Directory of Open Access Journals (Sweden)

    Ellen Evers

    Full Text Available Primate affiliative relationships are differentiated, individual-specific and often reciprocal. However, the required cognitive abilities are still under debate. Recently, we introduced the EMO-model, in which two emotional dimensions regulate social behaviour: anxiety-FEAR and satisfaction-LIKE. Emotional bookkeeping is modelled by providing each individual with partner-specific LIKE attitudes in which the emotional experiences of earlier affiliations with others are accumulated. Individuals also possess fixed partner-specific FEAR attitudes, reflecting the stable dominance hierarchy. In this paper, we focus on one key parameter of the model, namely the degree of partner selectivity, i.e. the extent to which individuals rely on their LIKE attitudes when choosing affiliation partners. Studying the effect of partner selectivity on the emergent affiliative relationships, we found that at high selectivity, individuals restricted their affiliative behaviours more to similar-ranking individuals and that reciprocity of affiliation was enhanced. We compared the emotional bookkeeping model with a control model, in which individuals had fixed LIKE attitudes simply based on the (fixed rank-distance, instead of dynamic LIKE attitudes based on earlier events. Results from the control model were very similar to the emotional bookkeeping model: high selectivity resulted in preference of similar-ranking partners and enhanced reciprocity. However, only in the emotional bookkeeping model did high selectivity result in the emergence of reciprocal affiliative relationships that were highly partner-specific. Moreover, in the emotional bookkeeping model, LIKE attitude predicted affiliative behaviour better than rank-distance, especially at high selectivity. Our model suggests that emotional bookkeeping is a likely candidate mechanism to underlie partner-specific reciprocal affiliation.

  4. Alveolar ridge dimensional changes following ridge preservation procedure: part-2 - CBCT 3D analysis in non-human primate model.

    Science.gov (United States)

    Omran, Mostafa; Min, Seiko; Abdelhamid, Alaa; Liu, Yi; Zadeh, Homayoun H

    2016-07-01

    The aim of this study was to evaluate the efficacy of ridge preservation involving novel devices used for obturation of socket orifice (Socket cap; SocketKAP(™) ) and resorbable cage used for space maintenance in sites with facial wall dehiscence (Socket cage; SocketKAGE(™) ). Eight teeth were extracted in each of six Macaca fascicularis non-human primates. Six intervention groups consisted of the following: Group A: intact socket negative control. Group B: intact socket: socket cap. Group C: intact socket filled with anorganic bovine bone mineral (ABBM) + socket cap. Group D: dehiscence: negative control. Group E: dehiscence: socket cap + socket cage. Group F: dehiscence: filled with ABBM + socket cap + socket cage. CBCT scans were obtained preoperatively and at 6 and 12 weeks following intervention. The pre- and postoperative scans were superimposed, to quantify 3D volumetric alveolar bone changes. Volumetric bone loss occurred in all sockets, not only within the cretal zone (0-3 mm) to the ridge crest, as has been commonly reported by other investigators, but significant bone loss was also detected in the zone which was 3-6 mm apical to the alveolar crest. For intact sockets, socket cap + ABBM led to significantly greater percentages of remaining bone volume when compared to groups A and B. A significant difference favoring socket cap + socket cage + ABBM treatment was observed for sockets with facial dehiscence defects compared to groups D and E. Socket cap in conjunction with ABBM appears effective in limiting post-extraction volumetric bone loss in intact sockets, while socket cap + socket cage + ABBM appears effective in limiting post-extraction bone loss in sockets with dehiscence defects. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Upregulation of dopamine D3, not D2, receptors correlates with tardive dyskinesia in a primate model.

    Science.gov (United States)

    Mahmoudi, Souha; Lévesque, Daniel; Blanchet, Pierre J

    2014-08-01

    Tardive dyskinesia (TD) is a delayed and potentially irreversible motor complication arising in patients chronically exposed to centrally active dopamine D2 receptor antagonists, including antipsychotic drugs and metoclopramide. The classical dopamine D2 receptor supersensitivity hypothesis in TD, which stemmed from rodent studies, lacks strong support in humans. To investigate the neurochemical basis of TD, we chronically exposed adult capuchin monkeys to haloperidol (median, 18.5 months; n = 11) or clozapine (median, 6 months; n = 6). Six unmedicated animals were used as controls. Five haloperidol-treated animals developed mild TD movements, and no TD was observed in the clozapine group. Using receptor autoradiography, we measured striatal dopamine D1, D2, and D3 receptor levels. We also examined the D3 receptor/preprotachykinin messenger RNA (mRNA) co-expression, and quantified preproenkephalin mRNA levels, in striatal sections. Unlike clozapine, haloperidol strongly induced dopamine D3 receptor binding sites in the anterior caudate-putamen, particularly in TD animals, and binding levels positively correlated with TD intensity. Interestingly, the D3 receptor upregulation was observed in striatonigral neurons. In contrast, D2 receptor binding was comparable to controls, and dopamine D1 receptor binding was reduced in the anterior putamen. Enkephalin mRNA widely increased in all animals, but to a greater extent in TD-free animals. These results suggest for the first time that upregulated striatal D3 receptors correlate with TD in nonhuman primates, adding new insights to the dopamine receptor supersensitivity hypothesis. The D3 receptor could provide a novel target for drug intervention in human TD. © 2014 International Parkinson and Movement Disorder Society.

  6. Comparing adjuvanted H28 and modified vaccinia virus ankara expressingH28 in a mouse and a non-human primate tuberculosis model.

    Directory of Open Access Journals (Sweden)

    Rolf Billeskov

    Full Text Available Here we report for the first time on the immunogenicity and protective efficacy of a vaccine strategy involving the adjuvanted fusion protein "H28" (consisting of Ag85B-TB10.4-Rv2660c and Modified Vaccinia Virus Ankara expressing H28. We show that a heterologous prime-boost regimen involving priming with H28 in a Th1 adjuvant followed by boosting with H28 expressed by MVA (H28/MVA28 induced the highest percentage of IFN-γ expressing T cells, the highest production of IFN-γ per single cell and the highest induction of CD8 T cells compared to either of the vaccines given alone. In contrast, in mice vaccinated with adjuvanted recombinant H28 alone (H28/H28 we observed the highest production of IL-2 per single cell and the highest frequency of antigen specific TNF-α/IL-2 expressing CD4 T cells pre and post infection. Interestingly, TNF-α/IL-2 expressing central memory-like CD4 T cells showed a significant positive correlation with protection at week 6 post infection, whereas the opposite was observed for post infection CD4 T cells producing only IFN-γ. Moreover, as a BCG booster vaccine in a clinically relevant non-human primate TB model, the H28/H28 vaccine strategy induced a slightly more prominent reduction of clinical disease and pathology for up to one year post infection compared to H28/MVA28. Taken together, our data showed that the adjuvanted subunit and MVA strategies led to different T cell subset combinations pre and post infection and that TNF-α/IL-2 double producing but not IFN-γ single producing CD4 T cell subsets correlated with protection in the mouse TB model. Moreover, our data demonstrated that the H28 vaccine antigen was able to induce strong protection in both a mouse and a non-human primate TB model.

  7. Can neonatal sepsis be predicted in late preterm premature rupture of membranes? Development of a prediction model

    NARCIS (Netherlands)

    van der Ham, David P.; van Kuijk, Sander; Opmeer, Brent C.; Willekes, Christine; van Beek, Johannes J.; Mulder, Antonius L. M.; van Loon, Aren J.; Groenewout, Martiët; Mantel, Gerald D.; Bloemenkamp, Kitty W. M.; Porath, Martina; Kwee, Anneke; Akerboom, Bettina M. C.; Papatsonis, Dimitri N. M.; Metz, Godfried C. H.; Nijhuis, Jan G.; Mol, Ben W. J.

    2014-01-01

    Women with late preterm premature rupture of membranes (PROM) have an increased risk that their child will develop neonatal sepsis. We evaluated whether neonatal sepsis can be predicted from antepartum parameters in these women. We used multivariable logistic regression to develop a prediction

  8. Can neonatal sepsis be predicted in late preterm premature rupture of membranes? Development of a prediction model

    NARCIS (Netherlands)

    van der Ham, David P.; van Kuijk, Sander; Opmeer, Brent C.; Willekes, Christine; van Beek, Johannes J.; Mulder, Antonius L. M.; van Loon, Aren J.; Groenewout, Martiet; Mantel, Gerald D.; Bloemenkamp, Kitty W. M.; Porath, Martina; Kwee, Anneke; Akerboom, Bettina M. C.; Papatsonis, Dimitri N. M.; Metz, Godfried C. H.; Nijhuis, Jan G.; Mol, Ben W. J.

    Objective: Women with late preterm premature rupture of membranes (PROM) have an increased risk that their child will develop neonatal sepsis. We evaluated whether neonatal sepsis can be predicted from antepartum parameters in these women. Study design: We used multivariable logistic regression to

  9. R5 clade C SHIV strains with tier 1 or 2 neutralization sensitivity: tools to dissect env evolution and to develop AIDS vaccines in primate models.

    Directory of Open Access Journals (Sweden)

    Nagadenahalli B Siddappa

    2010-07-01

    Full Text Available HIV-1 clade C (HIV-C predominates worldwide, and anti-HIV-C vaccines are urgently needed. Neutralizing antibody (nAb responses are considered important but have proved difficult to elicit. Although some current immunogens elicit antibodies that neutralize highly neutralization-sensitive (tier 1 HIV strains, most circulating HIVs exhibiting a less sensitive (tier 2 phenotype are not neutralized. Thus, both tier 1 and 2 viruses are needed for vaccine discovery in nonhuman primate models.We constructed a tier 1 simian-human immunodeficiency virus, SHIV-1157ipEL, by inserting an "early," recently transmitted HIV-C env into the SHIV-1157ipd3N4 backbone [1] encoding a "late" form of the same env, which had evolved in a SHIV-infected rhesus monkey (RM with AIDS. SHIV-1157ipEL was rapidly passaged to yield SHIV-1157ipEL-p, which remained exclusively R5-tropic and had a tier 1 phenotype, in contrast to "late" SHIV-1157ipd3N4 (tier 2. After 5 weekly low-dose intrarectal exposures, SHIV-1157ipEL-p systemically infected 16 out of 17 RM with high peak viral RNA loads and depleted gut CD4+ T cells. SHIV-1157ipEL-p and SHIV-1157ipd3N4 env genes diverge mostly in V1/V2. Molecular modeling revealed a possible mechanism for the increased neutralization resistance of SHIV-1157ipd3N4 Env: V2 loops hindering access to the CD4 binding site, shown experimentally with nAb b12. Similar mutations have been linked to decreased neutralization sensitivity in HIV-C strains isolated from humans over time, indicating parallel HIV-C Env evolution in humans and RM.SHIV-1157ipEL-p, the first tier 1 R5 clade C SHIV, and SHIV-1157ipd3N4, its tier 2 counterpart, represent biologically relevant tools for anti-HIV-C vaccine development in primates.

  10. Occurrence and distribution of Indian primates

    Science.gov (United States)

    Karanth, K.K.; Nichols, J.D.; Hines, J.E.

    2010-01-01

    Global and regional species conservation efforts are hindered by poor distribution data and range maps. Many Indian primates face extinction, but assessments of population status are hindered by lack of reliable distribution data. We estimated the current occurrence and distribution of 15 Indian primates by applying occupancy models to field data from a country-wide survey of local experts. We modeled species occurrence in relation to ecological and social covariates (protected areas, landscape characteristics, and human influences), which we believe are critical to determining species occurrence in India. We found evidence that protected areas positively influence occurrence of seven species and for some species are their only refuge. We found evergreen forests to be more critical for some primates along with temperate and deciduous forests. Elevation negatively influenced occurrence of three species. Lower human population density was positively associated with occurrence of five species, and higher cultural tolerance was positively associated with occurrence of three species. We find that 11 primates occupy less than 15% of the total land area of India. Vulnerable primates with restricted ranges are Golden langur, Arunachal macaque, Pig-tailed macaque, stump-tailed macaque, Phayre's leaf monkey, Nilgiri langur and Lion-tailed macaque. Only Hanuman langur and rhesus macaque are widely distributed. We find occupancy modeling to be useful in determining species ranges, and in agreement with current species ranking and IUCN status. In landscapes where monitoring efforts require optimizing cost, effort and time, we used ecological and social covariates to reliably estimate species occurrence and focus species conservation efforts. ?? Elsevier Ltd.

  11. Tolerance in Nonhuman Primates by Delayed Mixed Chimerism

    Science.gov (United States)

    2017-12-01

    human primate model SA2: To investigate the effect of T memory cell inhibition and in-vivo T regulatory cell up regulation on the delayed induction of VCA...life of the recipient to prevent rejection, remain significant areas in which improvement would enhance quality of life, improve the risk-benefit ratio...induction of mixed chimerism in a non- human primate (NHP) model. This approach, in contrast to protocols which have already reached clinical trials

  12. A Bayesian Stepwise Discriminant Model for Predicting Risk Factors of Preterm Premature Rupture of Membranes: A Case-control Study.

    Science.gov (United States)

    Zhang, Li-Xia; Sun, Yang; Zhao, Hai; Zhu, Na; Sun, Xing-De; Jin, Xing; Zou, Ai-Min; Mi, Yang; Xu, Ji-Ru

    2017-10-20

    Preterm premature rupture of membrane (PPROM) can lead to serious consequences such as intrauterine infection, prolapse of the umbilical cord, and neonatal respiratory distress syndrome. Genital infection is a very important risk which closely related with PPROM. The preliminary study only made qualitative research on genital infection, but there was no deep and clear judgment about the effects of pathogenic bacteria. This study was to analyze the association of infections with PPROM in pregnant women in Shaanxi, China, and to establish Bayesian stepwise discriminant analysis to predict the incidence of PPROM. In training group, the 112 pregnant women with PPROM were enrolled in the case subgroup, and 108 normal pregnant women in the control subgroup using an unmatched case-control method. The sociodemographic characteristics of these participants were collected by face-to-face interviews. Vaginal excretions from each participant were sampled at 28-36+6 weeks of pregnancy using a sterile swab. DNA corresponding to Chlamydia trachomatis (CT), Ureaplasma urealyticum (UU), Candida albicans, group B streptococci (GBS), herpes simplex virus-1 (HSV-1), and HSV-2 were detected in each participant by real-time polymerase chain reaction. A model of Bayesian discriminant analysis was established and then verified by a multicenter validation group that included 500 participants in the case subgroup and 500 participants in the control subgroup from five different hospitals in the Shaanxi province, respectively. The sociological characteristics were not significantly different between the case and control subgroups in both training and validation groups (all P > 0.05). In training group, the infection rates of UU (11.6% vs. 3.7%), CT (17.0% vs. 5.6%), and GBS (22.3% vs. 6.5%) showed statistically different between the case and control subgroups (all P case and control subgroups (P case and control subgroup were 84.1% and 86.8% in the training and validation groups, respectively

  13. Dual purpose use of preterm piglets as a model of pediatric GI disease

    DEFF Research Database (Denmark)

    Oosterloo, Berthe C; Premkumar, Muralidhar; Stoll, Barbara

    2014-01-01

    Necrotizing enterocolitis (NEC) is the most common gastrointestinal complication in human neonates, yet the pathogenesis of this disease remains poorly understood. A fundamental approach to understanding the etiology and underlying biology of NEC is the use of in vivo experimental animal models...... of mice is the abilty to test how genetic disruption of specific genes alters the NEC phenotype. More recently, pigs have emerged as an animal model of NEC and used to establish the role of bacterial colonization, prematurity, parenteral nutrition and antibiotic therapy. This review will outline some...

  14. Enhanced Expression of Contractile-Associated Proteins and Ion Channels in Preterm Delivery Model Mice With Chronic Odontogenic Porphyromonas Gingivalis Infection.

    Science.gov (United States)

    Miyoshi, Hiroshi; Konishi, Haruhisa; Teraoka, Yuko; Urabe, Satoshi; Furusho, Hisako; Miyauchi, Mutsumi; Takata, Takashi; Kudo, Yoshiki

    2016-07-01

    Inflammation and infection have been reported to induce preterm delivery. We have studied the relationship between inflammation and various ion channels, including the L-type Ca(2+) channel and P2X7 receptor, during acute inflammation of the pregnant rat uterus induced by lipopolysaccharides. Recently, we found that mice with odontogenic Porphyromonas gingivalis (P.g, an important odontogenic pathogen) infection delivered at day 18.3 of gestation (vs. day 20.5 in normal mice). The purpose of this study was to investigate the expression of myometrial contractile-associated proteins inducing contractions and confirm that these mice are useful as a model for preterm delivery induced by chronic inflammation. We examined the expression of the oxytocin receptor, connexin 43, prostaglandin F receptors, L-type Ca(2+) channel, and P2X7 receptor in the myometrium at day 18 of gestation by real-time PCR and western blot analyses. We also measured TNF-α and IL-1β levels in the blood serum, placenta, fetal membrane and myometrium on the same day. mRNA expression of the oxytocin receptor, connexin 43, prostaglandin F receptors, L-type Ca(2+) channel, and P2X7 receptor was elevated by 5.4, 3.2, 2.4, 2.5, and 1.7 fold, respectively, in the P.g-infected mice. Protein levels of the oxytocin receptor and connexin 43 also increased. Serum levels of TNF-α and IL-1β were elevated, showing that systemic inflammation continued during pregnancy. IL-1β levels in the placenta and fetal membrane also increased, suggesting inflammatory reactions were induced. Thus, mice with odontogenic infection may be useful as a model of chronic inflammation-induced preterm delivery. © The Author(s) 2015.

  15. Prediction model of RSV-hospitalization in late preterm infants: An update and validation study

    NARCIS (Netherlands)

    Korsten, K.; Blanken, M.O.; Nibbelke, E.E.; Moons, K.G.; Bont, L.; Liem, K.D.; et al.,

    2016-01-01

    BACKGROUND: New vaccines and RSV therapeutics have been developed in the past decade. With approval of these new pharmaceuticals on the horizon, new challenges lie ahead in selecting the appropriate target population. We aimed to improve a previously published prediction model for prediction of

  16. Preterm piglets are a clinically relevant model of pediatric GI disease

    Science.gov (United States)

    The goal of our research is to establish how nutritional support, enteral versus parenteral, affects gut function and susceptibility to disease in early development. We and others have used the neonatal pig to establish unique models of clinically relevant problems in pediatric gastroenterology, esp...

  17. Animal Models, Learning Lessons to Prevent and Treat Neonatal Chronic Lung Disease

    Science.gov (United States)

    Jobe, Alan H.

    2015-01-01

    Bronchopulmonary dysplasia (BPD) is a unique injury syndrome caused by prolonged injury and repair imposed on an immature and developing lung. The decreased septation and decreased microvascular development phenotype of BPD can be reproduced in newborn rodents with increased chronic oxygen exposure and in premature primates and sheep with oxygen and/or mechanical ventilation. The inflammation caused by oxidants, inflammatory agonists, and/or stretch injury from mechanical ventilation seems to promote the anatomic abnormalities. Multiple interventions targeted to specific inflammatory cells or pathways or targeted to decreasing ventilation-mediated injury can substantially prevent the anatomic changes associated with BPD in term rodents and in preterm sheep or primate models. Most of the anti-inflammatory therapies with benefit in animal models have not been tested clinically. None of the interventions that have been tested clinically are as effective as anticipated from the animal models. These inconsistencies in responses likely are explained by the antenatal differences in lung exposures of the developing animals relative to very preterm humans. The animals generally have normal lungs while the lungs of preterm infants are exposed variably to intrauterine inflammation, growth abnormalities, antenatal corticosteroids, and poorly understood effects from the causes of preterm delivery. The animal models have been essential for the definition of the mediators that can cause a BPD phenotype. These models will be necessary to develop and test future-targeted interventions to prevent and treat BPD. PMID:26301222

  18. Comparing adjuvanted H28 and modified vaccinia virus ankara expressingH28 in a mouse and a non-human primate tuberculosis model

    DEFF Research Database (Denmark)

    Billeskov, Rolf; Christensen, Jan Pravsgaard; Aagaard, Claus

    2013-01-01

    , in mice vaccinated with adjuvanted recombinant H28 alone (H28/H28) we observed the highest production of IL-2 per single cell and the highest frequency of antigen specific TNF-α/IL-2 expressing CD4 T cells pre and post infection. Interestingly, TNF-α/IL-2 expressing central memory-like CD4 T cells showed...... priming with H28 in a Th1 adjuvant followed by boosting with H28 expressed by MVA (H28/MVA28) induced the highest percentage of IFN-γ expressing T cells, the highest production of IFN-γ per single cell and the highest induction of CD8 T cells compared to either of the vaccines given alone. In contrast...... a significant positive correlation with protection at week 6 post infection, whereas the opposite was observed for post infection CD4 T cells producing only IFN-γ. Moreover, as a BCG booster vaccine in a clinically relevant non-human primate TB model, the H28/H28 vaccine strategy induced a slightly more...

  19. Touchscreen-based cognitive tasks reveal age-related impairment in a primate aging model, the grey mouse lemur (Microcebus murinus).

    Science.gov (United States)

    Joly, Marine; Ammersdörfer, Sandra; Schmidtke, Daniel; Zimmermann, Elke

    2014-01-01

    Mouse lemurs are suggested to represent promising novel non-human primate models for aging research. However, standardized and cross-taxa cognitive testing methods are still lacking. Touchscreen-based testing procedures have proven high stimulus control and reliability in humans and rodents. The aim of this study was to adapt these procedures to mouse lemurs, thereby exploring the effect of age. We measured appetitive learning and cognitive flexibility of two age groups by applying pairwise visual discrimination (PD) and reversal learning (PDR) tasks. On average, mouse lemurs needed 24 days of training before starting with the PD task. Individual performances in PD and PDR tasks correlate significantly, suggesting that individual learning performance is unrelated to the respective task. Compared to the young, aged mouse lemurs showed impairments in both PD and PDR tasks. They needed significantly more trials to reach the task criteria. A much higher inter-individual variation in old than in young adults was revealed. Furthermore, in the PDR task, we found a significantly higher perseverance in aged compared to young adults, indicating an age-related deficit in cognitive flexibility. This study presents the first touchscreen-based data on the cognitive skills and age-related dysfunction in mouse lemurs and provides a unique basis to study mechanisms of inter-individual variation. It furthermore opens exciting perspectives for comparative approaches in aging, personality, and evolutionary research.

  20. Touchscreen-based cognitive tasks reveal age-related impairment in a primate aging model, the grey mouse lemur (Microcebus murinus.

    Directory of Open Access Journals (Sweden)

    Marine Joly

    Full Text Available Mouse lemurs are suggested to represent promising novel non-human primate models for aging research. However, standardized and cross-taxa cognitive testing methods are still lacking. Touchscreen-based testing procedures have proven high stimulus control and reliability in humans and rodents. The aim of this study was to adapt these procedures to mouse lemurs, thereby exploring the effect of age. We measured appetitive learning and cognitive flexibility of two age groups by applying pairwise visual discrimination (PD and reversal learning (PDR tasks. On average, mouse lemurs needed 24 days of training before starting with the PD task. Individual performances in PD and PDR tasks correlate significantly, suggesting that individual learning performance is unrelated to the respective task. Compared to the young, aged mouse lemurs showed impairments in both PD and PDR tasks. They needed significantly more trials to reach the task criteria. A much higher inter-individual variation in old than in young adults was revealed. Furthermore, in the PDR task, we found a significantly higher perseverance in aged compared to young adults, indicating an age-related deficit in cognitive flexibility. This study presents the first touchscreen-based data on the cognitive skills and age-related dysfunction in mouse lemurs and provides a unique basis to study mechanisms of inter-individual variation. It furthermore opens exciting perspectives for comparative approaches in aging, personality, and evolutionary research.

  1. Characterization of circulating natural killer cells in neotropical primates.

    Directory of Open Access Journals (Sweden)

    Angela Carville

    Full Text Available Despite extensive use of nonhuman primates as models for infectious diseases and reproductive biology, imprecise phenotypic and functional definitions exist for natural killer (NK cells. This deficit is particularly significant in the burgeoning use of small, less expensive New World primate species. Using polychromatic flow cytometry, we identified peripheral blood NK cells as CD3-negative and expressing a cluster of cell surface molecules characteristic of NK cells (i.e., NKG2A, NKp46, NKp30 in three New World primate species - common marmosets, cotton-top tamarins, and squirrel monkeys. We then assessed subset distribution using the classical NK markers, CD56 and CD16. In all species, similar to Old World primates, only a minor subset of NK cells was CD56+, and the dominant subset was CD56-CD16+. Interestingly, CD56+ NK cells were primarily cytokine-secreting cells, whereas CD56-CD16+ NK cells expressed significantly greater levels of intracellular perforin, suggesting these cells might have greater potential for cytotoxicity. New World primate species, like Old World primates, also had a minor CD56-CD16- NK cell subset that has no obvious counterpart in humans. Herein we present phenotypic profiles of New World primate NK cell subpopulations that are generally analogous to those found in humans. This conservation among species should support the further use of these species for biomedical research.

  2. Differences in Risk Factors for Recurrent Versus Incident Preterm Delivery

    OpenAIRE

    Grantz, Katherine L.; Hinkle, Stefanie N.; Mendola, Pauline; Sjaarda, Lindsey A.; Leishear, Kira; Albert, Paul S.

    2015-01-01

    Risk factors for preterm delivery have been described, but whether risk factors differ in the context of prior preterm delivery history is less understood. We assessed whether known risk factors were different in women with versus without prior preterm delivery using medical records of the first and second singleton deliveries in 25,820 Utah women (2002–2010). Longitudinal transition models with modified Poisson regression calculated adjusted relative risks and 95% confidence intervals, with ...

  3. Genomics of Preterm Birth

    Science.gov (United States)

    Swaggart, Kayleigh A.; Pavlicev, Mihaela; Muglia, Louis J.

    2015-01-01

    The molecular mechanisms controlling human birth timing at term, or resulting in preterm birth, have been the focus of considerable investigation, but limited insights have been gained over the past 50 years. In part, these processes have remained elusive because of divergence in reproductive strategies and physiology shown by model organisms, making extrapolation to humans uncertain. Here, we summarize the evolution of progesterone signaling and variation in pregnancy maintenance and termination. We use this comparative physiology to support the hypothesis that selective pressure on genomic loci involved in the timing of parturition have shaped human birth timing, and that these loci can be identified with comparative genomic strategies. Previous limitations imposed by divergence of mechanisms provide an important new opportunity to elucidate fundamental pathways of parturition control through increasing availability of sequenced genomes and associated reproductive physiology characteristics across diverse organisms. PMID:25646385

  4. A Parallelized Pumpless Artificial Placenta System Significantly Prolonged Survival Time in a Preterm Lamb Model.

    Science.gov (United States)

    Miura, Yuichiro; Matsuda, Tadashi; Usuda, Haruo; Watanabe, Shimpei; Kitanishi, Ryuta; Saito, Masatoshi; Hanita, Takushi; Kobayashi, Yoshiyasu

    2016-05-01

    An artificial placenta (AP) is an arterio-venous extracorporeal life support system that is connected to the fetal circulation via the umbilical vasculature. Previously, we published an article describing a pumpless AP system with a small priming volume. We subsequently developed a parallelized system, hypothesizing that the reduced circuit resistance conveyed by this modification would enable healthy fetal survival time to be prolonged. We conducted experiments using a premature lamb model to test this hypothesis. As a result, the fetal survival period was significantly prolonged (60.4 ± 3.8 vs. 18.2 ± 3.2 h, P lamb fetuses to survive for a significantly longer period when compared with previous studies. Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals Inc.

  5. Male germline stem cells in non-human primates

    Directory of Open Access Journals (Sweden)

    S. Sharma

    2017-09-01

    Full Text Available Over the past few decades, several studies have attempted to decipher the biology of mammalian germline stem cells (GSCs. These studies provide evidence that regulatory mechanisms for germ cell specification and migration are evolutionarily conserved across species. The characteristics and functions of primate GSCs are highly distinct from rodent species; therefore the findings from rodent models cannot be extrapolated to primates. Due to limited availability of human embryonic and testicular samples for research purposes, two non-human primate models (marmoset and macaque monkeys are extensively employed to understand human germline development and differentiation. This review provides a broader introduction to the in vivo and in vitro germline stem cell terminology from primordial to differentiating germ cells. Primordial germ cells (PGCs are the most immature germ cells colonizing the gonad prior to sex differentiation into testes or ovaries. PGC specification and migratory patterns among different primate species are compared in the review. It also reports the distinctions and similarities in expression patterns of pluripotency markers (OCT4A, NANOG, SALL4 and LIN28 during embryonic developmental stages, among marmosets, macaques and humans. This review presents a comparative summary with immunohistochemical and molecular evidence of germ cell marker expression patterns during postnatal developmental stages, among humans and non-human primates. Furthermore, it reports findings from the recent literature investigating the plasticity behavior of germ cells and stem cells in other organs of humans and monkeys. The use of non-human primate models would enable bridging the knowledge gap in primate GSC research and understanding the mechanisms involved in germline development. Reported similarities in regulatory mechanisms and germ cell expression profile in primates demonstrate the preclinical significance of monkey models for development of

  6. Variability of Bio-Clinical Parameters in Chinese-Origin Rhesus Macaques Infected with Simian Immunodeficiency Virus: A Nonhuman Primate AIDS Model

    Science.gov (United States)

    Chen, Song; Lai, Chunhui; Wu, Xiaoxiang; Lu, Yaozheng; Han, Daishu; Guo, Weizhong; Fu, Linchun; Andrieu, Jean-Marie; Lu, Wei

    2011-01-01

    Background Although Chinese-origin Rhesus macaques (Ch RhMs) infected with simian immunodeficiency virus (SIV) have been used for many years to evaluate the efficacy of AIDS vaccines and therapeutics, the bio-clinical variability of such a nonhuman primate AIDS model was so far not established. Methodology/Principal Findings By randomizing 150 (78 male and 72 female) Ch RhMs with diverse MHC class I alleles into 3 groups (50 animals per group) challenged with intrarectal (ir) SIVmac239, intravenous (iv) SIVmac239, or iv SIVmac251, we evaluated variability in bio-clinical endpoints for 118 weeks. All SIV-challenged Ch RhMs became seropositive for SIV during 1–2 weeks. Plasma viral load (VL) peaked at weeks 1–2 and then declined to set-point levels as from week 5. The set-point VL was 30 fold higher in SIVmac239 (ir or iv)-infected than in SIVmac251 (iv)-infected animals. This difference in plasma VL increased overtime (>100 fold as from week 68). The rates of progression to AIDS or death were more rapid in SIVmac239 (ir or iv)-infected than in SIVmac251 (iv)-infected animals. No significant difference in bio-clinical endpoints was observed in animals challenged with ir or iv SIVmac239. The variability (standard deviation) in peak/set-point VL was nearly one-half lower in animals infected with SIVmac239 (ir or iv) than in those infected with SIVmac251 (iv), allowing that the same treatment-related difference can be detected with one-half fewer animals using SIVmac239 than using SIVmac251. Conclusion/Significance These results provide solid estimates of variability in bio-clinical endpoints needed when designing studies using the Ch RhM SIV model and contribute to the improving quality and standardization of preclinical studies. PMID:21850259

  7. Tracking the luminal exposure and lymphatic drainage pathways of intravaginal and intrarectal inocula used in nonhuman primate models of HIV transmission.

    Science.gov (United States)

    Smedley, Jeremy; Turkbey, Baris; Bernardo, Marcelino L; Del Prete, Gregory Q; Estes, Jacob D; Griffiths, Gary L; Kobayashi, Hisataka; Choyke, Peter L; Lifson, Jeffrey D; Keele, Brandon F

    2014-01-01

    Over 80% of sexual HIV-1 transmissions originate from a single viral variant, but the underlying basis for this transmission bottleneck remains to be elucidated. Nonhuman primate models of mucosal virus transmission allow opportunities to gain insight into the basis of this mucosal bottleneck. We used simulated inocula consisting of either non-infectious vital dye or contrast dye with non-invasive magnetic resonance imaging (MRI) to visualize mucosal exposure and passive lymphatic drainage patterns following vaginal and rectal exposures in Indian origin rhesus macaques. Results revealed a limited overall distance of dye coverage from the anal verge following 1 ml (n = 8) intrarectally administered, which greatly increased with a 3 ml (n = 8) volume. Intravaginal dye exposure using 2 ml revealed complete coverage of the mucosa of the vagina and ectocervix, however dye was not detectable in the endocervix, uterus, fallopian tubes or ovaries in nuliparous sexually mature rhesus macaques (n = 9). In addition, following submucosal and intranodal injections of vital dye or MRI contrast dye in the rectum (n = 9), or distal and proximal vagina (n = 4), the lymphatic drainage pathways were identified as first the internal then common iliac chain followed by para-aortic lymph nodes. Drainage from the distal descending colon (n = 8) was via the para-colonic lymph nodes followed by the inferior mesenteric and para-aortic lymph nodes. Analysis after vaginal challenge with infectious SIVmac239 followed by euthanasia at day 3 revealed a pattern of viral dissemination consistent with the imaging results. These results provide insights into potential patterns of viral dissemination that can help guide efforts to better elucidate the earliest events of virus transmission and potential intervention strategies.

  8. The use of discriminant analysis for evaluation of early-response multiple biomarkers of radiation exposure using non-human primate 6-Gy whole-body radiation model

    Energy Technology Data Exchange (ETDEWEB)

    Ossetrova, N.I. [Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Bethesda, MD 20889-5603 (United States)], E-mail: ossetrova@afrri.usuhs.mil; Farese, A.M.; MacVittie, T.J. [Marlene and Stewart Greenebaum Cancer Center, Bressler Research Building, Room 7-039, University of Maryland-Baltimore, 655 West Baltimore Street, Baltimore, MD 21201 (United States); Manglapus, G.L.; Blakely, W.F. [Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Bethesda, MD 20889-5603 (United States)

    2007-07-15

    The present need to rapidly identify severely irradiated individuals in mass-casualty and population-monitoring scenarios prompted an evaluation of potential protein biomarkers to provide early diagnostic information after exposure. The level of specific proteins measured using immunodiagnostic technologies may be useful as protein biomarkers to provide early diagnostic information for acute radiation exposures. Herein we present results from on-going studies using a non-human primate (NHP) 6-Gy X-rays ( 0.13Gymin{sup -1}) whole-body radiation model. Protein targets were measured by enzyme-linked immunosorbent assay (ELISA) in blood plasma before, 1, and 2 days after exposure. Exposure of 10 NHPs to 6 Gy resulted in the up-regulation of plasma levels of (a) p21 WAF1/CIP1, (b) interleukin 6 (IL-6), (c) tissue enzyme salivary {alpha}-amylase, and (d) C-reactive protein. Data presented show the potential utility of protein biomarkers selected from distinctly different pathways to detect radiation exposure. A correlation analysis demonstrated strong correlations among different combinations of four candidate radiation-responsive blood protein biomarkers. Data analyzed with use of multivariate discriminant analysis established very successful separation of NHP groups: 100% discrimination power for animals with correct classification for separation between groups before and 1 day after irradiation, and 95% discrimination power for separation between groups before and 2 days after irradiation. These results also demonstrate proof-in-concept that multiple protein biomarkers provide early diagnostic information to the medical community, along with classical biodosimetric methodologies, to effectively manage radiation casualty incidents.

  9. Tracking the luminal exposure and lymphatic drainage pathways of intravaginal and intrarectal inocula used in nonhuman primate models of HIV transmission.

    Directory of Open Access Journals (Sweden)

    Jeremy Smedley

    Full Text Available Over 80% of sexual HIV-1 transmissions originate from a single viral variant, but the underlying basis for this transmission bottleneck remains to be elucidated. Nonhuman primate models of mucosal virus transmission allow opportunities to gain insight into the basis of this mucosal bottleneck. We used simulated inocula consisting of either non-infectious vital dye or contrast dye with non-invasive magnetic resonance imaging (MRI to visualize mucosal exposure and passive lymphatic drainage patterns following vaginal and rectal exposures in Indian origin rhesus macaques. Results revealed a limited overall distance of dye coverage from the anal verge following 1 ml (n = 8 intrarectally administered, which greatly increased with a 3 ml (n = 8 volume. Intravaginal dye exposure using 2 ml revealed complete coverage of the mucosa of the vagina and ectocervix, however dye was not detectable in the endocervix, uterus, fallopian tubes or ovaries in nuliparous sexually mature rhesus macaques (n = 9. In addition, following submucosal and intranodal injections of vital dye or MRI contrast dye in the rectum (n = 9, or distal and proximal vagina (n = 4, the lymphatic drainage pathways were identified as first the internal then common iliac chain followed by para-aortic lymph nodes. Drainage from the distal descending colon (n = 8 was via the para-colonic lymph nodes followed by the inferior mesenteric and para-aortic lymph nodes. Analysis after vaginal challenge with infectious SIVmac239 followed by euthanasia at day 3 revealed a pattern of viral dissemination consistent with the imaging results. These results provide insights into potential patterns of viral dissemination that can help guide efforts to better elucidate the earliest events of virus transmission and potential intervention strategies.

  10. Bacterial Hyaluronidase Promotes Ascending GBS Infection and Preterm Birth

    Directory of Open Access Journals (Sweden)

    Jay Vornhagen

    2016-06-01

    Full Text Available Preterm birth increases the risk of adverse birth outcomes and is the leading cause of neonatal mortality. A significant cause of preterm birth is in utero infection with vaginal microorganisms. These vaginal microorganisms are often recovered from the amniotic fluid of preterm birth cases. A vaginal microorganism frequently associated with preterm birth is group B streptococcus (GBS, or Streptococcus agalactiae. However, the molecular mechanisms underlying GBS ascension are poorly understood. Here, we describe the role of the GBS hyaluronidase in ascending infection and preterm birth. We show that clinical GBS strains associated with preterm labor or neonatal infections have increased hyaluronidase activity compared to commensal strains obtained from rectovaginal swabs of healthy women. Using a murine model of ascending infection, we show that hyaluronidase activity was associated with increased ascending GBS infection, preterm birth, and fetal demise. Interestingly, hyaluronidase activity reduced uterine inflammation but did not impact placental or fetal inflammation. Our study shows that hyaluronidase activity enables GBS to subvert uterine immune responses, leading to increased rates of ascending infection and preterm birth. These findings have important implications for the development of therapies to prevent in utero infection and preterm birth.

  11. Evidence of cardiac involvement in the fetal inflammatory response syndrome: disruption of gene networks programming cardiac development in nonhuman primates.

    Science.gov (United States)

    Mitchell, Timothy; MacDonald, James W; Srinouanpranchanh, Sengkeo; Bammler, Theodor K; Merillat, Sean; Boldenow, Erica; Coleman, Michelle; Agnew, Kathy; Baldessari, Audrey; Stencel-Baerenwald, Jennifer E; Tisoncik-Go, Jennifer; Green, Richard R; Gale, Michael J; Rajagopal, Lakshmi; Adams Waldorf, Kristina M

    2018-04-01

    Most early preterm births are associated with intraamniotic infection and inflammation, which can lead to systemic inflammation in the fetus. The fetal inflammatory response syndrome describes elevations in the fetal interleukin-6 level, which is a marker for inflammation and fetal organ injury. An understanding of the effects of inflammation on fetal cardiac development may lead to insight into the fetal origins of adult cardiovascular disease. The purpose of this study was to determine whether the fetal inflammatory response syndrome is associated with disruptions in gene networks that program fetal cardiac development. We obtained fetal cardiac tissue after necropsy from a well-described pregnant nonhuman primate model (pigtail macaque, Macaca nemestrina) of intrauterine infection (n=5) and controls (n=5). Cases with the fetal inflammatory response syndrome (fetal plasma interleukin-6 >11 pg/mL) were induced by either choriodecidual inoculation of a hypervirulent group B streptococcus strain (n=4) or intraamniotic inoculation of Escherichia coli (n=1). RNA and protein were extracted from fetal hearts and profiled by microarray and Luminex (Millipore, Billerica, MA) for cytokine analysis, respectively. Results were validated by quantitative reverse transcriptase polymerase chain reaction. Statistical and bioinformatics analyses included single gene analysis, gene set analysis, Ingenuity Pathway Analysis (Qiagen, Valencia, CA), and Wilcoxon rank sum. Severe fetal inflammation developed in the context of intraamniotic infection and a disseminated bacterial infection in the fetus. Interleukin-6 and -8 in fetal cardiac tissues were elevated significantly in fetal inflammatory response syndrome cases vs controls (P1.5-fold change, Pfetal heart (analysis of variance). Altered expression of select genes was validated by quantitative reverse transcriptase polymerase chain reaction that included several with known functions in cardiac injury, morphogenesis, angiogenesis

  12. Realistic head model design and 3D brain imaging of NIRS signals using audio stimuli on preterm neonates for intra-ventricular hemorrhage diagnosis.

    Science.gov (United States)

    Fournier, Marc; Mahmoudzadeh, Mahdi; Kazemi, Kamran; Kongolo, Guy; Dehaene-Lambertz, Ghislaine; Grebe, Reinhard; Wallois, Fabrice

    2012-01-01

    In this paper we propose an auditory stimulation and near infra-red spectroscopy (NIRS) hemodynamic changes acquisition protocol for preterm neonates. This study is designed to assess the specific characteristics of neurovascular coupling to auditory stimuli in healthy and ill neonate brains. The method could lead to clinical application in intra-ventricular hemorrhage (IVH) diagnosis along with other techniques such as EEG. We propose a realistic head model creation with all useful head structures and brain tissues including the neonate fontanel for more accurate results from NIRS signals modeling. We also design a 3D imaging tool for dynamic mapping and analysis of brain activation onto the cortex surface. Results show significant differences in oxy-hemoglobin between healthy neonates and subjects with IVH.

  13. Molecular evolution of the primate antiviral restriction factor tetherin.

    Directory of Open Access Journals (Sweden)

    Jun Liu

    Full Text Available BACKGROUND: Tetherin is a recently identified antiviral restriction factor that restricts HIV-1 particle release in the absence of the HIV-1 viral protein U (Vpu. It is reminiscent of APOBEC3G and TRIM5a that also antagonize HIV. APOBEC3G and TRIM5a have been demonstrated to evolve under pervasive positive selection throughout primate evolution, supporting the red-queen hypothesis. Therefore, one naturally presumes that Tetherin also evolves under pervasive positive selection throughout primate evolution and supports the red-queen hypothesis. Here, we performed a detailed evolutionary analysis to address this presumption. METHODOLOGY/PRINCIPAL FINDINGS: Results of non-synonymous and synonymous substitution rates reveal that Tetherin as a whole experiences neutral evolution rather than pervasive positive selection throughout primate evolution, as well as in non-primate mammal evolution. Sliding-window analyses show that the regions of the primate Tetherin that interact with viral proteins are under positive selection or relaxed purifying selection. In particular, the sites identified under positive selection generally focus on these regions, indicating that the main selective pressure acting on the primate Tetherin comes from virus infection. The branch-site model detected positive selection acting on the ancestral branch of the New World Monkey lineage, suggesting an episodic adaptive evolution. The positive selection was also found in duplicated Tetherins in ruminants. Moreover, there is no bias in the alterations of amino acids in the evolution of the primate Tetherin, implying that the primate Tetherin may retain broad spectrum of antiviral activity by maintaining structure stability. CONCLUSIONS/SIGNIFICANCE: These results conclude that the molecular evolution of Tetherin may be attributed to the host-virus arms race, supporting the Red Queen hypothesis, and Tetherin may be in an intermediate stage in transition from neutral to pervasive

  14. Exploring of primate models of tick-borne flaviviruses infection for evaluation of vaccines and drugs efficacy.

    Directory of Open Access Journals (Sweden)

    Natalia S Pripuzova

    Full Text Available Tick-borne encephalitis virus (TBEV is one of the most prevalent and medically important tick-borne arboviruses in Eurasia. There are overlapping foci of two flaviviruses: TBEV and Omsk hemorrhagic fever virus (OHFV in Russia. Inactivated vaccines exist only against TBE. There are no antiviral drugs for treatment of both diseases. Optimal animal models are necessary to study efficacy of novel vaccines and treatment preparations against TBE and relative flaviviruses. The models for TBE and OHF using subcutaneous inoculation were tested in Cercopithecus aethiops and Macaca fascicularis monkeys with or without prior immunization with inactivated TBE vaccine. No visible clinical signs or severe pathomorphological lesions were observed in any monkey infected with TBEV or OHFV. C. aethiops challenged with OHFV showed massive hemolytic syndrome and thrombocytopenia. Infectious virus or viral RNA was revealed in visceral organs and CNS of C. aethiops infected with both viruses; however, viremia was low. Inactivated TBE vaccines induced high antibody titers against both viruses and expressed booster after challenge. The protective efficacy against TBE was shown by the absence of virus in spleen, lymph nodes and CNS of immunized animals after challenge. Despite the absence of expressed hemolytic syndrome in immunized C. aethiops TBE vaccine did not prevent the reproduction of OHFV in CNS and visceral organs. Subcutaneous inoculation of M. fascicularis with two TBEV strains led to a febrile disease with well expressed viremia, fever, and virus reproduction in spleen, lymph nodes and CNS. The optimal terms for estimation of the viral titers in CNS were defined as 8-16 days post infection. We characterized two animal models similar to humans in their susceptibility to tick-borne flaviviruses and found the most optimal scheme for evaluation of efficacy of preventive and therapeutic preparations. We also identified M. fascicularis to be more susceptible to

  15. Use of the cross-translational model to study self-injurious behavior in human and nonhuman primates.

    Science.gov (United States)

    Novak, Melinda A; El-Mallah, Saif N; Menard, Mark T

    2014-01-01

    Nonsuicidal self-injurious behavior occurs in the general human population, particularly among teenagers and young adults. Some rhesus macaques also develop self-injurious behavior (SIB) as adolescents or young adults. In both of these cases, the development of harmful behaviors is idiopathic, only coming to the attention of physicians or veterinarians after the disorder is established. Thus, a combination of retrospective, statistical, and empirical procedures are used to understand this disorder. Here, we identify concordances between macaques and humans across five different levels of analysis-(1) form and prevalence, (2) etiology, (3) triggering events, (4) function/maintenance, and (5) therapeutic intervention-and show the value of the cross-translational model (macaques to humans and humans to macaques) in understanding this phenomenon. Substantial concordance is present with respect to the range of severity, the presence of early life stress exposure, and emotional dysregulation. In the macaque model, additional information is available on the hypothalamic-pituitary-adrenal axis stress response system, possible genetic involvement, and the immediate contextual situations that appear to trigger or exacerbate SIB episodes. In contrast, considerably more information is available from human studies on the effectiveness of various treatment regimens. Veterinarians have drawn on this information to explore these therapeutic interventions in monkeys. We expect that models of SIB will continue to have cross-translational impact as scientists and practitioners move from preclinical to clinical research and treatment. © The Author 2014. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  16. Thrombus imaging in a primate model with antibodies specific for an external membrane protein of activated platelets

    International Nuclear Information System (INIS)

    Palabrica, T.M.; Furie, B.C.; Konstam, M.A.; Aronovitz, M.J.; Connolly, R.; Brockway, B.A.; Ramberg, K.L.; Furie, B.

    1989-01-01

    The activated platelet is a potential target for the localization of thrombi in vivo since, after stimulation and secretion of granule contents, activated platelets are concentrated at sites of blood clot formation. In this study, we used antibodies specific for a membrane protein of activated platelets to detect experimental thrombi in an animal model. PADGEM (platelet activation-dependent granule-external membrane protein), a platelet alpha-granule membrane protein, is translocated to the plasma membrane during platelet activation and granule secretion. Since PADGEM is internal in unstimulated platelets, polyclonal anti-PADGEM and monoclonal KC4 antibodies do not bind to circulating resting platelets but do interact with activated platelets. Dacron graft material incubated with radiolabeled KC4 or anti-PADGEM antibodies in the presence of thrombin-activated platelet-rich plasma bound most of the antibody. Imaging experiments with 123I-labeled anti-PADGEM in baboons with an external arterial-venous Dacron shunt revealed rapid uptake in the thrombus induced by the Dacron graft; control experiments with 123I-labeled nonimmune IgG exhibited minimal uptake. Deep venous thrombi, formed by using percutaneous balloon catheters to stop blood flow in the femoral vein of baboons, were visualized with 123I-labeled anti-PADGEM. Thrombi were discernible against blood pool background activity without subtraction techniques within 1 hr. No target enhancement was seen with 123I-labeled nonimmune IgG. 123I-labeled anti-PADGEM cleared the blood pool with an initial half-disappearance time of 6 min and did not interfere with hemostasis. These results indicate that radioimmunoscintigraphy with anti-PADGEM antibodies can visualize thrombi in baboon models and is a promising technique for clinical thrombus detection in humans

  17. Prevention of preterm birth.

    LENUS (Irish Health Repository)

    Flood, Karen

    2012-02-01

    Preterm birth (delivery before 37 completed weeks of gestation) is common and rates are increasing. In the past, medical efforts focused on ameliorating the consequences of prematurity rather than preventing its occurrence. This approach resulted in improved neonatal outcomes, but it remains costly in terms of both the suffering of infants and their families and the economic burden on society. Increased understanding of the pathophysiology of preterm labor has altered the approach to this problem, with increased focus on preventive strategies. Primary prevention is a limited strategy which involves public education, smoking cessation, improved nutritional status and avoidance of late preterm births. Secondary prevention focuses on recurrent preterm birth which is the most recognisable risk factor. Widely accepted strategies include cervical cerclage, progesterone and dedicated clinics. However, more research is needed to explore the role of antibiotics and anti-inflammatory treatments in the prevention of this complex problem.

  18. Preterm Labor and Birth

    Science.gov (United States)

    ... NICHD Research Information Find a Study More Information Pharmacology Condition Information NICHD Research Information Find a Study ... Pinterest Email Print Preterm Labor and Birth In general, a normal human pregnancy lasts about 40 weeks, ...

  19. Loop Mediated Isothermal Amplification for Detection of Trypanosoma brucei gambiense in Urine and Saliva Samples in Nonhuman Primate Model

    Directory of Open Access Journals (Sweden)

    Maina Ngotho

    2015-01-01

    Full Text Available Human African trypanosomiasis (HAT is a vector-borne parasitic zoonotic disease. The disease caused by Trypanosoma brucei gambiense is the most prevalent in Africa. Early diagnosis is hampered by lack of sensitive diagnostic techniques. This study explored the potential of loop mediated isothermal amplification (LAMP and polymerase chain reaction (PCR in the detection of T. b. gambiense infection in a vervet monkey HAT model. Six vervet monkeys were experimentally infected with T. b. gambiense IL3253 and monitored for 180 days after infection. Parasitaemia was scored daily. Blood, cerebrospinal fluid (CSF, saliva, and urine samples were collected weekly. PCR and LAMP were performed on serum, CSF, saliva, and urine samples. The detection by LAMP was significantly higher than that of parasitological methods and PCR in all the samples. The performance of LAMP varied between the samples and was better in serum followed by saliva and then urine samples. In the saliva samples, LAMP had 100% detection between 21 and 77 dpi, whereas in urine the detection it was slightly lower, but there was over 80% detection between 28 and 91 dpi. However, LAMP could not detect trypanosomes in either saliva or urine after 140 and 126 dpi, respectively. The findings of this study emphasize the importance of LAMP in diagnosis of HAT using saliva and urine samples.

  20. Activation of Liver AMPK with PF-06409577 Corrects NAFLD and Lowers Cholesterol in Rodent and Primate Preclinical Models.

    Science.gov (United States)

    Esquejo, Ryan M; Salatto, Christopher T; Delmore, Jake; Albuquerque, Bina; Reyes, Allan; Shi, Yuji; Moccia, Rob; Cokorinos, Emily; Peloquin, Matthew; Monetti, Mara; Barricklow, Jason; Bollinger, Eliza; Smith, Brennan K; Day, Emily A; Nguyen, Chuong; Geoghegan, Kieran F; Kreeger, John M; Opsahl, Alan; Ward, Jessica; Kalgutkar, Amit S; Tess, David; Butler, Lynne; Shirai, Norimitsu; Osborne, Timothy F; Steinberg, Gregory R; Birnbaum, Morris J; Cameron, Kimberly O; Miller, Russell A

    2018-04-08

    Dysregulation of hepatic lipid and cholesterol metabolism is a significant contributor to cardiometabolic health, resulting in excessive liver lipid accumulation and ultimately non-alcoholic steatohepatitis (NASH). Therapeutic activators of the AMP-Activated Protein Kinase (AMPK) have been proposed as a treatment for metabolic diseases; we show that the AMPK β1-biased activator PF-06409577 is capable of lowering hepatic and systemic lipid and cholesterol levels in both rodent and monkey preclinical models. PF-06409577 is able to inhibit de novo lipid and cholesterol synthesis pathways, and causes a reduction in hepatic lipids and mRNA expression of markers of hepatic fibrosis. These effects require AMPK activity in the hepatocytes. Treatment of hyperlipidemic rats or cynomolgus monkeys with PF-06409577 for 6weeks resulted in a reduction in circulating cholesterol. Together these data suggest that activation of AMPK β1 complexes with PF-06409577 is capable of impacting multiple facets of liver disease and represents a promising strategy for the treatment of NAFLD and NASH in humans. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  1. Variability of bio-clinical parameters in Chinese-origin Rhesus macaques infected with simian immunodeficiency virus: a nonhuman primate AIDS model.

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    Song Chen

    Full Text Available BACKGROUND: Although Chinese-origin Rhesus macaques (Ch RhMs infected with simian immunodeficiency virus (SIV have been used for many years to evaluate the efficacy of AIDS vaccines and therapeutics, the bio-clinical variability of such a nonhuman primate AIDS model was so far not established. METHODOLOGY/PRINCIPAL FINDINGS: By randomizing 150 (78 male and 72 female Ch RhMs with diverse MHC class I alleles into 3 groups (50 animals per group challenged with intrarectal (i.r. SIVmac239, intravenous (i.v. SIVmac239, or i.v. SIVmac251, we evaluated variability in bio-clinical endpoints for 118 weeks. All SIV-challenged Ch RhMs became seropositive for SIV during 1-2 weeks. Plasma viral load (VL peaked at weeks 1-2 and then declined to set-point levels as from week 5. The set-point VL was 30 fold higher in SIVmac239 (i.r. or i.v.-infected than in SIVmac251 (i.v.-infected animals. This difference in plasma VL increased overtime (>100 fold as from week 68. The rates of progression to AIDS or death were more rapid in SIVmac239 (i.r. or i.v.-infected than in SIVmac251 (i.v.-infected animals. No significant difference in bio-clinical endpoints was observed in animals challenged with i.r. or i.v. SIVmac239. The variability (standard deviation in peak/set-point VL was nearly one-half lower in animals infected with SIVmac239 (i.r. or i.v. than in those infected with SIVmac251 (i.v., allowing that the same treatment-related difference can be detected with one-half fewer animals using SIVmac239 than using SIVmac251. CONCLUSION/SIGNIFICANCE: These results provide solid estimates of variability in bio-clinical endpoints needed when designing studies using the Ch RhM SIV model and contribute to the improving quality and standardization of preclinical studies.

  2. Proton magnetic resonance spectroscopy reveals neuroprotection by oral minocycline in a nonhuman primate model of accelerated NeuroAIDS.

    Directory of Open Access Journals (Sweden)

    Eva-Maria Ratai

    2010-05-01

    Full Text Available Despite the advent of highly active anti-retroviral therapy (HAART, HIV-associated neurocognitive disorders continue to be a significant problem. In efforts to understand and alleviate neurocognitive deficits associated with HIV, we used an accelerated simian immunodeficiency virus (SIV macaque model of NeuroAIDS to test whether minocycline is neuroprotective against lentiviral-induced neuronal injury.Eleven rhesus macaques were infected with SIV, depleted of CD8+ lymphocytes, and studied until eight weeks post inoculation (wpi. Seven animals received daily minocycline orally beginning at 4 wpi. Neuronal integrity was monitored in vivo by proton magnetic resonance spectroscopy and post-mortem by immunohistochemistry for synaptophysin (SYN, microtubule-associated protein 2 (MAP2, and neuronal counts. Astrogliosis and microglial activation were quantified by measuring glial fibrillary acidic protein (GFAP and ionized calcium binding adaptor molecule 1 (IBA-1, respectively. SIV infection followed by CD8+ cell depletion induced a progressive decline in neuronal integrity evidenced by declining N-acetylaspartate/creatine (NAA/Cr, which was arrested with minocycline treatment. The recovery of this ratio was due to increases in NAA, indicating neuronal recovery, and decreases in Cr, likely reflecting downregulation of glial cell activation. SYN, MAP2, and neuronal counts were found to be higher in minocycline-treated animals compared to untreated animals while GFAP and IBA-1 expression were decreased compared to controls. CSF and plasma viral loads were lower in MN-treated animals.In conclusion, oral minocycline alleviates neuronal damage induced by the AIDS virus.

  3. Haloperidol-induced striatal Nur77 expression in a non-human primate model of tardive dyskinesia.

    Science.gov (United States)

    Mahmoudi, Souha; Blanchet, Pierre J; Lévesque, Daniel

    2013-07-01

    Tardive dyskinesia (TD) is a delayed and potentially irreversible motor complication arising in patients chronically exposed to antipsychotic drugs. As several modern (so-called atypical) antipsychotic drugs are common offenders, combined with the widening clinical indications for prescription as well as exposure of vulnerable individuals, TD will remain a significant drug-induced unwanted side effect. In addition, the pathophysiology of TD remains elusive and therapeutics are difficult. Based on rodent experiments, we have previously shown that the transcriptional factor Nur77 (also known as nerve growth factor inducible gene B or Nr4a1) is induced in the striatum following antipsychotic drug exposure as part of a long-term neuroadaptive process. To confirm this, we exposed adult capuchin (Cebus apella) monkeys to prolonged treatments with haloperidol (median 18.5 months, N = 11) or clozapine (median 6 months, N = 6). Six untreated animals were used as controls. Five haloperidol-treated animals developed mild TD movements similar to those found in humans. No TD was observed in the clozapine group. Postmortem analysis of Nur77 expression measured by in situ hybridization revealed a stark contrast between the two drugs, as Nur77 mRNA levels in the caudate-putamen were strongly upregulated in animals exposed to haloperidol but were spared following clozapine treatment. Interestingly, within the haloperidol-treated group, TD-free animals showed higher Nur77 expression in putamen subterritories compared with dyskinetic animals. This suggests that Nur77 expression might be associated with a reduced risk of TD in this experimental model and could provide a novel target for drug intervention. © 2013 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  4. The Effect of Citalopram on Midbrain CRF Receptors 1 and 2 in a Primate Model of Stress-Induced Amenorrhea

    Science.gov (United States)

    Senashova, Olga; Reddy, Arubala P.; Cameron, Judy L.; Bethea, Cynthia L.

    2012-01-01

    We have demonstrated marked differences in the neurobiology of the serotonin system between stress-sensitive (SS) and stress-resilient (SR) cynomolgus macaques characterized in a model of stress-induced amenorrhea, also called functional hypothalamic amenorrhea (FHA). Dysfunction of the serotonin system in SS monkeys suggested that administration of a selective serotonin reuptake inhibitor (SSRI) might correct FHA. This study examines the effect of escitalopram (CIT) administration to SS and SR monkeys on corticotrophin-releasing factor (CRF) receptor 1 (CRF-R1) and CRF receptor 2 (CRF-R2) gene expression in the serotonin cell body region of the midbrain dorsal raphe. CRF-R1 was not significantly different between groups. There was a significant effect of treatment and a significant interaction between treatment and stress sensitivity on the average CRF-R2-positive pixel area (P < .004 and P < .006, respectively) and on the average number of CRF-R2-positive cells (P < .023 and P < .025, respectively). CIT significantly increased CRF-R2-positive pixel area and cell number in the SS group (pixel area P < .001; cell number P < .01; Bonferoni) but not in the SR group. In summary, CIT administration tended to decrease CRF-R1, but the small animal number precluded significance. CIT administration significantly increased CRF-R2 only in SS animals. These data suggest that the administration of CIT reduces anxiogenic components and increases anxiolytic components of the CRF system in the midbrain serotonin network, which in turn leads to improved ovarian function. Moreover, these data raise the possibility that SSRIs may be effective in the treatment of stress-induced infertility. PMID:22412189

  5. The ecology of primate material culture.

    Science.gov (United States)

    Koops, Kathelijne; Visalberghi, Elisabetta; van Schaik, Carel P

    2014-11-01

    Tool use in extant primates may inform our understanding of the conditions that favoured the expansion of hominin technology and material culture. The 'method of exclusion' has, arguably, confirmed the presence of culture in wild animal populations by excluding ecological and genetic explanations for geographical variation in behaviour. However, this method neglects ecological influences on culture, which, ironically, may be critical for understanding technology and thus material culture. We review all the current evidence for the role of ecology in shaping material culture in three habitual tool-using non-human primates: chimpanzees, orangutans and capuchin monkeys. We show that environmental opportunity, rather than necessity, is the main driver. We argue that a better understanding of primate technology requires explicit investigation of the role of ecological conditions. We propose a model in which three sets of factors, namely environment, sociality and cognition, influence invention, transmission and retention of material culture. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  6. Impact of perinatal systemic hypoxic-ischemic injury on the brain of male offspring rats: an improved model of neonatal hypoxic-ischemic encephalopathy in early preterm newborns.

    Directory of Open Access Journals (Sweden)

    Yuejun Huang

    Full Text Available In this study, we attempted to design a model using Sprague-Dawley rats to better reproduce perinatal systemic hypoxic-ischemic encephalopathy (HIE in early preterm newborns. On day 21 of gestation, the uterus of pregnant rats were exposed and the blood supply to the fetuses of neonatal HIE groups were thoroughly abscised by hemostatic clamp for 5, 10 or 15 min. Thereafter, fetuses were moved from the uterus and manually stimulated to initiate breathing in an incubator at 37 °C for 1 hr in air. We showed that survival rates of offspring rats were decreased with longer hypoxic time. TUNEL staining showed that apoptotic cells were significant increased in the brains of offspring rats from the 10 min and 15 min HIE groups as compared to the offspring rats in the control group at postnatal day (PND 1, but there was no statistical difference between the offspring rats in the 5 min HIE and control groups. The perinatal hypoxic treatment resulted in decreased neurons and increased cleaved caspase-3 protein levels in the offspring rats from all HIE groups at PND 1. Platform crossing times and the percentage of the time spent in the target quadrant of Morris Water Maze test were significantly reduced in the offspring rats of all HIE groups at PND 30, which were associated with decreased brain-derived neurotrophic factor levels and neuronal cells in the hippocampus of offspring rats at PND 35. These data demonstrated that perinatal ischemic injury led to the death of neuronal cells and long-lasting impairment of memory. This model reproduced hypoxic ischemic encephalopathy in early preterm newborns and may be appropriate for investigating therapeutic interventions.

  7. Successful function of autologous iPSC-derived dopamine neurons following transplantation in a non-human primate model of Parkinson's disease

    DEFF Research Database (Denmark)

    Hallett, Penelope J; Deleidi, Michela; Astradsson, Arnar

    2015-01-01

    Autologous transplantation of patient-specific induced pluripotent stem cell (iPSC)-derived neurons is a potential clinical approach for treatment of neurological disease. Preclinical demonstration of long-term efficacy, feasibility, and safety of iPSC-derived dopamine neurons in non-human primat...... neurons and extensive outgrowth into the transplanted putamen. Our proof of concept findings support further development of autologous iPSC-derived cell transplantation for treatment of PD....

  8. Alveolar ridge dimensional changes following ridge preservation procedure with novel devices: part 3 - histological analysis in non-human primate model.

    Science.gov (United States)

    Su, Yingying; Tang, Jianxia; Min, Seiko; Guo, Lijia; Liu, Yitong; Xie, Yilin; Xiong, Jimin; Wang, Songlin; Araújo, Mauricio G; Zadeh, Homayoun H; Liu, Yi

    2017-11-01

    This study sought to investigate the histological changes following tooth extraction, ridge preservation and augmentation, using novel devices designed to obturate the oral orifice of extraction sockets (SocketKAP™) and provide structural support for sockets with defective bony walls (SocketKAGE™) in a non-human primate model. Six Macaca fascicularis were imaged by cone beam computed tomography to register their preoperative alveolar bone. Three teeth were extracted in each animal, yielding intact socket walls and were divided into three intervention groups: unassisted healing negative control (Group A); SocketKAP™ (Group B); filled with anorganic bovine bone mineral (ABBM) + SocketKAP™ (Group C). Three additional teeth were extracted in each animal, followed by surgical resection of the entire buccal alveolar bone and divided into three groups: negative control (Group D); SocketKAP™ + SocketKAGE™ (Group E); ABBM + SocketKAP™ + SocketKAGE™ (Group F). Animals were euthanized after 12 weeks, and treatment sites were examined by histology and histomorphometric analysis. Control sockets with unassisted healing (Groups A and D) underwent severe loss of bone width, height and total area (approximately 40-60% loss). Application of SocketKAP™ in sites with intact walls, as well as SocketKAP™ plus SocketKAGE™ in sites with defective buccal walls lead to higher preservation of alveolar bone height after 12 weeks post-intervention. Addition of ABBM leads to the highest degree of alveolar bone dimensional preservation. Control sites with unassisted healing (Groups A and D), as well as sites treated with extraction socket devices (Groups B and E) without ABBM yielded higher percentage of vital bone, compared with sites filled with ABBM (Groups C and F). No adverse histological responses were noted to SocketKAP™ or SocketKAGE™ devices. SocketKAP™ + SocketKAGE™ devices proved effective in reducing post-extraction alveolar bone resorption

  9. Breastfeeding the preterm infant

    Directory of Open Access Journals (Sweden)

    Luigi Corvaglia

    2013-06-01

    Full Text Available Due to its peculiar nutritional and non-nutritional contents, which include long-chain polyunsatured fatty acids (LC-PUFA, prebiotics, immunological factors, hormones and growth factors, breast milk shows significant advantages over infant formulas in nourishing preterm infants. Better neurocognitive outcomes, which are reported to persist far beyond the early childhood, have been largely observed in breastfed preterm infants; a role of LC-PUFA in promoting neural and retinal development is assumed. As far as the gastrointestinal tract is concerned, several evidences have reported a dose-related reduction in NEC incidence among preterm infants fed on human milk. Moreover, the higher amount of immunological factors as secretory IgA within preterm breast milk might play a remarkable role in reducing the overall infections. Despite breastfeeding in preterm infants is generally linked with lowered growth rates which might potentially affect neurocognitive outcomes, the beneficial effects of human milk on neurodevelopment prevail. Fortified human milk might better fulfill the particular nutritional needs of preterm infants. However, as breast milk fortification is difficult to carry out after the achievement of full oral feeding, some concerns on the nutritional adequacy of exclusive breastfeeding during hospitalization as well as after discharge have been raised. Finally, breastfeeding also entails maternal psychological beneficial effects, as promoting the motherhood process and the mother-child relationship, which could be undermined in those women experiencing preterm delivery. Proceedings of the 9th International Workshop on Neonatology · Cagliari (Italy · October 23rd-26th, 2013 · Learned lessons, changing practice and cutting-edge research

  10. Multilevel factors influencing preterm birth in an urban setting

    Directory of Open Access Journals (Sweden)

    Saba W. Masho

    2014-01-01

    Full Text Available Racial disparity in preterm is a major problem in the US. Although significant strides have been made in identifying some of the risk factors, the complexities between community and individual factors are not understood. This study examines the influence of individual and community level factors affecting preterm birth among Black and White women in an urban setting. A 10-year live birth registry dataset from a mid-sized, racially diverse city was analyzed (N = 30,591. Data were geocoded and merged with block group level Census data. Five hierarchical models were examined using PROC GLIMMIX. Education, illicit drug use, pregnancy complications, previous preterm birth, paternal presence, inadequate and adequate plus prenatal care, and poverty were associated with preterm births in both Blacks and Whites. In Black women, increasing maternal age, maternal smoking, and a previous infant death were significant predictors of preterm births, which was not the case for White women. Residing in medium or high poverty neighborhoods resulted in 19% and 28% higher odds, respectively, of preterm birth for Black women. In addition to individual level factors, neighborhood poverty is an important risk factor influencing preterm birth. It is essential to engage multisectoral agencies in addressing factors influencing preterm birth.

  11. Screening for spontaneous preterm birth

    NARCIS (Netherlands)

    van Os, M.A.; van Dam, A.J.E.M.

    2015-01-01

    Preterm birth is the most important cause of perinatal morbidity and mortality worldwide. In this thesis studies on spontaneous preterm birth are presented. The main objective was to investigate the predictive capacity of mid-trimester cervical length measurement for spontaneous preterm birth in a

  12. Risk Factor Models for Neurodevelopmental Outcomes in Children Born Very Preterm or With Very Low Birth Weight: A Systematic Review of Methodology and Reporting.

    Science.gov (United States)

    Linsell, Louise; Malouf, Reem; Morris, Joan; Kurinczuk, Jennifer J; Marlow, Neil

    2017-04-01

    The prediction of long-term outcomes in surviving infants born very preterm (VPT) or with very low birth weight (VLBW) is necessary to guide clinical management, provide information to parents, and help target and evaluate interventions. There is a large body of literature describing risk factor models for neurodevelopmental outcomes in VPT/VLBW children, yet few, if any, have been developed for use in routine clinical practice or adopted for use in research studies or policy evaluation. We sought to systematically review the methods and reporting of studies that have developed a multivariable risk factor model for neurodevelopment in surviving VPT/VLBW children. We searched the MEDLINE, Embase, and PsycINFO databases from January 1, 1990, to June 1, 2014, and identified 78 studies reporting 222 risk factor models. Most studies presented risk factor analyses that were not intended to be used for prediction, confirming that there is a dearth of specifically designed prognostic modeling studies for long-term outcomes in surviving VPT/VLBW children. We highlight the strengths and weaknesses of the research methodology and reporting to date, and provide recommendations for the design and analysis of future studies seeking to analyze risk prediction or develop prognostic models for VPT/VLBW children. © The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. A molecular phylogeny of living primates.

    Directory of Open Access Journals (Sweden)

    Polina Perelman

    2011-03-01

    Full Text Available Comparative genomic analyses of primates offer considerable potential to define and understand the processes that mold, shape, and transform the human genome. However, primate taxonomy is both complex and controversial, with marginal unifying consensus of the evolutionary hierarchy of extant primate species. Here we provide new genomic sequence (~8 Mb from 186 primates representing 61 (~90% of the described genera, and we include outgroup species from Dermoptera, Scandentia, and Lagomorpha. The resultant phylogeny is exceptionally robust and illuminates events in primate evolution from ancient to recent, clarifying numerous taxonomic controversies and providing new data on human evolution. Ongoing speciation, reticulate evolution, ancient relic lineages, unequal rates of evolution, and disparate distributions of insertions/deletions among the reconstructed primate lineages are uncovered. Our resolution of the primate phylogeny provides an essential evolutionary framework with far-reaching applications including: human selection and adaptation, global emergence of zoonotic diseases, mammalian comparative genomics, primate taxonomy, and conservation of endangered species.

  14. A molecular phylogeny of living primates.

    Science.gov (United States)

    Perelman, Polina; Johnson, Warren E; Roos, Christian; Seuánez, Hector N; Horvath, Julie E; Moreira, Miguel A M; Kessing, Bailey; Pontius, Joan; Roelke, Melody; Rumpler, Yves; Schneider, Maria Paula C; Silva, Artur; O'Brien, Stephen J; Pecon-Slattery, Jill

    2011-03-01

    Comparative genomic analyses of primates offer considerable potential to define and understand the processes that mold, shape, and transform the human genome. However, primate taxonomy is both complex and controversial, with marginal unifying consensus of the evolutionary hierarchy of extant primate species. Here we provide new genomic sequence (~8 Mb) from 186 primates representing 61 (~90%) of the described genera, and we include outgroup species from Dermoptera, Scandentia, and Lagomorpha. The resultant phylogeny is exceptionally robust and illuminates events in primate evolution from ancient to recent, clarifying numerous taxonomic controversies and providing new data on human evolution. Ongoing speciation, reticulate evolution, ancient relic lineages, unequal rates of evolution, and disparate distributions of insertions/deletions among the reconstructed primate lineages are uncovered. Our resolution of the primate phylogeny provides an essential evolutionary framework with far-reaching applications including: human selection and adaptation, global emergence of zoonotic diseases, mammalian comparative genomics, primate taxonomy, and conservation of endangered species.

  15. Preterm Life in Sterile Conditions: A Study on Preterm, Germ-Free Piglets.

    Science.gov (United States)

    Splichalova, Alla; Slavikova, Vera; Splichalova, Zdislava; Splichal, Igor

    2018-01-01

    Preterm infants born with immature organ systems, which can impede normal development, can also be highly sensitive to different biological and/or environmental factors. Animal models could aid in investigating and understanding the effects of different conditions on the health of these immunocompromised infants. The epitheliochorial placentation of the pig prevents the prenatal transfer of protective colostral immunoglobulins. Surgical colostrum-deprived piglets are free of maternal immunoglobulins, and the cells that are normally provided via colostrum. We bred preterm germ-free piglets in sterile conditions and compared them with their term counterparts. Enterocyte development and intestinal morphology, tight junction proteins claudin-1 and occludin, pattern-recognizing receptors, adaptor molecules and coreceptors (RAGE, TLR2, TLR4, TLR9, MyD88, TRIF, MD2, and CD14), and inflammasome NLRP3 transcription were all evaluated. The production of inflammatory mediators IFN-α, IL-4, IL-6, IL-8, IL-10, IL-12/23 p40, TNF-α, IFN-γ, and high mobility group box 1 (HMGB1) in the intestine of germ-free piglets was also assessed. In the preterm germ-free piglets, the ileum showed decreased lamina propria cellularity, reduced villous height, and thinner and less distinct stratification - especially muscle layer, in comparison with their term counterparts. Claudin-1 transcription increased in the intestine of the preterm piglets. The transcription levels of pattern-recognizing receptors and adaptor molecules showed ambiguous trends between the groups. The levels of IL-6, IL-8, IL-10, and TNF-α were increased in the preterm ileum numerically (though not significantly), with statistically significant increases in the colon. Additionally, IL-12/23 p40 and IFN-γ were statistically significantly higher in the preterm colon. Both blood plasma and intestinal HMGB1 levels were nonsignificantly higher in the preterm group. We propose that the intestine of the preterm germ

  16. A unified framework for the organisation of the primate auditory cortex

    Directory of Open Access Journals (Sweden)

    Simon eBaumann

    2013-04-01

    Full Text Available In nonhuman primates a scheme for the organisation of the auditory cortex is frequently used to localise auditory processes. The scheme allows a common basis for comparison of functional organisation across nonhuman primate species. However, although a body of functional and structural data in nonhuman primates supports an accepted scheme of nearly a dozen neighbouring functional areas, can this scheme be directly applied to humans? Attempts to expand the scheme of auditory cortical fields in humans have been severely hampered by a recent controversy about the organisation of tonotopic maps in humans, centred on two different models with radically different organisation. We point out observations that reconcile the previous models and suggest a distinct model in which the human cortical organisation is much more like that of other primates. This unified framework allows a more robust and detailed comparison of auditory cortex organisation across primate species including humans.

  17. Proton resonance frequency chemical shift thermometry: experimental design and validation toward high-resolution noninvasive temperature monitoring and in vivo experience in a nonhuman primate model of acute ischemic stroke.

    Science.gov (United States)

    Dehkharghani, S; Mao, H; Howell, L; Zhang, X; Pate, K S; Magrath, P R; Tong, F; Wei, L; Qiu, D; Fleischer, C; Oshinski, J N

    2015-06-01

    Applications for noninvasive biologic temperature monitoring are widespread in biomedicine and of particular interest in the context of brain temperature regulation, where traditionally costly and invasive monitoring schemes limit their applicability in many settings. Brain thermal regulation, therefore, remains controversial, motivating the development of noninvasive approaches such as temperature-sensitive nuclear MR phenomena. The purpose of this work was to compare the utility of competing approaches to MR thermometry by using proton resonance frequency chemical shift. We tested 3 methodologies, hypothesizing the feasibility of a fast and accurate approach to chemical shift thermometry, in a phantom study at 3T. A conventional, paired approach (difference [DIFF]-1), an accelerated single-scan approach (DIFF-2), and a new, further accelerated strategy (DIFF-3) were tested. Phantom temperatures were modulated during real-time fiber optic temperature monitoring, with MR thermometry derived simultaneously from temperature-sensitive changes in the water proton chemical shift (∼0.01 ppm/°C). MR thermometry was subsequently performed in a series of in vivo nonhuman primate experiments under physiologic and ischemic conditions, testing its reproducibility and overall performance. Chemical shift thermometry demonstrated excellent agreement with phantom temperatures for all 3 approaches (DIFF-1: linear regression R(2) = 0.994; P thermometry and present in vivo applications under physiologic and ischemic conditions in a primate stroke model. © 2015 by American Journal of Neuroradiology.

  18. Changes in Neuroactive Steroid Concentrations After Preterm Delivery in the Guinea Pig

    Science.gov (United States)

    Hirst, Jonathan J.; Palliser, Hannah K.

    2013-01-01

    Background: Preterm birth is a major cause of neurodevelopmental disorders. Allopregnanolone, a key metabolite of progesterone, has neuroprotective and developmental effects in the brain. The objectives of this study were to measure the neuroactive steroid concentrations following preterm delivery in a neonatal guinea pig model and assess the potential for postnatal progesterone replacement therapy to affect neuroactive steroid brain and plasma concentrations in preterm neonates. Methods: Preterm (62-63 days) and term (69 days) guinea pig pups were delivered by cesarean section and tissue was collected at 24 hours. Plasma progesterone, cortisol, allopregnanolone, and brain allopregnanolone concentrations were measured by immunoassay. Brain 5α-reductase (5αR) expression was determined by Western blot. Neurodevelopmental maturity of preterm neonates was assessed by immunohistochemistry staining for myelination, glial cells, and neurons. Results: Brain allopregnanolone concentrations were significantly reduced after birth in both preterm and term neonates. Postnatal progesterone treatment in preterm neonates increased brain and plasma allopregnanolone concentrations. Preterm neonates had reduced myelination, low birth weight, and high mortality compared to term neonates. Brain 5αR expression was also significantly reduced in neonates compared to fetal expression. Conclusions: Delivery results in a loss of neuroactive steroid concentrations resulting in a premature reduction in brain allopregnanolone in preterm neonates. Postnatal progesterone therapy reestablished neuroactive steroid levels in preterm brains, a finding that has implications for postnatal growth following preterm birth that occurs at a time of neurodevelopmental immaturity. PMID:23585339

  19. Extremely Preterm Birth

    Science.gov (United States)

    ... Search FAQs Extremely Preterm Birth Page Navigation ▼ ACOG Pregnancy Book Patient Education FAQs Patient Education Pamphlets - Spanish FAQ173, June 2016 ... Labor and Birth (FAQ087) Tobacco, Alcohol, Drugs, and Pregnancy (FAQ170) Patient Education ... Committee Opinions Practice Bulletins Patient ...

  20. Effects of socioeconomic position and clinical risk factors on spontaneous and iatrogenic preterm birth.

    Science.gov (United States)

    Joseph, K S; Fahey, John; Shankardass, Ketan; Allen, Victoria M; O'Campo, Patricia; Dodds, Linda; Liston, Robert M; Allen, Alexander C

    2014-03-27

    The literature shows a variable and inconsistent relationship between socioeconomic position and preterm birth. We examined risk factors for spontaneous and iatrogenic preterm birth, with a focus on socioeconomic position and clinical risk factors, in order to explain the observed inconsistency. We carried out a retrospective population-based cohort study of all singleton deliveries in Nova Scotia from 1988 to 2003. Data were obtained from the Nova Scotia Atlee Perinatal Database and the federal income tax T1 Family Files. Separate logistic models were used to quantify the association between socioeconomic position, clinical risk factors and spontaneous preterm birth and iatrogenic preterm birth. The study population included 132,714 singleton deliveries and the rate of preterm birth was 5.5%. Preterm birth rates were significantly higher among the women in the lowest (versus the highest) family income group for spontaneous (rate ratio 1.14, 95% confidence interval (CI) 1.03, 1.25) but not iatrogenic preterm birth (rate ratio 0.95, 95% CI 0.75, 1.19). Adjustment for maternal characteristics attenuated the family income-spontaneous preterm birth relationship but strengthened the relationship with iatrogenic preterm birth. Clinical risk factors such as hypertension were differentially associated with spontaneous (rate ratio 3.92, 95% CI 3.47, 4.44) and iatrogenic preterm (rate ratio 14.1, 95% CI 11.4, 17.4) but factors such as diabetes mellitus were not (rate ratio 4.38, 95% CI 3.21, 5.99 for spontaneous and 4.02, 95% CI 2.07, 7.80 for iatrogenic preterm birth). Socioeconomic position and clinical risk factors have different effects on spontaneous and iatrogenic preterm. Recent temporal increases in iatrogenic preterm birth appear to be responsible for the inconsistent relationship between socioeconomic position and preterm birth.

  1. Maternal Plasma Metabolomic Profiles in Spontaneous Preterm Birth: Preliminary Results

    Directory of Open Access Journals (Sweden)

    Barbara Lizewska

    2018-01-01

    Full Text Available Objective. To profile maternal plasma metabolome in spontaneous preterm birth. Method. In this retrospective case-control study, we have examined plasma of patient with preterm birth (between 22 and 36 weeks of pregnancy (n=57, with threatened preterm labor (between 23 and 36 weeks of pregnancy (n=49, and with term delivery (n=25. Plasma samples were analysed using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS in positive and negative polarity modes. Results. We found 168 differentially expressed metabolites that were significantly distinct between study groups. We determined 51 metabolites using publicly available databases that could be subdivided into one of the five groups: amino acids, fatty acids, lipids, hormones, and bile acids. PLS-DA models, verified by SVM classification accuracy, differentiated preterm birth and term delivery groups. Conclusions. Maternal plasma metabolites are different between term and preterm parturitions. Part of them may be related with preterm labor, while others may be affected by gestational age or the beginning of labor. Metabolite profile can classify preterm or term delivery groups raising the potential of metabolome as a biomarker to identify high-risk pregnancies. Metabolomic studies are also a tool to detect individual compounds that may be further tested in targeted researches.

  2. Quality Improvement Project to Reduce Delayed Vaccinations in Preterm Infants.

    Science.gov (United States)

    Cuna, Alain; Winter, Lindy

    2017-08-01

    Preterm infants are especially vulnerable to infectious diseases. Although vaccinations are a safe and effective measure to protect preterm infants from vaccine-preventable diseases, delays in vaccinations are not uncommon. The goal of this quality improvement project was to improve on time vaccinations of preterm infants hospitalized in the neonatal intensive care unit. The Plan-Do-Study-Act model of quality improvement was adopted to develop, test, and implement interventions aimed at improving timely vaccination of preterm infants. The primary outcome measure of interest was the rate of on time vaccination, which was defined as the proportion of medically eligible preterm infants who received vaccinations within 2 weeks of the recommended schedule. Baseline on time vaccination rate was only 36%. Following several Plan-Do-Study-Act cycles, a steady increase in on time vaccinations of eligible infants was observed, and a new baseline on time vaccination rate of 82% was achieved. Simple interventions implemented within the context of Plan-Do-Study-Act cycles are effective in improving timely vaccinations among preterm infants. Future research that focuses on vaccinations in preterm infants is needed to further reinforce the safety and efficacy of vaccines. Effective methods on how to disseminate and apply this knowledge to practice should also be studied.Video Abstract available at http://links.lww.com/ANC/A27.

  3. Surface Model and Tomographic Archive of Fossil Primate and Other Mammal Holotype and Paratype Specimens of the Ditsong National Museum of Natural History, Pretoria, South Africa.

    Science.gov (United States)

    Adams, Justin W; Olah, Angela; McCurry, Matthew R; Potze, Stephany

    2015-01-01

    Nearly a century of paleontological excavation and analysis from the cave deposits of the Cradle of Humankind UNESCO World Heritage Site in northeastern South Africa underlies much of our understanding of the evolutionary history of hominins, other primates and other mammal lineages in the late Pliocene and early Pleistocene of Africa. As one of few designated fossil repositories, the Plio-Pleistocene Palaeontology Section of the Ditsong National Museum of Natural History (DNMNH; the former Transvaal Museum) curates much of the mammalian faunas recovered from the fossil-rich deposits of major South African hominin-bearing localities, including the holotype and paratype specimens of many primate, carnivore, and other mammal species (Orders Primates, Carnivora, Artiodactyla, Eulipotyphla, Hyracoidea, Lagomorpha, Perissodactyla, and Proboscidea). Here we describe an open-access digital archive of high-resolution, full-color three-dimensional (3D) surface meshes of all 89 non-hominin holotype, paratype and significant mammalian specimens curated in the Plio-Pleistocene Section vault. Surface meshes were generated using a commercial surface scanner (Artec Spider, Artec Group, Luxembourg), are provided in formats that can be opened in both open-source and commercial software, and can be readily downloaded either via an online data repository (MorphoSource) or via direct request from the DNMNH. In addition to providing surface meshes for each specimen, we also provide tomographic data (both computerized tomography [CT] and microfocus [microCT]) for a subset of these fossil specimens. This archive of the DNMNH Plio-Pleistocene collections represents the first research-quality 3D datasets of African mammal fossils to be made openly available. This simultaneously provides the paleontological community with essential baseline information (e.g., updated listing and 3D record of specimens in their current state of preservation) and serves as a single resource of high

  4. Surface Model and Tomographic Archive of Fossil Primate and Other Mammal Holotype and Paratype Specimens of the Ditsong National Museum of Natural History, Pretoria, South Africa.

    Directory of Open Access Journals (Sweden)

    Justin W Adams

    Full Text Available Nearly a century of paleontological excavation and analysis from the cave deposits of the Cradle of Humankind UNESCO World Heritage Site in northeastern South Africa underlies much of our understanding of the evolutionary history of hominins, other primates and other mammal lineages in the late Pliocene and early Pleistocene of Africa. As one of few designated fossil repositories, the Plio-Pleistocene Palaeontology Section of the Ditsong National Museum of Natural History (DNMNH; the former Transvaal Museum curates much of the mammalian faunas recovered from the fossil-rich deposits of major South African hominin-bearing localities, including the holotype and paratype specimens of many primate, carnivore, and other mammal species (Orders Primates, Carnivora, Artiodactyla, Eulipotyphla, Hyracoidea, Lagomorpha, Perissodactyla, and Proboscidea. Here we describe an open-access digital archive of high-resolution, full-color three-dimensional (3D surface meshes of all 89 non-hominin holotype, paratype and significant mammalian specimens curated in the Plio-Pleistocene Section vault. Surface meshes were generated using a commercial surface scanner (Artec Spider, Artec Group, Luxembourg, are provided in formats that can be opened in both open-source and commercial software, and can be readily downloaded either via an online data repository (MorphoSource or via direct request from the DNMNH. In addition to providing surface meshes for each specimen, we also provide tomographic data (both computerized tomography [CT] and microfocus [microCT] for a subset of these fossil specimens. This archive of the DNMNH Plio-Pleistocene collections represents the first research-quality 3D datasets of African mammal fossils to be made openly available. This simultaneously provides the paleontological community with essential baseline information (e.g., updated listing and 3D record of specimens in their current state of preservation and serves as a single resource of

  5. Application of the genome editing tool CRISPR/Cas9 in non-human primates.

    Science.gov (United States)

    Luo, Xin; Li, Min; Su, Bing

    2016-07-18

    In the past three years, RNA-guided Cas9 nuclease from the microbial clustered regularly interspaced short palindromic repeats (CRISPR) adaptive immune system has been used to facilitate efficient genome editing in many model and non-model animals. However, its application in nonhuman primates is still at the early stage, though in view of the similarities in anatomy, physiology, behavior and genetics, closely related nonhuman primates serve as optimal models for human biology and disease studies. In this review, we summarize the current proceedings of gene editing using CRISPR/Cas9 in nonhuman primates.

  6. Language, motor and cognitive development of extremely preterm children: modeling individual growth trajectories over the first three years of life.

    Science.gov (United States)

    Sansavini, Alessandra; Pentimonti, Jill; Justice, Laura; Guarini, Annalisa; Savini, Silvia; Alessandroni, Rosina; Faldella, Giacomo

    2014-01-01

    Survival rate of extremely low gestational age (ELGA) newborns has increased over 80% in the last 15 years, but its consequences on the short- and longer-term developmental competencies may be severe. The aim of this study was to describe growth trajectories of linguistic, motor and cognitive skills among ELGA children, compared to full-term (FT) peers, from the first to the third year of life, a crucial period for development. Growth curve analysis was used to examine individual and group differences in terms of initial status at 12 months and rate of growth through the second and the third year of life with five points of assessment. Twenty-eight monolingual Italian children, of whom 17 were ELGA (mean GA 25.7 weeks) and 11 were FT children, were assessed through the BSID-III at 12, 18, 24, 30 and 36 months for language skills and at 12, 24 and 30 months for motor and cognitive skills. ELGA children presented significantly lower scores than FT peers in language, motor and cognitive skills and they did not overcome their disadvantage by 3 years, even if their corrected age was taken into account. Concerning growth curves, in motor development a significant increasing divergence was found showing a Matthew effect with the preterm sample falling further behind the FT sample. In linguistic and cognitive development, instead, a stable gap between the two samples was found. In addition, great inter-individual differences in rate of change were observed for language development in both samples. Our findings highlight the theoretical and clinical relevance of analyzing, through growth curve analyses, the developmental trajectories of ELGA children in language skills taking into account their inter-individual variability also across motor and cognitive domains. After reading this article, the reader will interpret: (a) characteristics and growth trajectories of ELGA children from the first to the third year of life with respect to FT children in language, motor and

  7. Melatonin prevents experimental preterm labor and increases offspring survival.

    Science.gov (United States)

    Domínguez Rubio, Ana P; Sordelli, Micaela S; Salazar, Ana I; Aisemberg, Julieta; Bariani, María V; Cella, Maximiliano; Rosenstein, Ruth E; Franchi, Ana M

    2014-03-01

    Preterm delivery is the leading cause of neonatal mortality and contributes to delayed physical and cognitive development in children. At present, there is no efficient therapy to prevent preterm labor. A large body of evidence suggests that intra-amniotic infections may be a significant and potentially preventable cause of preterm birth. This work assessed the effect of melatonin in a murine model of inflammation-associated preterm delivery which mimics central features of preterm infection in humans. For this purpose, preterm labor was induced in BALB/c mice by intraperitoneal injections of bacterial lipopolysaccharide (LPS) at 10.00 hr (10 μg LPS) and 13.00 hr (20 μg LPS) on day 15 of pregnancy. On day 14 of pregnancy, a pellet of melatonin (25 mg) had been subcutaneously implanted into a group of animals. In the absence of melatonin, a 100% incidence of preterm birth was observed in LPS-treated animals, and the fetuses showed widespread damage. By comparison, treatment with melatonin prevented preterm birth in 50% of the cases, and all pups from melatonin-treated females were born alive and their body weight did not differ from control animals. Melatonin significantly prevented the LPS-induced rises in uterine prostaglandin (PG) E2 , PGF2α, and cyclooxygenase-2 protein levels. In addition, melatonin prevented the LPS-induced increase in uterine nitric oxide (NO) production, inducible NO synthase protein, and tumor necrosis factor-alpha (TNFα) levels. Collectively, our results suggest that melatonin could be a new therapeutic tool to prevent preterm labor and to increase offspring survival. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Transgenic nonhuman primates for neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Chan Anthony WS

    2004-06-01

    Full Text Available Abstract Animal models that represent human diseases constitute an important tool in understanding the pathogenesis of the diseases, and in developing effective therapies. Neurodegenerative diseases are complex disorders involving neuropathologic and psychiatric alterations. Although transgenic and knock-in mouse models of Alzheimer's disease, (AD, Parkinson's disease (PD and Huntington's disease (HD have been created, limited representation in clinical aspects has been recognized and the rodent models lack true neurodegeneration. Chemical induction of HD and PD in nonhuman primates (NHP has been reported, however, the role of intrinsic genetic factors in the development of the diseases is indeterminable. Nonhuman primates closely parallel humans with regard to genetic, neuroanatomic, and cognitive/behavioral characteristics. Accordingly, the development of NHP models for neurodegenerative diseases holds greater promise for success in the discovery of diagnoses, treatments, and cures than approaches using other animal species. Therefore, a transgenic NHP carrying a mutant gene similar to that of patients will help to clarify our understanding of disease onset and progression. Additionally, monitoring disease onset and development in the transgenic NHP by high resolution brain imaging technology such as MRI, and behavioral and cognitive testing can all be carried out simultaneously in the NHP but not in other animal models. Moreover, because of the similarity in motor repertoire between NHPs and humans, it will also be possible to compare the neurologic syndrome observed in the NHP model to that in patients. Understanding the correlation between genetic defects and physiologic changes (e.g. oxidative damage will lead to a better understanding of disease progression and the development of patient treatments, medications and preventive approaches for high risk individuals. The impact of the transgenic NHP model in understanding the role which

  9. Cerebral oxygenation in preterm infants.

    Science.gov (United States)

    Fyfe, Karinna L; Yiallourou, Stephanie R; Wong, Flora Y; Odoi, Alexsandria; Walker, Adrian M; Horne, Rosemary S C

    2014-09-01

    Prone sleeping is a major risk factor for sudden infant death syndrome (SIDS) and preterm infants are at significantly increased risk. In term infants, prone sleeping is associated with reduced mean arterial pressure (MAP) and cerebral tissue oxygenation index (TOI). However, little is known about the effects of sleeping position on TOI and MAP in preterm infants. We aimed to examine TOI and MAP in preterm infants after term-equivalent age, during the period of greatest SIDS risk. Thirty-five preterm and 17 term infants underwent daytime polysomnography, including measurement of TOI (NIRO-200 spectrophotometer, Hamamatsu Photonics KK, Japan) and MAP (Finapress Medical Systems, Amsterdam, Netherlands) at 2 to 4 weeks, 2 to 3 months, and 5 to 6 months postterm age. Infants slept prone and supine in active and quiet sleep. The effects of sleep state and position were determined by using 2-way repeated measures analysis of variance and of preterm birth by using 2-way analysis of variance. In preterm infants, TOI was significantly lower when prone compared with supine in both sleep states at all ages (P preterm compared with term infants at 2 to 4 weeks, in both positions (P preterm infants in the prone position at 2 to 3 months (P position in preterm infants and is lower compared with age-matched term infants, predominantly in the prone position when MAP is also reduced. This may contribute to their increased SIDS risk. Copyright © 2014 by the American Academy of Pediatrics.

  10. Preterm labour: tsunami waves?

    Science.gov (United States)

    Douglas, Alison J

    2010-09-01

    Preterm labour and birth can be delayed but are generally unstoppable, threatening the health of the mother-baby duo. This may be a result of peripheral signals prematurely recruiting the oxytocin neurones that co-ordinate the timing of birth and, via specialised activity and secretion patterns, drive uterine contractions. Once sensitised, these neurones respond with waves of activity, even to weak stimuli, resulting in a positive-feedback loop that escalates towards inevitable birth.

  11. Bioactive Milk for Intestinal Maturation in Preterm Neonates

    DEFF Research Database (Denmark)

    Li, Yanqi

    of stage of lactation (e.g. colostrum versus mature milk), milk processing (e.g. homogenization, pasteurization, fractionation, spray-drying), and supplementation of a bioactive protein in intestinal maturation using preterm pigs as the model for preterm infants. We hope the results are able to contribute...... inflammatory response. This immaturity predisposes preterm infants to various nutritional challenges and clinical conditions, including feeding intolerance, growth restriction, necrotizing enterocolitis (NEC), sepsis and long-term consequences. The quality of milk fed to preterm infants during the first...... reduction or a loss in the levels/activities of various bioactive proteins (e.g. Igs, lactoferrin, IGF, TGF-β) throughout the lactation or during milk processing (e.g. homogenization, pasteurization, fractionation, spray-drying). We therefore made our effects in the PhD project to investigate the influences...

  12. Cellular scaling rules for primate brains

    OpenAIRE

    Herculano-Houzel, Suzana; Collins, Christine E.; Wong, Peiyan; Kaas, Jon H.

    2007-01-01

    Primates are usually found to have richer behavioral repertoires and better cognitive abilities than rodents of similar brain size. This finding raises the possibility that primate brains differ from rodent brains in their cellular composition. Here we examine the cellular scaling rules for primate brains and show that brain size increases approximately isometrically as a function of cell numbers, such that an 11× larger brain is built with 10× more neurons and ≈12× more nonneuronal cells of ...

  13. Modulation of Neuronal Activity in the Motor Thalamus during GPi-DBS in the MPTP Nonhuman Primate Model of Parkinson's Disease.

    Science.gov (United States)

    Muralidharan, Abirami; Zhang, Jianyu; Ghosh, Debabrata; Johnson, Mathew D; Baker, Kenneth B; Vitek, Jerrold L

    The motor thalamus is a key nodal point in the pallidothalamocortical "motor" circuit, which has been implicated in the pathogenesis of Parkinson's disease (PD) and other movement disorders. Although a critical structure in the motor circuit, the role of the motor thalamus in mediating the therapeutic effects of deep brain stimulation (DBS) of the internal segment of the globus pallidus (GPi) is not fully understood. To characterize the changes in neuronal activity in the pallidal (ventralis lateralis pars oralis (VLo) and ventralis anterior (VA)) and cerebellar (ventralis posterior lateralis pars oralis (VPLo)) receiving areas of the motor thalamus during therapeutic GPi DBS. Neuronal activity from the VA/VLo (n = 134) and VPLo (n = 129) was recorded from two non-human primates made parkinsonian using the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. For each isolated unit, one minute of data was recorded before, during and after DBS; a pulse width of 90 µs and a frequency of 135 Hz were used for DBS to replicate commonly used clinical settings. Stimulation amplitude was determined based on the parameters required to improve motor signs. Severity of motor signs was assessed using the UPDRS modified for nonhuman primates. Discharge rate, presence and characteristics of bursts, and oscillatory activity were computed and compared across conditions (pre-, during, and post-stimulation). Neurons in both the pallidal and cerebellar receiving areas demonstrated significant changes in their pattern of activity during therapeutic GPi DBS. A majority of the neurons in each nucleus were inhibited during DBS (VA/VLo: 47% and VPLo: 49%), while a smaller subset was excited (VA/VLo: 21% and VPLo: 17%). Bursts changed in structure, becoming longer in duration and both intra-burst and inter-spike intervals and variability were increased in both subnuclei. High frequency oscillatory activity was significantly increased during stimulation with 33% of VA

  14. Proton Resonance Frequency Chemical Shift Thermometry: Experimental Design and Validation Towards High-Resolution Non-Invasive Temperature Monitoring, and in vivo Experience in a Non-human Primate Model of Acute Ischemic Stroke

    Science.gov (United States)

    Dehkharghani, Seena; Mao, Hui; Howell, Leonard; Zhang, Xiaodong; Pate, K S; Magrath, P R; Tong, Frank; Wei, L; Qiu, D; Fleischer, C; Oshinski, J N

    2016-01-01

    BACKGROUND AND PURPOSE Applications for non-invasive biological temperature monitoring are widespread in biomedicine, and of particular interest in the context of brain temperature regulation, where traditionally costly and invasive monitoring schemes limit their applicability in many settings. Brain thermal regulation therefore remains controversial, motivating the development of non-invasive approaches such as temperature-sensitive NMR phenomena. The purpose of this work was to compare the utility of competing approaches to MR thermometry (MRT) employing proton resonance frequency chemical shift. Three methodologies were tested, hypothesizing the feasibility of a fast and accurate approach to chemical shift thermometry, in a phantom study at 3.0 Tesla. MATERIALS AND METHODS A conventional, paired approach (DIFF-1), an accelerated single-scan approach (DIFF-2), and a new, further accelerated strategy (DIFF-3) were tested. Phantom temperatures were modulated during real-time fiber optic temperature monitoring, with MRT derived simultaneously from temperature-sensitive changes in the water proton chemical shift (~0.01 ppm/°C). MRT was subsequently performed in a series of in vivo non-human primate experiments under physiologic and ischemic conditions testing its reproducibility and overall performance. RESULTS Chemical shift thermometry demonstrated excellent agreement with phantom temperatures for all three approaches (DIFF-1 linear regression R2=0.994, p<0.001, acquisition time 4 min 40 s; DIFF-2 R2=0.996, p<0.001, acquisition time 4 min; DIFF-3 R2=0.998, p<0.001, acquisition time 40 s). CONCLUSION These findings confirm the comparability in performance of three competing approaches MRT, and present in vivo applications under physiologic and ischemic conditions in a primate stroke model. PMID:25655874

  15. Different scaling of white matter volume, cortical connectivity, and gyrification across rodent and primate brains

    Science.gov (United States)

    Ventura-Antunes, Lissa; Mota, Bruno; Herculano-Houzel, Suzana

    2013-01-01

    Expansion of the cortical gray matter in evolution has been accompanied by an even faster expansion of the subcortical white matter volume and by folding of the gray matter surface, events traditionally considered to occur homogeneously across mammalian species. Here we investigate how white matter expansion and cortical folding scale across species of rodents and primates as the gray matter gains neurons. We find very different scaling rules of white matter expansion across the two orders, favoring volume conservation and smaller propagation times in primates. For a similar number of cortical neurons, primates have a smaller connectivity fraction and less white matter volume than rodents; moreover, as the cortex gains neurons, there is a much faster increase in white matter volume and in its ratio to gray matter volume in rodents than in primates. Order-specific scaling of the white matter can be attributed to different scaling of average fiber caliber and neuronal connectivity in rodents and primates. Finally, cortical folding increases as different functions of the number of cortical neurons in rodents and primates, scaling faster in the latter than in the former. While the neuronal rules that govern gray and white matter scaling are different across rodents and primates, we find that they can be explained by the same unifying model, with order-specific exponents. The different scaling of the white matter has implications for the scaling of propagation time and computational capacity in evolution, and calls for a reappraisal of developmental models of cortical expansion in evolution. PMID:23576961

  16. Pathological rate matrices: from primates to pathogens

    Directory of Open Access Journals (Sweden)

    Knight Rob

    2008-12-01

    Full Text Available Abstract Background Continuous-time Markov models allow flexible, parametrically succinct descriptions of sequence divergence. Non-reversible forms of these models are more biologically realistic but are challenging to develop. The instantaneous rate matrices defined for these models are typically transformed into substitution probability matrices using a matrix exponentiation algorithm that employs eigendecomposition, but this algorithm has characteristic vulnerabilities that lead to significant errors when a rate matrix possesses certain 'pathological' properties. Here we tested whether pathological rate matrices exist in nature, and consider the suitability of different algorithms to their computation. Results We used concatenated protein coding gene alignments from microbial genomes, primate genomes and independent intron alignments from primate genomes. The Taylor series expansion and eigendecomposition matrix exponentiation algorithms were compared to the less widely employed, but more robust, Padé with scaling and squaring algorithm for nucleotide, dinucleotide, codon and trinucleotide rate matrices. Pathological dinucleotide and trinucleotide matrices were evident in the microbial data set, affecting the eigendecomposition and Taylor algorithms respectively. Even using a conservative estimate of matrix error (occurrence of an invalid probability, both Taylor and eigendecomposition algorithms exhibited substantial error rates: ~100% of all exonic trinucleotide matrices were pathological to the Taylor algorithm while ~10% of codon positions 1 and 2 dinucleotide matrices and intronic trinucleotide matrices, and ~30% of codon matrices were pathological to eigendecomposition. The majority of Taylor algorithm errors derived from occurrence of multiple unobserved states. A small number of negative probabilities were detected from the Pad�� algorithm on trinucleotide matrices that were attributable to machine precision. Although the Pad

  17. Variations in breastfeeding rates for very preterm infants between regions and neonatal units in Europe

    DEFF Research Database (Denmark)

    Bonet, Mercedes; Blondel, Béatrice; Agostino, Rocco

    2011-01-01

    To compare breastfeeding rates at discharge for very preterm infants between European regions and neonatal units, and to identify characteristics associated with breast feeding using multilevel models.......To compare breastfeeding rates at discharge for very preterm infants between European regions and neonatal units, and to identify characteristics associated with breast feeding using multilevel models....

  18. Bilingualism as a potential strategy to improve executive function in preterm infants: a review.

    Science.gov (United States)

    Head, Lauren M; Baralt, Melissa; Darcy Mahoney, Ashley E

    2015-01-01

    Preterm birth is associated with long-term deficits in executive functioning and cognitive performance. Using the model of brain plasticity as a theoretical framework, it is possible that preterm infants' neurodevelopmental sequelae can be altered. Evidence suggests that bilingualism confers cognitive advantages on executive functioning, so it is possible that bilingualism may improve preterm infants' neurodevelopment. However, bilingualism has only been studied in term children. This review examined literature that compared the performance of preterm-born children to term children and bilingual children to monolingual children on executive function tasks. To address cognitive disparities in preterm-born children, studies investigating the effect of bilingualism on preterm infants' executive functioning is warranted. Copyright © 2015 National Association of Pediatric Nurse Practitioners. Published by Elsevier Inc. All rights reserved.

  19. Collagen Sponge Functionalized with Chimeric Anti-BMP-2 Monoclonal Antibody Mediates Repair of Critical-Size Mandibular Continuity Defects in a Nonhuman Primate Model

    Directory of Open Access Journals (Sweden)

    Yilin Xie

    2017-01-01

    Full Text Available Antibody-mediated osseous regeneration (AMOR has been introduced by our research group as a tissue engineering approach to capture of endogenous growth factors through the application of specific monoclonal antibodies (mAbs immobilized on a scaffold. Specifically, anti-Bone Morphogenetic Protein- (BMP- 2 mAbs have been demonstrated to be efficacious in mediating bone repair in a number of bone defects. The present study sought to investigate the application of AMOR for repair of mandibular continuity defect in nonhuman primates. Critical-sized mandibular continuity defects were created in Macaca fascicularis locally implanted with absorbable collagen sponges (ACS functionalized with chimeric anti-BMP-2 mAb or isotype control mAb. 2D and 3D analysis of cone beam computed tomography (CBCT imaging demonstrated increased bone density and volume observed within mandibular continuity defects implanted with collagen scaffolds functionalized with anti-BMP-2 mAb, compared with isotype-matched control mAb. Both CBCT imaging and histologic examination demonstrated de novo bone formation that was in direct apposition to the margins of the resected bone. It is hypothesized that bone injury may be necessary for AMOR. This is evidenced by de novo bone formation adjacent to resected bone margins, which may be the source of endogenous BMPs captured by anti-BMP-2 mAb, in turn mediating bone repair.

  20. Neurodevelopmental outcome in preterm infants

    NARCIS (Netherlands)

    Bos, Arend F.; Roze, Elise

    AIM To determine the distribution of cognitive and motor scores in preterm children, and to establish the influence of brain lesions and decreasing gestational age thereon. METHOD One hundred and six very preterm children (63 males, 43 females; gestational age 24.0-31.6wk; birthweight 480-2275g)

  1. Prediction of Spontaneous Preterm Birth

    NARCIS (Netherlands)

    Dijkstra, Karolien

    2002-01-01

    Preterm birth is a leading cause of neonatal morbidity and mortality. It is a major goal in obstetrics to lower the incidence of spontaneous preterm birth (SPB) and related neonatal morbidity and mortality. One of the principal objectives is to discover early markers that would allow us to identify

  2. Cerebral oximetry in preterm infants

    DEFF Research Database (Denmark)

    Greisen, Gorm; Andresen, Bjørn; Plomgaard, Anne Mette

    2016-01-01

    Preterm birth constitutes a major cause of death before 5 years of age and it is a major cause of neurodevelopmental impairment across the world. Preterm infants are most unstable during the transition between fetal and newborn life during the first days of life and most brain damage occurs...

  3. Preterm Birth: Transition to Adulthood

    Science.gov (United States)

    Allen, Marilee C.; Cristofalo, Elizabeth; Kim, Christina

    2010-01-01

    Preterm birth is associated with greater difficulty with transitions from childhood to adolescence to adulthood. Adolescents and young adults born preterm have higher rates of cerebral palsy, intellectual disability, cognitive impairment, learning disability, executive dysfunction, attention deficit disorder, and social-emotional difficulties than…

  4. The gateway to the brain: dissecting the primate eye.

    Science.gov (United States)

    Burke, Mark; Zangenehpour, Shahin; Bouskila, Joseph; Boire, Denis; Ptito, Maurice

    2009-05-27

    The visual system in humans is considered the gateway to the world and plays a principal role in the plethora of sensory, perceptual and cognitive processes. It is therefore not surprising that quality of vision is tied to quality of life . Despite widespread clinical and basic research surrounding the causes of visual disorders, many forms of visual impairments, such as retinitis pigmentosa and macular degeneration, lack effective treatments. Non-human primates have the closest general features of eye development to that of humans. Not only do they have a similar vascular anatomy, but amongst other mammals, primates have the unique characteristic of having a region in the temporal retina specialized for high visual acuity, the fovea(1). Here we describe a general technique for dissecting the primate retina to provide tissue for retinal histology, immunohistochemistry, laser capture microdissection, as well as light and electron microscopy. With the extended use of the non-human primate as a translational model, our hope is that improved understanding of the retina will provide insights into effective approaches towards attenuating or reversing the negative impact of visual disorders on the quality of life of affected individuals.

  5. Psychological, cultural and neuroendocrine profiles of risk for preterm birth.

    Science.gov (United States)

    Ruiz, R Jeanne; Dwivedi, Alok Kumar; Mallawaarachichi, Indika; Balcazar, Hector G; Stowe, Raymond P; Ayers, Kimberly S; Pickler, Rita

    2015-09-03

    Preterm birth remains a major obstetrical problem and identification of risk factors for preterm birth continues to be a priority in providing adequate care. Therefore, the purpose of this study was to elucidate risk profiles for preterm birth using psychological, cultural and neuroendocrine measures. From a cross sectional study of 515 Mexican American pregnant women at 22-24 weeks gestation, a latent profile analysis of risk for preterm birth using structural equation modeling (SEM) was conducted. We determined accurate gestational age at delivery from the prenatal record and early ultrasounds. We also obtained demographic and prenatal data off of the chart, particularly for infections, obstetrical history, and medications. We measured depression (Beck Depression Inventory), mastery (Mastery scale), coping (The Brief Cope), and acculturation (Multidimensional Acculturation Scale) with reliable and valid instruments. We obtained maternal whole blood and separated it into plasma for radioimmunoassay of Corticotrophin Releasing Hormone (CRH). Delivery data was obtained from hospital medical records. Using a latent profile analysis, three psychological risk profiles were identified. The "low risk" profile had a 7.7% preterm birth rate. The "moderate risk" profile had a 12% preterm birth rate. The "highest risk" profile had a 15.85% preterm birth rate. The highest risk profile had double the percentage of total infections compared to the low risk profile. High CRH levels were present in the moderate and highest risk profiles. These risk profiles may provide a basis for screening for Mexican American women to predict risk of preterm birth, particularly after they are further validated in a prospective cohort study. Future research might include use of such an identified risk profile with targeted interventions tailored to the Hispanic culture.

  6. Conservation strategies for understanding and combating the primate bushmeat trade on Bioko Island, Equatorial Guinea.

    Science.gov (United States)

    Cronin, Drew T; Sesink Clee, Paul R; Mitchell, Matthew W; Bocuma Meñe, Demetrio; Fernández, David; Riaco, Cirilo; Fero Meñe, Maximiliano; Esara Echube, Jose Manuel; Hearn, Gail W; Gonder, Mary Katherine

    2017-11-01

    Bioko Island, Equatorial Guinea is among the important places in Africa for the conservation of primates, but a cultural preference for bushmeat and a lack of effective law enforcement has encouraged commercial bushmeat hunting, threatening the survival of the remaining primate population. For over 13 years, we collected bushmeat market data in the Malabo market, recording over 35,000 primate carcasses, documenting "mardi gras" consumption patterns, seasonal carcass availability, and negative effects resulting from government intervention. We also conducted forest surveys throughout Bioko's two protected areas in order to localize and quantify primate populations and hunting pressure. Using these data, we were able to document the significant negative impact bushmeat hunting had on monkey populations, estimate which species are most vulnerable to hunting, and develop ecological niche models to approximate the distribution of each of Bioko's diurnal primate species. These results also have allowed for the identification of primate hotspots, such as the critically important southwest region of the Gran Caldera Scientific Reserve, and thus, priority areas for conservation on Bioko, leading to more comprehensive conservation recommendations. Current and future efforts now focus on bridging the gap between investigators and legislators in order to develop and effectively implement a management plan for Bioko's Gran Caldera Scientific Reserve and to develop a targeted educational campaign to reduce demand by changing consumer attitudes toward bushmeat. Using this multidisciplinary approach, informed by biological, socioeconomic, and cultural research, there may yet be a positive future for the primates of Bioko. © 2017 Wiley Periodicals, Inc.

  7. A Bayesian Stepwise Discriminant Model for Predicting Risk Factors of Preterm Premature Rupture of Membranes: A Case-control Study

    Directory of Open Access Journals (Sweden)

    Li-Xia Zhang

    2017-01-01

    Conclusions: This study established a Bayesian stepwise discriminant model to predict the incidence of PPROM. The UU, CT, and GBS infections were discriminant factors for PPROM according to a Bayesian stepwise discriminant analysis. This model could provide a new method for the early predicting of PPROM in pregnant women.

  8. Bion 11 mission: primate experiments

    Science.gov (United States)

    Ilyin, E. A.; Korolkov, V. I.; Skidmore, M. G.; Viso, M.; Kozlovskaya, I. B.; Grindeland, R. E.; Lapin, B. A.; Gordeev, Y. V.; Krotov, V. P.; Fanton, J. W.; hide

    2000-01-01

    A summary is provided of the major operations required to conduct the wide range of primate experiments on the Bion 11 mission, which flew for 14 days beginning December 24, 1996. Information is given on preflight preparations, including flight candidate selection and training; attachment and implantation of bioinstrumentation; flight and ground experiment designs; onboard life support and test systems; ground and flight health monitoring; flight monkey selection and transport to the launch site; inflight procedures and data collection; postflight examinations and experiments; and assessment of results.

  9. The pyrophilic primate hypothesis.

    Science.gov (United States)

    Parker, Christopher H; Keefe, Earl R; Herzog, Nicole M; O'connell, James F; Hawkes, Kristen

    2016-01-01

    Members of genus Homo are the only animals known to create and control fire. The adaptive significance of this unique behavior is broadly recognized, but the steps by which our ancestors evolved pyrotechnic abilities remain unknown. Many hypotheses attempting to answer this question attribute hominin fire to serendipitous, even accidental, discovery. Using recent paleoenvironmental reconstructions, we present an alternative scenario in which, 2 to 3 million years ago in tropical Africa, human fire dependence was the result of adapting to progressively fire-prone environments. The extreme and rapid fluctuations between closed canopy forests, woodland, and grasslands that occurred in tropical Africa during that time, in conjunction with reductions in atmospheric carbon dioxide levels, changed the fire regime of the region, increasing the occurrence of natural fires. We use models from optimal foraging theory to hypothesize benefits that this fire-altered landscape provided to ancestral hominins and link these benefits to steps that transformed our ancestors into a genus of active pyrophiles whose dependence on fire for survival contributed to its rapid expansion out of Africa. © 2016 Wiley Periodicals, Inc.

  10. Alveolar ridge dimensional changes following ridge preservation procedure with novel devices: Part 1--CBCT linear analysis in non-human primate model.

    Science.gov (United States)

    Min, Seiko; Liu, Yi; Tang, Jianxia; Xie, Yilin; Xiong, Jimin; You, Hyung-Keun; Zadeh, Homayoun H

    2016-01-01

    This study sought to investigate dimensional changes to the alveolar bone following extraction and application of novel devices used for obturation of socket orifice (socket cap) and space maintenance in sockets with facial dehiscence (socket cage). Six Macaca fascicularis had six teeth each removed according to the following intervention groups (groups A-C intact alveolar bone; D-E facial dehiscence): negative control (A); socket obturated with cap (B); filled with anorganic bovine bone mineral (ABBM) + socket cap (C); dehiscence negative control (D); socket cap + socket cage (E); ABBM + socket cap + socket cage (F). Serial CBCT scans at preoperatively, 6 and 12 weeks following intervention were compared to quantify linear alveolar bone alterations. Without therapeutic intervention, intact sockets exhibited significant reduction in width at the crestal 2 mm of the ridge crest within 6 weeks. Compared with the negative control sites which lost up to 52% of crestal bone width, sites treated with socket cap + ABBM lost at most 4% of bone width at the crestal 2 mm. Similar results were seen in the dehiscence groups, with the combination of socket cap + socket cage + ABBM maintaining the greatest socket width and height dimensions. Results from the current non-human primate study suggest that the socket cap and socket cage devices, when used in conjunction with xenograft proved effective in minimizing post-extraction socket width loss and height seen in both intact sockets and sockets with facial dehiscence defects. © 2015 The Authors. Clinical Oral Implants Research Published by John Wiley & Sons Ltd.

  11. Antibody signature of spontaneous clearance of Chlamydia trachomatis ocular infection and partial resistance against re-challenge in a nonhuman primate trachoma model.

    Directory of Open Access Journals (Sweden)

    Laszlo Kari

    Full Text Available Chlamydia trachomatis is the etiological agent of trachoma the world's leading cause of infectious blindness. Here, we investigate whether protracted clearance of a primary infection in nonhuman primates is attributable to antigenic variation or related to the maturation of the anti-chlamydial humoral immune response specific to chlamydial antigens.Genomic sequencing of organisms isolated throughout the protracted primary infection revealed that antigenic variation was not related to the inability of monkeys to efficiently resolve their infection. To explore the maturation of the humoral immune response as a possible reason for delayed clearance, sera were analyzed by radioimmunoprecipitation using intrinsically radio-labeled antigens prepared under non-denaturing conditions. Antibody recognition was restricted to the antigenically variable major outer membrane protein (MOMP and a few antigenically conserved antigens. Recognition of MOMP occurred early post-infection and correlated with reduction in infectious ocular burdens but not with infection eradication. In contrast, antibody recognition of conserved antigens, identified as PmpD, Hsp60, CPAF and Pgp3, appeared late and correlated with infection eradication. Partial immunity to re-challenge was associated with a discernible antibody recall response against all antigens. Antibody recognition of PmpD and CPAF was destroyed by heat treatment while MOMP and Pgp3 were partially affected, indicating that antibody specific to conformational epitopes on these proteins may be important to protective immunity.Our findings suggest that delayed clearance of chlamydial infection in NHP is not the result of antigenic variation but rather a consequence of the gradual maturation of the C. trachomatis antigen-specific humoral immune response. However, we cannot conclude that antibodies specific for these proteins play the primary role in host protective immunity as they could be surrogate markers of T cell

  12. Towards a Non-Human Primate Model of Alpha-Synucleinopathy for Development of Therapeutics for Parkinson's Disease: Optimization of AAV1/2 Delivery Parameters to Drive Sustained Expression of Alpha Synuclein and Dopaminergic Degeneration in Macaque.

    Directory of Open Access Journals (Sweden)

    James B Koprich

    Full Text Available Recent failures in clinical trials for disease modification in Parkinson's disease have highlighted the need for a non-human primate model of the synucleinopathy underpinning dopaminergic neuron degeneration. The present study was defined to begin the development of such a model in cynomolgus macaque. We have validated surgical and vector parameters to define a means to provide a robust over-expression of alpha-synuclein which is associated with Lewy-like pathology and robust degeneration of the nigrostriatal pathway. Thus, an AAV1/2 vector incorporating strong transcription and transduction regulatory elements was used to deliver the gene for the human A53T mutation of alpha-synuclein. When injected into 4 sites within each substantia nigra (7 μl per site, 1.7 x 1012 gp/ml, this vector provided expression lasting at least 4 months, and a 50% loss of nigral dopaminergic neurons and a 60% reduction in striatal dopamine. Further studies will be required to develop this methodology into a validated model of value as a drug development platform.

  13. Twin transvaginal cervical length at 16-20 weeks and prediction of preterm birth.

    Science.gov (United States)

    Hester, Ashley E; Ankumah, Nana-Ama E; Chauhan, Suneet P; Blackwell, Sean C; Sibai, Baha M

    2017-10-08

    Our objective was to determine if transvaginal cervical length at 16-20 weeks is predictive of preterm birth preterm birth. Transvaginal cervical length was performed at 16-20-week gestation. The inclusion criteria were non-anomalous twins with transvaginal cervical length at 16-20 weeks. Receiver-operating characteristic (ROC) curves were generated to determine the transvaginal cervical length associated with preterm birth. Of 655 pregnancies, 27% (N = 178) women met our inclusion criteria. The rate of spontaneous preterm birth before 34 weeks was 16% (N = 29). A receiver operator characteristic curve was generated for all preterm birth preterm birth (n = 15) were excluded, the area under the curve was 0.59 (95% CI 0.47-0.70), indicating that transvaginal cervical length values were not a clinically useful test for the prediction of spontaneous preterm birth. A transvaginal cervical length of 30 mm from this model would produce a sensitivity of detecting spontaneous preterm birth of 95% and a specificity of 14%. In an asymptomatic twin population, a single transvaginal cervical length between 16 and 20 weeks was not predictive of spontaneous preterm birth before 34 weeks. Thus, our findings suggest that routine transvaginal cervical length screening of twins should not be performed between 16-20 weeks.

  14. Deep Hierarchies in the Primate Visual Cortex: What Can We Learn for Computer Vision?

    OpenAIRE

    Kruger, Norbert; Janssen, Peter; Kalkan, Sinan; Lappe, Markus; Leonardis, Ales; Piater, Justus; Rodriguez-Sanchez, Antonio J.; Wiskott, Laurenz

    2013-01-01

    Computational modeling of the primate visual system yields insights of potential relevance to some of the challenges that computer vision is facing, such as object recognition and categorization, motion detection and activity recognition or vision-based navigation and manipulation. This article reviews some functional principles and structures that are generally thought to underlie the primate visual cortex, and attempts to extract biological principles that could further advance computer ...

  15. Social inequalities in health in nonhuman primates

    Directory of Open Access Journals (Sweden)

    Carol A. Shively

    2015-01-01

    Full Text Available Overall health has been linked to socioeconomic status, with the gap between social strata increasing each year. Studying the impact of social position on health and biological functioning in nonhuman primates has allowed researchers to model the human condition while avoiding ethical complexities or other difficulties characteristic of human studies. Using female cynomolgus macaques (Macaca fascicularis, our lab has examined the link between social status and stress for 30 years. Female nonhuman primates are especially sensitive to social stressors which can deleteriously affect reproductive health, leading to harmful consequences to their overall health. Subordinates have lower progesterone concentrations during the luteal phase of menstrual cycle, which is indicative of absence or impairment of ovulation. Subordinate animals receive more aggression, less affiliative attention, and are more likely to exhibit depressive behaviors. They also express higher stress-related biomarkers such as increased heart rates and lower mean cortisol. While no differences in body weight between dominant and subordinate animals are observed, subordinates have lower bone density and more visceral fat than their dominant counterparts. The latter increases risk for developing inflammatory diseases. Differences are also observed in neurological and autonomic function. A growing body of data suggests that diet composition may amplify or diminish physiological stress responses which have deleterious effects on health. More experimental investigation of the health effects of diet pattern is needed to further elucidate these differences in an ongoing search to find realistic and long-term solutions to the declining health of individuals living across the ever widening socioeconomic spectrum.

  16. Adult outcomes of preterm children.

    Science.gov (United States)

    Hack, Maureen

    2009-10-01

    The survivors of the initial years of neonatal intensive care of preterm infants reached adulthood during the last decade. Reports of their adult outcomes examined have included neurodevelopmental, behavioral and health outcomes as well as social functioning and reproduction. Despite statistically significant differences between preterm young adults and controls in most outcomes studied, the majority of preterm survivors do well and live fairly normal lives. The two major predictors of adult outcomes are lower gestational age that reflect perinatal injury and family sociodemographic status which reflects both genetic and environmental effects.

  17. Vitamin D, pre-eclampsia, and preterm birth among pregnancies at high risk for pre-eclampsia: an analysis of data from a low-dose aspirin trial.

    Science.gov (United States)

    Gernand, A D; Simhan, H N; Baca, K M; Caritis, S; Bodnar, L M

    2017-11-01

    To examine the relation between maternal vitamin D status and risk of pre-eclampsia and preterm birth in women at high risk for pre-eclampsia. Analysis of prospectively collected data and blood samples from a trial of prenatal low-dose aspirin. Thirteen sites across the USA. Women at high risk for pre-eclampsia. We measured 25-hydroxyvitamin D [25(OH)D] concentrations in stored maternal serum samples drawn at 12-26 weeks' gestation (n = 822). We used mixed effects models to examine the association between 25(OH)D and risk of pre-eclampsia and preterm birth, controlling for confounders including prepregnancy BMI and race. Pre-eclampsia and preterm birth. Twelve percent of women were vitamin D deficient [25(OH)D preterm birth at preterm births at preterm birth at preterm birth at preterm birth at <35 weeks in high-risk pregnancies. © 2016 Royal College of Obstetricians and Gynaecologists.

  18. Pregnancy Outcomes in Women With a History of Previable, Preterm Prelabor Rupture of Membranes.

    Science.gov (United States)

    Monson, Martha A; Gibbins, Karen J; Esplin, M Sean; Varner, Michael W; Manuck, Tracy A

    2016-11-01

    To characterize subsequent pregnancy outcomes among women with a history of previable, preterm prelabor rupture of membranes (PROM) and assess factors associated with recurrent preterm birth. This was a retrospective cohort study of women cared for with a history of one or more singleton pregnancy complicated by preterm PROM at less than 24 weeks of gestation between 2002 and 2013 who were cared for in two tertiary care health systems by a single group of maternal-fetal medicine specialists. Women were identified using International Classification of Diseases, 9th Revision codes and obstetric databases. Those with iatrogenic preterm PROM and those whose index preterm PROM at less than 24 weeks of gestation was preceded by advanced cervical dilation were excluded. All women with one or more pregnancies reaching the second trimester after an index previable, preterm PROM pregnancy were included. The primary outcome was recurrent preterm birth at less than 37 weeks of gestation. Data were analyzed by χ, Fisher exact, t test, Wilcoxon rank-sum, and logistic regression. Two hundred ninety-four women had one or more pregnancies complicated by previable, preterm PROM. One hundred eight of 294 (37%) had one or more subsequent pregnancies in our health care systems and 50 of 108 (46%) had two or more. In the pregnancy immediately after the index delivery, the risk of prematurity was high: 50 (46%) delivered at less than 37 weeks of gestation, 31 (30%) at less than 34 weeks of gestation, 25 (23%) at less than 28 weeks of gestation, and 18 (17%) before 24 weeks of gestation. Fewer than half (n=49 [45%]) of women received preterm birth prophylaxis (progesterone or cerclage) in a subsequent pregnancy; rates of recurrent preterm birth were similar among women who received preterm birth prophylaxis compared with those who did not. In regression models, the only factor significantly associated with recurrent preterm birth at less than 37 weeks of gestation was a history of

  19. Dengue viruses cleave STING in humans but not in nonhuman primates, their presumed natural reservoir

    Science.gov (United States)

    Stabell, Alex C; Meyerson, Nicholas R; Gullberg, Rebekah C; Gilchrist, Alison R; Webb, Kristofor J; Old, William M; Perera, Rushika

    2018-01-01

    Human dengue viruses emerged from primate reservoirs, yet paradoxically dengue does not reach high titers in primate models. This presents a unique opportunity to examine the genetics of spillover versus reservoir hosts. The dengue virus 2 (DENV2) - encoded protease cleaves human STING, reducing type I interferon production and boosting viral titers in humans. We find that both human and sylvatic (reservoir) dengue viruses universally cleave human STING, but not the STING of primates implicated as reservoir species. The special ability of dengue to cleave STING is thus specific to humans and a few closely related ape species. Conversion of residues 78/79 to the human-encoded ‘RG’ renders all primate (and mouse) STINGs sensitive to viral cleavage. Dengue viruses may have evolved to increase viral titers in the dense and vast human population, while maintaining decreased titers and pathogenicity in the more rare animals that serve as their sustaining reservoir in nature. PMID:29557779

  20. Population pharmacokinetic modelling of total and unbound cefazolin plasma concentrations as a guide for dosing in preterm and term neonates.

    Science.gov (United States)

    De Cock, R F W; Smits, A; Allegaert, K; de Hoon, J; Saegeman, V; Danhof, M; Knibbe, C A J

    2014-05-01

    Cefazolin is frequently administered for antimicrobial prophylaxis and treatment of infections. In neonates, pharmacokinetic observations are limited and dosing regimens variable. The aim of this study was to describe the pharmacokinetics of cefazolin in neonates based on total and unbound concentrations to optimize cefazolin dosing. Thirty-six neonates [median birth body weight 2720 (range 540-4200) g, current body weight (cBW) 2755 (830-4200) g and postnatal age (PNA) 9 (1-30) days] receiving intravenous cefazolin (50 mg/kg/8 h) were included. Based on 119 total and unbound plasma concentrations, a population pharmacokinetic analysis with a covariate analysis was performed. Monte Carlo simulations were performed aiming for unbound concentrations above an MIC of 8 mg/L (>60% of the time) in all patients. A one-compartment pharmacokinetic model was developed in which total and unbound concentrations were linked by maximum protein binding (Bmax) of 136 mg/L and a dissociation constant (KD) for cefazolin protein binding of 46.5 mg/L. cBW was identified as covariate for volume of distribution (V), bBW and PNA for clearance and albumin plasma concentration for Bmax, explaining 50%, 58% and 41% of inter-individual variability in V, clearance and Bmax, respectively. Based on Monte Carlo simulations, a body weight- and PNA-adapted dosing regimen that resulted in similar exposure across different weight and age groups was proposed. A neonatal pharmacokinetic model taking into account total and unbound cefazolin concentrations with saturable plasma protein binding was identified. As cBW and PNA were the most important covariates, these may be used for individualized dosing in neonates.

  1. Comparing primate crania: The importance of fossils.

    Science.gov (United States)

    Fleagle, John G; Gilbert, Christopher C; Baden, Andrea L

    2016-10-01

    Extant primate crania represent a small subset of primate crania that have existed. The main objective here is to examine how the inclusion of fossil crania changes our understanding of primate cranial diversity relative to analyses of extant primates. We hypothesize that fossil taxa will change the major axes of cranial shape, occupy new areas of morphospace, change the relative diversity of major primate clades, and fill in notable gaps separating major primate taxa/clades. Eighteen 3D landmarks were collected on 157 extant and fossil crania representing 90 genera. Data were subjected to a Generalized Procrustes Analysis then principal components analysis. Relative diversity between clades was assessed using an F-statistic. Fossil taxa do not significantly alter major axes of cranial shape, but they do occupy unique areas of morphospace, change the relative diversity between clades, and fill in notable gaps in primate cranial evolution. Strepsirrhines remain significantly less diverse than anthropoids. Fossil hominins fill the gap in cranial morphospace between extant great apes and modern humans. The morphospace outlined by living primates largely includes that occupied by fossil taxa, suggesting that the cranial diversity of living primates generally encompasses the total diversity that has evolved in this Order. The evolution of the anthropoid cranium was a significant event allowing anthropoids to achieve significantly greater cranial diversity compared to strepsirrhines. Fossil taxa fill in notable gaps within and between clades, highlighting their transitional nature and eliminating the appearance of large morphological distances between extant taxa, particularly in the case of extant hominids. © 2016 Wiley Periodicals, Inc.

  2. Neck function in early hominins and suspensory primates: Insights from the uncinate process.

    Science.gov (United States)

    Meyer, Marc R; Woodward, Charles; Tims, Amy; Bastir, Markus

    2018-02-28

    Uncinate processes are protuberances on the cranial surface of subaxial cervical vertebrae that assist in stabilizing and guiding spinal motion. Shallow uncinate processes reduce cervical stability but confer an increased range of motion in clinical studies. Here we assess uncinate processes among extant primates and model cervical kinematics in early fossil hominins. We compare six fossil hominin vertebrae with 48 Homo sapiens and 99 nonhuman primates across 20 genera. We quantify uncinate morphology via geometric morphometric methods to understand how uncinate process shape relates to allometry, taxonomy, and mode of locomotion. Across primates, allometry explains roughly 50% of shape variation, as small, narrow vertebrae feature the relatively tallest, most pronounced uncinate processes, whereas larger, wider vertebrae typically feature reduced uncinates. Taxonomy only weakly explains the residual variation, however, the association between Uncinate Shape and mode of locomotion is robust, as bipeds and suspensory primates occupy opposite extremes of the morphological continuum and are distinguished from arboreal generalists. Like humans, Australopithecus afarensis and Homo erectus exhibit shallow uncinate processes, whereas A. sediba resembles more arboreal taxa, but not fully suspensory primates. Suspensory primates exhibit the most pronounced uncinates, likely to maintain visual field stabilization. East African hominins exhibit reduced uncinate processes compared with African apes and A. sediba, likely signaling different degrees of neck motility and modes of locomotion. Although soft tissues constrain neck flexibility beyond limits suggested by osteology alone, this study may assist in modeling cervical kinematics and positional behaviors in extinct taxa. © 2018 Wiley Periodicals, Inc.

  3. Did trichromatic color vision and red hair color coevolve in primates?

    Science.gov (United States)

    Kamilar, Jason M; Heesy, Christopher P; Bradley, Brenda J

    2013-07-01

    Reddish pelage and red hair ornaments have evolved many times, independently, during primate evolution. It is generally assumed that these red-coat phenotypes, like red skin phenotypes, play a role in sociosexual signaling and, thus evolved in tandem with conspecific color vision. This study examines the phylogenetic distribution of color vision and pelage coloration across the primate order to ask: (1) did red pelage and trichromacy coevolve; or (2) did trichromacy evolve first, and then subsequently red pelage evolved as an exaptation? We collected quantitative, color-corrected photographic color data for 142 museum research skins from 92 species representing 41 genera spanning all major primate lineages. For each species, we quantified the ratio of Red/Green values (from a RGB color model) at 20 anatomical landmarks. For these same species, we compiled data on color vision type (routine trichromatic, polymorphic, routine dichromatic, monochromatic) and data on variables that potentially covary with visual system (VS) and coloration, including activity pattern and body mass dimorphism (proxy for sexual selection). We also considered whether the long-term storage of research skins might influence coloration. Therefore, we included the time since the specimen was collected as an additional predictor. Analyzing the data with phylogenetic generalized least squares models, we found that the amount of red hair present in primates is associated with differences in VSs, but not in the direction expected. Surprisingly, trichromatic primate species generally exhibited less red hair compared to red-green colorblind species. Thus, our results do not support the general assumption that color vision and red pelage coloration are a coevolutionary product of sociosexual signaling in primates. In addition, we did not find an effect of activity pattern, body mass dimorphism, or time since collection on the redness of primate hair. Our results have important implications for the

  4. Jean-Jacques Petter. Primates

    Directory of Open Access Journals (Sweden)

    Bruno Simmen

    2010-12-01

    Full Text Available Voici un magnifique ouvrage grand format sur les Primates dont l’auteur principal est le regretté Jean Jacques Petter, l’un des spécialistes historiques des prosimiens de Madagascar. Ce livre, publié à titre posthume, a une histoire que nous découvrons dans la préface d’Yves Coppens. A l’origine pensé et rédigé par Jean-Jacques Petter, qui a été professeur au Muséum National d’Histoire Naturelle, l’ouvrage interrompu à sa mort en 2002 a été remis en chantier sous l’impulsion de sa femme Arlet...

  5. [Relation Between Stress During Pregnancy and Spontaneous Preterm Birth].

    Science.gov (United States)

    Ortiz Martínez, Roberth Alirio; Castillo, Alejandro

    2016-01-01

    Preterm birth occurs before 37 completed weeks, its causes are multifactorial and vary according to the gestational age, ethnicity and geographical context. Although several medical/social factors have been clearly identified, over 50% of cases are unknown or unclear; however, psychopathological components emerge as potentially important risk factors. To determine the relationship between the presence of stress during pregnancy and spontaneous preterm birth. Through a study of cases and controls in a level III hospital, with a sample of 360 patients during the period from March to November of 2013, where sociodemographic characteristics were collected. In addition, they were applied scales social adjustment, coping strategies and social support. Logistic regression models were developed; psychological, biological and social. Based on the significant variables in each of these generated a final one. The final model was found that stress during pregnancy increases the odds of spontaneous preterm birth 1.91 times (adjusted OR=2.91; 95%CI, 1.67-5.08; P<.05). Other significant variables were: history of preterm delivery, unplanned pregnancy, no emotional support, rural residence, inadequate prenatal care and non-stable partner. The findings support the hypothesis that stress during pregnancy is associated with spontaneous preterm delivery. Copyright © 2015 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  6. Optimizing Nutrition in Preterm Infants

    Directory of Open Access Journals (Sweden)

    Bai-Horng Su

    2014-02-01

    Full Text Available Extrauterine growth restriction is common in very preterm infants. The incidence in very-low-birth-weight infants ranges between 43% and 97% in various centers, with a wide variability due to the use of different reference growth charts and nonstandard nutritional strategies. Extrauterine growth restriction is associated with an increased risk of poor neurodevelopmental outcome. Inadequate postnatal nutrition is an important factor contributing to growth failure, as most very preterm infants experience major protein and energy deficits during neonatal intensive care unit hospitalization. First-week protein and energy intake are associated with 18-month developmental outcomes in very preterm infants. Early aggressive nutrition, including parenteral and enteral, is well tolerated in the very preterm infant and is effective in improving growth. Continued provision of appropriate nutrition (fortified human milk or premature formula is important throughout the growing care during the hospitalization. After discharge, exclusively breast-fed infants require additional supplementation. If formula-fed, nutrient-enriched postdischarge formula should be continued for approximately 9 months corrected age. Supplementation of the preterm formulas with protein would increase the protein/energy ratio (3 g/100 kcal, leading to increased lean mass with relatively decreased fat deposition. Further research is required to optimize the nutritional needs of preterm infants and to evaluate the effects of nutritional interventions on long-term growth, neurodevelopment, and other health outcomes.

  7. Comparison of autologous cell therapy and granulocyte-colony stimulating factor (G-CSF) injection vs. G-CSF injection alone for the treatment of acute radiation syndrome in a non-human primate model

    International Nuclear Information System (INIS)

    Bertho, Jean-Marc; Frick, Johanna; Prat, Marie; Demarquay, Christelle; Dudoignon, Nicolas; Trompier, Francois; Gorin, Norbert-Claude; Thierry, Dominique; Gourmelon, Patrick

    2005-01-01

    Purpose: To compare the efficacy of autologous cell therapy after irradiation combined with granulocyte-colony stimulating factor (G-CSF) injections with G-CSF treatment alone in a heterogeneous model of irradiation representative of an accidental situation. Material and Methods: Non-human primates were irradiated at 8.7 Gy whole-body dose with the right arm shielded to receive 4.8 Gy. The first group of animals received G-CSF (lenograstim) injections starting 6 h after irradiation, and a second group received a combination of G-CSF (lenograstim) injections and autologous expanded hematopoietic cells. Animals were followed up for blood cell counts, circulating progenitors, and bone marrow cellularity. Results: No significant differences were seen between the two treatment groups, whatever the parameter observed: time to leukocyte or platelet recovery and duration and severity of aplasia. Conclusion: Our results indicated that identical recovery kinetic was observed when irradiated animals are treated with G-CSF independently of the reinjection of ex vivo expanded autologous hematopoietic cells. Thus G-CSF injections might be chosen as a first-line therapeutic strategy in the treatment of accidental acute radiation victims

  8. Role of perceived stress in the occurrence of preterm labor and preterm birth among urban women.

    Science.gov (United States)

    Seravalli, Laura; Patterson, Freda; Nelson, Deborah B

    2014-01-01

    This study examined whether prenatal perceived stress levels during pregnancy were associated with preterm labor or preterm birth. Perceived stress levels were measured at 16 weeks' gestation or less and between 20 and 24 weeks' gestation in a sample of 1069 low-income pregnant women attending Temple University prenatal care clinics. Scores were averaged to create a single measure of prenatal stress. Preterm birth was defined as the occurrence of a spontaneous birth prior to 37 weeks' gestation. Preterm labor was defined as the occurrence of regular contractions between 20 and 37 weeks' gestation that were associated with changes in the cervix. Independent of potential confounding factors, prenatal perceived stress was not associated with preterm labor (odds ratio [OR], 1.10; 95% confidence interval [CI], 0.69-1.78; P = .66); however, prenatal stress trended toward an association with preterm birth (OR, 1.49; 95% CI, 1.00-2.23; P = .05). The strongest predictor of preterm labor was a history of preterm labor in a prior pregnancy. Women with a history of preterm labor were 2 times more likely to experience preterm labor in the current pregnancy than women who did not have a preterm labor history (OR, 2.16; 95% CI, 1.05-4.41; P = .04). Historical risk factors for preterm birth, such as African American race, a history of abortion, or a history of preterm birth, were not related to preterm labor. The strongest predictor of preterm birth was having a history of preterm birth in a prior pregnancy (OR, 2.55; 95% CI, 1.54-4.24; P stress levels may be a risk factor for preterm birth independent of preterm labor; however, prenatal stress was not associated with preterm labor. Risk factors for preterm labor may be different from those of preterm birth. © 2014 by the American College of Nurse-Midwives.

  9. Use of metabolomics for the identification and validation of clinical biomarkers for preterm birth: Preterm SAMBA

    OpenAIRE

    Cecatti, Jose G.; Souza, Renato T.; Sulek, Karolina; Costa, Maria L.; Kenny, Louise C.; McCowan, Lesley M. E.; Pacagnella, Rodolfo C.; Villas-Boas, Silas G.; Mayrink, Jussara; Passini, Renato; Franchini, Kleber G.; Baker, Philip N.

    2016-01-01

    Background: Spontaneous preterm birth is a complex syndrome with multiple pathways interactions determining its occurrence, including genetic, immunological, physiologic, biochemical and environmental factors. Despite great worldwide efforts in preterm birth prevention, there are no recent effective therapeutic strategies able to decrease spontaneous preterm birth rates or their consequent neonatal morbidity/mortality. The Preterm SAMBA study will associate metabolomics technologies to identi...

  10. Personality, social hierarchy and hormones in primates

    OpenAIRE

    KONEČNÁ, Martina

    2010-01-01

    This thesis deals with two main issues: personality (stable individual differences in behavior) and behavioral endocrinology (or socioendocrinology) in nonhuman primates. The first part of the thesis comprises of two primate personality studies of two species: Hanuman langurs and Barbary macaques. Two basic methods of animal personality research (behavioral coding and trait rating) were compared. Stability of personality assessments has been demonstrated. Social rank of individuals was used t...

  11. Intake of probiotic food and risk of spontaneous preterm delivery.

    Science.gov (United States)

    Myhre, Ronny; Brantsæter, Anne Lise; Myking, Solveig; Gjessing, Håkon Kristian; Sengpiel, Verena; Meltzer, Helle Margrete; Haugen, Margaretha; Jacobsson, Bo

    2011-01-01

    Preterm delivery represents a substantial problem in perinatal medicine worldwide. Current knowledge on potential influences of probiotics in food on pregnancy complications caused by microbes is limited. We hypothesized that intake of food with probiotics might reduce pregnancy complications caused by pathogenic microorganisms and, through this, reduce the risk of spontaneous preterm delivery. This study was performed in the Norwegian Mother and Child Cohort on the basis of answers to a food-frequency questionnaire. We studied intake of milk-based products containing probiotic lactobacilli and spontaneous preterm delivery by using a prospective cohort study design (n = 950 cases and 17,938 controls) for the pregnancy outcome of spontaneous preterm delivery (delivery were associated with any intake of milk-based probiotic products in an adjusted model [odds ratio (OR): 0.857; 95% CI: 0.741, 0.992]. By categorizing intake into none, low, and high intakes of the milk-based probiotic products, a significant association was observed for high intake (OR: 0.820; 95% CI: 0.681, 0.986). Women who reported habitual intake of probiotic dairy products had a reduced risk of spontaneous preterm delivery.

  12. Grooming Up the Hierarchy: The Exchange of Grooming and Rank-Related Benefits in a New World Primate

    OpenAIRE

    Tiddi, Barbara; Aureli, Filippo; Schino, Gabriele

    2012-01-01

    Seyfarth’s model assumes that female primates derive rank-related benefits from higher-ranking females in exchange for grooming. As a consequence, the model predicts females prefer high-ranking females as grooming partners and compete for the opportunity to groom them. Therefore, allogrooming is expected to be directed up the dominance hierarchy and to occur more often between females with adjacent ranks. Although data from Old World primates generally support the model, studies o...

  13. Early gradual feeding with bovine colostrum improves gut function and NEC resistance relative to infant formula in preterm pigs

    DEFF Research Database (Denmark)

    Shen, René L.; Thymann, Thomas; Østergaard, Mette V.

    2015-01-01

    It is unclear when and how to start enteral feeding for preterm infants when mother’s milk is not available. We hypothesized that early and slow advancement with either formula or bovine colostrum stimulates gut maturation and prevents necrotizing enterocolitis (NEC) in preterm pigs, used as models...... intestinal permeability, compared with BC pigs (all P Early feeding with formula induces intestinal dysfunction whereas bovine colostrum supports gut maturation when mother’s milk is absent during the first week after preterm birth...

  14. Assessment of tropism and effectiveness of new primate-derived hybrid recombinant AAV serotypes in the mouse and primate retina.

    Directory of Open Access Journals (Sweden)

    Peter Charbel Issa

    Full Text Available Adeno-associated viral vectors (AAV have been shown to be safe in the treatment of retinal degenerations in clinical trials. Thus, improving the efficiency of viral gene delivery has become increasingly important to increase the success of clinical trials. In this study, structural domains of different rAAV serotypes isolated from primate brain were combined to create novel hybrid recombinant AAV serotypes, rAAV2/rec2 and rAAV2/rec3. The efficacy of these novel serotypes were assessed in wild type mice and in two models of retinal degeneration (the Abca4(-/- mouse which is a model for Stargardt disease and in the Pde6b(rd1/rd1 mouse in vivo, in primate tissue ex-vivo, and in the human-derived SH-SY5Y cell line, using an identical AAV2 expression cassette. We show that these novel hybrid serotypes can transduce retinal tissue in mice and primates efficiently, although no more than AAV2/2 and rAAV2/5 serotypes. Transduction efficiency appeared lower in the Abca4(-/- mouse compared to wild type with all vectors tested, suggesting an effect of specific retinal diseases on the efficiency of gene delivery. Shuffling of AAV capsid domains may have clinical applications for patients who develop T-cell immune responses following AAV gene therapy, as specific peptide antigen sequences could be substituted using this technique prior to vector re-treatments.

  15. Evidence for catch-up in cognition and receptive vocabulary among adolescents born very preterm.

    Science.gov (United States)

    Luu, Thuy Mai; Vohr, Betty R; Allan, Walter; Schneider, Karen C; Ment, Laura R

    2011-08-01

    Very preterm adolescents display persistent deficits in neuropsychological functions. To compare cognitive and language outcomes at 16 years and cognitive and receptive vocabulary trajectories throughout school years between very preterm and term children and to determine child and family factors associated with better developmental trajectories. At 8, 12, and 16 years, 322 very preterm children with birth weights of 1250 g or less and 41 term children had cognitive and language testing. Hierarchical growth-curve modeling was used to delineate the differences in cognitive and receptive vocabulary development between participants. Cluster analyses allowed for the characterization of very preterm children with different patterns of cognitive and receptive vocabulary development. At 16 years, very preterm adolescents had deficits in general cognition and higher-order language skills (phonological awareness and phonemic decoding) compared with term peers. Although the between-group difference in cognitive scores remained stable from 8 to 16 years, very preterm children demonstrated catch-up gains in receptive vocabulary during the same period. Moreover, subgroups of very preterm children displayed developmental trajectories in cognition similar to term children (55% on the vocabulary and 46% on the block-design subtests). These children had lower rates of neurosensory impairment and mothers with higher education and were from an ethnic nonminority. Significant catch-up in receptive vocabulary is observed by the age of 16 years among very preterm children compared to term peers. The absence of neurosensory impairment and residing in a favorable socioeconomic milieu are associated with the most optimal developmental trajectories.

  16. Inhibition of gingipains prevents Porphyromonas gingivalis-induced preterm birth and fetal death in pregnant mice.

    Science.gov (United States)

    Takii, Ryosuke; Kadowaki, Tomoko; Tsukuba, Takayuki; Yamamoto, Kenji

    2018-04-05

    Accumulating epidemiological evidence indicates that infection with Porphyromonas gingivalis which is a major periodontal pathogen, causes preterm birth and low birth weight. However, virulence factors of P. gingivalis responsible for preterm birth/low birth weight remain to be elucidated. In this study, using P. gingivalis-infected pregnant mice as an in vivo model, we investigated whether gingipains-cysteine proteinases produced by P. gingivalis-affect preterm birth and low birth weight. We found that intravenous infection of pregnant mice with P. gingivalis induced higher accumulation of the bacterium in the placenta than that in other organs. Compared to infection with P. gingivalis wild-type, infection with a gingipain-deficient P. gingivalis mutant KDP136 led to significant reduction in preterm birth and pregnancy loss. Although repetitive low-level infections of P. gingivalis failed to induce preterm birth and fetal death, it induced suppressive effects on IFN-γ production. Therapeutically, treatment with ginginpain inhibitors prevented fetal death and preterm birth caused by P. gingivalis infection and resulted in recovery of IFN-γ suppression caused by repetitive chronic P. gingivalis infection. These results indicate that gingipains are major virulence factors of P. gingivalis responsible for preterm birth/low birth, and gingipain inhibitors may be useful not only as a therapeutic agent for periodontal diseases, but also as a preventive medicine for preterm birth/low birth weight. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. Maternal race and intergenerational preterm birth recurrence.

    Science.gov (United States)

    Smid, Marcela C; Lee, Jong Hyung; Grant, Jacqueline H; Miles, Gandarvaka; Stoddard, Gregory J; Chapman, Derek A; Manuck, Tracy A

    2017-10-01

    Preterm birth is a complex disorder with a heritable genetic component. Studies of primarily White women born preterm show that they have an increased risk of subsequently delivering preterm. This risk of intergenerational preterm birth is poorly defined among Black women. Our objective was to evaluate and compare intergenerational preterm birth risk among non-Hispanic Black and non-Hispanic White mothers. This was a population-based retrospective cohort study, using the Virginia Intergenerational Linked Birth File. All non-Hispanic Black and non-Hispanic White mothers born in Virginia 1960 through 1996 who delivered their first live-born, nonanomalous, singleton infant ≥20 weeks from 2005 through 2009 were included. We assessed the overall gestational age distribution between non-Hispanic Black and White mothers born term and preterm (preterm (preterm birth, 34-36 weeks; and early preterm birth, preterm birth among all eligible births; and (2) suspected spontaneous preterm birth among births to women with medical complications (eg, diabetes, hypertension, preeclampsia and thus higher risk for a medically indicated preterm birth). Multivariable logistic regression was used to estimate odds of preterm birth and spontaneous preterm birth by maternal race and maternal gestational age after adjusting for confounders including maternal education, maternal age, smoking, drug/alcohol use, and infant gender. Of 173,822 deliveries captured in the intergenerational birth cohort, 71,676 (41.2%) women met inclusion criteria for this study. Of the entire cohort, 30.0% (n = 21,467) were non-Hispanic Black and 70.0% were non-Hispanic White mothers. Compared to non-Hispanic White mothers, non-Hispanic Black mothers were more likely to have been born late preterm (6.8% vs 3.7%) or early preterm (2.8 vs 1.0%), P preterm were not at an increased risk of early or late preterm delivery compared to non-Hispanic White mothers born term. The risk of early preterm birth was most

  18. Adaptive cultural transmission biases in children and nonhuman primates.

    Science.gov (United States)

    Price, Elizabeth E; Wood, Lara A; Whiten, Andrew

    2017-08-01

    Comparative and evolutionary developmental analyses seek to discover the similarities and differences between humans and non-human species that might illuminate both the evolutionary foundations of our nature that we share with other animals, and the distinctive characteristics that make human development unique. As our closest animal relatives, with whom we last shared common ancestry, non-human primates have been particularly important in this endeavour. Such studies have focused on social learning, traditions, and culture, and have discovered much about the 'how' of social learning, concerned with key underlying processes such as imitation and emulation. One of the core discoveries is that the adaptive adjustment of social learning options to different contexts is not unique to human, therefore multiple new strands of research have begun to focus on more subtle questions about when, from whom, and why such learning occurs. Here we review illustrative studies on both human infants and young children and on non-human primates to identify the similarities shared more broadly across the primate order, and the apparent specialisms that distinguish human development. Adaptive biases in social learning discussed include those modulated by task comprehension, experience, conformity to majorities, and the age, skill, proficiency and familiarity of potential alternative cultural models. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  19. Cerebral oxygenation in the preterm neonate

    NARCIS (Netherlands)

    Dix, L.M.L.

    2017-01-01

    Although survival rates of preterm infants are improving, preterm birth is still associated with significant morbidity.The brain is one of the most vulnerable organs in preterm infants. Neonatal brain injury can have a large impact on the quality of life. Monitoring the immature brain is therefore

  20. Spontaneous preterm birth : prevention, management and outcome

    NARCIS (Netherlands)

    Vermeulen, Gustaaf Michiel

    1999-01-01

    Preterm birth (birth before 37 completed weeks of pregnancy) is a major cause of perinatal morbidity and mortality. Strategies to prevent and adequately treat preterm labour, in order to postpone birth and to identify risk factors for neonatal damage due to preterm birth, have to be developed by

  1. Effects of the distribution of female primates on the number of males.

    Directory of Open Access Journals (Sweden)

    Laurel Mariah Carnes

    Full Text Available The spatiotemporal distribution of females is thought to drive variation in mating systems, and hence plays a central role in understanding animal behavior, ecology and evolution. Previous research has focused on investigating the links between female spatiotemporal distribution and the number of males in haplorhine primates. However, important questions remain concerning the importance of spatial cohesion, the generality of the pattern across haplorhine and strepsirrhine primates, and the consistency of previous findings given phylogenetic uncertainty. To address these issues, we examined how the spatiotemporal distribution of females influences the number of males in primate groups using an expanded comparative dataset and recent advances in bayesian phylogenetic and statistical methods. Specifically, we investigated the effect of female distributional factors (female number, spatial cohesion, estrous synchrony, breeding season duration and breeding seasonality on the number of males in primate groups. Using bayesian approaches to control for uncertainty in phylogeny and the model of trait evolution, we found that the number of females exerted a strong influence on the number of males in primate groups. In a multiple regression model that controlled for female number, we found support for temporal effects, particularly involving female estrous synchrony: the number of males increases when females are more synchronously receptive. Similarly, the number of males increases in species with shorter birth seasons, suggesting that greater breeding seasonality makes defense of females more difficult for male primates. When comparing primate suborders, we found only weak evidence for differences in traits between haplorhines and strepsirrhines, and including suborder in the statistical models did not affect our conclusions or give compelling evidence for different effects in haplorhines and strepsirrhines. Collectively, these results demonstrate that

  2. Kinetic modeling of [18F]VAT, a novel radioligand for positron emission tomography imaging vesicular acetylcholine transporter in non-human primate brain.

    Science.gov (United States)

    Jin, Hongjun; Yue, Xuyi; Liu, Hui; Han, Junbin; Flores, Hubert; Su, Yi; Parsons, Stanley M; Perlmutter, Joel S; Tu, Zhude

    2018-01-06

    Molecular imaging of vesicular acetylcholine transporter (VAChT) in the brain provides an important cholinergic biomarker for the pathophysiology and treatment of dementias including Alzheimer's disease. In this study, kinetics modeling methods were applied and compared for quantifying regional brain uptake of the VAChT-specific positron emission tomography radiotracer, ((-)-(1-(-8-(2-fluoroethoxy)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)piperidin-4-yl)(4-fluorophenyl)-methanone) ([ 18 F]VAT) in macaques. Total volume distribution (V T ) estimates were compared for one-tissue compartment model (1TCM), two-tissue compartment model (2TCM), Logan graphic analysis (LoganAIF) and multiple linear analysis (MA1) with arterial blood input function using data from three macaques. Using the cerebellum-hemispheres as the reference region with data from seven macaques, three additional models were compared: reference tissue model (RTM), simplified RTM (SRTM), and Logan graphic analysis (LoganREF). Model selection criterion indicated that a) 2TCM and SRTM were the most appropriate kinetics models for [ 18 F]VAT; and b) SRTM was strongly correlated with 2TCM (Pearson's coefficients r > 0.93, p VAT has good reproducibility and reliability (TRV  0.72). These studies demonstrate [ 18 F]VAT is a promising VAChT positron emission tomography tracer for quantitative assessment of VAChT levels in the brain of living subjects. © 2018 International Society for Neurochemistry.

  3. Prediction of imminent preterm delivery in women with preterm premature rupture of membranes.

    Science.gov (United States)

    Park, Kyo Hoon; Lee, Sung Youn; Kim, Shi Nae; Jeong, Eun Ha; Oh, Kyung Joon; Ryu, Aeli

    2011-11-16

    To develop a model based on non-invasive clinical parameters to predict the probability of imminent preterm delivery (delivery within 48 h) in women with preterm premature rupture of membranes (PPROM), and to determine if additional invasive test results improve the prediction of imminent delivery based on the non-invasive model. Transvaginal ultrasonographic assessment of cervical length was performed and maternal serum C-reactive protein (CRP) and white blood cell (WBC) count were determined immediately after amniocentesis in 102 consecutive women with PPROM at 23-33+6 weeks. Amniotic fluid (AF) obtained by amniocentesis was cultured and interleukin-6 (IL-6) levels and WBC counts were determined. Serum CRP, cervical length, and gestational age were chosen for the non-invasive model (model 1), which has an area under the curve (AUC) of 0.804. When adding AF IL-6 as an invasive marker to the non-invasive model, serum CRP was excluded from the final model (model 2) as not significant, whereas AF IL-6, cervical length, and gestational age remained in model 2. No significant difference in AUC was found between models 1 and 2. The non-invasive model based on cervical length, gestational age, and serum CRP is highly predictive of imminent delivery in women with PPROM. However, invasive test results did not add predictive information to the non-invasive model in this setting.

  4. A comparison of early neonatal deaths among preterm infants with ...

    African Journals Online (AJOL)

    user

    multivariate logistic regression model to identify obstetric determinants amongst deaths in neonates that were ... multivariate regression analysis, poor Apgar score was associated with six-fold odds of RDS. More preterm ... remains a significant perinatal challenge, with pre- term babies accounting for 5-25% of all deliveries.

  5. Cerebral NIRS patterns in late preterm and very preterm infants becoming late preterm.

    Science.gov (United States)

    Grometto, Alice; Pizzo, Benedetta; Strozzi, Maria Chiara; Gazzolo, Francesca; Gazzolo, Diego

    2017-11-20

    Near Infrared Spectroscopy (NIRS) has been proposed as a useful, noninvasive monitoring technique providing reliable information about central nervous system (CNS) oximetry and function. Recently, brain damage has been reconsidered as a dynamic process evolving over the weeks of gestation. We therefore investigated NIRS cerebral pattern differences between healthy late preterm infants (LPTo) and very preterm infants becoming late preterm (LPT). We conducted an observational study in 40 healthy late preterm infants, matched for gestational age at monitoring, of whom 20 where LPTo and 20 LPT. Clinical, diagnostic and laboratory monitoring procedures and cerebral oximetry (crSO 2 ) and function (cFTOE) were recorded on admission into the study. No significant differences (p > .05, for all) were found between groups regarding clinical, diagnostic or laboratory parameters. Higher crSO 2 and lower cFTOE (p preterm infants becoming LPT. Future studies correlating NIRS variables and long-term neurological outcome in LPT are needed to elucidate the concept of dynamic brain damage pathogenesis.

  6. Opium use during pregnancy and risk of preterm delivery: A population-based cohort study.

    Science.gov (United States)

    Maghsoudlou, Siavash; Cnattingius, Sven; Montgomery, Scott; Aarabi, Mohsen; Semnani, Shahriar; Wikström, Anna-Karin; Bahmanyar, Shahram

    2017-01-01

    Use of narcotic or "recreational" drugs has been associated with adverse pregnancy outcomes such as preterm delivery. However, the associations might be confounded by other factors related to high-risk behaviours. This is the first study to investigate the association between traditional opium use during pregnancy and risk of preterm delivery. We performed a population-based cohort study in the rural areas of the Golestan province, Iran between 2008 and 2010. We randomly selected 920 women who used (usually smoked) opium during pregnancy and 920 women who did not. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the associations between the opium use during pregnancy and preterm delivery and adjustment was made for potential confounding factors. This study shows compared with non-use of opium and tobacco, use of only opium during pregnancy was associated with an increased risk of preterm delivery (OR = 1.56; 95% CI 1.05-2.32), and the risk was more than two-fold increased among dual users of opium and tobacco (OR = 2.31; 95% CI 1.37-3.90). We observed that opium use only was associated with a doubled risk for preterm caesarean delivery (OR = 2.05; 95% CI 1.10-3.82) but not for preterm vaginal delivery (OR = 1.25; 95% CI 0.75-2.07). Dual use of opium and tobacco was associated with a substantially increased risk of vaginal preterm delivery (OR = 2.58; 95% CI 1.41-4.71). Opium use during pregnancy among non-tobacco smokers is associated with an increased risk of preterm caesarean delivery, indicating an increased risk of a compromised foetus before or during labour. Women who use both opium and smoked during pregnancy have an increased risk of preterm vaginal delivery, indicating an increased risk of spontaneous preterm delivery.

  7. The heritability of preterm delivery.

    Science.gov (United States)

    Ward, Kenneth; Argyle, VeeAnn; Meade, Mary; Nelson, Lesa

    2005-12-01

    To study the heritability of preterm delivery. Women who delivered a singleton infant at less than 36 weeks of gestation were asked about their family history. Twenty-eight families were identified in which the proband had at least five first- or second-degree relatives with preterm delivery. An extensive genealogy database (GenDB) was constructed using more than 9,000 genealogy sources in the public domain (records before 1929). GenDB documents the relationships between more than 17.5 million ancestors and 3.5 million descendants of approximately 10,000 individuals who moved to Utah in the mid 1800s. This database was searched for the names, birth dates, and birthplaces of the four grandparents for each of the 28 probands. Pairwise coefficients of kinship were determined for the 93 preterm delivery grandparents identified, and for sets of 100 individuals born in the 1920s who were randomly selected from the population database. Probands had a mean of 3.3 grandparents included in this database. The average coefficient of kinship for controls was 1.5 x 10(6) (standard deviation = 0.6 x 10(6)). This measure agrees with previous calculations for the Utah population. The coefficient of kinship for familial preterm delivery grandparents was more than 50 standard deviations higher (3.4 x 10(5) [P < .001]). This study confirms the familial nature of preterm delivery. On average, gravidae randomly selected from our population are 23rd degree relatives, while these preterm delivery probands are eighth-degree relatives. A genome-wide scan using these affected families is underway.

  8. Caffeine therapy in preterm infants

    Science.gov (United States)

    Abdel-Hady, Hesham; Nasef, Nehad; Shabaan, Abd Elazeez; Nour, Islam

    2015-01-01

    Caffeine is the most commonly used medication for treatment of apnea of prematurity. Its effect has been well established in reducing the frequency of apnea, intermittent hypoxemia, and extubation failure in mechanically ventilated preterm infants. Evidence for additional short-term benefits on reducing the incidence of bronchopulmonary dysplasia and patent ductus arteriosus has also been suggested. Controversies exist among various neonatal intensive care units in terms of drug efficacy compared to other methylxanthines, dosage regimen, time of initiation, duration of therapy, drug safety and value of therapeutic drug monitoring. In the current review, we will summarize the available evidence for the best practice in using caffeine therapy in preterm infants. PMID:26566480

  9. Primate disease ecology in comparative and theoretical perspective.

    Science.gov (United States)

    Nunn, Charles L

    2012-06-01

    Infectious disease plays a major role in the lives of wild primates, and the past decade has witnessed significant strides in our understanding of primate disease ecology. In this review, I briefly describe some key findings from phylogenetic comparative approaches, focusing on analyses of parasite richness that use the Global Mammal Parasite Database. While these studies have provided new answers to fundamental questions, new questions have arisen, including questions about the underlying epidemiological mechanisms that produce the broader phylogenetic patterns. I discuss two examples in which theoretical models have given us new traction on these comparative questions. First, drawing on findings of a positive association between range use intensity and the richness of helminth parasites, we developed a spatially explicit agent-based model to investigate the underlying drivers of this pattern. From this model, we are gaining deeper understanding of how range use intensity results in greater exposure to parasites, thus producing higher prevalence in the simulated populations-and, plausibly, higher parasite richness in comparative analyses. Second, I show how a model of disease spread on social networks provides solid theoretical foundations for understanding the effects of sociality and group size on parasitism across primate species. This study further revealed that larger social groups are more subdivided, which should slow the spread of infectious diseases. This effect could offset the increased disease risk expected in larger social groups, which has yet to receive strong empirical support in our comparative analyses. In addition to these examples, I discuss the need for more meta-analyses of individual-level phenomena documented in the field, and for greater linkage between theoretical modeling and field research. © 2012 Wiley Periodicals, Inc.

  10. Racial/ethnic differences in preterm perinatal outcomes.

    Science.gov (United States)

    Wallace, Maeve E; Mendola, Pauline; Kim, Sung Soo; Epps, Nikira; Chen, Zhen; Smarr, Melissa; Hinkle, Stefanie N; Zhu, Yeyi; Grantz, Katherine L

    2017-03-01

    Racial disparities in preterm birth and infant death have been well documented. Less is known about racial disparities in neonatal morbidities among infants who are born at death among infants who are born preterm differs by maternal race. A retrospective cohort design included medical records from preterm deliveries of 19,325 black, Hispanic, and white women in the Consortium on Safe Labor. Sequentially adjusted Poisson models with generalized estimating equations estimated racial differences in the risk for neonatal morbidities and death, controlling for maternal demographics, health behaviors, and medical history. Sex differences between and within race were examined. Black preterm infants had an elevated risk for perinatal death, but there was no difference in risk for neonatal death across racial groups. Relative to white infants, black infants were significantly more likely to experience sepsis (9.1% vs 13.6%), peri- or intraventricular hemorrhage (2.6% vs 3.3%), intracranial hemorrhage (0.6% vs 1.8%), and retinopathy of prematurity (1.0% vs 2.6%). Hispanic and white preterm neonates had similar risk profiles. In general, female infants had lower risk relative to male infants, with white female infants having the lowest prevalence of a composite indicator of perinatal death or any morbidity across all races (30.9%). Differences in maternal demographics, health behaviors, and medical history did little to influence these associations, which were robust to sensitivity analyses of pregnancy complications as potential underlying mechanisms. Preterm infants were at similar risk for neonatal death, regardless of race; however, there were notable racial disparities and sex differences in rare, but serious, adverse neonatal morbidities. Published by Elsevier Inc.

  11. A Role for the Liver in Parturition and Preterm Birth.

    Science.gov (United States)

    Mawson, Anthony R

    Neither the mechanisms of parturition nor the pathogenesis of preterm birth are well understood. Poor nutritional status has been suspected as a major causal factor, since vitamin A concentrations are low in preterm infants. However, even large enteral doses of vitamin A from birth fail to increase plasma concentrations of vitamin A or improve outcomes in preterm and/or extremely low birthweight infants. These findings suggest an underlying impairment in the secretion of vitamin A from the liver, where about 80% of the vitamin is stored. Vitamin A accumulates in the liver and breast during pregnancy in preparation for lactation. While essential in low concentration for multiple biological functions, vitamin A in higher concentration can be pro-oxidant, mutagenic, teratogenic and cytotoxic, acting as a highly surface-active, membrane-seeking and destabilizing compound. Regarding the mechanism of parturition, it is conjectured that by nine months of gestation the hepatic accumulation of vitamin A (retinol) from the liver is such that mobilization and secretion are impaired to the point where stored vitamin A compounds in the form of retinyl esters and retinoic acid begin to spill or leak into the circulation, resulting in amniotic membrane destabilization and the initiation of parturition. If, however, the accumulation and spillage of stored retinoids reaches a critical threshold prior to nine months, e.g., due to cholestatic liver disease, which is common in mothers of preterm infants, the increased retinyl esters and/or retinoic acid rupture the fetal membranes, inducing preterm birth and its complications, including retinopathy, necrotizing enterocolitis and bronchopulmonary dysplasia. Subject to testing, the model suggests that measures taken prior to and during pregnancy to improve liver function could reduce the risk of adverse birth outcomes, including preterm birth.

  12. The nociceptin/orphanin FQ (NOP) receptor antagonist J-113397 enhances the effects of levodopa in the MPTP-lesioned nonhuman primate model of Parkinson's disease

    NARCIS (Netherlands)

    Visanji, Naomi P.; de Bie, Rob M. A.; Johnston, Tom H.; McCreary, Andrew C.; Brotchie, Jonathan M.; Fox, Susan H.

    2008-01-01

    The anti-parkinsonian and levodopa-sparing potential of the nociceptin/orphanin FQ receptor (NOP) antagonist J-113397 has been demonstrated in rodent models of Parkinson's disease. Here, we describe the levodopa-sparing potential of J-113397 in MPTP-lesioned marmosets. Coadministration of J-113397

  13. Three-dimensional primate molar enamel thickness.

    Science.gov (United States)

    Olejniczak, Anthony J; Tafforeau, Paul; Feeney, Robin N M; Martin, Lawrence B

    2008-02-01

    Molar enamel thickness has played an important role in the taxonomic, phylogenetic, and dietary assessments of fossil primate teeth for nearly 90 years. Despite the frequency with which enamel thickness is discussed in paleoanthropological discourse, methods used to attain information about enamel thickness are destructive and record information from only a single plane of section. Such semidestructive planar methods limit sample sizes and ignore dimensional data that may be culled from the entire length of a tooth. In light of recently developed techniques to investigate enamel thickness in 3D and the frequent use of enamel thickness in dietary and phylogenetic interpretations of living and fossil primates, the study presented here aims to produce and make available to other researchers a database of 3D enamel thickness measurements of primate molars (n=182 molars). The 3D enamel thickness measurements reported here generally agree with 2D studies. Hominoids show a broad range of relative enamel thicknesses, and cercopithecoids have relatively thicker enamel than ceboids, which in turn have relatively thicker enamel than strepsirrhine primates, on average. Past studies performed using 2D sections appear to have accurately diagnosed the 3D relative enamel thickness condition in great apes and humans: Gorilla has the relatively thinnest enamel, Pan has relatively thinner enamel than Pongo, and Homo has the relatively thickest enamel. Although the data set presented here has some taxonomic gaps, it may serve as a useful reference for researchers investigating enamel thickness in fossil taxa and studies of primate gnathic biology.

  14. Associations Among Perinatal Factors and Age of Achievement of Full Oral Feeding in Very Preterm Infants

    Directory of Open Access Journals (Sweden)

    Yea-Shwu Hwang

    2013-10-01

    Conclusion: A regression model incorporating significant predictors to estimate the PMA of full oral feeding in very preterm infants was suggested. It could enhance communication between health professionals and parents about the feeding progress of infants born very prematurely.

  15. Socioeconomic inequality in preterm birth in four Brazilian birth cohort studies

    Directory of Open Access Journals (Sweden)

    Ana Daniela Izoton de Sadovsky

    2018-01-01

    Conclusion: In a final model, economic inequities resulting from income were found in relation to preterm births only in 2004, although a higher prevalence of prematurity continued to be observed in the poorest population, in all the studies.

  16. Anatomical network analysis shows decoupling of modular lability and complexity in the evolution of the primate skull.

    Science.gov (United States)

    Esteve-Altava, Borja; Boughner, Julia C; Diogo, Rui; Villmoare, Brian A; Rasskin-Gutman, Diego

    2015-01-01

    Modularity and complexity go hand in hand in the evolution of the skull of primates. Because analyses of these two parameters often use different approaches, we do not know yet how modularity evolves within, or as a consequence of, an also-evolving complex organization. Here we use a novel network theory-based approach (Anatomical Network Analysis) to assess how the organization of skull bones constrains the co-evolution of modularity and complexity among primates. We used the pattern of bone contacts modeled as networks to identify connectivity modules and quantify morphological complexity. We analyzed whether modularity and complexity evolved coordinately in the skull of primates. Specifically, we tested Herbert Simon's general theory of near-decomposability, which states that modularity promotes the evolution of complexity. We found that the skulls of extant primates divide into one conserved cranial module and up to three labile facial modules, whose composition varies among primates. Despite changes in modularity, statistical analyses reject a positive feedback between modularity and complexity. Our results suggest a decoupling of complexity and modularity that translates to varying levels of constraint on the morphological evolvability of the primate skull. This study has methodological and conceptual implications for grasping the constraints that underlie the developmental and functional integration of the skull of humans and other primates.

  17. Ethanol for preventing preterm birth in threatened preterm labor.

    Science.gov (United States)

    Haas, David M; Morgan, Amanda M; Deans, Samantha J; Schubert, Frank P

    2015-11-05

    Preterm birth is the leading cause of death and disability in newborns worldwide. A wide variety of tocolytic agents have been utilized to delay birth for women in preterm labor. One of the earliest tocolytics utilized for this purpose was ethanol infusion, although this is not generally used in current practice due to safety concerns for both the mother and her baby. To determine the efficacy of ethanol in stopping preterm labor, preventing preterm birth, and the impact of ethanol on neonatal outcomes. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2015) and reference lists of retrieved studies. We included randomized and quasi-randomized studies. Cluster-randomized trials and cross-over design trials were not eligible for inclusion. We only included studies published in abstract form if there was enough information on methods and relevant outcomes. Trials were included if they compared ethanol infusion to stop preterm labor versus placebo/control or versus other tocolytic drugs. At least two review authors independently assessed studies for inclusion and risk of bias. At least two review authors independently extracted data. Data were checked for accuracy. Twelve trials involving 1586 women met inclusion criteria for this review. One trial did not report on the outcomes of interest in this review.Risk of bias of included studies: The included studies generally were of low quality based on inadequate reporting of methodology. Only three trials had low risk of bias for random sequence generation and one had low risk of bias for allocation concealment and participant blinding. Most studies were either high risk of bias or uncertain in these key areas. Comparison 1: Ethanol versus placebo/control (two trials, 77 women) Compared to controls receiving pain medications and dextrose solution, ethanol did not improve any of the primary outcomes: birth confidence interval (CI) 0.43 to 2.00), or neonatal mortality (one trial, 35 women; RR

  18. Local Tacrolimus (FK506) Delivery for Prevention of Acute Rejection in the Nonhuman Primate Delayed Mixed Chimerism Vascularized Composite Allograft Tolerance Induction Protocol

    Science.gov (United States)

    2016-10-01

    Chimerism Vascularized Composite Allograft Tolerance Induction Protocol PRINCIPAL INVESTIGATORS: Dr. Curtis L. Cetrulo CONTRACTING ORGANIZATION...Tacrolimus (FK506) Delivery for Prevention of Acute Rejection in the Nonhuman Primate Delayed Mixed Chimerism Vascularized Composite Allograft Tolerance...tacrolimus, FK506, vascularized composite allografts, immune rejection, preclinical, transplant, nonhuman primate model, degradable polymer, tyrosine

  19. Postsacral vertebral morphology in relation to tail length among primates and other mammals.

    Science.gov (United States)

    Russo, Gabrielle A

    2015-02-01

    Tail reduction/loss independently evolved in a number of mammalian lineages, including hominoid primates. One prerequisite to appropriately contextualizing its occurrence and understanding its significance is the ability to track evolutionary changes in tail length throughout the fossil record. However, to date, the bony correlates of tail length variation among living taxa have not been comprehensively examined. This study quantifies postsacral vertebral morphology among living primates and other mammals known to differ in relative tail length (RTL). Linear and angular measurements with known biomechanical significance were collected on the first, mid-, and transition proximal postsacral vertebrae, and their relationship with RTL was assessed using phylogenetic generalized least-squares regression methods. Compared to shorter-tailed primates, longer-tailed primates possess a greater number of postsacral vertebral features associated with increased proximal tail flexibility (e.g., craniocaudally longer vertebral bodies), increased intervertebral body joint range of motion (e.g., more circularly shaped cranial articular surfaces), and increased leverage of tail musculature (e.g., longer spinous processes). These observations are corroborated by the comparative mammalian sample, which shows that distantly related short-tailed (e.g., Phascolarctos, Lynx) and long-tailed (e.g., Dendrolagus, Acinonyx) nonprimate mammals morphologically converge with short-tailed (e.g., Macaca tonkeana) and long-tailed (e.g., Macaca fascicularis) primates, respectively. Multivariate models demonstrate that the variables examined account for 70% (all mammals) to 94% (only primates) of the variance in RTL. Results of this study may be used to infer the tail lengths of extinct primates and other mammals, thereby improving our understanding about the evolution of tail reduction/loss. © 2014 Wiley Periodicals, Inc.

  20. Convergent evolution in primates and an insectivore

    Energy Technology Data Exchange (ETDEWEB)

    Boffelli, Dario; Cheng, Jan-Fang; Rubin, Edward M.

    2003-04-16

    The cardiovascular risk factor apolipoprotein(a) (apo(a)) has a puzzling distribution among mammals, its presence being limited to a subset of primates and a member of the insectivore lineage, the hedgehog. To explore the evolutionary history of apo(a), we performed extensive genomic sequence comparisons of multiple species with and without an apo(a) gene product, such as human, baboon, hedgehog, lemurand mouse. This analysis indicated that apo(a) arose independently in a subset of primates, including baboon and human, and an insectivore, the hedgehog, and was not simply lost by species lacking it. The similar structural domains shared by the hedgehog and primate apo(a) indicate that they were formed by a unique molecular mechanism involving the convergent evolution of paralogous genes in these distantspecies.

  1. A surgical technique using the ovarian vein in non-human primate models of potential living-donor surgery of uterus transplantation.

    Science.gov (United States)

    Kisu, Iori; Banno, Kouji; Mihara, Makoto; Hara, Hisako; Umene, Kiyoko; Adachi, Masataka; Nogami, Yuya; Aoki, Daisuke

    2015-09-01

    Living donor surgery in organ transplantation should be performed in a minimally invasive manner under conditions that are as safe as possible. The objective of this study is to examine whether the procedure for using the ovarian vein makes donor surgery less invasive in a cynomolgus monkey model of potential living-donor surgery of uterus transplantation. Twenty-two female cynomolgus monkeys aged 6-9 years and with body weights of 3.55 ± 1.28 kg were used in the study. Vessels and tissues surrounding the uterus were dissected while preserving the uterine artery/vein. The deep uterine vein was used as a venous pedicle in four monkeys (Group 1), and the ovarian vein was used instead of the deep uterine vein in 18 monkeys (Group 2). With the uterine artery/vein and deep uterine vein (Group 1) or ovarian vein (Group 2) connected to the uterus, the vaginal canal was cut. The vessels were then clamped to produce a donor surgery model. Surgical time, intraoperative organ and vascular injury were examined in each animal. The average surgical time from laparotomy to clamping of vessels was 230 ± 112 min in all 22 cynomolgus monkeys, and significantly longer in Group 1 (n = 4) than in Group 2 (n = 18) (393 ± 71 vs. 194 ± 84 min, p uterus transplantation. © 2015 Nordic Federation of Societies of Obstetrics and Gynecology.

  2. Clinical Laboratory Values as Early Indicators of Ebola Virus Infection in Nonhuman Primates.

    Science.gov (United States)

    Reisler, Ronald B; Yu, Chenggang; Donofrio, Michael J; Warren, Travis K; Wells, Jay B; Stuthman, Kelly S; Garza, Nicole L; Vantongeren, Sean A; Donnelly, Ginger C; Kane, Christopher D; Kortepeter, Mark G; Bavari, Sina; Cardile, Anthony P

    2017-08-01

    The Ebola virus (EBOV) outbreak in West Africa during 2013-2016 demonstrated the need to improve Ebola virus disease (EVD) diagnostics and standards of care. This retrospective study compared laboratory values and clinical features of 3 nonhuman primate models of lethal EVD to assess associations with improved survival time. In addition, the study identified laboratory values useful as predictors of survival, surrogates for EBOV viral loads, and triggers for initiation of therapeutic interventions in these nonhuman primate models. Furthermore, the data support that, in nonhuman primates, the Makona strain of EBOV may be less virulent than the Kikwit strain of EBOV. The applicability of these findings as potential diagnostic and management tools for EVD in humans warrants further investigation.

  3. CD4 T cell immunity is critical for the control of simian varicella virus infection in a nonhuman primate model of VZV infection.

    Directory of Open Access Journals (Sweden)

    Kristen Haberthur

    2011-11-01

    Full Text Available Primary infection with varicella zoster virus (VZV results in varicella (more commonly known as chickenpox after which VZV establishes latency in sensory ganglia. VZV can reactivate to cause herpes zoster (shingles, a debilitating disease that affects one million individuals in the US alone annually. Current vaccines against varicella (Varivax and herpes zoster (Zostavax are not 100% efficacious. Specifically, studies have shown that 1 dose of varivax can lead to breakthrough varicella, albeit rarely, in children and a 2-dose regimen is now recommended. Similarly, although Zostavax results in a 50% reduction in HZ cases, a significant number of recipients remain at risk. To design more efficacious vaccines, we need a better understanding of the immune response to VZV. Clinical observations suggest that T cell immunity plays a more critical role in the protection against VZV primary infection and reactivation. However, no studies to date have directly tested this hypothesis due to the scarcity of animal models that recapitulate the immune response to VZV. We have recently shown that SVV infection of rhesus macaques models the hallmarks of primary VZV infection in children. In this study, we used this model to experimentally determine the role of CD4, CD8 and B cell responses in the resolution of primary SVV infection in unvaccinated animals. Data presented in this manuscript show that while CD20 depletion leads to a significant delay and decrease in the antibody response to SVV, loss of B cells does not alter the severity of varicella or the kinetics/magnitude of the T cell response. Loss of CD8 T cells resulted in slightly higher viral loads and prolonged viremia. In contrast, CD4 depletion led to higher viral loads, prolonged viremia and disseminated varicella. CD4 depleted animals also had delayed and reduced antibody and CD8 T cell responses. These results are similar to clinical observations that children with agammaglobulinemia have

  4. Recent advances in primate nutritional ecology.

    Science.gov (United States)

    Righini, Nicoletta

    2017-04-01

    Nutritional ecology seeks to explain, in an ecological and evolutionary context, how individuals choose, acquire, and process food to satisfy their nutritional requirements. Historically, studies of primate feeding ecology have focused on characterizing diets in terms of the botanical composition of the plants consumed. Further, dietary studies have demonstrated how patch and food choice in relation to time spent foraging and feeding are influenced by the spatial and temporal distribution of resources and by social factors such as feeding competition, dominance, or partner preferences. From a nutritional perspective, several theories including energy and protein-to-fiber maximization, nutrient mixing, and toxin avoidance, have been proposed to explain the food choices of non-human primates. However, more recently, analytical frameworks such as nutritional geometry have been incorporated into primatology to explore, using a multivariate approach, the synergistic effects of multiple nutrients, secondary metabolites, and energy requirements on primate food choice. Dietary strategies associated with nutrient balancing highlight the tradeoffs that primates face in bypassing or selecting particular feeding sites and food items. In this Special Issue, the authors bring together a set of studies focusing on the nutritional ecology of a diverse set of primate taxa characterized by marked differences in dietary emphasis. The authors present, compare, and discuss the diversity of strategies used by primates in diet selection, and how species differences in ecology, physiology, anatomy, and phylogeny can affect patterns of nutrient choice and nutrient balancing. The use of a nutritionally explicit analytical framework is fundamental to identify the nutritional requirements of different individuals of a given species, and through its application, direct conservation efforts can be applied to regenerate and protect specific foods and food patches that offer the opportunity of a

  5. Prophylactic Probiotics for Preterm Infants

    DEFF Research Database (Denmark)

    Olsen, Rie; Greisen, Gorm; Schrøder, Morten

    2016-01-01

    BACKGROUND: Necrotizing enterocolitis (NEC) is a major morbidity and cause of mortality in preterm neonates. Probiotics seem to have a beneficial role in preventing NEC, which is confirmed in meta-analyses of randomized controlled trials (RCTs). We therefore aimed to review and confirm the effica...

  6. Particulate matter and preterm birth

    Science.gov (United States)

    Particulate matter (PM) has been variably associated with preterm birth (PTB) (gestation <37 weeks), but the role played by specific chemical components of PM has been little studied. We examined the association between ambient PM <2.5 micrometers in aerodynamic diameter (PM2.S) ...

  7. Early gradual feeding with bovine colostrum improves gut function and NEC resistance relative to infant formula in preterm pigs

    DEFF Research Database (Denmark)

    Shen, René Liang; Thymann, Thomas; Østergaard, Mette Viberg

    2015-01-01

    It is unclear when and how to start enteral feeding for preterm infants when mother's milk is not available. We hypothesized that early and slow advancement with either formula or bovine colostrum stimulates gut maturation and prevents necrotizing enterocolitis (NEC) in preterm pigs, used as models...

  8. Iron and cell death in Parkinson's disease: a nuclear microscopic study into iron-rich granules in the parkinsonian substantia nigra of primate models

    International Nuclear Information System (INIS)

    Thong, P.S.P.; Watt, F.; Ponraj, D.; Leong, S.K.; He, Y.; Lee, T.K.Y.

    1999-01-01

    Parkinson's disease is a degenerative brain disease characterised by a loss of cells in the substantia nigra (SN) region of the brain and accompanying biochemical changes such as inhibition of mitochondrial function, increased iron concentrations and decreased glutathione levels in the parkinsonian SN. Though the aetiology of the disease is still unknown, the observed biochemical changes point to the involvement of oxidative stress. In particular, iron is suspected to play a role by promoting free radical production, leading to oxidative stress and cell death. The increase in iron in the parkinsonian SN has been confirmed by several research groups, both in human post-mortem brains and in brain tissue from parkinsonian animal models. However, the question remains as to whether the observed increase in iron is a cause or a consequence of the SN cell death process. Our previous study using unilaterally 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP)-lesioned monkeys in a time sequence experiment has shown that the increase in bulk iron concentrations follow rather than precede dopaminergic cell death. However, changes in the localised iron concentrations, which may play a more direct role in SN cell death, may not be reflected at the bulk level. Indeed, we have observed iron-rich granules in parkinsonian SNs. From this time sequence study into the iron content of iron-rich granules in the SNs of an untreated control and unilaterally MPTP-lesioned parkinsonian models, we present the following observations: (1) Iron-rich granules are found in both control and parkinsonian SNs and are variable in size and iron content in any one model. (2) These iron-rich granules may be associated with neuromelanin granules found in the SN and are known to accumulate transition metal ions such as iron. (3) The early onset of bulk SN cell loss (35%) was accompanied by a significant elevation of iron in granules found in the MPTP-injected SN compared to the contra-lateral SN. This

  9. Learning about primates' learning, language, and cognition

    Science.gov (United States)

    Rumbaugh, Duane M.

    1992-01-01

    Results are presented of many years of research on the methods of teaching primates the language and cognitive skills which were long considered to be unteachable to particular species of primates. It was found that chimpanzee subjects could not only learn a number of 'stock sentences' but to use them in variations and several combinations for the purpose of solving various problems. Apes placed in different rooms could be taught to communicate via computer, and collaborate with each other on doing specific tasks. Contrary to expectations, young rhesus monkeys proved to be able to learn as much as the chimpanzee species.

  10. Long-term persistence and function of hematopoietic stem cell-derived chimeric antigen receptor T cells in a nonhuman primate model of HIV/AIDS.

    Directory of Open Access Journals (Sweden)

    Anjie Zhen

    2017-12-01

    Full Text Available Chimeric Antigen Receptor (CAR T-cells have emerged as a powerful immunotherapy for various forms of cancer and show promise in treating HIV-1 infection. However, significant limitations are persistence and whether peripheral T cell-based products can respond to malignant or infected cells that may reappear months or years after treatment remains unclear. Hematopoietic Stem/Progenitor Cells (HSPCs are capable of long-term engraftment and have the potential to overcome these limitations. Here, we report the use of a protective CD4 chimeric antigen receptor (C46CD4CAR to redirect HSPC-derived T-cells against simian/human immunodeficiency virus (SHIV infection in pigtail macaques. CAR-containing cells persisted for more than 2 years without any measurable toxicity and were capable of multilineage engraftment. Combination antiretroviral therapy (cART treatment followed by cART withdrawal resulted in lower viral rebound in CAR animals relative to controls, and demonstrated an immune memory-like response. We found CAR-expressing cells in multiple lymphoid tissues, decreased tissue-associated SHIV RNA levels, and substantially higher CD4/CD8 ratios in the gut as compared to controls. These results show that HSPC-derived CAR T-cells are capable of long-term engraftment and immune surveillance. This study demonstrates for the first time the safety and feasibility of HSPC-based CAR therapy in a large animal preclinical model.

  11. Immune Responses in the Central Nervous System Are Anatomically Segregated in a Non-Human Primate Model of Human Immunodeficiency Virus Infection

    Directory of Open Access Journals (Sweden)

    Barbara Tavano

    2017-03-01

    Full Text Available The human immunodeficiency virus (HIV accesses the central nervous system (CNS early during infection, leading to HIV-associated cognitive impairment and establishment of a viral reservoir. Here, we describe a dichotomy in inflammatory responses in different CNS regions in simian immunodeficiency virus (SIV-infected macaques, a model for HIV infection. We found increased expression of inflammatory genes and perivascular leukocyte infiltration in the midbrain of SIV-infected macaques. Conversely, the frontal lobe showed downregulation of inflammatory genes associated with interferon-γ and interleukin-6 pathways, and absence of perivascular cuffing. These immunologic alterations were not accompanied by differences in SIV transcriptional activity within the tissue. Altered expression of genes associated with neurotoxicity was observed in both midbrain and frontal lobe. The segregation of inflammatory responses to specific regions of the CNS may both account for HIV-associated neurological symptoms and constitute a critical hurdle for HIV eradication by shielding the CNS viral reservoir from antiviral immunity.

  12. of bullies and buddies : socio-spatial behavior and emotional regulation drives primate-like social complexity in silico

    OpenAIRE

    Evers, Ellen

    2014-01-01

    Groups of primates form complex spatial and social structures. Often, dominance rank is reflected in an individual's spatial position within the group, and individuals maintain individualized reciprocal relationships with affiliates, which reflect earlier interactions. The hypothesized underlying mechanisms and the cognitive capacities thought necessary differ in their complexity. While primates have been shown to possess advanced socio-cognitive abilities, computer models have proven that co...

  13. An observational study of type, timing, and severity of childhood maltreatment and preterm birth.

    Science.gov (United States)

    Selk, Sabrina C; Rich-Edwards, Janet W; Koenen, Karestan; Kubzansky, Laura D

    2016-06-01

    Childhood maltreatment has been linked to preterm birth (preterm birth. The aim of this observational study was to explore type of maltreatment (child and adolescent physical and sexual abuse and harsh parenting) as risk factors for preterm birth. We examined these associations in a cross-sectional analysis of the Nurses' Health Study II cohort of female nurses. Women completed a questionnaire about experiences of sexual abuse, physical abuse or harsh parenting, along with pregnancy outcomes. Logistic regression models adjusted for relevant covariates including age, race, alcohol and cigarette use during pregnancy, age at menarche, marital status, adult income, body mass index (kg/m(2)) at age 18, physical abuse in pregnancy, and childhood socioeconomic position. Among 51 434 first births, 4110 were preterm (8% of births). Forced sexual activity in childhood or adolescence was associated with a 22% increased odds of preterm birth (OR=1.22, 95% CI 1.10 to 1.35). Maltreatment involving sexual touch, physical abuse or harsh parenting was not associated with preterm birth in this sample. Women who experience forced sexual activity in childhood or adolescence may have an increased likelihood of delivering preterm in adulthood. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  14. Socioeconomic inequality in preterm birth in four Brazilian birth cohort studies.

    Science.gov (United States)

    Sadovsky, Ana Daniela Izoton de; Matijasevich, Alicia; Santos, Iná S; Barros, Fernando C; Miranda, Angelica Espinosa; Silveira, Mariangela Freitas

    To analyze economic inequality (absolute and relative) due to family income in relation to the occurrence of preterm births in Southern Brazil. Four birth cohort studies were conducted in the years 1982, 1993, 2004, and 2011. The main exposure was monthly family income and the primary outcome was preterm birth. The inequalities were calculated using the slope index of inequality and the relative index of inequality, adjusted for maternal skin color, education, age, and marital status. The prevalence of preterm births increased from 5.8% to approximately 14% (p-trend<0.001). Late preterm births comprised the highest proportion among the preterm births in all studies, although their rates decreased over the years. The analysis on the slope index of inequality demonstrated that income inequality arose in the 1993, 2004, and 2011 studies. After adjustment, only the 2004 study maintained the difference between the poorest and the richest subjects, which was 6.3 percentage points. The relative index of inequality showed that, in all studies, the poorest mothers were more likely to have preterm newborns than the richest. After adjustment for confounding factors, it was observed that the poorest mothers only had a greater chance of this outcome in 2004. In a final model, economic inequalities resulting from income were found in relation to preterm births only in 2004, although a higher prevalence of prematurity continued to be observed in the poorest population, in all the studies. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  15. Deep hierarchies in the primate visual cortex: what can we learn for computer vision?

    Science.gov (United States)

    Krüger, Norbert; Janssen, Peter; Kalkan, Sinan; Lappe, Markus; Leonardis, Ales; Piater, Justus; Rodríguez-Sánchez, Antonio J; Wiskott, Laurenz

    2013-08-01

    Computational modeling of the primate visual system yields insights of potential relevance to some of the challenges that computer vision is facing, such as object recognition and categorization, motion detection and activity recognition, or vision-based navigation and manipulation. This paper reviews some functional principles and structures that are generally thought to underlie the primate visual cortex, and attempts to extract biological principles that could further advance computer vision research. Organized for a computer vision audience, we present functional principles of the processing hierarchies present in the primate visual system considering recent discoveries in neurophysiology. The hierarchical processing in the primate visual system is characterized by a sequence of different levels of processing (on the order of 10) that constitute a deep hierarchy in contrast to the flat vision architectures predominantly used in today's mainstream computer vision. We hope that the functional description of the deep hierarchies realized in the primate visual system provides valuable insights for the design of computer vision algorithms, fostering increasingly productive interaction between biological and computer vision research.

  16. Visual cortical areas of the mouse: comparison of parcellation and network structure with primates

    Science.gov (United States)

    Laramée, Marie-Eve; Boire, Denis

    2015-01-01

    Brains have evolved to optimize sensory processing. In primates, complex cognitive tasks must be executed and evolution led to the development of large brains with many cortical areas. Rodents do not accomplish cognitive tasks of the same level of complexity as primates and remain with small brains both in relative and absolute terms. But is a small brain necessarily a simple brain? In this review, several aspects of the visual cortical networks have been compared between rodents and primates. The visual system has been used as a model to evaluate the level of complexity of the cortical circuits at the anatomical and functional levels. The evolutionary constraints are first presented in order to appreciate the rules for the development of the brain and its underlying circuits. The organization of sensory pathways, with their parallel and cross-modal circuits, is also examined. Other features of brain networks, often considered as imposing constraints on the development of underlying circuitry, are also discussed and their effect on the complexity of the mouse and primate brain are inspected. In this review, we discuss the common features of cortical circuits in mice and primates and see how these can be useful in understanding visual processing in these animals. PMID:25620914

  17. Visual cortical areas of the mouse: comparison of parcellation and network structure with primates

    Directory of Open Access Journals (Sweden)

    Marie-Eve eLaramée

    2015-01-01

    Full Text Available Brains have evolved to optimize sensory processing. In primates, complex cognitive tasks must be executed and evolution led to the development of large brains with many cortical areas. Rodents do not accomplish cognitive tasks of the same level of complexity as primates and remain with small brains both in relative and absolute terms. But is a small brain necessarily a simple brain? In this review, several aspects of the visual cortical networks have been compared between rodents and primates. The visual system has been used as a model to evaluate the level of complexity of the cortical circuits at the anatomical and functional levels. The evolutionary constraints are first presented in order to appreciate the rules for the development of the brain and its underlying circuits. The organization of sensory pathways, with their parallel and cross-modal circuits, is also examined. Other features of brain networks, often considered as imposing constraints on the development of underlying circuitry, are also discussed and their effect on the complexity of the mouse and primate brain are inspected. In this review, we discuss the common features of cortical circuits in mice and primates and see how these can be useful in understanding visual processing in these animals.

  18. The inverse relationship between species diversity and body mass: do primates play by the "rules"?

    Science.gov (United States)

    Conroy, Glenn C

    2003-07-01

    Evolutionary biologists have long commented on a seemingly universal "rule" of nature-that in large taxonomic assemblages from groups as diverse as bacteria, plants, insects, marine invertebrates, fish, reptiles, amphibians, birds, and mammals, there exists a frequency distribution of body sizes among species that is highly skewed to the right (positive skewness). This distribution reflects the strong inverse, or negative, relationship often noted between mean body size of taxa and the number of species they contain--i.e., the observation that small body size is often associated with high species diversity (speciosity). This is sometimes "explained" by recourse to the idea that smaller-bodied taxa are able to subdivide their environments more finely than larger-bodied taxa. With but few exceptions, the applicability of this "rule" to the Order Primates has not been studied in any detail. In this study I address the following questions of (paleo)anthropological interest: (1) How speciose is the Order Primates? (2) Does this biological "rule" characterize the Order Primates (at any taxonomic level) in any meaningful way? (3) Does the association between speciosity and body mass within the Order Primates provide any useful models for interpreting and/or predicting speciosity in the fossil primate record? Using phylogenetically independent contrasts methods, I conclude that the answers to those three questions are: (1) not very; (2) no; and (3) not particularly (with the possible exception of larger-bodied taxa).

  19. Welfare based primate rehabilitation as a potential conservation strategy: does it measure up?

    Science.gov (United States)

    Guy, Amanda J; Curnoe, Darren; Banks, Peter B

    2014-01-01

    Many primate species are threatened with extinction and are the focus of extensive conservation efforts including re-introduction, captive breeding and habitat conservation. Welfare-based rehabilitation (hereafter also 'rehabilitation') is a management strategy commonly used for primates, particularly those species targeted by the pet and bush meat trades. Rehabilitation of rescued primates typically has the dual motivation of welfare and conservation, but has not been assessed as a conservation strategy. As the species involved in rehabilitation are often endangered (e.g. chimpanzees, gorillas, orang-utans), it is important for rehabilitation projects to follow a 'best practice' model in order to increase positive outcomes. In this study, we compared the approaches of 28 welfare-based primate rehabilitation projects to the 'IUCN guidelines for nonhuman primate re-introductions', in addition to components of the 'Best practice guidelines for the re-introduction of great apes' in order to assess where additional work might be needed for released animals to contribute to conservation outcomes. Few projects examined complied with the guidelines for re-introduction, failing to incorporate important factors such as quarantine, long term post-release monitoring and training for predator awareness. Further development of species-specific rehabilitation guidelines may improve the outcomes of future rehabilitation projects. To support this, we recommend that detailed methods and results be published for all rehabilitation efforts, regardless of the outcome.

  20. [Does Alzheimer's disease exist in all primates? Alzheimer pathology in non-human primates and its pathophysiological implications (II)].

    Science.gov (United States)

    Toledano, A; Álvarez, M I; López-Rodríguez, A B; Toledano-Díaz, A; Fernández-Verdecia, C I

    2014-01-01

    In the ageing process there are some species of non-human primates which can show some of the defining characteristics of the Alzheimer's disease (AD) of man, both in neuropathological changes and cognitive-behavioural symptoms. The study of these species is of prime importance to understand AD and develop therapies to combat this neurodegenerative disease. In this second part of the study, these AD features are discussed in the most important non-experimental AD models (Mouse Lemur -Microcebus murinus, Caribbean vervet -Chlorocebus aethiops, and the Rhesus and stump-tailed macaque -Macaca mulatta and M. arctoides) and experimental models (lesional, neurotoxic, pharmacological, immunological, etc.) non-human primates. In all these models cerebral amyloid neuropathology can occur in senility, although with different levels of incidence (100% in vervets;Alzheimer's) senility in these species are difficult to establish due to the lack of cognitive-behavioural studies in the many groups analysed, as well as the controversy in the results of these studies when they were carried out. However, in some macaques, a correlation between a high degree of functional brain impairment and a large number of neuropathological changes ("possible AD") has been found. In some non-human primates, such as the macaque, the existence of a possible continuum between "normal" ageing process, "normal" ageing with no deep neuropathological and cognitive-behavioural changes, and "pathological ageing" (or "Alzheimer type ageing"), may be considered. In other cases, such as the Caribbean vervet, neuropathological changes are constant and quite marked, but its impact on cognition and behaviour does not seem to be very important. This does assume the possible existence in the human senile physiological regression of a stable phase without dementia even if neuropathological changes appeared. Copyright © 2011 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  1. Symbolic interactionism: a framework for the care of parents of preterm infants.

    Science.gov (United States)

    Edwards, L D; Saunders, R B

    1990-04-01

    Because of stressors surrounding preterm birth, parents can be expected to have difficulty in early interactions with their preterm infants. Care givers who work with preterm infants and their parents can positively affect the early parental experiences of these mothers and fathers. If care givers are consciously guided by a conceptual model, therapeutic care for distressed parents is more likely to be provided. A logical framework, such as symbolic interactionism, helps care givers to proceed systematically in assessing parental behaviors, in intervening appropriately, and in evaluating both the process and outcome of the care. Selected aspects of the symbolic interaction model are described in this article and applied to the care of parents of preterm infants.

  2. Neurodevelopmental pathways to preterm children's specific and general mathematic abilities.

    Science.gov (United States)

    Jaekel, Julia; Bartmann, Peter; Schneider, Wolfgang; Wolke, Dieter

    2014-10-01

    Preterm children have problems with mathematics but knowledge about the predictors of specific mathematic abilities in preterm populations is scarce. This study investigated neurodevelopmental pathways to children's general and specific mathematic abilities across the full gestational age range. Prospective geographically defined longitudinal investigation in Germany. 947 children across the full gestational age range (23-41 weeks). Outcome measures. At 8 years, children's cognitive and mathematic abilities were measured and residuals of a regression predicting mathematic scores by IQ were used to identify specific mathematic abilities. Neurodevelopmental cascade models revealed that adverse effects of preterm birth on mathematic abilities were mediated by neonatal risk. Specific mathematic abilities were uniquely predicted by the duration of hospitalization and ventilation. Prolonged neonatal medical treatment and, in particular, mechanical ventilation may lead to specific impairments in mathematic tasks. These findings have implications for the mode of respiratory support in neonates, routine follow-up and intervention planning as well as research about brain reorganization after preterm birth. Copyright © 2014. Published by Elsevier Ireland Ltd.

  3. Obstructive sleep apnea and the risk of preterm delivery.

    Science.gov (United States)

    Na-Rungsri, Kunyalak; Lertmaharit, Somrat; Lohsoonthorn, Vitool; Totienchai, Surachart; Jaimchariyatam, Nattapong

    2016-09-01

    The aim of this study was to evaluate the risk of obstructive sleep apnea (OSA) to preterm delivery (PTD), using the Berlin Questionnaire (BQ). This was a large, prospective cohort study among pregnant Thai women. The BQ was employed for symptom-based OSA screening during the second trimester, and PTD was recorded in 1345 pregnant women. Multivariate models were applied in controlling for potential confounders. The overall prevalence of the high risk of OSA was 10.1 %, and it was significantly associated with pre-pregnancy body mass index and score on the Perceived Stress Scale. An adjusted odds ratio for PTD in women with a high risk of OSA was 2.00 (95 % confidence intervals (CIs) = 1.20, 3.34). Stratified analyses, after adjusting for confounding factors, indicated that a high risk of OSA was associated with an increased risk of spontaneous preterm delivery (odds ratio (OR) = 2.45, 95 % CI = 1.20, 5.02), but not with preterm premature rupture of membranes (OR = 1.61, 95 % CI = 0.61, 4.26), and medically indicated preterm delivery (OR = 1.83, 95 % CI = 0.72, 4.64). Pregnant women with a high risk of OSA are at an increased risk of having PTD, compared with pregnant women with a low risk of OSA.

  4. Quantifying the impact of deprivation on preterm births: a retrospective cohort study.

    Directory of Open Access Journals (Sweden)

    David Taylor-Robinson

    Full Text Available Social deprivation is associated with higher rates of preterm birth and subsequent infant mortality. Our objective was to identify risk factors for preterm birth in the UK's largest maternity unit, with a particular focus on social deprivation, and related factors.Retrospective cohort study of 39,873 women in Liverpool, UK, from 2002-2008. Singleton pregnancies were stratified into uncomplicated low risk pregnancies and a high risk group complicated by medical problems. Multiple logistic regression, and generalized additive models were used to explore the effect of covariates including area deprivation, smoking status, BMI, parity and ethnicity on the risk of preterm birth (34⁺⁰ weeks. In the low risk group, preterm birth rates increased with deprivation, reaching 1.6% (CI₉₅ 1.4 to 1.8 in the most deprived quintile; the unadjusted odds ratio comparing an individual in the most deprived quintile, to one in the least deprived quintile was 1.5 (CI₉₅ 1.2 to 1.9. Being underweight and smoking were both independently associated with preterm birth in the low risk group, and adjusting for these factors explained the association between deprivation and preterm birth. Preterm birth was five times more likely in the high risk group (RR 4.8 CI₉₅ 4.3 to 5.4, and there was no significant relationship with deprivation.Deprivation has significant impact on preterm birth rates in low risk women. The relationship between low socio-economic status and preterm births appears to be related to low maternal weight and smoking in more deprived groups.

  5. Quantifying the impact of deprivation on preterm births: a retrospective cohort study.

    Science.gov (United States)

    Taylor-Robinson, David; Agarwal, Umber; Diggle, Peter J; Platt, Mary Jane; Yoxall, Bill; Alfirevic, Zarko

    2011-01-01

    Social deprivation is associated with higher rates of preterm birth and subsequent infant mortality. Our objective was to identify risk factors for preterm birth in the UK's largest maternity unit, with a particular focus on social deprivation, and related factors. Retrospective cohort study of 39,873 women in Liverpool, UK, from 2002-2008. Singleton pregnancies were stratified into uncomplicated low risk pregnancies and a high risk group complicated by medical problems. Multiple logistic regression, and generalized additive models were used to explore the effect of covariates including area deprivation, smoking status, BMI, parity and ethnicity on the risk of preterm birth (34⁺⁰ weeks). In the low risk group, preterm birth rates increased with deprivation, reaching 1.6% (CI₉₅ 1.4 to 1.8) in the most deprived quintile; the unadjusted odds ratio comparing an individual in the most deprived quintile, to one in the least deprived quintile was 1.5 (CI₉₅ 1.2 to 1.9). Being underweight and smoking were both independently associated with preterm birth in the low risk group, and adjusting for these factors explained the association between deprivation and preterm birth. Preterm birth was five times more likely in the high risk group (RR 4.8 CI₉₅ 4.3 to 5.4), and there was no significant relationship with deprivation. Deprivation has significant impact on preterm birth rates in low risk women. The relationship between low socio-economic status and preterm births appears to be related to low maternal weight and smoking in more deprived groups.

  6. Disproportional representation of primates in the ecological literature.

    Science.gov (United States)

    Heymann, Eckhard W; Zinner, Dietmar; Ganzhorn, Jörg U

    2013-01-01

    We address the question why papers dealing with the ecology of primates are so sparsely represented in the general ecological literature. A literature analyses based on entries in Web of Science and PrimateLit reveals that despite a large number of papers published on primates in general and on the ecology of primates, only a very small fraction of these papers is published in high-ranking international ecological journals. We discuss a number of potential reasons for the disproportion and highlight the problems associated with experimental research on wild primates and constraints on sample size as major issues.

  7. Primate Innovation: Sex, Age and Social Rank

    NARCIS (Netherlands)

    Reader, S.M.; Laland, K.N.

    2001-01-01

    Analysis of an exhaustive survey of primate behavior collated from the published literature revealed significant variation in rates of innovation among individuals of different sex, age and social rank. We searched approximately 1,000 articles in four primatology journals, together with other

  8. Primacy and recency effects in nonhuman primates.

    Science.gov (United States)

    Castro, C A; Larsen, T

    1992-10-01

    The reports of primacy and recency memory effects in nonhuman primates have been criticized because they have all used an initiating response. That is, the presentation of the to-be-remembered list of items was always contingent on a response being initiated by the nonhuman primate. It has been argued that this initiating response improves performance for early items in the list, resulting in the occurrence of the primacy effect, independent of any memory processing mechanism. This criticism was addressed in the present study by not using an initiating response prior to the presentation of the list. Nevertheless, both a primacy and a recency effect were observed in all 6 rhesus monkeys evaluated using a serial probe recognition task. Thus, the results are similar to those for humans, in that both primacy and recency effects can be obtained in nonhuman primates. A brief literature review is included, and it is proposed that the primacy and recency effects observed in humans, nonhuman primates, and infraprimates can be explained within the context of the configural-association theory.

  9. Homeostasis in primates in hyperacceleration fields

    Science.gov (United States)

    Fuller, C. A.

    1984-01-01

    Various homeostatic responses of a nonhuman primate, the squirrel monkey (Saimiri sciureus) to acute changes in the acceleration environment were examined. When these animals were exposed to a hyperdynamic field the body temperature was consistently depressed and the animals showed behavioral indications of increased drowsiness. Further, time of day played a significant role in influencing these responses.

  10. Assessing the growth of preterm infants using detailed anthropometry.

    Science.gov (United States)

    Ashton, James J; Johnson, Mark J; Pond, Jenny; Crowley, Philippa; Dimitrov, Borislav D; Pearson, Freya; Beattie, R Mark

    2017-06-01

    Preterm infants display altered body composition compared to term infants, and weight gain is a crude indicator body composition. Childhood mid-upper arm circumference (MUAC) is a measure of nutritional status. This study investigates MUAC and mid-thigh circumference (MTC) to monitor growth in preterm infants. Preterm infants (<30-week gestation) were recruited. MUAC, MTC, weight, length and head circumference (HC) were measured at recruitment and weekly intervals until discharge. Descriptive, correlation and regression analyses were used. Ninety-three infants were recruited. Median measurement duration was eight weeks (1-19). Median gestational age was 27 weeks (23-29). Analysis by curve estimation displayed a mean increase of 2.58 mm/week (left MUAC) (p ≤ 0.0001), 2.56 mm/week (right MUAC) (p ≤ 0.0001), 4.16 mm/week (left MTC) (p ≤ 0.0001), 4.20 mm/week (right MTC) (p ≤ 0.0001). Coefficients of determination (R 2 ) were calculated using a growth regression model for MUAC and MTC (0.866-0.917); measures were comparable to growth modelling of weight (0.913), length (0.945) and HC (0.928). High concordance between left and right MUAC and MTC generated a Pearson's correlation coefficient of 0.999 (MUAC) (p ≤ 0.001) and 0.994 (MTC) (p ≤ 0.001). Data demonstrate the potential utility of MUAC and MTC as additional measures of growth in preterm infants that are reproducible over time. There is potential to gain insights to improve lean-mass accretion in preterm infants. ©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  11. Tempo and mode of climatic niche evolution in Primates.

    Science.gov (United States)

    Duran, Andressa; Pie, Marcio R

    2015-09-01

    Climatic niches have increasingly become a nexus in our understanding of a variety of ecological and evolutionary phenomena, from species distributions to latitudinal diversity gradients. Despite the increasing availability of comprehensive datasets on species ranges, phylogenetic histories, and georeferenced environmental conditions, studies on the evolution of climate niches have only begun to understand how niches evolve over evolutionary timescales. Here, using primates as a model system, we integrate recently developed phylogenetic comparative methods, species distribution patterns, and climatic data to explore primate climatic niche evolution, both among clades and over time. In general, we found that simple, constant-rate models provide a poor representation of how climatic niches evolve. For instance, there have been shifts in the rate of climatic niche evolution in several independent clades, particularly in response to the increasingly cooler climates of the past 10 My. Interestingly, rate accelerations greatly outnumbered rate decelerations. These results highlight the importance of considering more realistic evolutionary models that allow for the detection of heterogeneity in the tempo and mode of climatic niche evolution, as well as to infer possible constraining factors for species distributions in geographical space. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

  12. Preterm delivery predicted by soluble CD163 and CRP in women with symptoms of preterm delivery

    DEFF Research Database (Denmark)

    Vogel, Ida; Grove, Jakob; Thorsen, Poul

    2005-01-01

    : High levels of sCD163 or CRP are associated with an increased risk of preterm delivery in women with symptoms of delivery. Good prediction of preterm delivery before 34 weeks of gestation was obtained by a combination of preterm prelabour rupture of membranes (PPROM), overweight, relaxin, CRP and s...

  13. Early vs delayed clamping of the umbilical cord in full term, preterm and very preterm infants

    DEFF Research Database (Denmark)

    Moller, N.K.; Weber, T.

    2008-01-01

    Randomized studies from 2006 and two meta-analyses published in 2007 agree that clamping of the umbilical cord can be delayed. For the preterm and very preterm infant benefits include less need for blood transfusion and less morbidity, especially for the very preterm male infant. For the term...

  14. Recurrence risk of preterm birth in subsequent twin pregnancy after preterm singleton delivery

    NARCIS (Netherlands)

    Schaaf, J. M.; Hof, M. H. P.; Mol, B. W. J.; Abu-Hanna, A.; Ravelli, A. C. J.

    2012-01-01

    Please cite this paper as: Schaaf J, Hof M, Mol B, Abu-Hanna A, Ravelli A. Recurrence risk of preterm birth in subsequent twin pregnancy after preterm singleton delivery.BJOG 2012;119:16241629. Objective To determine the risk of preterm birth in a subsequent twin pregnancy after previous singleton

  15. Phalangeal morphology of Shanghuang fossil primates.

    Science.gov (United States)

    Gebo, Daniel L; Dagosto, Marian; Ni, Xijun; Beard, K Christopher

    2017-12-01

    Here, we describe hundreds of isolated phalanges attributed to middle Eocene fossil primates from the Shanghuang fissure-fillings from southern Jiangsu Province, China. Extending knowledge based on previous descriptions of postcranial material from Shanghuang, this sample of primate finger and toe bones includes proximal phalanges, middle phalanges, and over three hundred nail-bearing distal phalanges. Most of the isolated proximal and middle phalanges fall within the range of small-bodied individuals, suggesting an allocation to the smaller haplorhine primates identified at Shanghuang, including eosimiids. In contrast to the proximal and middle phalanges from Shanghuang, there are a variety of shapes, sizes, and possible taxonomic allocations for the distal phalanges. Two distal phalangeal morphologies are numerically predominant at Shanghuang. The sample of larger bodied specimens is best allocated to the medium-sized adapiform Adapoides while the smaller ones are allocated to eosimiids on the basis of the commonality of dental and tarsal remains of these taxa at Shanghuang. The digit morphology of Adapoides is similar morphologically to that of notharctines and cercamoniines, while eosimiid digit morphology is unlike living anthropoids. Other primate distal phalangeal morphologies at Shanghuang include grooming "claws" as well as specimens attributable to tarsiids, tarsiiforms, the genus Macrotarsius, and a variety of adapiforms. One group of distal phalanges at Shanghuang is morphologically indistinguishable from those of living anthropoids. All of the phalanges suggest long fingers and toes for the fossil primates of Shanghaung, and their digit morphology implies arboreality with well-developed digital flexion and strong, grasping hands and feet. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Functional morphology of cercopithecoid primate metacarpals.

    Science.gov (United States)

    Patel, Biren A

    2010-04-01

    The primate fossil record suggests that terrestriality was more common in the past than it is today, particularly among cercopithecoid primates. Whether or not a fossil primate habitually preferred terrestrial substrates has typically been inferred from its forelimb anatomy. Because extant large-bodied terrestrial cercopithecine monkeys utilize digitigrade hand postures during locomotion, being able to identify if a fossil primate habitually adopted digitigrade postures would be particularly revealing of terrestriality in this group. This paper examines the functional morphology of metacarpals in order to identify osteological correlates of digitigrade versus palmigrade hand postures. Linear measurements were obtained from 324 individuals belonging to digitigrade and palmigrade cercopithecoid species and comparisons were made between hand posture groups. Digitigrade taxa have shorter metacarpals, relative to both body mass and humerus length, than palmigrade taxa. Also, digitigrade taxa tend to have metacarpals with smaller dorsoventral diameters, relative to the product of body mass and metacarpal length, compared to palmigrade taxa. The size and shape of the metacarpal heads do not significantly differ between hand posture groups. Multivariate analyses suggest that metacarpal shape can only weakly discriminate between hand posture groups. In general, while there are some morphological differences in the metacarpals between hand posture groups, similarities also exist that are likely related to the fact that even digitigrade cercopithecoids can adopt palmigrade hand postures in different situations (e.g., terrestrial running, arboreal locomotion), and/or that the functional demands of different hand postures are not reflected in all aspects of metacarpal morphology. Therefore, the lack of identifiable adaptations for specific hand postures in extant cercopithecoids makes it difficult to determine a preference for specific habitats from fossil primate hand bones

  17. Genetic Factors Contribute to Risk for Neonatal Respiratory Distress Syndrome among Moderately Preterm, Late Preterm, and Term Infants

    Science.gov (United States)

    Shen, Carol L.; Zhang, Qunyuan; Meyer, Julia; Cole, F. Sessions; Wambach, Jennifer A.

    2016-01-01

    Objective To determine the genetic contribution to risk for respiratory distress syndrome (RDS) among moderately preterm, late preterm, and term infants (estimated gestational age ≥32 weeks) of African and European-descent. Study Design We reviewed clinical records for 524 consecutive twin pairs ≥32 weeks gestation. We identified pairs in which at least 1 twin had RDS (n=225) and compared the concordance of RDS between monozygotic (MZ) and dizygotic twins (DZ). Using mixed effects logistic regression, we identified covariates that increased disease risk. We performed additive genetic, common environmental, and residual effects modeling to estimate genetic variance and used the ratio of genetic variance to total variance to estimate genetic contribution to RDS disease risk. Results Monozygotic twins were more concordant for RDS than dizygotic twins (p=0.0040). Estimated gestational age, European-descent, male sex, delivery by cesarean, and five minute Apgar score each independently increased risk for RDS. After adjusting for these covariates, genetic effects accounted for 58% (p=0.0002) of the RDS disease risk variance for all twin pairs. Conclusions In addition to environmental factors, genetic factors may contribute to RDS risk among moderately preterm, late preterm, and term infants. Discovery of risk alleles may be important for prediction and management of RDS risk. PMID:26935785

  18. Does fish oil prevent preterm birth?

    DEFF Research Database (Denmark)

    Secher, Niels Jørgen

    2007-01-01

    A literature review was performed on the effect of fish oil on preterm birth in observational and randomized studies. The only weak effect on preterm birth found in meta-analyses could be caused by the low compliance, and the fact that many women stop supplementation before term together with a f......A literature review was performed on the effect of fish oil on preterm birth in observational and randomized studies. The only weak effect on preterm birth found in meta-analyses could be caused by the low compliance, and the fact that many women stop supplementation before term together...... with a fast acting effect on fish oil....

  19. Socio-economic inequality in preterm birth

    DEFF Research Database (Denmark)

    Petersen, Christina Bjørk; Mortensen, Laust Hvas; Morgen, Camilla Schmidt

    2009-01-01

    by maternal educational attainment and analysed in 5-year intervals from 1981 to 2000. Compared with mothers with >12 years of education, mothers with years of education had similarly increased risks of very, and to a lesser extent moderately, preterm birth in all four countries. The educational gradient...... increased slightly over time in very preterm births in Denmark, while there was a slight narrowing of the gap in Sweden. In moderately preterm births, the educational inequality gap was constant over the study period in Denmark, Norway and Sweden, but narrowed in Finland. The educational gradient in preterm...

  20. Progesterone to prevent spontaneous preterm birth

    Science.gov (United States)

    Romero, Roberto; Yeo, Lami; Chaemsaithong, Piya; Chaiworapongsa, Tinnakorn; Hassan, Sonia

    2014-01-01

    Summary Preterm birth is the leading cause of perinatal morbidity and mortality worldwide, and its prevention is an important healthcare priority. Preterm parturition is one of the ‘great obstetrical syndromes’ and is caused by multiple etiologies. One of the mechanisms of disease is the untimely decline in progesterone action, which can be manifested by a sonographic short cervix in the midtrimester. The detection of a short cervix in the midtrimester is a powerful risk factor for preterm delivery. Vaginal progesterone can reduce the rate of preterm delivery by 45%, and the rate of neonatal morbidity (admission to neonatal intensive care unit, respiratory distress syndrome, need for mechanical ventilation, etc.). To prevent one case of spontaneous preterm birth birth in women with a short cervix both with and without a prior history of preterm birth. In patients with a prior history of preterm birth, vaginal progesterone is as effective as cervical cerclage to prevent preterm delivery. 17α-Hydroxyprogesterone caproate has not been shown to be effective in reducing the rate of spontaneous preterm birth in women with a short cervix. PMID:24315687

  1. Evaluation of ex vivo produced endothelial progenitor cells for autologous transplantation in primates.

    Science.gov (United States)

    Qin, Meng; Guan, Xin; Zhang, Yu; Shen, Bin; Liu, Fang; Zhang, Qingyu; Ma, Yupo; Jiang, Yongping

    2018-01-22

    Autologous transplantation of endothelial progenitor cells (EPCs) is a promising therapeutic approach in the treatment of various vascular diseases. We previously reported a two-step culture system for scalable generation of human EPCs derived from cord blood CD34 + cells ex vivo. Here, we now apply this culture system to expand and differentiate human and nonhuman primate EPCs from mobilized peripheral blood (PB) CD34 + cells for the therapeutic potential of autologous transplantation. The human and nonhuman primate EPCs from mobilized PB CD34 + cells were cultured according to our previously reported system. The generated adherent cells were then characterized by the morphology, surface markers, nitric oxide (NO)/endothelial NO synthase (eNOS) levels and Dil-acetylated low-density lipoprotein (Dil-Ac-LDL) uptake/fluorescein isothiocyanate (FITC)-lectin binding actives. Furthermore, the efficacy and safety studies were performed by autologous transplantation via hepatic portal vein injection in a nonhuman primate model with acute liver sinusoidal endothelial cell injury. The mobilized PB CD34 + cells from both human and nonhuman primate were efficiently expanded and differentiated. Over 2 × 10 8 adherent cells were generated from 20 mL mobilized primate PB (1.51 × 10 6  ± 3.39 × 10 5 CD34 + cells) by 36-day culture and more than 80% of the produced cells were identified as EPCs/endothelial cells (ECs). In the autologous transplant model, the injected EPC/ECs from nonhuman primate PB were scattered in the intercellular spaces of hepatocytes at the hepatic tissues 14 days post-transplantation, indicating successful migration and reconstitution in the liver structure as the functional EPCs/ECs. We successfully applied our previous two-step culture system for the generation of primate EPCs from mobilized PB CD34 + cells, evaluated the phenotypes ex vivo, and transplanted autologous EPCs/ECs in a nonhuman primate model. Our study indicates that

  2. Strategies to Prevent Preterm Birth

    Science.gov (United States)

    Newnham, John P.; Dickinson, Jan E.; Hart, Roger J.; Pennell, Craig E.; Arrese, Catherine A.; Keelan, Jeffrey A.

    2014-01-01

    After several decades of research, we now have evidence that at least six interventions are suitable for immediate use in contemporary clinical practice within high-resource settings and can be expected to safely reduce the rate of preterm birth. These interventions involve strategies to prevent non-medically indicated late preterm birth; use of maternal progesterone supplementation; surgical closure of the cervix with cerclage; prevention of exposure of pregnant women to cigarette smoke; judicious use of fertility treatments; and dedicated preterm birth prevention clinics. Quantification of the extent of success is difficult to predict and will be dependent on other clinical, cultural, societal, and economic factors operating in each environment. Further success can be anticipated in the coming years as other research discoveries are translated into clinical practice, including new approaches to treating intra-uterine infection, improvements in maternal nutrition, and lifestyle modifications to ameliorate maternal stress. The widespread use of human papillomavirus vaccination in girls and young women will decrease the need for surgical interventions on the cervix and can be expected to further reduce the risk of early birth. Together, this array of clinical interventions, each based on a substantial body of evidence, is likely to reduce rates of preterm birth and prevent death and disability in large numbers of children. The process begins with an acceptance that early birth is not an inevitable and natural feature of human reproduction. Preventative strategies are now available and need to be applied. The best outcomes may come from developing integrated strategies designed specifically for each health-care environment. PMID:25477878

  3. Cerebral palsy in preterm infants

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    Demeši-Drljan Čila

    2016-01-01

    Full Text Available Background/Aim. Cerebral palsy (CP is one of the leading causes of neurological impairment in childhood. Preterm birth is a significant risk factor in the occurrence of CP. Clinical outcomes may include impairment of gross motor function and intellectual abilities, visual impairment and epilepsy. The aim of this study was to examine the relationships among gestational age, type of CP, functional ability and associated conditions. Methods. The sample size was 206 children with CP. The data were obtained from medical records and included gestational age at birth, clinical characteristics of CP and associated conditions. Clinical CP type was determined according to Surveillance of Cerebral Palsy in Europe (SCPE and topographically. Gross motor function abilities were evaluated according to the Gross Motor Function Classification System (GMFCS. Results. More than half of the children with CP were born prematurely (54.4%. Statistically significant difference was noted with respect to the distribution of various clinical types of CP in relation to gestational age (p < 0.001. In the group with spastic bilateral CP type, there is a greater proportion of children born preterm. Statistically significant difference was noted in the functional classification based on GMFCS in terms of gestational age (p = 0.049, children born at earlier gestational age are classified at a higher GMFCS level of functional limitation. The greatest percentage of children (70.0% affected by two or more associated conditions was found in the group that had extremely preterm birth, and that number declined with increasing maturity at birth. Epilepsy was more prevalent in children born at greater gestational age, and this difference in distribution was statistically significant (p = 0.032. Conclusion. The application of antenatal and postnatal protection of preterm children should be a significant component of the CP prevention strategy. [Projekat Ministarstva nauke Republike

  4. Mandibular biomechanics and temporomandibular joint function in primates.

    Science.gov (United States)

    Smith, R J

    1978-09-01

    There is disagreement as to whether the mandibular condyles are stress-bearing or stress-free during mastication. In support of alternative models, analogies have been drawn with Class III levers, links, and couple systems. Physiological data are reviewed which indicate that maximum masticatory forces are generated when maxillary and mandibular teeth are in contact, and that this phase lasts for over 100 msec during many chewing strokes. During this period, the mandible can be modeled as a beam with multiple supports. Equations of simple beam theory suggest that large condylar reaction forces are present during mastication. With unilateral molar biting in man, the total condylar reaction force may be over 75% of the bite force. Analysis of a frontal projection demonstrates that up to 80% of the total condylar reaction force is borne by the contralateral (balancing side) condyle during unilateral molar biting. A comparison of human, chimpanzee (P. troglodytes), spider monkey (A. belzebuth), and macaque (Macaca sp.) morphology indicates that the frugivorous chimpanzee and spider monkey have a relatively lower condylar reaction force than the omnivorous macaque or man during molar biting. The percentage reaction force during incisal biting is lower in man than in the other primates, and lower in the frugivorous primates than in the macaque.

  5. Development of an inexpensive, low attenuation styrofoam primate chair for use in a PET scanner

    NARCIS (Netherlands)

    Kortekaas, R; van Waarde, A; Maguire, RP; Leenders, KL; Elsinga, PH

    Pharmacokinetic modelling of radiotracers for positron emission tomography (PET) imaging of neuroreceptors can be performed with time-activity data for brain and blood. We aimed to develop an alternative to withdrawal of arterial blood samples for acquisition of a blood curve. A supportive primate

  6. Patch size, functional isolation, visibility and matrix permeability influences neotropical primate occurrence within highly fragmented landscapes.

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    Lucas Goulart da Silva

    Full Text Available Forest fragmentation and habitat loss are among the major current extinction causes. Remaining fragments are mostly small, isolated and showing poor quality. Being primarily arboreal, Neotropical primates are generally sensitive to fragmentation effects. Furthermore, primates are involved in complex ecological process. Thus, landscape changes that negatively interfere with primate population dynamic affect the structure, composition, and ultimately the viability of the whole community. We evaluated if fragment size, isolation and visibility and matrix permeability are important for explaining the occurrence of three Neotropical primate species. Employing playback, we verified the presence of Callicebus nigrifrons, Callithrix aurita and Sapajus nigritus at 45 forest fragments around the municipality of Alfenas, Brazil. We classified the landscape and evaluated the metrics through predictive models of occurrence. We selected the best models through Akaike Selection Criterion. Aiming at validating our results, we applied the plausible models to another region (20 fragments at the neighboring municipality of Poço Fundo, Brazil. Twelve models were plausible, and three were validated, two for Sapajus nigritus (Area and Area+Visibility and one for Callicebus nigrifrons (Area+Matrix. Our results reinforce the contribution of fragment size to maintain biodiversity within highly degraded habitats. At the same time, they stress the importance of including novel, biologically relevant metrics in landscape studies, such as visibility and matrix permeability, which can provide invaluable help for similar studies in the future and on conservation practices in the long run.

  7. Rapid gut growth but persistent delay in digestive function in the postnatal period of preterm pigs

    DEFF Research Database (Denmark)

    Hansen, Carl Frederik; Thymann, Thomas; Andersen, Anders Daniel

    2016-01-01

    BACKGROUND: Preterm infants often tolerate full enteral nutrition few weeks after birth but it is not known how this is related to gut maturation. Using pigs as models, we hypothesized that intestinal structure and digestive function are similar in preterm and term individuals at 3-4 weeks after...... to term pigs. CONCLUSION: Intestinal structure shows a remarkable growth adaptation in the first week after preterm birth, especially with enteral nutrition, while some digestive functions remain immature until at least 3-4 weeks. It is important to identify feeding regimens that stimulate intestinal...... birth and that early enteral nutrition promotes maturation. METHODS: Preterm or term cesarean-delivered pigs were fed total parenteral nutrition (TPN), or partial enteral nutrition (ENT, 16-64 mL/kg/d of bovine colostrum) for 5 d, followed by full enteral milk feeding until d 26. The intestine...

  8. Neurologic and metabolic issues in moderately preterm, late preterm, and early term infants.

    Science.gov (United States)

    Laptook, Abbot R

    2013-12-01

    Common neurologic morbidities encountered in very preterm and extremely preterm infants (intracranial hemorrhage, white matter injury and periventricular leukomalacia, and apnea of prematurity) are much less common in moderately preterm and late preterm infants. The frequency of germinal matrix hemorrhage-intraventricular hemorrhage and white matter injury are reported to be low, but selection bias in neuroimaging surveillance prevents ascertainment of precise frequencies. The major neurologic morbidity of moderately and late preterm infants is feeding difficulty reflecting developmental integration of suck, swallow, and breathing. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Pretreatment with Pancaspase Inhibitor (Z-VAD-FMK Delays but Does Not Prevent Intraperitoneal Heat-Killed Group B Streptococcus-Induced Preterm Delivery in a Pregnant Mouse Model

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    Ozlem Equils

    2009-01-01

    Full Text Available Caspases and apoptosis are thought to play a role in infection-associated preterm-delivery. We have shown that in vitro treatment with pancaspase inhibitor Z-VAD-FMK protects trophoblasts from microbial antigen-induced apoptosis. Objective. To examine whether in vivo administration of Z-VAD-FMK would prevent infection-induced preterm-delivery. Methods. We injected 14.5 day-pregnant-mice with heat-killed group B streptococcus (HK-GBS. Apoptosis within placentas and membranes was assessed by TUNEL staining. Calpain expression and caspase-3 activation were assessed by immunohistochemistry. Preterm-delivery was defined as expulsion of a fetus within 48 hours after injection. Results. Intrauterine (i.u. or intraperitoneal (i.p. HK-GBS injection led to preterm-delivery and induced apoptosis in placentas and membranes at 14 hours. The expression of calpain, a caspase-independent inducer of apoptosis, was increased in placenta. Treatment with the specific caspase inhibitor Z-VAD-FMK (i.p. prior to HK-GBS (i.p. delayed but did not prevent preterm-delivery. Conclusion. Caspase-dependent apoptosis appears to play a role in the timing but not the occurrence of GBS-induced preterm delivery in the mouse.

  10. Studying primate cognition in a social setting to improve validity and welfare: a literature review highlighting successful approaches.

    Science.gov (United States)

    Cronin, Katherine A; Jacobson, Sarah L; Bonnie, Kristin E; Hopper, Lydia M

    2017-01-01

    models for researchers wishing to overcome potential practical and statistical challenges to studying cognition in a social setting, ultimately increasing validity and improving the welfare of the primates we study.

  11. Challenges in understanding the impact of blood pressure management on cerebral oxygenation in the preterm brain

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    Aminath eAzhan

    2012-12-01

    Full Text Available Systemic hypotension in preterm infants has been related to increased mortality, cerebrovascular lesions and neurodevelopmental morbidity. Treatment of hypotension with inotropic medications aims at preservation of end organ perfusion and oxygen delivery, especially the brain. The common inotropic medications in preterm infants include dopamine, dobutamine, adrenalin, with adjunctive use of corticosteroids in cases of refractory hypotension. Whether maintenance of mean arterial blood pressure (MAP by use of inotropic medication is neuroprotective or not remains unclear. This review explores the different inotropic agents and their effects on perfusion and oxygenation in the preterm brain, in clinical studies as well as in animal models. Dopamine and adrenalin, because of their -adrenergic vasoconstrictor actions, have raised concerns of reduction in cerebral blood flow (CBF. Several studies in hypotensive preterm infants have shown that dopamine elevates CBF together with increased MAP, in keeping with limited cerebro-autoregulation. Adrenaline is also effective in raising cerebral perfusion together with MAP in preterm infants. Experimental studies in immature animals show no cerebro-vasoconstrictive effects of dopamine or adrenaline, but demonstrate the consistent findings of increased cerebral perfusion and oxygenation with the use of dopamine, dobutamine and adrenaline, alongside with raised MAP. Both clinical and animal studies report the transitory effects of adrenaline in increasing plasma lactate, and blood glucose, which might render its use as a 2nd line therapy. To investigate the cerebral effects of inotropic agents in long-term outcome in hypotensive preterm infants, carefully designed prospective research possibly including preterm infants with permissive hypotension is required. Preterm animal models would be useful in investigating the relationship between the physiological effects of inotropes and histopathology outcomes in

  12. Taxonomy and conservation of Vietnam's primates: a review.

    Science.gov (United States)

    Blair, Mary E; Sterling, Eleanor J; Hurley, Martha M

    2011-11-01

    Vietnam has the highest number of primate taxa overall (24-27) and the highest number of globally threatened primate taxa (minimum 20) in Mainland Southeast Asia. Conservation management of these species depends in part on resolving taxonomic uncertainties, which remain numerous among the Asian primates. Recent research on genetic, morphological, and acoustic diversity in Vietnam's primates has clarified some of these uncertainties, although a number of significant classification issues still remain. Herein, we summarize and compare the major current taxonomic classifications of Vietnam's primates, discuss recent advances in the context of these taxonomies, and suggest key areas for additional research to best inform conservation efforts in a region crucial to global primate diversity. Among the most important next steps for the conservation of Vietnam's primates is a new consensus list of Asian primates that resolves current differences between major taxonomies, incorporates recent research advances, and recognizes units of diversity at scales below the species-level, whether termed populations, morphs, or subspecies. Priority should be placed on recognizing distinct populations, regardless of the species concept in use, in order to foster the evolutionary processes necessary for primate populations to cope with inevitable environmental changes. The long-term conservation of Vietnam's primates depends not only on an accepted and accurate taxonomy but also on funding for on-the-ground conservation activities, including training, and the continued dedication and leadership of Vietnamese researchers and managers. © 2011 Wiley Periodicals, Inc.

  13. Born Too Soon: Care during pregnancy and childbirth to reduce preterm deliveries and improve health outcomes of the preterm baby

    Science.gov (United States)

    2013-01-01

    implemented in conjunction with antenatal care models that promote women's empowerment as a strategy for reducing preterm delivery. The global community needs to support more discovery research on normal and abnormal pregnancies to facilitate the development of preventive interventions for universal application. As new evidence is generated, resources need to be allocated to its translation into new and better screening and diagnostic tools, and other interventions aimed at saving maternal and newborn lives that can be brought to scale in all countries. Declaration This article is part of a supplement jointly funded by Save the Children's Saving Newborn Lives programme through a grant from The Bill & Melinda Gates Foundation and March of Dimes Foundation and published in collaboration with the Partnership for Maternal, Newborn and Child Health and the World Health Organization (WHO). The original article was published in PDF format in the WHO Report "Born Too Soon: the global action report on preterm birth" (ISBN 978 92 4 150343 30), which involved collaboration from more than 50 organizations. The article has been reformatted for journal publication and has undergone peer review according to Reproductive Health's standard process for supplements and may feature some variations in content when compared to the original report. This co-publication makes the article available to the community in a full-text format. PMID:24625215

  14. Patterns of gut bacterial colonization in three primate species.

    Science.gov (United States)

    McKenney, Erin A; Rodrigo, Allen; Yoder, Anne D

    2015-01-01

    Host fitness is impacted by trillions of bacteria in the gastrointestinal tract that facilitate development and are inextricably tied to life history. During development, microbial colonization primes the gut metabolism and physiology, thereby setting the stage for adult nutrition and health. However, the ecological rules governing microbial succession are poorly understood. In this study, we examined the relationship between host lineage, captive diet, and life stage and gut microbiota characteristics in three primate species (infraorder, Lemuriformes). Fecal samples were collected from captive lemur mothers and their infants, from birth to weaning. Microbial DNA was extracted and the v4 region of 16S rDNA was sequenced on the Illumina platform using protocols from the Earth Microbiome Project. Here, we show that colonization proceeds along different successional trajectories in developing infants from species with differing dietary regimes and ecological profiles: frugivorous (fruit-eating) Varecia variegata, generalist Lemur catta, and folivorous (leaf-eating) Propithecus coquereli. Our analyses reveal community membership and succession patterns consistent with previous studies of human infants, suggesting that lemurs may serve as a useful model of microbial ecology in the primate gut. Each lemur species exhibits distinct species-specific bacterial diversity signatures correlating to life stages and life history traits, implying that gut microbial community assembly primes developing infants at species-specific rates for their respective adult feeding strategies.

  15. Patterns of gut bacterial colonization in three primate species.

    Directory of Open Access Journals (Sweden)

    Erin A McKenney

    Full Text Available Host fitness is impacted by trillions of bacteria in the gastrointestinal tract that facilitate development and are inextricably tied to life history. During development, microbial colonization primes the gut metabolism and physiology, thereby setting the stage for adult nutrition and health. However, the ecological rules governing microbial succession are poorly understood. In this study, we examined the relationship between host lineage, captive diet, and life stage and gut microbiota characteristics in three primate species (infraorder, Lemuriformes. Fecal samples were collected from captive lemur mothers and their infants, from birth to weaning. Microbial DNA was extracted and the v4 region of 16S rDNA was sequenced on the Illumina platform using protocols from the Earth Microbiome Project. Here, we show that colonization proceeds along different successional trajectories in developing infants from species with differing dietary regimes and ecological profiles: frugivorous (fruit-eating Varecia variegata, generalist Lemur catta, and folivorous (leaf-eating Propithecus coquereli. Our analyses reveal community membership and succession patterns consistent with previous studies of human infants, suggesting that lemurs may serve as a useful model of microbial ecology in the primate gut. Each lemur species exhibits distinct species-specific bacterial diversity signatures correlating to life stages and life history traits, implying that gut microbial community assembly primes developing infants at species-specific rates for their respective adult feeding strategies.

  16. Evolution of the hepcidin gene in primates

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    Tossi Alessandro

    2008-03-01

    Full Text Available Abstract Background Hepcidin/LEAP-1 is an iron regulatory hormone originally identified as an antimicrobial peptide. As part of a systematic analysis of the evolution of host defense peptides in primates, we have sequenced the orthologous gene from 14 species of non-human primates. Results The sequence of the mature peptide is highly conserved amongst all the analyzed species, being identical to the human one in great apes and gibbons, with a single residue conservative variation in Old-World monkeys and with few substitutions in New-World monkeys. Conclusion Our analysis indicates that hepcidin's role as a regulatory hormone, which involves interaction with a conserved receptor (ferroportin, may result in conservation over most of its sequence, with the exception of the stretch between residues 15 and 18, which in New-World monkeys (as well as in other mammals shows a significant variation, possibly indicating that this structural region is involved in other functions.

  17. [Ecotourism disturbances to non-human primates].

    Science.gov (United States)

    Fan, Peng-Lai; Xiang, Zuo-Fu

    2013-02-01

    In tandem with economic growth and rising living conditions, ecotourism has increasingly gained popularity among the Chinese public. Non-human primates, as charismatic animals and the closest relatives of human beings, have shown a strong affinity in attracting the general public and raising money, and for that reason a variety of monkey parks, valleys, and islands are becoming increasingly popular in China. Though successful in raising a substantial sum of money for the managing agency of a nature reserve, there may be negative impacts on monkey groups used in ecotourism. Here, to establish effective guards for non-human primates involved in ecotourism, we present a review on tourism disturbance and summarize the negative impacts on behavioral patterns, reproduction, and health condition of animals.

  18. Nonhuman primate dermatology: a literature review

    Science.gov (United States)

    Bernstein, Joseph A.; Didier, Peter J.

    2015-01-01

    In general, veterinary dermatologists do not have extensive clinical experience of nonhuman primate (NHP) dermatoses. The bulk of the published literature does not provide an organized evidence-based approach to the NHP dermatologic case. The veterinary dermatologist is left to extract information from both human and veterinary dermatology, an approach that can be problematic as it forces the clinician to make diagnostic and therapeutic decisions based on two very disparate bodies of literature. A more cohesive approach to NHP dermatology – without relying on assumptions that NHP pathology most commonly behaves similarly to other veterinary and human disease – is required. This review of the dermatology of NHP species includes discussions of primary dermatoses, as well as diseases where dermatologic signs represent a significant secondary component, provides a first step towards encouraging the veterinary community to study and report the dermatologic diseases of nonhuman primates. PMID:19490576

  19. Immune evasion strategies of the primate lentiviruses.

    Science.gov (United States)

    Evans, D T; Desrosiers, R C

    2001-10-01

    Individuals infected with human immunodeficiency virus (HIV) and macaques infected with simian immunodeficiency virus (SIV) make vigorous virus-specific antibody and cellular immune responses. Despite these responses, virus replication continues at all stages of infection and ultimately leads to immunological collapse, onset of opportunistic infections and death of infected hosts. Thus, the strategies by which HIV and SIV evade antiviral immune surveillance are fundamental to understanding lentiviral pathogenesis and crucial for our ability to develop effective strategies. It has become increasingly clear that the primate lentiviruses have evolved multiple and complementary mechanisms to circumvent host immune responses. Here we review these mechanisms of immune evasion considering contributions from both human and non-human primate systems.

  20. Leading causes of preterm delivery as risk factors for intraventricular hemorrhage in very preterm infants: results of the EPIPAGE 2 cohort study.

    Science.gov (United States)

    Chevallier, Marie; Debillon, Thierry; Pierrat, Veronique; Delorme, Pierre; Kayem, Gilles; Durox, Mélanie; Goffinet, François; Marret, Stephane; Ancel, Pierre Yves

    2017-05-01

    Intraventricular hemorrhage is a major risk factor for neurodevelopmental disabilities in preterm infants. However, few studies have investigated how pregnancy complications responsible for preterm delivery are related to intraventricular hemorrhage. We sought to investigate the association between the main causes of preterm delivery and intraventricular hemorrhage in very preterm infants born in France during 2011 between 22-31 weeks of gestation. The study included 3495 preterm infants from the national EPIPAGE 2 cohort study who were admitted to neonatal intensive care units and had at least 1 cranial ultrasound assessment. The primary outcome was grade I-IV intraventricular hemorrhage according to the Papile classification. Multinomial logistic regression models were used to study the relationship between risk of intraventricular hemorrhage and the leading causes of preterm delivery: vascular placental diseases, isolated intrauterine growth retardation, placental abruption, preterm labor, and premature rupture of membranes, with or without associated maternal inflammatory syndrome. The overall frequency of grade IV, III, II, and I intraventricular hemorrhage was 3.8% (95% confidence interval, 3.2-4.5), 3.3% (95% confidence interval, 2.7-3.9), 12.1% (95% confidence interval, 11.0-13.3), and 17.0% (95% confidence interval, 15.7-18.4), respectively. After adjustment for gestational age, antenatal magnesium sulfate therapy, level of care in the maternity unit, antenatal corticosteroids, and chest compressions, infants born after placental abruption had a higher risk of grade IV and III intraventricular hemorrhage compared to those born under placental vascular disease conditions, with adjusted odds ratios of 4.3 (95% confidence interval, 1.1-17.0) and 4.4 (95% confidence interval, 1.1-17.6), respectively. Similarly, preterm labor with concurrent inflammatory syndrome was associated with an increased risk of grade IV intraventricular hemorrhage (adjusted odds ratio

  1. Hypothyroxinaemia and thyroid function after preterm birth

    NARCIS (Netherlands)

    van Wassenaer, Aleid G.; Kok, Joke H.

    2004-01-01

    The concentration of thyroid hormone in preterm infants is lower than that in term infants. This phenomenon is referred to as transient hypothyroxinaemia of prematurity. Low thyroid hormone levels after very preterm birth are associated with worse developmental outcome in childhood, but only one

  2. Immune cells in term and preterm labor

    Science.gov (United States)

    Gomez-Lopez, Nardhy; StLouis, Derek; Lehr, Marcus A; Sanchez-Rodriguez, Elly N; Arenas-Hernandez, Marcia

    2014-01-01

    Labor resembles an inflammatory response that includes secretion of cytokines/chemokines by resident and infiltrating immune cells into reproductive tissues and the maternal/fetal interface. Untimely activation of these inflammatory pathways leads to preterm labor, which can result in preterm birth. Preterm birth is a major determinant of neonatal mortality and morbidity; therefore, the elucidation of the process of labor at a cellular and molecular level is essential for understanding the pathophysiology of preterm labor. Here, we summarize the role of innate and adaptive immune cells in the physiological or pathological activation of labor. We review published literature regarding the role of innate and adaptive immune cells in the cervix, myometrium, fetal membranes, decidua and the fetus in late pregnancy and labor at term and preterm. Accumulating evidence suggests that innate immune cells (neutrophils, macrophages and mast cells) mediate the process of labor by releasing pro-inflammatory factors such as cytokines, chemokines and matrix metalloproteinases. Adaptive immune cells (T-cell subsets and B cells) participate in the maintenance of fetomaternal tolerance during pregnancy, and an alteration in their function or abundance may lead to labor at term or preterm. Also, immune cells that bridge the innate and adaptive immune systems (natural killer T (NKT) cells and dendritic cells (DCs)) seem to participate in the pathophysiology of preterm labor. In conclusion, a balance between innate and adaptive immune cells is required in order to sustain pregnancy; an alteration of this balance will lead to labor at term or preterm. PMID:24954221

  3. Does fish oil prevent preterm birth?

    DEFF Research Database (Denmark)

    Secher, Niels Jørgen

    2007-01-01

    A literature review was performed on the effect of fish oil on preterm birth in observational and randomized studies. The only weak effect on preterm birth found in meta-analyses could be caused by the low compliance, and the fact that many women stop supplementation before term together...

  4. Literacy Skills of Children Born Preterm

    Science.gov (United States)

    Holm, Alison; Crosbie, Sharon

    2010-01-01

    Most children born preterm are considered neurologically normal and free of disability. However in follow-up studies at school age, preterm children, born without major impairment, have been shown to have lower cognitive abilities and associated academic, social and behavioural difficulties. This study investigated the literacy, phonological…

  5. First middle Miocene sivaladapid primate from Thailand

    Energy Technology Data Exchange (ETDEWEB)

    Chaimanee, Y.; Yamee, C.; Tian, P.; Chavasseau, O.; Jaeger, J.J. [Bureau for Paleontology & Museum, Bangkok (Thailand). Dept. for Mineral Resources

    2008-03-15

    Sivaladapids are a group of Asian adapiform primates that were previously documented from deposits dating to the middle Eocene through the late Miocene in Pakistan, India, Myanmar, Thailand, and China. The group is notable for the persistence of three genera, Sivaladapis, Indraloris and Sinoadapis, into the late Miocene. In Thailand, sivaladapids were previously documented only from late Eocene deposits of the Krabi mine. Here, we describe the first Southeast Asian Miocene sivaladapid, Siamoadapis maemohensis gen. et sp. nov. from a 13.3 to 13.1 Ma lignite layer from the Mae Moh coal mine, Thailand. It differs from other Miocene sivaladapids by its distinctly smaller size and in features of the dentition. This discovery enhances the paleoecological diversity of the middle Miocene primate fauna of Thailand, which now includes sivaladapids, a loris, tarsiids, and hominoids. In this respect, the fossil primate community from the middle Miocene of Thailand is similar in its composition to roughly contemporaneous assemblages from southern China, India, and Pakistan. However, the Thai fossils represent a distinct genus, suggesting a different biogeographic province with distinctive paleoenvironments.

  6. Pervasive adaptive evolution in primate seminal proteins.

    Directory of Open Access Journals (Sweden)

    Nathaniel L Clark

    2005-09-01

    Full Text Available Seminal fluid proteins show striking effects on reproduction, involving manipulation of female behavior and physiology, mechanisms of sperm competition, and pathogen defense. Strong adaptive pressures are expected for such manifestations of sexual selection and host defense, but the extent of positive selection in seminal fluid proteins from divergent taxa is unknown. We identified adaptive evolution in primate seminal proteins using genomic resources in a tissue-specific study. We found extensive signatures of positive selection when comparing 161 human seminal fluid proteins and 2,858 prostate-expressed genes to those in chimpanzee. Seven of eight outstanding genes yielded statistically significant evidence of positive selection when analyzed in divergent primates. Functional clues were gained through divergent analysis, including several cases of species-specific loss of function in copulatory plug genes, and statistically significant spatial clustering of positively selected sites near the active site of kallikrein 2. This study reveals previously unidentified positive selection in seven primate seminal proteins, and when considered with findings in Drosophila, indicates that extensive positive selection is found in seminal fluid across divergent taxonomic groups.

  7. Pervasive Adaptive Evolution in Primate Seminal Proteins.

    Directory of Open Access Journals (Sweden)

    2005-09-01

    Full Text Available Seminal fluid proteins show striking effects on reproduction, involving manipulation of female behavior and physiology, mechanisms of sperm competition, and pathogen defense. Strong adaptive pressures are expected for such manifestations of sexual selection and host defense, but the extent of positive selection in seminal fluid proteins from divergent taxa is unknown. We identified adaptive evolution in primate seminal proteins using genomic resources in a tissue-specific study. We found extensive signatures of positive selection when comparing 161 human seminal fluid proteins and 2,858 prostate-expressed genes to those in chimpanzee. Seven of eight outstanding genes yielded statistically significant evidence of positive selection when analyzed in divergent primates. Functional clues were gained through divergent analysis, including several cases of species-specific loss of function in copulatory plug genes, and statistically significant spatial clustering of positively selected sites near the active site of kallikrein 2. This study reveals previously unidentified positive selection in seven primate seminal proteins, and when considered with findings in Drosophila, indicates that extensive positive selection is found in seminal fluid across divergent taxonomic groups.

  8. Dietary quality and encephalization in platyrrhine primates

    Science.gov (United States)

    Allen, Kari L.; Kay, Richard F.

    2012-01-01

    The high energetic costs of building and maintaining large brains are thought to constrain encephalization. The ‘expensive-tissue hypothesis’ (ETH) proposes that primates (especially humans) overcame this constraint through reduction of another metabolically expensive tissue, the gastrointestinal tract. Small guts characterize animals specializing on easily digestible diets. Thus, the hypothesis may be tested via the relationship between brain size and diet quality. Platyrrhine primates present an interesting test case, as they are more variably encephalized than other extant primate clades (excluding Hominoidea). We find a high degree of phylogenetic signal in the data for diet quality, endocranial volume and body size. Controlling for phylogenetic effects, we find no significant correlation between relative diet quality and relative endocranial volume. Thus, diet quality fails to account for differences in platyrrhine encephalization. One taxon, in particular, Brachyteles, violates predictions made by ETH in having a large brain and low-quality diet. Dietary reconstructions of stem platyrrhines further indicate that a relatively high-quality diet was probably in place prior to increases in encephalization. Therefore, it is unlikely that a shift in diet quality was a primary constraint release for encephalization in platyrrhines and, by extrapolation, humans. PMID:21831898

  9. Preterm Infants and Parents’ self-esteem

    DEFF Research Database (Denmark)

    Aagaard, Hanne; Madsen, Mette Kold

    Background: Little is known about parents to preterm infants and their self-esteem. The care of preterm infants in the neonatal intensive care unit (NICU) is in accordance with the principles of Family Centered Care. Previously, focus has mainly been on the mother-infant-dyad. Current research has...... shown that involving the father at an early stage improves the psychological dynamic of fatherhood and encourages bonding with the infant. The self-esteem of parents appears to be negatively affected after preterm birth. Objective: To get more knowledge and a deeper understanding of the preterm parents......’ experiences of their self-esteem during admission to the NICU and later eight months after discharge. Method and data collection: A qualitative semi-structured interview was conducted in two phases: 1) Three weeks after giving birth to a preterm infant and eight months after discharge. Parents were...

  10. preterm births in a resource constrained setting: soci

    African Journals Online (AJOL)

    2015-12-01

    Dec 1, 2015 ... cerebral palsy, visual and hearing impairment are also more common in preterm infants. Preterm birth in it- ... vious history of induced abortion, previous history of pre-term delivery, history of antenatal ..... cioeconomic status with stress which has been found to be a trigger for preterm labour and delivery.6 ...

  11. Preterm Birth: An Overview of Risk Factors and Obstetrical Management

    Science.gov (United States)

    Stewart, Amanda; Graham, Ernest

    2010-01-01

    Preterm birth is the leading cause of neonatal mortality and a major public health concern. Risk factors for preterm birth include a history of preterm birth, short cervix, infection, short interpregnancy interval, smoking, and African-American race. The use of progesterone therapy to treat mothers at risk for preterm delivery is becoming more…

  12. A qualitative study: Mothers of late preterm infants relate their experiences of community-based care.

    Directory of Open Access Journals (Sweden)

    Shahirose S Premji

    Full Text Available In Alberta, the high occurrence of late preterm infants and early hospital discharge of mother-infant dyads has implications for postpartum care in the community. Shortened hospital stay and complexities surrounding the care of biologically and developmentally immature late preterm infants heighten anxiety and fears. Our descriptive phenomenological study explores mothers' experience of caring for their late preterm infants in the community.Eleven mothers were interviewed using a semi-structured interview guide. Interview transcripts were analysed using an interpretive thematic approach.The mothers' hospital experience informed their perspective that being a late preterm infant was not a "big deal," and they tended to treat their infant as normal. "Feeding was really problem," especially the variability in feeding effectiveness, which was not anticipated. Failing to recognize late preterm infants' feeding distress exemplified lack of knowledge of feeding cues and tendencies to either rationalize or minimize feeding concerns. Public health nurses represent a source of informational support for managing neonatal morbidities associated with being late preterm; however, maternal experiences with public health nurses varied. Some nurses used a directive style that overwhelmed certain mothers. Seeing multiple public health nurses and care providers was not always effective, given inconsistent and contradictory guidance to care. These new and changing situations increased maternal anxiety and stress and influenced maternal confidence in care. Fathers, family, and friends were important sources of emotional support.After discharge, mothers report their lack of preparation to meet the special needs of their late preterm infants. Current approaches to community-based care can threaten maternal confidence in care. New models and pathways of care for late preterm infants and their families need to be responsive to the spectrum of feeding issues encountered

  13. Association of Antenatal Depression Symptoms and Antidepressant Treatment With Preterm Birth.

    Science.gov (United States)

    Venkatesh, Kartik K; Riley, Laura; Castro, Victor M; Perlis, Roy H; Kaimal, Anjali J

    2016-05-01

    To evaluate the association of antenatal depression symptoms with preterm birth and small for gestational age (SGA). This was an observational cohort study conducted among women who completed Edinburgh Postnatal Depression Scale screening and delivered at 20 weeks of gestation or greater. The primary outcomes were preterm birth and an SGA neonate at birth (less than 10th percentile for gestational age); the primary predictor was an Edinburgh Postnatal Depression Scale antepartum score of 10 or greater, indicating symptoms of depression. Logistic regression models were used with and without consideration of antidepressant exposure during pregnancy. Among 7,267 women, 831 (11%) screened positive for depression. In multivariable analyses adjusting for maternal age, race, income, body mass index, tobacco use, lifetime diagnosis of major depression and anxiety, diabetes, hypertension, and preeclampsia, women who screened positive for depression experienced an increased risk of preterm birth (less than 37 weeks of gestation) (adjusted odds ratio [OR] 1.27, 95% confidence interval [CI] 1.04-1.55) and very preterm birth (less than 32 weeks of gestation) (adjusted OR 1.82, 95% CI 1.09-3.02) as well as of having an SGA neonate (adjusted OR 1.28, 95% CI 1.04-1.58). In secondary analyses, among women who were treated with an antidepressant during pregnancy (19% of those who screened positive and 5% of those who screened negative), depressive symptoms were not associated with a significantly increased risk of preterm and very preterm birth or an SGA neonate. In a large cohort of women screened for depression antepartum, those with depressive symptoms had an increased likelihood of preterm and very preterm delivery as well having an SGA neonate. Such risk was not apparent among women who were treated with an antidepressant medication.

  14. Preclinical Evaluation of a P2X7 Receptor-Selective Radiotracer: PET Studies in a Rat Model with Local Overexpression of the Human P2X7 Receptor and in Nonhuman Primates.

    Science.gov (United States)

    Ory, Dieter; Celen, Sofie; Gijsbers, Rik; Van Den Haute, Chris; Postnov, Andrey; Koole, Michel; Vandeputte, Caroline; Andrés, José-Ignacio; Alcazar, Jesus; De Angelis, Meri; Langlois, Xavier; Bhattacharya, Anindya; Schmidt, Mark; Letavic, Michael A; Vanduffel, Wim; Van Laere, Koen; Verbruggen, Alfons; Debyser, Zeger; Bormans, Guy

    2016-09-01

    The P2X7 receptor (P2X7R) orchestrates neuroinflammation, and this is the basis for an increased interest in the development of antagonists inhibiting P2X7R function in the brain. This study provides the preclinical evaluation of (11)C-JNJ-54173717, a PET tracer for P2X7R in both rats and nonhuman primates. (11)C-JNJ-54173717 is a high-affinity radiotracer for the human P2X7R (hP2X7R). Biodistribution and radiometabolite studies were performed. Viral vectors encoding either enhanced green fluorescent protein-hP2X7R or 3flag-hP2X7R were engineered and validated in cell culture. hP2X7R was regionally overexpressed in the rat striatum after stereotactic injection of viral vectors. Dynamic small-animal PET studies were performed in vector-injected rats and in healthy monkeys using (11)C-JNJ-54173717. The affinity of JNJ-54173717 was 1.6 ± 0.1 nM in a rat cortex P2X7R membrane binding assay. In a functional assay at the recombinant human and rat P2X7R orthologs, the half maximal inhibitory concentration (IC50) of JNJ-54173717 was 4.2 ± 0.01 nM and 7.6 ± 0.01 nM, respectively. The rat biodistribution study showed that (11)C-JNJ-54173717 crossed the blood-brain barrier and was cleared from plasma mainly via the hepatobiliary pathway. A polar radiometabolite was found in rat plasma. No radiometabolites were detected in rat brain. Dynamic small-animal PET showed binding of (11)C-JNJ-54173717 in the striatum expressing hP2X7R, with rapid washout from the noninjected control striatum and other brain regions. Likewise, (11)C-JNJ-54173717 PET signal was blocked by a chemically distinct P2X7R ligand, indicating specific binding to P2X7R in the monkey brain. JNJ-54173717 is a high-affinity P2X7R antagonist. An animal rat model stably expressing hP2X7R was developed and validated, identifying favorable characteristics for (11)C-JNJ-54173717 as a PET radioligand for in vivo visualization of hP2X7R. (11)C-JNJ-54173717 selectively visualized P2X7R in the monkey brain, and this

  15. The effects of preterm birth and its antecedents on the cardiovascular system.

    Science.gov (United States)

    Bensley, Jonathan G; De Matteo, Robert; Harding, Richard; Black, Mary J

    2016-06-01

    Preterm birth occurs in approximately 10% of all births worldwide. It prematurely exposes the developing cardiovascular system to the hemodynamic transition that occurs at birth and to the subsequent functional demands of life ex utero. This review describes the current knowledge of the effects of preterm birth, and some of its common antecedents (chorioamnionitis, intra-uterine growth restriction, and maternal antenatal corticosteroid administration), on the structure of the myocardium. A thorough literature search was conducted for articles relating to how preterm birth, and its antecedents, affect development of the heart. Given that sheep are an excellent model for the studies of cardiac development, this review has focused on experimental studies in sheep as well as clinical findings. Our review of the literature demonstrates that individuals born preterm are at an increased risk of cardiovascular disease later in life, including increased mean arterial pressure, abnormally shaped and sub-optimally performing hearts and changes in the vasculature. The review highlights how antenatal corticosteroids, intra-uterine growth restriction, and exposure to chorioamnionitis also have the potential to impact cardiac growth in the preterm newborn. Preterm birth and its common antecedents (antenatal corticosteroids, intra-uterine growth restriction, and chorioamnionitis) have the potential to adversely impact cardiac structure immediately following birth and in later life. © 2016 Nordic Federation of Societies of Obstetrics and Gynecology.

  16. Fetal exposure to lead during pregnancy and the risk of preterm and early-term deliveries.

    Science.gov (United States)

    Cheng, Lu; Zhang, Bin; Huo, Wenqian; Cao, Zhongqiang; Liu, Wenyu; Liao, Jiaqiang; Xia, Wei; Xu, Shunqing; Li, Yuanyuan

    2017-08-01

    Studies have reported the association between lead exposure during pregnancy and preterm birth. However, findings are still inconsistent. This prospective birth cohort study evaluated the risks of preterm and early-term births and its association with prenatal lead exposure in Hubei, China. A total of 7299 pregnant women were selected from the Healthy Baby Cohort. Maternal urinary lead levels were measured by the Inductively Coupled Plasma Mass Spectrometry. The associations between tertiles of urinary lead levels and the risks of preterm and early-term deliveries were assessed using multiple logistic regression models. The geometric mean of creatinine-adjusted urinary lead concentrations among all participating mothers, preterm birth, and early-term birth were 3.19, 3.68, and 3.17μg/g creatinine, respectively. A significant increase in the risk of preterm births was associated with the highest urinary lead tertile after adjusting for confounders with odds ratio (OR) of 1.96. The association was more pronounced among 25-36 years old mothers with OR of 2.03. Though significant p trends were observed between lead exposure (medium and high tertiles) and the risk of early-term births, their ORs were not significant. Our findings indicate that the risk of preterm birth might increase with higher fetal lead exposure, particularly among women between the age of 25 and 36 years. Copyright © 2017 Elsevier GmbH. All rights reserved.

  17. Targeting inflammation in the preterm infant: The role of the omega-3 fatty acid docosahexaenoic acid

    Directory of Open Access Journals (Sweden)

    Naomi H. Fink

    2016-09-01

    Full Text Available Long-chain polyunsaturated fatty acids are critical for the normal growth and development of preterm infants. Interest in these compounds rests in their anti-inflammatory properties. Clinical conditions with an inflammatory component such as bronchopulmonary dysplasia, necrotising enterocolitis and sepsis are risks to the survival of these infants. Dysregulation of inflammatory responses plays a central role in the aetiology of many of these neonatal disorders. There is evidence to suggest that the omega-3 long chain polyunsaturated fatty acid docosahexaenoic acid (DHA can down-regulate local and systemic inflammation in adults and animal models; however, very little is known about its protective effects in infants, especially preterm infants. Due to their immunological immaturity, preterm infants are particularly sensitive to diseases with an inflammatory aetiology in the early postnatal period. This makes DHA supplementation immediately after birth to combat neonatal inflammation an attractive therapy. Mechanistic data for DHA use in preterm infants are lacking and results from adult and animal studies may not be relevant to this population because of fundamental immune system differences. While there is increasing evidence from randomised controlled trials to support a beneficial effect of DHA for the preterm infant, more evidence is required to establish short and long-term effects of DHA on the immune status of preterm infants.

  18. Neonatal MRI is associated with future cognition and academic achievement in preterm children.

    Science.gov (United States)

    Ullman, Henrik; Spencer-Smith, Megan; Thompson, Deanne K; Doyle, Lex W; Inder, Terrie E; Anderson, Peter J; Klingberg, Torkel

    2015-11-01

    School-age children born preterm are particularly at risk for low mathematical achievement, associated with reduced working memory and number skills. Early identification of preterm children at risk for future impairments using brain markers might assist in referral for early intervention. This study aimed to examine the use of neonatal magnetic resonance imaging measures derived from automated methods (Jacobian maps from deformation-based morphometry; fractional anisotropy maps from diffusion tensor images) to predict skills important for mathematical achievement (working memory, early mathematical skills) at 5 and 7 years in a cohort of preterm children using both univariable (general linear model) and multivariable models (support vector regression). Participants were preterm children born children born ≥37 weeks' gestational age at the Royal Women's Hospital in Melbourne, Australia between July 2001 and December 2003 and recruited into a prospective longitudinal cohort study. At term-equivalent age ( ±2 weeks) 224 preterm and 46 control infants were recruited for magnetic resonance imaging. Working memory and early mathematics skills were assessed at 5 years (n = 195 preterm; n = 40 controls) and 7 years (n = 197 preterm; n = 43 controls). In the preterm group, results identified localized regions around the insula and putamen in the neonatal Jacobian map that were positively associated with early mathematics at 5 and 7 years (both P memory at 7 years (models ranging from P = 0.07 to P = 0.05). Neonatal fractional anisotropy was positively associated with working memory and early mathematics at 5 years (both P < 0.001) even after covarying for clinical factors using support vector regression but not general linear model. These significant relationships were not observed in the control group. In summary, we identified, in the preterm brain, regions around the insula and putamen using neonatal deformation-based morphometry, and brain microstructural

  19. Adaptive evolution of facial colour patterns in Neotropical primates

    OpenAIRE

    Santana, Sharlene E.; Lynch Alfaro, Jessica; Alfaro, Michael E.

    2012-01-01

    The rich diversity of primate faces has interested naturalists for over a century. Researchers have long proposed that social behaviours have shaped the evolution of primate facial diversity. However, the primate face constitutes a unique structure where the diverse and potentially competing functions of communication, ecology and physiology intersect, and the major determinants of facial diversity remain poorly understood. Here, we provide the first evidence for an adaptive role of facial co...

  20. Total matrix metalloproteinase-8 serum levels in patients labouring preterm and patients with threatened preterm delivery.

    Directory of Open Access Journals (Sweden)

    Piotr Laudański

    2010-11-01

    Full Text Available Preterm labour and prematurity are still a main cause of perinatal morbidity nowadays. The aim of our study was to assess the role of MMP-8 as a predictive marker of preterm delivery. Four groups of patients were involved to the study: I - pregnant women at 24-34 weeks of gestation with any symptoms of threatened preterm labour; II - threatened preterm labour patients between 24-34 weeks of gestation; III - preterm vaginal delivery patients; IV - healthy term vaginal delivery patients. Serum concentration of total MMP-8 was measured using two enzyme-linked immunosorbent assays. There were no significant differences in the median concentrations of total MMP-8 between physiological pregnancy and threatened preterm labour patients with existing uterine contractility. No significant differences of total MMP-8 were either found between healthy term and preterm labouring patients. The studies on a larger population are needed to reject the hypothesis that preterm labour is connected with increased MMP-8 plasma concentrations of women in preterm labour and threatened preterm delivery.

  1. Differential effects of parenting in preterm and full-term children on developmental outcomes.

    Science.gov (United States)

    Maupin, Angela N; Fine, Jodene Goldenring

    2014-12-01

    To examine the relations between preterm birth, parenting behavior during early childhood, cognitive development, and social-emotional outcomes at Kindergarten entry, and to determine whether parenting behavior differentially influences this developing system in children born preterm compared to children born full-term. The nationally representative sample comprised 3600 full-term and 1300 preterm children born in the US in the year 2001. All children who entered Kindergarten and who participated in data collection at 9 months, 24 months, and Kindergarten entry were included in the study. Measures of parenting behavior were collected at 9 and 24 months and cognitive development at 24 months via home visits. Social-emotional outcomes were assessed at Kindergarten entry via parent and teacher report. Multiple-sample Structural Equation Modeling was used to analyze group differences in a model whereby early childhood parenting behavior predicted cognitive outcomes, and social-emotional outcomes at Kindergarten entry, and indirectly predicted social-emotional outcomes via early cognitive processes. The full sample developmental model indicated excellent fit to the data. Preterm birth status indirectly influenced social-emotional outcomes at Kindergarten entry via its effect on early childhood parenting behavior and cognitive development. The multi-sample model revealed significant differences in the way in which early parenting behavior exerted its influence on outcomes at Kindergarten entry in preterm children compared to full-term children. For preterm children, parenting indirectly influenced social-emotional outcomes via early cognitive functioning. Findings highlight the importance of early identification and targeted parenting programs to support early cognitive development in preterm children. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Why is a landscape perspective important in studies of primates?

    Science.gov (United States)

    Arroyo-Rodríguez, Víctor; Fahrig, Lenore

    2014-10-01

    With accelerated deforestation and fragmentation through the tropics, assessing the impact that landscape spatial changes may have on biodiversity is paramount, as this information is required to design and implement effective management and conservation plans. Primates are expected to be particularly dependent on the landscape context; yet, our understanding on this topic is limited as the majority of primate studies are at the local scale, meaning that landscape-scale inferences are not possible. To encourage primatologists to assess the impact of landscape changes on primates, and help future studies on the topic, we describe the meaning of a "landscape perspective" and evaluate important assumptions of using such a methodological approach. We also summarize a number of important, but unanswered, questions that can be addressed using a landscape-scale study design. For example, it is still unclear if habitat loss has larger consistent negative effects on primates than habitat fragmentation per se. Furthermore, interaction effects between habitat area and other landscape effects (e.g., fragmentation) are unknown for primates. We also do not know if primates are affected by synergistic interactions among factors at the landscape scale (e.g., habitat loss and diseases, habitat loss and climate change, hunting, and land-use change), or whether landscape complexity (or landscape heterogeneity) is important for primate conservation. Testing for patterns in the responses of primates to landscape change will facilitate the development of new guidelines and principles for improving primate conservation. © 2014 Wiley Periodicals, Inc.

  3. Choriodecidual group B streptococcal inoculation induces fetal lung injury without intra-amniotic infection and preterm labor in Macaca nemestrina.

    Directory of Open Access Journals (Sweden)

    Kristina M Adams Waldorf

    Full Text Available BACKGROUND: Early events leading to intrauterine infection and fetal lung injury remain poorly defined, but may hold the key to preventing neonatal and adult chronic lung disease. Our objective was to establish a nonhuman primate model of an early stage of chorioamnionitis in order to determine the time course and mechanisms of fetal lung injury in utero. METHODOLOGY/PRINCIPAL FINDINGS: Ten chronically catheterized pregnant monkeys (Macaca nemestrina at 118-125 days gestation (term=172 days received one of two treatments: 1 choriodecidual and intra-amniotic saline (n=5, or 2 choriodecidual inoculation of Group B Streptococcus (GBS 1×10(6 colony forming units (n=5. Cesarean section was performed regardless of labor 4 days after GBS or 7 days after saline infusion to collect fetal and placental tissues. Only two GBS animals developed early labor with no cervical change in the remaining animals. Despite uterine quiescence in most cases, blinded review found histopathological evidence of fetal lung injury in four GBS animals characterized by intra-alveolar neutrophils and interstitial thickening, which was absent in controls. Significant elevations of cytokines in amniotic fluid (TNF-α, IL-8, IL-1β, IL-6 and fetal plasma (IL-8 were detected in GBS animals and correlated with lung injury (p<0.05. Lung injury was not directly caused by GBS, because GBS was undetectable in amniotic fluid (~10 samples tested/animal, maternal and fetal blood by culture and polymerase chain reaction. In only two cases was GBS cultured from the inoculation site in low numbers. Chorioamnionitis occurred in two GBS animals with lung injury, but two others with lung injury had normal placental histology. CONCLUSIONS/SIGNIFICANCE: A transient choriodecidual infection can induce cytokine production, which is associated with fetal lung injury without overt infection of amniotic fluid, chorioamnionitis or preterm labor. Fetal lung injury may, thus, occur silently without

  4. Population-level correlates of preterm delivery among black and white women in the U.S.

    Directory of Open Access Journals (Sweden)

    Suzan L Carmichael

    Full Text Available OBJECTIVE: This study examined the ability of social, demographic, environmental and health-related factors to explain geographic variability in preterm delivery among black and white women in the US and whether these factors explain black-white disparities in preterm delivery. METHODS: We examined county-level prevalence of preterm delivery (20-31 or 32-36 weeks gestation among singletons born 1998-2002. We conducted multivariable linear regression analysis to estimate the association of selected variables with preterm delivery separately for each preterm/race-ethnicity group. RESULTS: The prevalence of preterm delivery varied two- to three-fold across U.S. counties, and the distributions were strikingly distinct for blacks and whites. Among births to blacks, regression models explained 46% of the variability in county-level risk of delivery at 20-31 weeks and 55% for delivery at 32-36 weeks (based on R-squared values. Respective percentages for whites were 67% and 71%. Models included socio-environmental/demographic and health-related variables and explained similar amounts of variability overall. CONCLUSIONS: Much of the geographic variability in preterm delivery in the US can be explained by socioeconomic, demographic and health-related characteristics of the population, but less so for blacks than whites.

  5. Challenges and Consequences of Preterm Birth

    Directory of Open Access Journals (Sweden)

    Sribas Goswami

    2014-11-01

    Full Text Available Preterm births have been a challenge to obstetricians and paediatricians. Preterm births affect all population irrespective of age, race and economic status due to lack of seriousness and awareness among the pregnant women. Preterm birth is one of the leading causes of infant morbidity and mortality, amounting to billions of dollars each year, thus increasing the cost for health care. Proper awareness programs about preterm birth may help the women population to know and understand better the signs and symptoms of preterm labour. Preterm birth is a complex cluster of problems with a set of overlapping factors of influence. Its causes may include individual-level behavioral and psychosocial factors, neighborhood characteristics, environmental exposures, medical conditions, infertility treatments, biological factors and genetics. Many of these factors occur in combination, particularly in those who are socioeconomically disadvantaged or who are members of racial and ethnic minority groups. The empirical investigation was carried out to draw correlation between preterm birth and eventuality through this study.

  6. Born too soon: preterm birth matters.

    Science.gov (United States)

    Howson, Christopher P; Kinney, Mary V; McDougall, Lori; Lawn, Joy E

    2013-01-01

    Urgent action is needed to address preterm birth given that the fi rst country-level estimates show that globally 15 million babies are born too soon and rates are increasing in most countries with reliable time trend data. As the fi rst in a supplement entitled “Born Too Soon”, this paper focuses on the global policy context. Preterm birth is critical for progress on Millennium Development Goal 4 (MDG) for child survival by 2015 and beyond, and gives added value to maternal health (MDG 5) investments also linking to non-communicable diseases. For preterm babies who survive, the additional burden of prematurity-related disability may aff ect families and health systems. Prematurity is an explicit priority in many high-income settings; however, more attention is needed especially in low- and middle-income countries where the invisibility of preterm birth as well as its myths and misconceptions have slowed action on prevention and care. Recent global attention to preterm birth hit a tipping point in 2012, with the May 2 publication of Born Too Soon: The Global Action Report on Preterm Birth and with the 2nd annual World Prematurity Day on November 17 which mobilised the actions of partners in many countries to address preterm birth and newborn health. Interventions to strengthen preterm birth prevention and care span the continuum of care for reproductive, maternal, newborn and child health. Both prevention of preterm birth and implementation of care of premature babies require more research, as well as more policy attention and programmatic investment.

  7. Primate malarias: Diversity, distribution and insights for zoonotic Plasmodium

    Directory of Open Access Journals (Sweden)

    Christina Faust

    2015-12-01

    Full Text Available Protozoans within the genus Plasmodium are well-known as the causative agents of malaria in humans. Numerous Plasmodium species parasites also infect a wide range of non-human primate hosts in tropical and sub-tropical regions worldwide. Studying this diversity can provide critical insight into our understanding of human malarias, as several human malaria species are a result of host switches from non-human primates. Current spillover of a monkey malaria, Plasmodium knowlesi, in Southeast Asia highlights the permeability of species barriers in Plasmodium. Also recently, surveys of apes in Africa uncovered a previously undescribed diversity of Plasmodium in chimpanzees and gorillas. Therefore, we carried out a meta-analysis to quantify the global distribution, host range, and diversity of known non-human primate malaria species. We used published records of Plasmodium parasites found in non-human primates to estimate the total diversity of non-human primate malarias globally. We estimate that at least three undescribed primate malaria species exist in sampled primates, and many more likely exist in unstudied species. The diversity of malaria parasites is especially uncertain in regions of low sampling such as Madagascar, and taxonomic groups such as African Old World Monkeys and gibbons. Presence–absence data of malaria across primates enables us to highlight the close association of forested regions and non-human primate malarias. This distribution potentially reflects a long coevolution of primates, forest-adapted mosquitoes, and malaria parasites. The diversity and distribution of primate malaria are an essential prerequisite to understanding the mechanisms and circumstances that allow Plasmodium to jump species barriers, both in the evolution of malaria parasites and current cases of spillover into humans.

  8. Comparison of the social systems of primates and feral horses: data from a newly established horse research site on Serra D'Arga, northern Portugal.

    Science.gov (United States)

    Ringhofer, Monamie; Inoue, Sota; Mendonça, Renata S; Pereira, Carlos; Matsuzawa, Tetsuro; Hirata, Satoshi; Yamamoto, Shinya

    2017-10-01

    Horses are phylogenetically distant from primates, but considerable behavioral links exist between the two. The sociality of horses, characterized by group stability, is similar to that of primates, but different from that of many other ungulates. Although horses and primates are good models for exploring the evolution of societies in human and non-human animals, fewer studies have been conducted on the social system of horses than primates. Here, we investigated the social system of feral horses, particularly the determinant factors of single-male/multi-male group dichotomy, in light of hypotheses derived from studies of primate societies. Socioecological data from 26 groups comprising 208 feral horses on Serra D'Arga, northern Portugal suggest that these primate-based hypotheses cannot adequately explain the social system of horses. In view of the sympatric existence of multi- and single-male groups, and the frequent intergroup transfers and promiscuous mating of females with males of different groups, male-female relationships of horses appear to differ from those of polygynous primates.

  9. Survival and neurodevelopmental outcomes of preterm infants.

    Science.gov (United States)

    Hack, Maureen

    2007-12-01

    Survival of preterm infants, which increased dramatically during the years after the introduction of neonatal intensive care, reached a plateau in the mid- to late 1990s. Neonatal morbidity, which increased initially, has decreased since 2000 and resulted in a decrease in the rates of cerebral palsy. Follow-up of preterm infants to early childhood and school age reveals higher rates of asthma, cerebral palsy, subnormal cognitive function, poorer academic achievement, and behavioral problems. Although many of the problems persist into adulthood, preterm survivors regard their overall health and quality of life similar to that of normal birth weight controls.

  10. Persistent Expression of FLAG-tagged Micro dystrophin in Nonhuman Primates Following Intramuscular and Vascular Delivery

    OpenAIRE

    Rodino-Klapac, Louise R; Montgomery, Chrystal L; Bremer, William G; Shontz, Kimberly M; Malik, Vinod; Davis, Nancy; Sprinkle, Spencer; Campbell, Katherine J; Sahenk, Zarife; Clark, K Reed; Walker, Christopher M; Mendell, Jerry R; Chicoine, Louis G

    2009-01-01

    Animal models for Duchenne muscular dystrophy (DMD) have species limitations related to assessing function, immune response, and distribution of micro- or mini-dystrophins. Nonhuman primates (NHPs) provide the ideal model to optimize vector delivery across a vascular barrier and provide accurate dose estimates for widespread transduction. To address vascular delivery and dosing in rhesus macaques, we have generated a fusion construct that encodes an eight amino-acid FLAG epitope at the C-term...

  11. An overview of nonhuman primates in aging research.

    Science.gov (United States)

    Mattison, Julie A; Vaughan, Kelli L

    2017-08-01

    A graying human population and the rising costs of healthcare have fueled the growing need for a sophisticated translational model of aging. Nonhuman primates (NHPs) experience aging processes similar to humans and, as a result, provide an excellent opportunity to study a closely related species. Rhesus monkeys share >92% homology and are the most commonly studied NHP. However, their substantial size, long lifespan, and the associated expense are prohibitive factors. Marmosets are rapidly becoming the preferred NHP for biomedical testing due to their small size, low zoonotic risk, reproductive efficiency, and relatively low-cost. Both species experience age-related pathology similar to humans, such as cancer, diabetes, arthritis, cardiovascular disease, and neurological decline. As a result, their use in aging research is paving the way to improved human health through a better understanding of the mechanisms of aging. Published by Elsevier Inc.

  12. Investigating the Prevalence of Preterm Birth in Iranian Population: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Sharifi, Nasibeh; Khazaeian, Somayyeh; Pakzad, Reza; Fathnezhad Kazemi, Azita; Chehreh, Hashemmieh

    2017-12-01

    Introduction: Despite medical advances, preterm delivery remains a global problem in developed and developing countries. The present study was aimed at conducting a systematic review and meta-analysis of studies on the prevalence of preterm delivery in Iran. Methods: This study was carried out on studies conducted in Iran by searching databases of SID, Magiran, Irandoc, MEDLIB, Iranmedex, PubMed, Web of science, Google Scholar and Scopus. The search was conducted using advanced search and keywords of preterm delivery and equivalents of it in Mesh and their Farsi's Synonymous in all articles from 2000-2016.After extracting the data, the data were combined using a random model. Heterogeneity of the studies was assessed using Q test I2 index and the data were analyzed using STATA Ver.11 software. Results: The total number of samples in this study was 41773. In 19 reviewed articles, the overall prevalence of preterm delivery, based on the random effects model, was estimated to be a total of 10% (95% CI, 9-12). The lowest prevalence of preterm labor was 5.4% in Bam and the highest prevalence was 19.85% in Tehran. There was no significant difference between the prevalence of preterm delivery compared to year of study and sample size. Conclusion: This study reviewed the findings of previous studies and showed that preterm delivery is a relatively prevalent problem in Iran. Therefore, adopting appropriate interventions in many cases including life skills training, self-care and increasing pregnancy care to reduce these consequences and their following complications in high risk patients seem necessary.

  13. Preterm birth–associated neurodevelopmental impairment estimates at regional and global levels for 2010

    Science.gov (United States)

    Blencowe, Hannah; Lee, Anne CC; Cousens, Simon; Bahalim, Adil; Narwal, Rajesh; Zhong, Nanbert; Chou, Doris; Say, Lale; Modi, Neena; Katz, Joanne; Vos, Theo; Marlow, Neil; Lawn, Joy E.

    2013-01-01

    Background: In 2010, there were an estimated 15 million preterm births worldwide (preterm babies according to the level of care. A compartmental model was used to estimate the number of impaired postneonatal survivors following preterm birth in 2010. A separate model (DisMod-MR) was used to estimate years lived with disability (YLDs) for the global burden of disease 2010 study. Disability adjusted life years (DALYs) were calculated as the sum of YLDs and years of life lost (YLLs). Results: In 2010, there were an estimated 13 million preterm births who survived beyond the first month. Of these, 345,000 (2.7%, uncertainty range: 269,000–420,000) were estimated to have moderate or severe neurodevelopmental impairment, and a further 567,000 (4.4%, (445,000–732,000)) were estimated to have mild neurodevelopmental impairment. Many more have specific learning or behavioral impairments or reduced physical or mental health. Fewest data are available where the burden is heaviest. Preterm birth was responsible for 77 million DALYs, 3.1% of the global total, of which only 3 million were YLDs. Conclusion: Most preterm births (>90%) survive without neurodevelopmental impairment. Developing effective means of prevention of preterm birth should be a longer term priority, but major burden reduction could be made immediately with improved coverage and quality of care. Improved newborn care would reduce mortality, especially in low-income countries and is likely to reduce impairment in survivors, particularly in middle-income settings. PMID:24366461

  14. Cellular Scaling Rules for Primate Spinal Cords

    OpenAIRE

    Burish, Mark J.; Peebles, J. Klint; Baldwin, Mary K.; Tavares, Luciano; Kaas, Jon H.; Herculano-Houzel, Suzana

    2010-01-01

    The spinal cord can be considered a major sensorimotor interface between the body and the brain. How does the spinal cord scale with body and brain mass, and how are its numbers of neurons related to the number of neurons in the brain across species of different body and brain sizes? Here we determine the cellular composition of the spinal cord in eight primate species and find that its number of neurons varies as a linear function of cord length, and accompanies body mass raised to an expone...

  15. Two Influential Primate Classifications Logically Aligned.

    Science.gov (United States)

    Franz, Nico M; Pier, Naomi M; Reeder, Deeann M; Chen, Mingmin; Yu, Shizhuo; Kianmajd, Parisa; Bowers, Shawn; Ludäscher, Bertram

    2016-07-01

    Classifications and phylogenies of perceived natural entities change in the light of new evidence. Taxonomic changes, translated into Code-compliant names, frequently lead to name:meaning dissociations across succeeding treatments. Classification standards such as the Mammal Species of the World (MSW) may experience significant levels of taxonomic change from one edition to the next, with potential costs to long-term, large-scale information integration. This circumstance challenges the biodiversity and phylogenetic data communities to express taxonomic congruence and incongruence in ways that both humans and machines can process, that is, to logically represent taxonomic alignments across multiple classifications. We demonstrate that such alignments are feasible for two classifications of primates corresponding to the second and third MSW editions. Our approach has three main components: (i) use of taxonomic concept labels, that is name sec. author (where sec. means according to), to assemble each concept hierarchy separately via parent/child relationships; (ii) articulation of select concepts across the two hierarchies with user-provided Region Connection Calculus (RCC-5) relationships; and (iii) the use of an Answer Set Programming toolkit to infer and visualize logically consistent alignments of these input constraints. Our use case entails the Primates sec. Groves (1993; MSW2-317 taxonomic concepts; 233 at the species level) and Primates sec. Groves (2005; MSW3-483 taxonomic concepts; 376 at the species level). Using 402 RCC-5 input articulations, the reasoning process yields a single, consistent alignment and 153,111 Maximally Informative Relations that constitute a comprehensive meaning resolution map for every concept pair in the Primates sec. MSW2/MSW3. The complete alignment, and various partitions thereof, facilitate quantitative analyses of name:meaning dissociation, revealing that nearly one in three taxonomic names are not reliable across treatments

  16. Primates, Provisioning and Plants: Impacts of Human Cultural Behaviours on Primate Ecological Functions.

    Directory of Open Access Journals (Sweden)

    Asmita Sengupta

    Full Text Available Human provisioning of wildlife with food is a widespread global practice that occurs in multiple socio-cultural circumstances. Provisioning may indirectly alter ecosystem functioning through changes in the eco-ethology of animals, but few studies have quantified this aspect. Provisioning of primates by humans is known to impact their activity budgets, diets and ranging patterns. Primates are also keystone species in tropical forests through their role as seed dispersers; yet there is no information on how provisioning might affect primate ecological functions. The rhesus macaque is a major human-commensal species but is also an important seed disperser in the wild. In this study, we investigated the potential impacts of provisioning on the role of rhesus macaques as seed dispersers in the Buxa Tiger Reserve, India. We studied a troop of macaques which were provisioned for a part of the year and were dependent on natural resources for the rest. We observed feeding behaviour, seed handling techniques and ranging patterns of the macaques and monitored availability of wild fruits. Irrespective of fruit availability, frugivory and seed dispersal activities decreased when the macaques were provisioned. Provisioned macaques also had shortened daily ranges implying shorter dispersal distances. Finally, during provisioning periods, seeds were deposited on tarmac roads that were unconducive for germination. Provisioning promotes human-primate conflict, as commensal primates are often involved in aggressive encounters with humans over resources, leading to negative consequences for both parties involved. Preventing or curbing provisioning is not an easy task as feeding wild animals is a socio-cultural tradition across much of South and South-East Asia, including India. We recommend the initiation of literacy programmes that educate lay citizens about the ill-effects of provisioning and strongly caution them against the practice.

  17. High reinforcing efficacy of nicotine in non-human primates.

    Directory of Open Access Journals (Sweden)

    Bernard Le Foll

    Full Text Available Although tobacco appears highly addictive in humans, there has been persistent controversy about the ability of its psychoactive ingredient nicotine to induce self-administration behavior in laboratory animals, bringing into question nicotine's role in reinforcing tobacco smoking. Because of ethical difficulties in inducing nicotine dependence in naïve human subjects, we explored reinforcing effects of nicotine in experimentally-naive non-human primates given access to nicotine for periods of time up to two years. Five squirrel monkeys with no experimental history were allowed to intravenously self-administer nicotine by pressing one of two levers. The number of presses on the active lever needed to obtain each injection was fixed (fixed-ratio schedule or increased progressively with successive injections during the session (progressive-ratio schedule, allowing evaluation of both reinforcing and motivational effects of nicotine under conditions of increasing response cost. Over time, a progressive shift toward high rates of responding on the active lever, but not the inactive lever, developed. The monkeys' behavior was clearly directed toward nicotine self-administration, rather than presentation of environmental stimuli associated with nicotine injection. Both schedules of reinforcement revealed a high motivation to self-administer nicotine, with monkeys continuing to press the lever when up to 600 lever-presses were needed for each injection of nicotine. Thus, nicotine, by itself, in the absence of behavioral or drug-exposure history, is a robust and highly effective reinforcer of drug-taking behavior in a non-human primate model predictive of human behavior. This supports the use of nicotinic ligands for the treatment of smokers, and this novel preclinical model offers opportunities to test future medications for the treatment of nicotine dependence.

  18. Primate cathelicidin orthologues display different structures and membrane interactions.

    Science.gov (United States)

    Morgera, Francesca; Vaccari, Lisa; Antcheva, Nikolinka; Scaini, Denis; Pacor, Sabrina; Tossi, Alessandro

    2009-02-01

    The human cathelicidin LL-37 displays both direct antibacterial activities and the capacity to modulate host-cell activities. These depend on structural characteristics that are subject to positive selection for variation, as observed in a previous analysis of the CAMP gene (encoding LL-37) in primates. The altered balance between cationic and anionic residues in different primate orthologues affects intramolecular salt-bridging and influences the stability of the helical conformation and tendency to aggregate in solution of the peptide. In the present study, we have analysed the effects of these structural variations on membrane interactions for human LL-37, rhesus RL-37 and orang-utan LL-37, using several complementary biophysical and biochemical methods. CD and ATR (attenuated total reflection)-FTIR (Fourier-transform IR) spectroscopy on model membranes indicate that RL-37, which is monomeric and unstructured in bulk solution [F-form (free form)], and human LL-37, which is partly structured and probably aggregated [A-form (aggregated form)], bind biological membranes in different manners. RL-37 may insert more deeply into the lipid bilayer than LL-37, which remains aggregated. AFM (atomic force microscopy) performed on the same supported bilayer as used for ATR-FTIR measurements suggests a carpet-like mode of permeabilization for RL37 and formation of more defined worm-holes for LL-37. Comparison of data from the biological activity on bacterial cells with permeabilization of model membranes indicates that the structure/aggregation state also affects the trajectory of the peptides from bulk solution through the outer cell-wall layers to the membrane. The results of the present study suggest that F-form cathelicidin orthologues may have evolved to have primarily a direct antimicrobial defensive capacity, whereas the A-forms have somewhat sacrificed this to gain host-cell modulating functions.

  19. Multimedia in Anthropology: A Guide to the Nonhuman Primates.

    Science.gov (United States)

    Burton, Frances D.

    This paper describes a primatology project using computer assisted learning and interactive multimedia to help students at the University of Toronto (Canada) learn about non-human primates. The purpose of the interactive program is to present the "natural history" of the majority of the 200-plus species of non-human primates in constant…

  20. Importance of achromatic contrast in short-range fruit foraging of primates.

    Directory of Open Access Journals (Sweden)

    Chihiro Hiramatsu

    2008-10-01

    Full Text Available Trichromatic primates have a 'red-green' chromatic channel in addition to luminance and 'blue-yellow' channels. It has been argued that the red-green channel evolved in primates as an adaptation for detecting reddish or yellowish objects, such as ripe fruits, against a background of foliage. However, foraging advantages to trichromatic primates remain unverified by behavioral observation of primates in their natural habitats. New World monkeys (platyrrhines are an excellent model for this evaluation because of the highly polymorphic nature of their color vision due to allelic variation of the L-M opsin gene on the X chromosome. In this study we carried out field observations of a group of wild, frugivorous black-handed spider monkeys (Ateles geoffroyi frontatus, Gray 1842, Platyrrhini, consisting of both dichromats (n = 12 and trichromats (n = 9 in Santa Rosa National Park, Costa Rica. We determined the color vision types of individuals in this group by genotyping their L-M opsin and measured foraging efficiency of each individual for fruits located at a grasping distance. Contrary to the predicted advantage for trichromats, there was no significant difference between dichromats and trichromats in foraging efficiency and we found that the luminance contrast was the main determinant of the variation of foraging efficiency among red-green, blue-yellow and luminance contrasts. Our results suggest that luminance contrast can serve as an important cue in short-range foraging attempts despite other sensory cues that could be available. Additionally, the advantage of red-green color vision in primates may not be as salient as previously thought and needs to be evaluated in further field observations.

  1. Scaling of Primate Forearm Muscle Architecture as It Relates to Locomotion and Posture.

    Science.gov (United States)

    Leischner, Carissa L; Crouch, Michael; Allen, Kari L; Marchi, Damiano; Pastor, Francisco; Hartstone-Rose, Adam

    2018-03-01

    It has been previously proposed that distal humerus morphology may reflect the locomotor pattern and substrate preferred by different primates. However, relationships between these behaviors and the morphological capabilities of muscles originating on these osteological structures have not been fully explored. Here, we present data about forearm muscle architecture in a sample of 44 primate species (N = 55 specimens): 9 strepsirrhines, 15 platyrrhines, and 20 catarrhines. The sample includes all major locomotor and substrate use groups. We isolated each antebrachial muscle and categorized them into functional groups: wrist and digital extensors and flexors, antebrachial mm. that do not cross the wrist, and functional combinations thereof. Muscle mass, physiological cross-sectional area (PCSA), reduced PCSA (RPCSA), and fiber length (FL) are examined in the context of higher taxonomic group, as well as locomotor/postural and substrate preferences. Results show that muscle masses, PCSA, and RPCSA scale with positive allometry while FL scales with isometry indicating that larger primates have relatively stronger, but neither faster nor more flexible, forearms across the sample. When accounting for variation in body size, we found no statistically significant difference in architecture among higher taxonomic groups or locomotor/postural groups. However, we found that arboreal primates have significantly greater FL than terrestrial ones, suggesting that these species are adapted for greater speed and/or flexibility in the trees. These data may affect our interpretation of the mechanisms for variation in humeral morphology and provide information for refining biomechanical models of joint stress and movement in extant and fossil primates. Anat Rec, 301:484-495, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

  2. Characterization of a 2016 Clinical Isolate of Zika Virus in Non-human Primates

    Directory of Open Access Journals (Sweden)

    Xiao-Feng Li

    2016-10-01

    Full Text Available Animal models are critical to understand disease and to develop countermeasures for the ongoing epidemics of Zika virus (ZIKV. Here we report a non-human primate model using a 2016 contemporary clinical isolate of ZIKV. Upon subcutaneous inoculation, rhesus macaques developed fever and viremia, with robust excretion of ZIKV RNA in urine, saliva, and lacrimal fluid. Necropsy of two infected animals revealed that systematic infections involving central nervous system and visceral organs were established at the acute phrase. ZIKV initially targeted the intestinal tracts, spleen, and parotid glands, and retained in spleen and lymph nodes till 10 days post infection. ZIKV-specific immune responses were readily induced in all inoculated animals. The non-human primate model described here provides a valuable platform to study ZIKV pathogenesis and to evaluate vaccine and therapeutics.

  3. Primate theory of mind: a state of the art review

    DEFF Research Database (Denmark)

    Byrnit, Jill

    2006-01-01

    Såvel mennesket som andre primater have store hjerner med store hjernebarker. Det er blevet foreslået, at primaters store hjerner skyldes de komplekse sociale krav, der kommer af at skulle leve i store grupper. Inden for de sidste 40 år er der blevet lavet meget forskning inden for primaters socio-cognitive...... evner og siden Premack & Woodruff (1978) for første gang introducerede begrebet "theory of mind", er der blevet foretaget mange laboratorie-forsøg om mennesker og andre primaters evne til at attribuere mentale tilstande til andre. I nærværende artikel er størstedelen af disse forsøg med andre primater...

  4. Antimicrobials for Preterm Birth Prevention: An Overview

    Directory of Open Access Journals (Sweden)

    Akila Subramaniam

    2012-01-01

    Full Text Available Objective. Preterm birth (PTB remains a major cause of neonatal morbidity and mortality. The association between PTB and infection is clear. The purpose of this report is to present a focused review of information on the use of antibiotics to prevent PTB. Methods. We performed a search of the PubMed database restricted to clinical trials or meta-analyses published in English from 1990 through May 2011 using keywords “antibiotics or antimicrobials” and “preterm.” Results. The search yielded 67 abstracts for review. We selected 31 clinical trials (n=26 or meta-analysis (n=5 for further full-text review. Discussion of each eligible clinical trial, its specific inclusion criteria, antibiotic regimen used, and study results are presented. Overall, trials evaluating antibiotic treatment to prevent preterm birth have yielded mixed results regarding any benefit. Conclusion. Routine antibiotic prophylaxis is not recommended for prevention of preterm birth.

  5. Preterm twin gestation and cystic periventricular leucomalacia

    NARCIS (Netherlands)

    Resch, B; Jammernegg, A; Vollaard, E; Maurer, U; Mueller, WD; Pertl, B

    Objective: To identify risk factors for the development of cystic periventricular leucomalacia (PVL) in twin gestation. Design: Retrospective case-control study. Setting: Tertiary care university hospital, Department of Paediatrics, Division of Neonatology, Graz, Austria. Patients: Preterm twin

  6. SOCIODEMOGRAPHIC DOAMINS OF DEPRIVATION AND PRETERM BIRTH

    Science.gov (United States)

    Background. Neighborhood-level deprivation has long been associated with adverse outcomes, including preterm birth (PTB), as observed in the authors' previous work using a composite deprivation index. Area disadvantage is multifaceted comprising income, employment, education and...

  7. INCOME INCONGRUITY, RACE AND PRETERM BIRTH

    Science.gov (United States)

    Previous research with vital records finds income incongruity associated with adverse birth outcomes. We examined the effects of negative income incongruity (reporting lower household income than the census tract median household income) on preterm birth (PTB <37 weeks completed ...

  8. Maintenance therapy with oxytocin antagonists for inhibiting preterm birth after threatened preterm labour.

    Science.gov (United States)

    Papatsonis, Dimitri N M; Flenady, Vicki; Liley, Helen G

    2013-10-13

    In some women, an episode of preterm labour settles and does not result in immediate preterm birth. Subsequent treatment with tocolytic agents such as oxytocin receptor antagonists may then have the potential to prevent the recurrence of preterm labour, prolonging gestation, and preventing the adverse consequences of prematurity for the infant. To assess the effects of maintenance therapy with oxytocin antagonists administered by any route after an episode of preterm labour in order to delay or prevent preterm birth. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 July 2013), sought ongoing and unpublished trials by contacting experts in the field and searched the reference lists of relevant articles. Randomised controlled trials comparing oxytocin antagonists with any alternative tocolytic agent, placebo or no treatment, used for maintenance therapy after an episode of preterm labour. We used the standard methods of The Cochrane Collaboration and the Cochrane Pregnancy and Childbirth Group. Two review authors independently undertook evaluation of methodological quality and extracted trial data. This review includes one trial of 513 women. When compared with placebo, atosiban did not reduce preterm birth before 37 weeks (risk ratio (RR) 0.89; 95% confidence intervals (CI) 0.71 to 1.12), 32 weeks (RR 0.85; 95% CI 0.47 to 1.55), or 28 weeks (RR 0.75; 95% CI 0.28 to 2.01). No difference was shown in neonatal morbidity, or perinatal mortality. There is insufficient evidence to support the use of oxytocin receptor antagonists to inhibit preterm birth after a period of threatened or actual preterm labour. Any future trials using oxytocin antagonists or other drugs as maintenance therapy for preventing preterm birth should examine a variety of important infant outcome measures, including reduction of neonatal morbidity and mortality, and long-term infant follow-up. Future research should also focus on the pathophysiological pathways that

  9. Predicting primate responses to "Stochastic" demographic events.

    Science.gov (United States)

    Strier, K B

    1999-01-01

    Comparative approaches in contemporary primate behavioral ecology have tended to emphasize the deterministic properties of stochastic ecological variables. Yet, primate responses to ecological fluctuations may be mediated by the interactions among demographic processes at the levels of individuals, groups, and populations. In this paper I examine long-term data collected from June 1982-July 1998 on one expanding group of muriquis (Brachyteles arachnoides) at the Estação Biologica de Caratinga, Minas Gerais, Brazil to explore the demographic and life history correlates of reproductive seasonality and skewed infant sex ratios. Variation in the size of annual birth cohorts (≥2 infants) was positively related to variation in the annual distribution of births (r (s)=0.96,n=10,p<0.01), indicating the importance of considering the effects that the number of reproductive females may have on interpretations of reproductive seasonality. The female-biased infants sex ratio documented from 59 births was attributed exclusively to multiparous mothers. Primiparous mothers produced comparable numbers of sons (n=6) and daughters (n=7), and were increasingly likely to produce daughters with each subsequent reproductive event. Seven of the 11 females that have produced≥3 infants to date exhibited biases in favor of daughters whereas only 1 was biased in favor of sons. Variation in female sensitivity to local resource competition at different stages of their life histories may account for the female-biased infant sex ration in this population.

  10. Primate pelvic anatomy and implications for birth.

    Science.gov (United States)

    Trevathan, Wenda

    2015-03-05

    The pelvis performs two major functions for terrestrial mammals. It provides somewhat rigid support for muscles engaged in locomotion and, for females, it serves as the birth canal. The result for many species, and especially for encephalized primates, is an 'obstetric dilemma' whereby the neonate often has to negotiate a tight squeeze in order to be born. On top of what was probably a baseline of challenging birth, locomotor changes in the evolution of bipedalism in the human lineage resulted in an even more complex birth process. Negotiation of the bipedal pelvis requires a series of rotations, the end of which has the infant emerging from the birth canal facing the opposite direction from the mother. This pattern, strikingly different from what is typically seen in monkeys and apes, places a premium on having assistance at delivery. Recently reported observations of births in monkeys and apes are used to compare the process in human and non-human primates, highlighting similarities and differences. These include presentation (face, occiput anterior or posterior), internal and external rotation, use of the hands by mothers and infants, reliance on assistance, and the developmental state of the neonate. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  11. The role of piloerection in primate thermoregulation.

    Science.gov (United States)

    Chaplin, George; Jablonski, Nina G; Sussman, Robert W; Kelley, Elizabeth A

    2014-01-01

    The insulating properties of the primate integument are influenced by many factors, including piloerection, which raises the hair and insulates the body by creating motionless air near the skin's surface. The involuntary muscles that control piloerection, the musculi arrectores pilorum (MAP), are mostly absent except on the tail in most strepsirhines, and are entirely absent in tarsiers and some lorisids. The absence of piloerection and the reduced effectiveness of pilary insulation in preventing heat loss affected the evolution of behavior and metabolic thermoregulation in these animals. In lemurs, this situation contributed to the use of positional and social behaviors such as sunning and huddling that help maintain thermal homeostasis during day-night and seasonal temperature cycles. It also contributed in many lemurs and lorises to the evolution of a wide variety of activity patterns and energy-conserving metabolic patterns such as cathemerality, daily torpor, and hibernation. The absence of functional MAP in strepsirhines and tarsiers implies the absence of effective piloerection in early primates, and the reacquisition of whole-body MAP in ancestral anthropoids prior to the separation of platyrrhine and catarrhine lineages. © 2013 S. Karger AG, Basel.

  12. Primate pelvic anatomy and implications for birth

    Science.gov (United States)

    Trevathan, Wenda

    2015-01-01

    The pelvis performs two major functions for terrestrial mammals. It provides somewhat rigid support for muscles engaged in locomotion and, for females, it serves as the birth canal. The result for many species, and especially for encephalized primates, is an ‘obstetric dilemma’ whereby the neonate often has to negotiate a tight squeeze in order to be born. On top of what was probably a baseline of challenging birth, locomotor changes in the evolution of bipedalism in the human lineage resulted in an even more complex birth process. Negotiation of the bipedal pelvis requires a series of rotations, the end of which has the infant emerging from the birth canal facing the opposite direction from the mother. This pattern, strikingly different from what is typically seen in monkeys and apes, places a premium on having assistance at delivery. Recently reported observations of births in monkeys and apes are used to compare the process in human and non-human primates, highlighting similarities and differences. These include presentation (face, occiput anterior or posterior), internal and external rotation, use of the hands by mothers and infants, reliance on assistance, and the developmental state of the neonate. PMID:25602069

  13. Postradiation regional cerebral blood flow in primates

    International Nuclear Information System (INIS)

    Cockerham, L.G.; Cerveny, T.J.; Hampton, J.D.

    1986-01-01

    Early transient incapacitation (ETI) is the complete cessation of performance during the first 30 min after radiation exposure and performance decrement (PD) is a reduction in performance at the same time. Supralethal doses of radiation have been shown to produce a marked decrease in regional cerebral blood flow in primates concurrent with hypotension and a dramatic release of mast cell histamine. In an attempt to elucidate mechanisms underlying the radiation-induced ETI/PD phenomenon and the postradiation decrease in cerebral blood flow, primates were exposed to 100 Gy (1 Gy = 100 rads), whole-body, gamma radiation. Pontine and cortical blood flows were measured by hydrogen clearance, before and after radiation exposure. Systemic blood pressures were determined simultaneously. Systemic arterial histamine levels were determined preradiation and postradiation. Data obtained indicated that radiated animals showed a decrease in blood flow of 63% in the motor cortex and 51% in the pons by 10 min postradiation. Regional cerebral blood flow of radiated animals showed a slight recovery 20 min postradiation, followed by a fall to the 10 min nadir by 60 min postradiation. Immediately, postradiation systemic blood pressure fell 67% and remained at that level for the remainder of the experiment. Histamine levels in the radiated animals increased a hundredfold 2 min postradiation. This study indicates that regional cerebral blood flow decreases postradiation with the development of hypotension and may be associated temporally with the postradiation release of histamine

  14. Biomarkers of spontaneous preterm birth

    DEFF Research Database (Denmark)

    Polettini, Jossimara; Cobo, Teresa; Kacerovsky, Marian

    2017-01-01

    predictors of pregnancy outcome. This systematic review was conducted to synthesize the knowledge on PTB biomarkers identified using multiplex analysis. Three electronic databases (PubMed, EMBASE and Web of Science) were searched for studies in any language reporting the use of multiplex assays for maternal......Despite decades of research on risk indicators of spontaneous preterm birth (PTB), reliable biomarkers are still not available to screen or diagnose high-risk pregnancies. Several biomarkers in maternal and fetal compartments have been mechanistically linked to PTB, but none of them are reliable......) followed by MIP-1β, GM-CSF, Eotaxin, and TNF-RI (two studies) were reported more than once in maternal serum. However, results could not be combined due to heterogeneity in type of sample, study population, assay, and analysis methods. By this systematic review, we conclude that multiplex assays...

  15. Pathomorphological findings in preterm infants

    International Nuclear Information System (INIS)

    Amann, G.

    2000-01-01

    Pathomorphology in the preterm infant represents an interaction of morphological organ immaturity and neonatal management with their respective sequelae. Pathomorphological examples include the modification in the morphology of hyaline membrane disease and bronchopulmonary dysplasia as a consequence of modern neonatal therapy. Hemorrhagic and ischemic/hypoxic lesions of the central nervous system may occur in age- and agent-related distributional patterns, with subependymal hemorrhage and periventricular leukomalacia representing the most important examples. The most common intestinal finding, namely, necrotizing enterocolitis, typically shows segmental alterations, the morphology of which largely depends on the dominating causative agent. Hepatic cholestasis and fatty change are mostly consequences of parenteral nutrition or hypoxic/ischemic stress. Hepatic necrosis can be associated with the latter, but may also indicate disseminated intravascular coagulation. Vascular pathomorphology is represented by thromembolic lesions, in most instances corresponding to sequelae of neonatal management. (orig.) [de

  16. Epidemiological trends among preterm infants with apnea. A twelve-year database review.

    Science.gov (United States)

    Regenbogen, Elliot; Zhang, Shouling; Yang, Jie; Shroyer, Annie; Zhu, Chencan; DeCristofaro, Joseph

    2018-04-01

    This study sought to characterize trends in the diagnosis of apnea, associated comorbidities and complications, and 30-day readmission rates in preterm singleton infants. The study design was a retrospective, longitudinal, observational study. 2003-2014 New York State Statewide Planning and Research Cooperative System and New York City Vital Statistics databases were merged identifying preterm live singleton births. Hospitalizations of preterm newborns with and without apnea were compared; multivariable logistic regression and log-linear Poisson regression models applied. Of 1,384,013 singleton births, 7.5% were identified as preterm. While relative risk of preterm birth rates declined (RR = 0.987, 95% CI = 0.982-0.991), the diagnosis of apnea increased significantly (RR = 1.069, 95% CI = 1.049-1.089). Multivariable analysis identified two apnea predictors, gastric reflux (OR = 3.19, 95% CI = 2.80-3.63) and early gestational age (OR = 0.83 for 1 week GA increase, 95% CI = 0.82-0.84). Preterm newborns with apnea were more likely to be readmitted within the first 30 days and total charges were 5.4 times higher. While the preterm birth rate has declined the rate of diagnosis of apnea with associated comorbidities and complications has increased. Given the additional findings of higher 30-day readmission rates and charges, more multidisciplinary research appears warranted to identify ways to optimize the quality of high risk newborn care. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. Behavioral influences on preterm birth: a review.

    Science.gov (United States)

    Savitz, David A; Murnane, Pamela

    2010-05-01

    Epidemiologic studies of potential behavioral influences on preterm birth have proliferated and yet, with the exception of tobacco smoking, none can be considered an established cause. We conducted a comprehensive summary of the epidemiologic evidence on tobacco, alcohol, and illicit drug use, and physical, sexual, and occupational activity, to identify promising research directions, as well as research topics that are at an impasse based on currently available methods. Tobacco use is weakly but consistently associated with preterm birth-stronger for heavier smoking, and for spontaneous preterm birth and earlier preterm births. Weaker evidence suggests an adverse effect of environmental tobacco smoke, heavy alcohol or cocaine use, and physically strenuous work. Low levels of alcohol use, caffeine, sexual activity, and employment have generally not been found to be associated with preterm birth, and leisure-time physical activity has generated mixed results. Progress will require more detailed consideration of antecedents, new technologies for assessing exposure, and examination of biologic consequences of the behaviors of interest, focusing on pathways thought to mediate preterm delivery. New strategies-rather than more applications of the same approaches used in past studies-will move the research toward identifying causal relationships and, ultimately, may suggest preventive measures.

  18. Oral Supplementation with Bovine Colostrum Prevents Septic Shock and Brain Barrier Disruption During Bloodstream Infection in Preterm Newborn Pigs

    DEFF Research Database (Denmark)

    Brunse, Anders; Worsøe, Päivi; Pors, Susanne Elisabeth

    2018-01-01

    Preterm infants have increased risk of neonatal sepsis, potentially inducing brain injury, and they may benefit from early initiation of enteral milk feeding. Using preterm pigs as models, we hypothesized that early provision of bovine colostrum to parentally nourished newborns protects against...... hemorrhages, cellular responses (leukopenia, thrombocytopenia), brain barrier disruption and neuroinflammation. At 24 h, colostrum supplementation reduced the SE abundance in blood and cerebrospinal fluid (CSF, both p

  19. Recurrence risk of preterm birth in subsequent singleton pregnancy after preterm twin delivery

    NARCIS (Netherlands)

    Schaaf, Jelle M.; Hof, Michel H. P.; Mol, Ben Willem J.; Abu-Hanna, Ameen; Ravelli, Anita C. J.

    2012-01-01

    OBJECTIVE: The purpose of this study was to investigate the recurrence risk of preterm birth ( <37 weeks' gestation) in a subsequent singleton pregnancy after a previous nulliparous preterm twin delivery. STUDY DESIGN: We included 1957 women who delivered a twin gestation and a subsequent singleton

  20. A modular mind? A test using individual data from seven primate species.

    Directory of Open Access Journals (Sweden)

    Federica Amici

    Full Text Available It has long been debated whether the mind consists of specialized and independently evolving modules, or whether and to what extent a general factor accounts for the variance in performance across different cognitive domains. In this study, we used a hierarchical Bayesian model to re-analyse individual level data collected on seven primate species (chimpanzees, bonobos, orangutans, gorillas, spider monkeys, brown capuchin monkeys and long-tailed macaques across 17 tasks within four domains (inhibition, memory, transposition and support. Our modelling approach evidenced the existence of both a domain-specific factor and a species factor, each accounting for the same amount (17% of the observed variance. In contrast, inter-individual differences played a minimal role. These results support the hypothesis that the mind of primates is (at least partially modular, with domain-specific cognitive skills undergoing different evolutionary pressures in different species in response to specific ecological and social demands.

  1. Role of mechanical factors in the morphology of the primate cerebral cortex.

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    Claus C Hilgetag

    2006-03-01

    Full Text Available The convoluted cortex of primates is instantly recognizable in its principal morphologic features, yet puzzling in its complex finer structure. Various hypotheses have been proposed about the mechanisms of its formation. Based on the analysis of databases of quantitative architectonic and connection data for primate prefrontal cortices, we offer support for the hypothesis that tension exerted by corticocortical connections is a significant factor in shaping the cerebral cortical landscape. Moreover, forces generated by cortical folding influence laminar morphology, and appear to have a previously unsuspected impact on cellular migration during cortical development. The evidence for a significant role of mechanical factors in cortical morphology opens the possibility of constructing computational models of cortical development based on physical principles. Such models are particularly relevant for understanding the relationship of cortical morphology to the connectivity of normal brains, and structurally altered brains in diseases of developmental origin, such as schizophrenia and autism.

  2. Brazilian multicentre study on preterm birth (EMIP: prevalence and factors associated with spontaneous preterm birth.

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    Renato Passini

    Full Text Available BACKGROUND: Preterm birth rate is increasing and is currently a worldwide concern. The purpose of this study was to estimate the prevalence of preterm birth in a sample of health facilities in Brazil and to identify the main risk factors associated with spontaneous preterm births. METHODS AND FINDINGS: This was a multicentre cross sectional study on preterm births in 20 referral obstetric hospitals with a case-control component to identify factors associated with spontaneous preterm birth. Surveillance was implemented at all centres to identify preterm births. For eligible consenting women, data were collected through a post-delivery questionnaire completed with information from all mother-newborn medical records until death or discharge or at a maximum of 60 days post-delivery, whichever came first. The risk of spontaneous preterm birth was estimated with OR and 95%CI for several predictors. A non-conditional logistic regression analysis was then performed to identify independently associated factors. The overall prevalence of preterm birth was 12.3%. Among them, 64.6% were spontaneous and 35.4% therapeutic. In the case-control component, 2,682 spontaneous preterm births were compared to a sample of 1,146 term births. Multivariate analyses identified the following as risk factors for spontaneous preterm birth among women with at least one previous birth: a previous preterm birth (ORadj = 3.19, 2.30-4.43, multiple pregnancy (ORadj = 29.06, 8.43-100.2, cervical insufficiency (ORadj = 2.93, 1.07-8.05, foetal malformation (ORadj = 2.63, 1.43-4.85, polyhydramnios (ORadj = 2.30, 1.17-4.54, vaginal bleeding (ORadj = 2.16, 1.50-3.11, and previous abortion (ORadj = 1.39, 1.08-1.78. High BMI (ORadj = 0.94, 0.91-0.97 and weight gain during gestation (ORadj = 0.92, 0.89-0.95 were found to be protective factors. CONCLUSIONS: The preterm birth rate in these health facilities in Brazil is high and spontaneous preterm births

  3. Retinol-Binding Protein 4 and Lipids Prospectively Measured During Early to Mid-Pregnancy in Relation to Preeclampsia and Preterm Birth Risk.

    Science.gov (United States)

    Mendola, Pauline; Ghassabian, Akhgar; Mills, James L; Zhang, Cuilin; Tsai, Michael Y; Liu, Aiyi; Yeung, Edwina H

    2017-06-01

    Maternal retinol-binding protein 4 (RBP4) and lipids may relate to preeclampsia and preterm birth risk but longitudinal data are lacking. This study examines these biomarkers longitudinally during pregnancy in relation to preeclampsia and preterm birth risk. Maternal serum samples from the Calcium for Preeclampsia Prevention (CPEP) trial were analyzed at baseline: average 15 gestational weeks; mid-pregnancy: average 27 weeks; and at >34 weeks. We measured RBP4, total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides and lipoprotein (a) (Lp(a)). Cross-sectional logistic regression analyses estimated the odds ratio (OR) and 95% confidence intervals (CI) for preterm preeclampsia (n = 63), term preeclampsia (n = 104), and preterm delivery (n = 160) associated with RBP4 and lipids at baseline and mid-pregnancy compared with controls (n = 136). Longitudinal trajectories across pregnancy were assessed using mixed linear models with fixed effects. Adjusted models included clinical and demographic factors. RBP4 concentrations at baseline and mid-pregnancy were associated with a 4- to 8-fold increase in preterm preeclampsia risk but were not associated with term preeclampsia. RBP4 measured mid-pregnancy was also associated with preterm birth (OR = 6.67, 95% CI: 1.65, 26.84). Higher triglyceride concentrations in mid-pregnancy were associated with a 2- to 4-fold increased risk for both preeclampsia and preterm birth. Longitudinal models demonstrate that both preterm preeclampsia and preterm birth cases had elevated RBP4 throughout gestation. Elevated RBP4 is detectable early in pregnancy and its strong relation with preterm preeclampsia merits further investigation and confirmation to evaluate its potential use as a predictor, particularly among high-risk women. © Published by Oxford University Press on behalf of American Journal of Hypertension Ltd 2017. This work is written by (a) US Government employees(s) and is in the public domain in the US.

  4. The impact of domestic violence and depressive symptoms on preterm birth in South India.

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    Rao, Deepa; Kumar, Shuba; Mohanraj, Rani; Frey, Sarah; Manhart, Lisa E; L Kaysen, Debra

    2016-02-01

    India has the highest absolute number of maternal deaths, preterm birth cases, and under-5 mortality in the world, as well as high domestic violence (DV) rates. We sought to examine the impact of DV and its psychosocial correlates on pregnancy and birth outcomes. Women seeking antenatal care in Tamil Nadu, South India (N = 150) were assessed during pregnancy, and birth outcomes were abstracted from medical records after the babies were born. We found that psychological abuse (OR 3.9; 95% CI 1.19-12.82) and mild or greater depressive symptoms (OR 3.3; 95% CI 0.99-11.17) were significantly associated with increased risk of preterm birth. Physical abuse was also associated with increased risk of preterm birth, but this was not statistically significant (OR 1.9; 95% CI 0.59-6.19). In each of the above adjusted models, low maternal education was associated with increased risk of preterm birth, in the analysis with depressive symptoms OR 0.18, CI 0.04-0.86 and in the analyses with psychological abuse OR 0.19, CI 0.04-0.91. These findings suggest that future research should focus on understanding the psychosocial antecedents to preterm birth, to better target interventions and improve maternal child health in limited resource settings.

  5. Association of Mothers’ Perception of Neighborhood Quality and Maternal Resilience with Risk of Preterm Birth

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    Namrata Bhatia

    2015-08-01

    Full Text Available We examined the associations of mothers’ perception of neighborhood quality and maternal resilience with risk of preterm birth and whether maternal resilience moderated the effect of neighborhood quality perception. We analyzed data from 10,758 women with singleton births who participated in 2010–2012 Los Angeles Mommy and Baby surveys. Multilevel logistic regression models assessed the effects of mothers’ perception of neighborhood quality and maternal resilience on preterm birth (yes/no, controlling for potential confounders and economic hardship index, a city-level measure of neighborhood quality. Interaction terms were assessed for moderation. Mothers’ perception of neighborhood quality and maternal resilience were each uniquely associated with preterm birth, independent of potential confounders (p-values < 0.05. The risk of preterm birth among mothers who perceived their neighborhood as of poor quality was about 30% greater compared to mothers who perceived their neighborhood as of good quality; the risk was 12% greater among mothers with low resilience compared to those with high resilience. Effects of neighborhood quality were not modified by maternal resilience. The findings suggest that mothers’ perception of neighborhood quality and resilience are associated with the risk of preterm birth. Further research should explore whether initiatives aimed at improving neighborhood quality and women’s self-esteem may improve birth outcomes.

  6. Surface displacement based shape analysis of central brain structures in preterm-born children

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    Garg, Amanmeet; Grunau, Ruth E.; Popuri, Karteek; Miller, Steven; Bjornson, Bruce; Poskitt, Kenneth J.; Beg, Mirza Faisal

    2016-03-01

    Many studies using T1 magnetic resonance imaging (MRI) data have found associations between changes in global metrics (e.g. volume) of brain structures and preterm birth. In this work, we use the surface displacement feature extracted from the deformations of the surface models of the third ventricle, fourth ventricle and brainstem to capture the variation in shape in these structures at 8 years of age that may be due to differences in the trajectory of brain development as a result of very preterm birth (24-32 weeks gestation). Understanding the spatial patterns of shape alterations in these structures in children who were born very preterm as compared to those who were born at full term may lead to better insights into mechanisms of differing brain development between these two groups. The T1 MRI data for the brain was acquired from children born full term (FT, n=14, 8 males) and preterm (PT, n=51, 22 males) at age 8-years. Accurate segmentation labels for these structures were obtained via a multi-template fusion based segmentation method. A high dimensional non-rigid registration algorithm was utilized to register the target segmentation labels to a set of segmentation labels defined on an average-template. The surface displacement data for the brainstem and the third ventricle were found to be significantly different (p MRI data and reveal shape changes that may be due to preterm birth.

  7. Association of Mothers’ Perception of Neighborhood Quality and Maternal Resilience with Risk of Preterm Birth

    Science.gov (United States)

    Bhatia, Namrata; Chao, Shin Margaret; Higgins, Chandra; Patel, Suvas; Crespi, Catherine M.

    2015-01-01

    We examined the associations of mothers’ perception of neighborhood quality and maternal resilience with risk of preterm birth and whether maternal resilience moderated the effect of neighborhood quality perception. We analyzed data from 10,758 women with singleton births who participated in 2010–2012 Los Angeles Mommy and Baby surveys. Multilevel logistic regression models assessed the effects of mothers’ perception of neighborhood quality and maternal resilience on preterm birth (yes/no), controlling for potential confounders and economic hardship index, a city-level measure of neighborhood quality. Interaction terms were assessed for moderation. Mothers’ perception of neighborhood quality and maternal resilience were each uniquely associated with preterm birth, independent of potential confounders (p-values < 0.05). The risk of preterm birth among mothers who perceived their neighborhood as of poor quality was about 30% greater compared to mothers who perceived their neighborhood as of good quality; the risk was 12% greater among mothers with low resilience compared to those with high resilience. Effects of neighborhood quality were not modified by maternal resilience. The findings suggest that mothers’ perception of neighborhood quality and resilience are associated with the risk of preterm birth. Further research should explore whether initiatives aimed at improving neighborhood quality and women’s self-esteem may improve birth outcomes. PMID:26274966

  8. Association of Mothers' Perception of Neighborhood Quality and Maternal Resilience with Risk of Preterm Birth.

    Science.gov (United States)

    Bhatia, Namrata; Chao, Shin Margaret; Higgins, Chandra; Patel, Suvas; Crespi, Catherine M

    2015-08-12

    We examined the associations of mothers' perception of neighborhood quality and maternal resilience with risk of preterm birth and whether maternal resilience moderated the effect of neighborhood quality perception. We analyzed data from 10,758 women with singleton births who participated in 2010-2012 Los Angeles Mommy and Baby surveys. Multilevel logistic regression models assessed the effects of mothers' perception of neighborhood quality and maternal resilience on preterm birth (yes/no), controlling for potential confounders and economic hardship index, a city-level measure of neighborhood quality. Interaction terms were assessed for moderation. Mothers' perception of neighborhood quality and maternal resilience were each uniquely associated with preterm birth, independent of potential confounders (p-values < 0.05). The risk of preterm birth among mothers who perceived their neighborhood as of poor quality was about 30% greater compared to mothers who perceived their neighborhood as of good quality; the risk was 12% greater among mothers with low resilience compared to those with high resilience. Effects of neighborhood quality were not modified by maternal resilience. The findings suggest that mothers' perception of neighborhood quality and resilience are associated with the risk of preterm birth. Further research should explore whether initiatives aimed at improving neighborhood quality and women's self-esteem may improve birth outcomes.

  9. Heightened risk of preterm birth and growth restriction after a first-born son.

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    Bruckner, Tim A; Mayo, Jonathan A; Gould, Jeffrey B; Stevenson, David K; Lewis, David B; Shaw, Gary M; Carmichael, Suzan L

    2015-10-01

    In Scandinavia, delivery of a first-born son elevates the risk of preterm delivery and intrauterine growth restriction of the next-born infant. External validity of these results remains unclear. We test this hypothesis for preterm delivery and growth restriction using the linked California birth cohort file. We examined the hypothesis separately by race and/or ethnicity. We retrieved data on 2,852,976 births to 1,426,488 mothers with at least two live births. Our within-mother tests applied Cox proportional hazards (preterm delivery, defined as less than 37 weeks gestation) and linear regression models (birth weight for gestational age percentiles). For non-Hispanic whites, Hispanics, Asians, and American Indian and/or Alaska Natives, analyses indicate heightened risk of preterm delivery and growth restriction after a first-born male. The race-specific hazard ratios for preterm delivery range from 1.07 to 1.18. Regression coefficients for birth weight for gestational age percentile range from -0.73 to -1.49. The 95% confidence intervals for all these estimates do not contain the null. By contrast, we could not reject the null for non-Hispanic black mothers. Whereas California findings generally support those from Scandinavia, the null results among non-Hispanic black mothers suggest that we do not detect adverse outcomes after a first-born male in all racial and/or ethnic groups. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Anesthetic management in intrauterine surgery to evaluate an experimental model of myelomeningocele in non human primates (Macaca mulatta Anestesia em cirurgia intra-uterina para avaliar um modelo experimental de mielomeningocele em primatas não humanos (Macaca mulatta

    Directory of Open Access Journals (Sweden)

    Alfonso Galván-Montaño

    2010-06-01

    Full Text Available PURPOSE: Evaluate the anesthetic management in intrauterine surgery to induce myelomeningocele in non human primates Macaca mulatta. METHODS: A total of nine fetuses had intrauterine surgery; laminectomy was performed on them in L5 and L6. The studied variables were: maternal death, fetus death, cardiac frequency, respiratory frequency, arterial pressure, temperature, and oxygen saturation. RESULTS: No maternal or fetal deaths occurred; the only variable that was reported below the normal ranges was temperature. CONCLUSION: No maternal or fetal deaths occurred; the only variable that was reported below the normal ranges was temperature.OBJETIVO: Avaliar o manejo anestésico em cirurgia intra-uterina para induzir mielomeningocelo em primatas não humanos, Macaca mulatta. MÉTODOS: Operaram-se um total de nove fetos in útero que foram submetidos à laminectomia em L5 e L6. As variáveis a estudar foram mortes maternas ou fetais, freqüência cardíaca e respiratória, pressão arterial, temperatura e saturação de oxigênio. RESULTADOS: Não se apresentaram mortes maternas ou fetais, a temperatura se manteve abaixo dos 36°C, não tendo repercussões no bem-estar dos macacos. CONCLUSÃO: Não ocorreu nenhum óbito materno ou fetal, sendo que a única variável abaixo do normal foi a temperatura.

  11. Preterm Birth Reduces Nutrient Absorption With Limited Effect on Immune Gene Expression and Gut Colonization in Pigs

    DEFF Research Database (Denmark)

    Østergaard, Mette V; Cilieborg, Malene S.; Skovgaard, Kerstin

    2015-01-01

    The primary risk factors for necrotizing enterocolitis (NEC) are preterm birth, enteral feeding, and gut colonization. It is unclear whether feeding and colonization induce excessive expression of immune genes that lead to NEC. Using a pig model, we hypothesized that reduced gestational age would...... upregulate immune-related genes and cause bacterial imbalance after birth. Preterm (85%-92% gestation, n = 53) and near-term (95%-99% gestation, n = 69) pigs were delivered by cesarean section and euthanized at birth or after 2 days of infant formula or bovine colostrum feeding. At birth, preterm delivery...... reduced 5 of 30 intestinal genes related to nutrient absorption and innate immunity, relative to near-term pigs, whereas 2 genes were upregulated. Preterm birth also reduced ex vivo intestinal glucose and leucine uptake (40%-50%), but failed to increase cytokine secretions from intestinal explants...

  12. Interactions between plants and primates shape community diversity in a rainforest in Madagascar.

    Science.gov (United States)

    Herrera, James P

    2016-07-01

    Models of ecological community assembly predict how communities of interacting organisms may be shaped by abiotic and biotic factors. Competition and environmental filtering are the predominant factors hypothesized to explain community assembly. This study tested the effects of habitat, phylogenetic and phenotypic trait predictors on species co-occurrence patterns and abundances, with the endemic primates of Madagascar as an empirical system. The abundance of 11 primate species was estimated along gradients of elevation, food resource abundance and anthropogenic habitat disturbance at local scales in south-east Madagascar. Community composition was compared to null models to test for phylogenetic and functional structure, and the effects of phylogenetic relatedness of co-occurring species, their trait similarity and environmental variables on species' abundances were tested using mixed models and quantile regressions. Resource abundance was the strongest predictor of community structure. Where food tree abundance was high, closely related species with similar traits dominated communities. High-elevation communities with lower food tree abundance consisted of species that were distantly related and had divergent traits. Closely related species had dissimilar abundances where they co-occurred, partially driven by trait dissimilarity, indicating character displacement. By integrating local-scale variation in primate community composition, evolutionary relatedness and functional diversity, this study found strong evidence that community assembly in this system can be explained by competition and character displacement along ecological gradients. © 2016 The Authors. Journal of Animal Ecology © 2016 British Ecological Society.

  13. Variable responses of human and non-human primate gut microbiomes to a Western diet.

    Science.gov (United States)

    Amato, Katherine R; Yeoman, Carl J; Cerda, Gabriela; Schmitt, Christopher A; Cramer, Jennifer Danzy; Miller, Margret E Berg; Gomez, Andres; Turner, Trudy R; Wilson, Brenda A; Stumpf, Rebecca M; Nelson, Karen E; White, Bryan A; Knight, Rob; Leigh, Steven R

    2015-11-16

    The human gut microbiota interacts closely with human diet and physiology. To better understand the mechanisms behind this relationship, gut microbiome research relies on complementing human studies with manipulations of animal models, including non-human primates. However, due to unique aspects of human diet and physiology, it is likely that host-gut microbe interactions operate differently in humans and non-human primates. Here, we show that the human microbiome reacts differently to a high-protein, high-fat Western diet than that of a model primate, the African green monkey, or vervet (Chlorocebus aethiops sabaeus). Specifically, humans exhibit increased relative abundance of Firmicutes and reduced relative abundance of Prevotella on a Western diet while vervets show the opposite pattern. Predictive metagenomics demonstrate an increased relative abundance of genes associated with carbohydrate metabolism in the microbiome of only humans consuming a Western diet. These results suggest that the human gut microbiota has unique properties that are a result of changes in human diet and physiology across evolution or that may have contributed to the evolution of human physiology. Therefore, the role of animal models for understanding the relationship between the human gut microbiota and host metabolism must be re-focused.

  14. [Prevention of spontaneous preterm birth in asymptomatic twin pregnancies].

    Science.gov (United States)

    Sentilhes, L; Bouhours, A-C; Bouet, P-E; Boussion, F; Biquard, F; Gillard, P; Descamps, P

    2009-12-01

    To determine prenatal methods to predict and prevent spontaneous preterm birth in asymptomatic twin pregnancies. Articles were searched using PubMed, Embase and Cochrane library. Uterine activity monitoring and bacterial vaginosis screening are not useful to predict preterm birth (EL2 and EL3 respectively). Current literature data are contradictory and insufficient to determine whether fetal fibronectin and digital cervical assessment are predictors of preterm birth. History of preterm birth (EL4), and cervical length measurement by transvaginal ultrasonography (EL2) predict preterm birth. Nevertheless, there are no intervention studies that have evaluated cervical length measurement in the prevention of preterm birth. Hospital bedrest, prophylactic tocolytic and progesterone therapy, and prophylactic cervical cerclage in patients with or without short cervix have not been shown to be effective in preventing preterm birth. Prenatal methods to prevent spontaneous preterm birth in asymptomatic twin pregnancies are currently very limited. Copyright © 2009 Elsevier Masson SAS. All rights reserved.

  15. The immune consequences of preterm birth

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    Jacqueline M Melville

    2013-05-01

    Full Text Available Preterm birth occurs in 11% of live births globally and accounts for 35% of all newborn deaths. Preterm newborns have immature immune systems, with reduced innate and adaptive immunity; their immune systems may be further compromised by various factors associated with preterm birth.The immune systems of preterm infants have a smaller pool of monocytes and neutrophils, impaired ability of these cells to kill pathogens, and lower production of cytokines which limits T cell activation and reduces the ability to fight bacteria and detect viruses in cells, compared to term infants.Intrauterine inflammation is a major contributor to preterm birth, and causes premature immune activation and cytokine production. This can induce immune tolerance leading to reduced newborn immune function. Intrauterine inflammation is associated with an increased risk of early-onset sepsis and likely has long-term adverse immune consequences.Requisite medical interventions further impact on immune development and function. Antenatal corticosteroid treatment to prevent newborn respiratory disease is routine but may be immunosuppressive, and has been associated with febrile responses, reductions in lymphocyte proliferation and cytokine production, and increased risk of infection. Invasive medical procedures result in an increased risk of late-onset sepsis. Respiratory support can cause chronic inflammatory lung disease associated with increased risk of long-term morbidity.Colonisation of the infant by microorganisms at birth is a significant contributor to the establishment of the microbiome. Caesarean section affects infant colonisation, potentially contributing to lifelong immune function and wellbeing.Several factors associated with preterm birth alter immune function. A better understanding of perinatal modification of the preterm immune system will allow for the refinement of care to minimise lifelong adverse immune consequences.

  16. Temporal Variation in Air Pollution Concentrations and Preterm Birth—A Population Based Epidemiological Study

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    Bertil Forsberg

    2012-01-01

    Full Text Available There is growing evidence of adverse birth outcomes due to exposure to air pollution during gestation. However, recent negative studies are also reported. The aim of this study was to assess the effect of ozone and vehicle exhaust exposure (NO2 on the length of the gestational period and risk of preterm delivery. We used data from the Swedish Medical Birth Registry on all vaginally delivered singleton births in the Greater Stockholm area who were conceived during 1987–1995 (n = 115,588. Daily average levels of NO2 (from three measuring stations and ozone (two stations were used to estimate trimester and last week of gestation average exposures. Linear regression models were used to assess the association between the two air pollutants and three exposure windows, while logistic regression models were used when analyzing associations with preterm delivery ( < 37 weeks gestation. Five percent were born preterm. The median gestational period was 40 weeks. Higher levels of ozone during the first trimester were associated with shorter gestation as well as with an elevated risk of preterm delivery, the odds ratio from the most complex model was 1.06 (95% CI: 1.00–1.13 per 10 μg/m3 increase in the mean daily 8-h maximum concentration. Higher levels of ozone during the second trimester were associated with shorter gestation but the elevated risk of preterm delivery was not statistically significant. Higher levels of ozone and NO2 during the last week of gestation were associated with a shorter duration of gestation and NO2 also with preterm delivery. There were no significant associations between first and second trimester NO2 exposure estimates and studied outcomes. The effect of first trimester ozone exposure, known to cause oxidative stress, was smallest among women who conceived during autumn when vitamin D status, important for fetal health, in Scandinavian women is the highest.

  17. Comprehensive transcriptional map of primate brain development

    Science.gov (United States)

    Bakken, Trygve E.; Miller, Jeremy A.; Ding, Song-Lin; Sunkin, Susan M.; Smith, Kimberly A.; Ng, Lydia; Szafer, Aaron; Dalley, Rachel A.; Royall, Joshua J.; Lemon, Tracy; Shapouri, Sheila; Aiona, Kaylynn; Arnold, James; Bennett, Jeffrey L.; Bertagnolli, Darren; Bickley, Kristopher; Boe, Andrew; Brouner, Krissy; Butler, Stephanie; Byrnes, Emi; Caldejon, Shiella; Carey, Anita; Cate, Shelby; Chapin, Mike; Chen, Jefferey; Dee, Nick; Desta, Tsega; Dolbeare, Tim A.; Dotson, Nadia; Ebbert, Amanda; Fulfs, Erich; Gee, Garrett; Gilbert, Terri L.; Goldy, Jeff; Gourley, Lindsey; Gregor, Ben; Gu, Guangyu; Hall, Jon; Haradon, Zeb; Haynor, David R.; Hejazinia, Nika; Hoerder-Suabedissen, Anna; Howard, Robert; Jochim, Jay; Kinnunen, Marty; Kriedberg, Ali; Kuan, Chihchau L.; Lau, Christopher; Lee, Chang-Kyu; Lee, Felix; Luong, Lon; Mastan, Naveed; May, Ryan; Melchor, Jose; Mosqueda, Nerick; Mott, Erika; Ngo, Kiet; Nyhus, Julie; Oldre, Aaron; Olson, Eric; Parente, Jody; Parker, Patrick D.; Parry, Sheana; Pendergraft, Julie; Potekhina, Lydia; Reding, Melissa; Riley, Zackery L.; Roberts, Tyson; Rogers, Brandon; Roll, Kate; Rosen, David; Sandman, David; Sarreal, Melaine; Shapovalova, Nadiya; Shi, Shu; Sjoquist, Nathan; Sodt, Andy J.; Townsend, Robbie; Velasquez, Lissette; Wagley, Udi; Wakeman, Wayne B.; White, Cassandra; Bennett, Crissa; Wu, Jennifer; Young, Rob; Youngstrom, Brian L.; Wohnoutka, Paul; Gibbs, Richard A.; Rogers, Jeffrey; Hohmann, John G.; Hawrylycz, Michael J.; Hevner, Robert F.; Molnár, Zoltán; Phillips, John W.; Dang, Chinh; Jones, Allan R.; Amaral, David G.; Bernard, Amy; Lein, Ed S.

    2017-01-01

    The transcriptional underpinnings of brain development remain poorly understood, particularly in humans and closely related non-human primates. We describe a high resolution transcriptional atlas of rhesus monkey brain development that combines dense temporal sampling of prenatal and postnatal periods with fine anatomical parcellation of cortical and subcortical regions associated with human neuropsychiatric disease. Gene expression changes more rapidly before birth, both in progenitor cells and maturing neurons, and cortical layers and areas acquire adult-like molecular profiles surprisingly late postnatally. Disparate cell populations exhibit distinct developmental timing but also unexpected synchrony of processes underlying neural circuit construction including cell projection and adhesion. Candidate risk genes for neurodevelopmental disorders including primary microcephaly, autism spectrum disorder, intellectual disability, and schizophrenia show disease-specific spatiotemporal enrichment within developing neocortex. Human developmental expression trajectories are more similar to monkey than rodent, and approximately 9% of genes show human-specific regulation with evidence for prolonged maturation or neoteny. PMID:27409810

  18. Neurogenetics of aggressive behavior: studies in primates.

    Science.gov (United States)

    Barr, Christina S; Driscoll, Carlos

    2014-01-01

    Aggressive behavior can have adaptive value in certain environmental contexts, but when extreme or executed inappropriately, can also lead to maladaptive outcomes. Neurogenetic studies performed in nonhuman primates have shown that genetic variation that impacts reward sensitivity, impulsivity, and anxiety can contribute to individual differences in aggressive behavior. Genetic polymorphisms in the coding or promoter regions of the Mu-Opioid Receptor (OPRM1), Corticotropin Releasing Hormone (CRH), Monoamine Oxidase A (MAOA), Dopamine D4 Receptor (DRD4), and Serotonin Transporter (SLC6A4) genes have been shown to be functionally similar in humans and rhesus macaques and have been demonstrated to contribute to individual differences in aggression. This body of literature suggests mechanisms by which genetic variation that promotes aggressivity could simultaneously increase evolutionary success while making modern humans more vulnerable to psychopathology.

  19. IOP telemetry in the nonhuman primate.

    Science.gov (United States)

    Downs, J Crawford

    2015-12-01

    This review is focused on continuous IOP monitoring using telemetry systems in the nonhuman primate (NHP), presented in the context that IOP fluctuations at various timescales may be involved in glaucoma pathogenesis and progression. We use glaucoma as the primary framework to discuss how the dynamic nature of IOP might change with age, racial heritage, and disease in the context of glaucoma susceptibility and progression. We focus on the limited work that has been published in IOP telemetry in NHPs, as well as the emerging data and approaches. We review the ongoing efforts to measure continuous IOP, and the strengths, weaknesses and general pitfalls of the various approaches. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Mediodorsal thalamus and cognition in nonhuman primates

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    Mark G Baxter

    2013-08-01

    Full Text Available Several recent studies in nonhuman primates have provided new insights into the role of the medial thalamus in different aspects of cognitive function. The mediodorsal nucleus of the thalamus (MD, by virtue of its connectivity with the frontal cortex, has been implicated in an array of cognitive functions. Rather than serving as an engine or relay for the prefrontal cortex, this area seems to be more specifically involved in regulating plasticity and flexibility of prefrontal-dependent cognitive functions. Focal damage to MD may also exacerbate the effects of damage to other subcortical relays. Thus a wide range of distributed circuits and cognitive functions may be disrupted from focal damage within the medial thalamus (for example as a consequence of stroke or brain injury. Conversely, this region may make an interesting target for neuromodulation of cognitive function via deep brain stimulation or related methods, in conditions associated with dysfunction of these neural circuits.

  1. The Evolution of Primate Communication and Metacommunication.

    Science.gov (United States)

    Proust, Joëlle

    2016-04-01

    Against the prior view that primate communication is based only on signal decoding, comparative evidence suggests that primates are able, no less than humans, to intentionally perform or understand impulsive or habitual communicational actions with a structured evaluative nonconceptual content. These signals convey an affordance-sensing that immediately motivates conspecifics to act. Although humans have access to a strategic form of propositional communication adapted to teaching and persuasion, they share with nonhuman primates the capacity to communicate in impulsive or habitual ways. They are also similarly able to monitor fluency, informativeness and relevance of messages or signals through nonconceptual cues.

  2. Mapping arealisation of the visual cortex of non-primate species: lessons for development and evolution

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    Jihane eHomman-Ludiye

    2014-07-01

    Full Text Available In order to integrate and interpret visual stimuli and build a representation of the surrounding environment, the visual cortex is organised in anatomically distinct and functionally unique areas. Each area processes a particular aspect of the visual scene, with the signal flowing from one area to the next in a bottom-up processing sequence. Areal borders can be demarcated both functionally by systematic electrophysiology mapping, and anatomically by sharp changes in cellular distribution and molecular expression profiles. Primates, including humans, are heavily dependent on vision, with approximately 50% of their neocortical surface dedicated to visual processing and possess many more visual areas than any other mammal, making them often the model of choice to study visual arealisation. However, the recent identification of differential gene expression profiles between cortices in a number of species has allowed for the introduction of non-primate animal models in the field to better understand development and evolution. Profiling the mosaic of visual areas in less complex species was pivotal in understanding the mechanisms responsible for patterning the developing neocortex, specifying area identity as well as the evolutionary events that have allowed for primates to develop more areas. In addition, species with fewer areas provide a simpler system in which to study and map cortical connectivity. In this review we focus on non-primate species that have contributed to elucidating the evolution and development of the visual cortex, including small nocturnal species and carnivores. We present the current understanding of the mechanisms supporting the establishment of areal borders during development and the limitations of the predominant mouse model and the need for alternate species.

  3. Psychomotor development of preterm babies in the context of biomedical predictors in a Polish sample

    Directory of Open Access Journals (Sweden)

    Mariola Bidzan

    2014-02-01

    Full Text Available Background Preterm birth represents the most frequent complication of pregnancy all over the world. Much research is addressed to psychomotor development of preterm infants during the initial years of their life. Many authors emphasize the role of birth weight, gestational age, and gender in determining the child’s psychomotor development. This study adds to this knowledge as we analyzed the synergistic effect of biomedical predictors such as gestational age, birth weight, Apgar score, time in incubator, type of pregnancy defined based on its outcome, neonatal status immediately after delivery, infant’s gender, and possessing twin sibling. Combined effects of these factors represent an important niche in the studies of the developmental psychology of preterm infants. Participants and procedure The study included 49 preterm infants born in 2008-2009 at the Department of Obstetrics of the Medical University of Gdańsk. The psychomotor development of preterm infants was evaluated according to the Bayley Scales of Infant and Toddler Development®, Third Edition (BSID-III at a mean, non-corrected age of 33.80 months (SD = 5.16. For the purpose of the study we developed a basic model in the form of a pathway diagram, describing the cumulative influence of eight biomedical predictors on the development of the infants during early childhood. Results Our study revealed a synergistic influence of biomedical predictors on the development of preterm infants with regards to cognitive functioning (28% of variance, language skills (10% of variance, motor skills (18% of variance, fine motor skills (16% of variance, and gross motor skills (20% of variance. Moreover, we observed an independent effect of birth weight, child’s gender, and final Apgar score on the psychomotor development of preterm infants. Higher birth weight was associated with higher level of cognitive function and fine motor skills. Male gender of a child was reflected by a higher level of

  4. Effect of periodontal treatment on preterm birth rate: a systematic review of meta-analyses.

    Science.gov (United States)

    López, Néstor J; Uribe, Sergio; Martinez, Benjamín

    2015-02-01

    Preterm birth is a major cause of neonatal morbidity and mortality in both developed and developing countries. Preterm birth is a highly complex syndrome that includes distinct clinical subtypes in which many different causes may be involved. The results of epidemiological, molecular, microbiological and animal-model studies support a positive association between maternal periodontal disease and preterm birth. However, the results of intervention studies carried out to determine the effect of periodontal treatment on reducing the risk of preterm birth are controversial. This systematic review critically analyzes the methodological issues of meta-analyses of the studies to determine the effect of periodontal treatment to reduce preterm birth. The quality of the individual randomized clinical trials selected is of highest relevance for a systematic review. This article describes the methodological features that should be identified a priori and assessed individually to determine the quality of a randomized controlled trial performed to evaluate the effect of periodontal treatment on pregnancy outcomes. The AMSTAR and the PRISMA checklist tools were used to assess the quality of the six meta-analyses selected, and the bias domain of the Cochrane Collaboration's Tool was applied to evaluate each of the trials included in the meta-analyses. In addition, the methodological characteristics of each clinical trial were assessed. The majority of the trials included in the meta-analyses have significant methodological flaws that threaten their internal validity. The lack of effect of periodontal treatment on preterm birth rate concluded by four meta-analyses, and the positive effect of treatment for reducing preterm birth risk concluded by the remaining two meta-analyses are not based on consistent scientific evidence. Well-conducted randomized controlled trials using rigorous methodology, including appropriate definition of the exposure, adequate control of confounders for

  5. Early primate evolution in Afro-Arabia.

    Science.gov (United States)

    Seiffert, Erik R

    2012-11-01

    The peculiar mammalian fauna that inhabited Afro-Arabia during the Paleogene first came to the attention of the scientific community in the early part of the twentieth century, when Andrews1 and Schlosser2 published their landmark descriptions of fossil mammals from the Fayum Depression in northern Egypt. Their studies revealed a highly endemic assemblage of land mammals that included the first known Paleogene records of hyraxes, proboscideans, and anthropoid primates, but which lacked ancestors of many iconic mammalian lineages that are found in Africa today, such as rhinos, zebras, bovids, giraffes, and cats. Over the course of the last century, the Afro-Arabian Paleogene has yielded fossil remains of several other endemic mammalian lineages,3 as well as a diversity of prosimian primates,4 but we are only just beginning to understand how the continent's faunal composition came to be, through ancient processes such as the movement of tectonic plates, changes in climate and sea level, and early phylogenetic splits among the major groups of placental mammals. These processes, in turn, made possible chance dispersal events that were critical in determining the competitive landscape--and, indeed, the survival--of our earliest anthropoid ancestors. Newly discovered fossils indicate that the persistence and later diversification of Anthropoidea was not an inevitable result of the clade's competitive isolation or adaptive superiority, as has often been assumed, but rather was as much due to the combined influences of serendipitous geographic conditions, global cooling, and competition with a group of distantly related extinct strepsirrhines with anthropoid-like adaptations known as adapiforms. Many of the important details of this story would not be known, and could never have been predicted, without the fossil evidence that has recently been unearthed by field paleontologists. Copyright © 2012 Wiley Periodicals, Inc.

  6. Effect of sitting position on respiratory status in preterm infants.

    Science.gov (United States)

    Shiraishi, Mika; Hirasawa, Kyoko; Shimizu, Satoru; Nishida, Hiroshi; Osawa, Makiko

    2009-01-01

    To evaluate whether using a sitting-type car safety seats for preterm infants is advisable. A total of 65 preterm infants underwent polysomnography in the supine and sitting positions. The infants with position were suspected to cause DS in infants. Sitting-type car safety seats should be used with caution for preterm infants, and all preterm infants need to be screened by polysomnographic examination in the sitting position.

  7. Thymic size in preterm neonates: a sonographic study

    DEFF Research Database (Denmark)

    Jeppesen, Dorthe Lisbeth; Hasselbalch, H; Poulsen, Susanne Dam

    2003-01-01

    AIM: To assess the variation in size of the thymus in vivo in preterm neonates and to identify relations between thymic size and gestational age (GA), birthweight, occurrence of postnatal infections and maternal alcohol and tobacco intake during pregnancy. METHODS: Eighty preterm neonates with a GA...... neonates. A normal range for Ti in preterm neonates has been established. The sonographic method is a safe and effective technique for measuring the size of the thymus in preterm infants....

  8. Occupational lifting of heavy loads and preterm birth:

    DEFF Research Database (Denmark)

    Runge, Stine Bjerrum; Pedersen, Jacob Krabbe; Svendsen, Susanne Wulff

    2013-01-01

    To examine the association between occupational lifting during pregnancy and preterm birth. The risk of preterm birth was estimated for total burden lifted per day and number of medium and heavy loads lifted per day.......To examine the association between occupational lifting during pregnancy and preterm birth. The risk of preterm birth was estimated for total burden lifted per day and number of medium and heavy loads lifted per day....

  9. Maternal and fetal factors observed with late preterm births

    OpenAIRE

    Madhusudan Dey; Raju Agarwal; Devkalyan Maji; Uttara A. Kohli

    2015-01-01

    Backround: Although neonatal morbidity and mortality rates are fallen in recent decades, the prevalence of preterm deliveries has increased especially late preterm births. Late preterm deliveries are at increased risk of various neonatal complications compared to term deliveries. This study was carried out to identify the maternal characteristics and co-morbidites found with late preterm births and feto-maternal outcome in terms of indication of delivery, route of delivery, Apgar score and...

  10. Cytokine expression in malaria-infected non-human primate placentas

    OpenAIRE

    Barasa, M.; Ng'ang'a, Z. W.; Sowayi, G. A.; Okoth, J. M.; Barasa, M. B. O.; Namulanda, F. B. M.; Kagasi, E. A.; Gicheru, M. M.; Ozwara, S. H.

    2012-01-01

    Malaria parasites are known to mediate the induction of inflammatory immune responses at the maternal-foetal interface during placental malaria (PM) leading to adverse consequences like pre-term deliveries and abortions. Immunological events that take place within the malaria-infected placental micro-environment leading to retarded foetal growth and disruption of pregnancies are among the critical parameters that are still in need of further elucidation. The establishment of more animal model...

  11. Taste responsiveness to two steviol glycosides in three species of nonhuman primates

    OpenAIRE

    Nicklasson, Sandra; Sjöström, Desirée; Amundin, Mats; Roth, Daniel; Hernandez Salazar, Laura Teresa; Laska, Matthias

    2018-01-01

    Primates have been found to differ widely in their taste perception and studies suggest that a co-evolution between plant species bearing a certain taste substance and primate species feeding on these plants may contribute to such between-species differences. Considering that only platyrrhine primates, but not catarrhine or prosimian primates, share an evolutionary history with the neotropical plant Stevia rebaudiana, we assessed whether members of these three primate taxa differ in their abi...

  12. Pathways of job style and preterm low birth weight.

    Science.gov (United States)

    Salehi, Katayoun; Mahmoodi, Zohreh; Kabir, Kourosh; Dolatian, Mahrokh

    2016-09-01

    Preterm and low birth weight tend to occur as a direct result of prenatal risky behaviors, diseases, as well as fetal exposure to harmful social and environmental factors. The present study aimed to investigate the relationship between job style and preterm low birth weight. The present case-control study was conducted in the Kamali hospital, Teheran, Iran in 2014. Participants included 156 mothers having a gestational age of less than 37 weeks and infants weighing less than 2500 gm. Additionally, the control group consisted of 433 mothers with a gestational age of over 37 weeks and having infants weighing between 2500-4000 gm. The data were collected using the Mother's Lifestyle Scale (MLS) during pregnancy based on recognized social determinants of health and those developed by the researchers. The domain of the mother's job style was assessed using a questionnaire consisting of 18 items on topics such as working conditions, job satisfaction, and perceived employer empathy. Higher overall scores in this instrument indicate the mother's poore