A Common Marmoset Model of Mother-Infant Intervention for Breastfeeding Disorders in the Presence of Paternal Inhibition and Maternal Neglect.

Objective. Spinal cord injury remains an ailment with no comprehensive cure, and affected patients suffer from a greatly diminished quality of life. This large population could significantly benefit from prosthetic technologies to replace missing limbs, reanimate nonfunctional limbs, and enable new modes of technologies to restore muscle control and function. While cortically driven brain machine interfaces have achieved great success in interfacing with an external device to restore lost functions, interfacing with the spinal cord can provide an additional site to record motor control signals, which can have its own advantages, despite challenges from using a smaller non-human primate (NHP) model. The goal of this study is to develop such a spinal cord neural interface to record motor signals from the high cervical levels of the spinal cord in a common marmoset (Callithrix jacchus) model. Approach and main results. Detailed methods are discussed for this smaller NHP model that includes behavioral training, surgical methods for electrode placement, connector placement and wire handling, electrode specifications and modifications for accessing high cervical level interneurons and motorneurons. The study also discusses the methods and challenges involved in behavioral multi-channel extracellular recording from the marmoset spinal cord, including the major recording failure mechanisms encountered during the study. Significance. Marmosets provide a good step between rodent and larger NHP models due to their small size, ease of handling, cognitive abilities, and similarities to other primate motor systems. The study shows the feasibility of recording spinal cord signals and using marmosets as a smaller NHP model in behavioral neuroscience studies. Interfacing with the spinal cord in chronically implanted animals can provide useful information about how motor control signals within the spinal cord are transformed to cause limb movements.

Rift Valley fever (RVF) virus (RVFV) can cause severe human disease characterized by either acute-onset hepatitis, delayed-onset encephalitis, retinitis and blindness, or a hemorrhagic syndrome. The existing nonhuman primate (NHP) model for RVF utilizes an intravenous (i.v.) exposure route in rhesus macaques (Macaca mulatta). Severe disease in these animals is infrequent, and large cohorts are needed to observe significant morbidity and mortality. To overcome these drawbacks, we evaluated the infectivity and pathogenicity of RVFV in the common marmoset (Callithrix jacchus) by i.v., subcutaneous (s.c.), and intranasal exposure routes to more closely mimic natural exposure. Marmosets were more susceptible to RVFV than rhesus macaques and experienced higher rates of morbidity, mortality, and viremia and marked aberrations in hematological and chemistry values. An overwhelming infection of hepatocytes was a major consequence of infection of marmosets by the i.v. and s.c. exposure routes. Additionally, these animals displayed signs of hemorrhagic manifestations and neurological impairment. Based on our results, the common marmoset model more closely resembles severe human RVF disease and is therefore an ideal model for the evaluation of potential vaccines and therapeutics.

Murine and human iPSC-NS/PCs (induced pluripotent stem cell-derived neural stem/progenitor cells) promote functional recovery following transplantation into the injured spinal cord in rodents. However, for clinical applicability, it is critical to obtain proof of the concept regarding the efficacy of grafted human iPSC-NS/PCs (hiPSC-NS/PCs) for the repair of spinal cord injury (SCI) in a non-human primate model. This study used a pre-evaluated “safe” hiPSC-NS/PC clone and an adult common marmoset (Callithrix jacchus) model of contusive SCI. SCI was induced at the fifth cervical level (C5), followed by transplantation of hiPSC-NS/PCs at 9 days after injury. Behavioral analyses were performed from the time of the initial injury until 12 weeks after SCI. Grafted hiPSC-NS/PCs survived and differentiated into all three neural lineages. Furthermore, transplantation of hiPSC-NS/PCs enhanced axonal sparing/regrowth and angiogenesis, and prevented the demyelination after SCI compared with that in vehicle control animals. Notably, no tumor formation occurred for at least 12 weeks after transplantation. Quantitative RT-PCR showed that mRNA expression levels of human neurotrophic factors were significantly higher in cultured hiPSC-NS/PCs than in human dermal fibroblasts (hDFs). Finally, behavioral tests showed that hiPSC-NS/PCs promoted functional recovery after SCI in the common marmoset. Taken together, these results indicate that pre-evaluated safe hiPSC-NS/PCs are a potential source of cells for the treatment of SCI in the clinic.

Current neuroprosthetics rely on stable, high quality recordings from chronically implanted microelectrode arrays (MEAs) in neural tissue. While chronic electrophysiological recordings and electrode failure modes have been reported from rodent and larger non-human primate (NHP) models, chronic recordings from the marmoset model have not been previously described. The common marmoset is a New World primate that is easier to breed and handle compared to larger NHPs and has a similarly organized brain, making it a potentially useful smaller NHP model for neuroscience studies. This study reports recording stability and signal quality of MEAs chronically implanted in behaving marmosets. Six adult male marmosets, trained for reaching tasks, were implanted with either a 16-channel tungsten microwire array (five animals) or a Pt-Ir floating MEA (one animal) in the hand-arm region of the primary motor cortex (M1) and another MEA in the striatum targeting the nucleus accumbens (NAcc). Signal stability and quality was quantified as a function of array yield (active electrodes that recorded action potentials), neuronal yield (isolated single units during a recording session), and signal-to-noise ratio (SNR). Out of 11 implanted MEAs, nine provided functional recordings for at least three months, with two arrays functional for 10 months. In general, implants had high yield, which remained stable for up to several months. However, mechanical failure attributed to MEA connector was the most common failure mode. In the longest implants, signal degradation occurred, which was characterized by gradual decline in array yield, reduced number of isolated single units, and changes in waveform shape of action potentials. This work demonstrates the feasibility of long-term recordings from MEAs implanted in cortical and deep brain structures in the marmoset model. The ability to chronically record cortical signals for neural prosthetics applications in the common marmoset extends the potential of this model in neural interface research.

Pharmacokinetic and efficacy studies with levofloxacin were performed in the common marmoset (Callithrix jacchus) model of inhalational tularemia. Plasma levofloxacin pharmacokinetics were determined in six animals in separate single-dose and multidose studies. Plasma drug concentrations were analyzed using liquid chromatography-tandem mass spectrometry-electrospray ionization. On day 7 of a twice-daily dosing regimen of 40 mg/kg, the levofloxacin half-life, maximum concentration, and area under the curve in marmoset plasma were 2.3 h, 20.9 microg/ml, and 81.4 microg/liter/h, respectively. An efficacy study was undertaken using eight treated and two untreated control animals. Marmosets were challenged with a mean of 1.5 x 10(2) CFU of Francisella tularensis by the airborne route. Treated animals were administered 16.5 mg/kg levofloxacin by mouth twice daily, based on the pharmacokinetic parameters, beginning 24 h after challenge. Control animals had a raised core body temperature by 57 h postchallenge and died from infection by day 5. All of the other animals survived, remained afebrile, and lacked overt clinical signs. No bacteria were recovered from the organs of these animals at postmortem after culling at day 24 postchallenge. In conclusion, postexposure prophylaxis with orally administered levofloxacin was efficacious against acute inhalational tularemia in the common marmoset. The marmoset appears to be an appropriate animal model for the evaluation of postexposure therapies.

Educational treatment to support social development of children with autism spectrum disorder (ASD) is an important topic in developmental psychiatry. However, it remains difficult to objectively quantify the socio-emotional development of ASD children. To address this problem, we developed a novel analytical method that assesses subjects' complex behaviors using multivariate analysis, 'Behavior Output analysis for Quantitative Emotional State Translation' (BOUQUET). Here, we examine the potential for psycho-cognitive ASD therapy based on comparative evaluations of clinical (human) and experimental (animal) models. Our observations of ASD children (vs. their normally developing siblings) and the domestic chick in socio-sensory deprivation models show the importance of unimodal sensory stimulation, particularly important for tactile- and auditory-biased socialization. Identifying psycho-cognitive elements in early neural development, human newborn infants in neonatal intensive care unit as well as a New World monkey, the common marmoset, also prompted us to focus on the development of voluntary movement against gravity. In summary, striking behavioral similarities between children with ASD and domestic chicks' socio-sensory deprivation models support the role of multimodal sensory-motor integration as a prerequisite step for normal development of socio-emotional and psycho-cognitive functions. Data obtained in the common marmoset model also suggest that switching from primitive anti-gravity reflexes to complex voluntary movement may be a critical milestone for psycho-cognitive development. Combining clinical findings with these animal models, and using multivariate integrative analyses may facilitate the development of effective interventions to improve social functions in infants and in children with neurodevelopmental disorders.

The common marmoset, Callithrix jacchus, is increasingly being used as the preferred nonhuman primate (NHP) model in biomedical research. Marmosets share severalphysiological and biological similarities with humans, as a Simiiformes species, and their use in research programs advances knowledge in several fields. Their unique characteristics, suchas their small size, high fecundity, and rapid growth, offer additional advances in laboratory settings. This article reviews the developments in experimental disease models using marmosetsbased on our experience at the Central Institute for Experimental Animals (CIEA) in Japan. The development of genetically modified marmoset models using advanced genome editing technology isattracting researchers, particularly in neuroscience-related fields. In parallel, various marmoset models of human diseases induced by surgery or drug administration have contributed topreclinical and translational studies. Among these are models for Parkinson’s disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, spinal cord injury models, a model for type 1diabetes induced by the combination of partial pancreatectomy and streptozotocin administration, and a hepatic fibrosis model induced by thioacetamide. The development of these models hasbeen supported by refinements in veterinary care, such as the careful design of anesthetic protocols and better understanding of pathogenic microorganisms. In the second part of this review,we present a compilation of practices currently in use at CIEA that provide optimal animal care and enable safe experimentation.

B lymphocyte stimulator (BLyS, also indicated as BAFF (B-cell activating factor) and CD257), and A Proliferation Inducing Ligand (APRIL, CD256) are two members of the TNF superfamily with a central role in B cell survival. Antibodies against these factors have potential therapeutic relevance in autoimmune inflammatory disorders with a proven pathogenic contribution of B cells, such as multiple sclerosis (MS). In the current study we performed a multi-parameter efficacy comparison of monoclonal antibodies against human anti-BLyS and anti-APRIL in a common marmoset (Callithrix jacchus) model of experimental autoimmune encephalomyelitis (EAE). A MS-like disease was induced by immunization with recombinant human myelin/oligodendrocyte glycoprotein (rhMOG) in complete Freund’s adjuvant. The results show that the anti-BLyS and anti-APRIL antibody cause significant depletion of circulating CD20+ B cells, but a small subset of CD20 + CD40high B cells was not depleted. Induction of CD20+ B cell depletion from lymph nodes was only observed in the anti-BLyS treated monkeys. Both antibodies had a significant inhibitory effect on disease development, but all monkeys developed clinically evident EAE. Anti-BLyS treated monkeys were sacrificed with the same clinical signs as saline-treated monkeys, but nevertheless displayed significantly reduced spinal cord demyelination. This effect was not observed in the anti-APRIL treated monkeys. The two antibodies had a different effect on T cell subset activation and the profiles of ex vivo released cytokines. In conclusion, treatment with anti-BLyS and anti-APRIL delays the development of neurological disease in a relevant preclinical model of MS. The two mAbs achieve this effect via different mechanisms.

1H-NMR spectroscopy combined with pattern recognition analysis reveals characteristic chemical patterns in urines of MS patients and non-human primates with MS-like disease

The emergence of the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 marked the second time that a new, highly pathogenic coronavirus has emerged in the human population in the 21st century. In this review, we discuss the current state of knowledge of animal models of MERS-CoV infection. Commonly used laboratory animal species such as Syrian hamsters, mice and ferrets are not susceptible to MERS-CoV, due to differences in the MERS-CoV receptor dipeptidyl peptidase 4 (DPP4). The initially developed animal models comprise two nonhuman primate species, the rhesus macaque and the common marmoset. Rhesus macaques develop a mild to moderate respiratory disease upon inoculation, reminiscent of milder MERS cases, whereas marmosets develop a moderate to severe respiratory disease, recapitulating the severe disease observed in some patients. Dromedary camels, considered to be the reservoir for MERS-CoV, develop a mild upper respiratory tract infection with abundant viral shedding. Although normal mice are not susceptible to MERS-CoV, expression of the human DPP4 (hDPP4) overcomes the lack of susceptibility. Transgenic hDPP4 mice develop severe and lethal respiratory disease upon inoculation with MERS-CoV. These hDPP4 transgenic mice are potentially the ideal first line animal model for efficacy testing of therapeutic and prophylactic countermeasures. Further characterization of identified countermeasures would ideally be performed in the common marmoset model, due to the more severe disease outcome. This article forms part of a symposium in Antiviral Research on “From SARS to MERS: research on highly pathogenic human coronaviruses.”

The common marmoset (Callithrix jacchus) is useful as a nonhuman primate model of human diseases. Although the marmoset model has great potential for studying autoimmune diseases and immune responses against pathogens, little information is available regarding the genes involved in adaptive immunity. Here, we identified one TCR alpha constant (TRAC), 46 TRAJ (joining), and 35 TRAV (variable) segments from marmoset cDNA. Marmoset TRAC, TRAJ, and TRAV shared 80%, 68-100%, and 79-98% identity with their human counterparts at the amino acid level, respectively. The amino acid sequences were less conserved in TRAC than in TCRbeta chain constant (TRBC). Comparative analysis of TRAV between marmosets and humans showed that the rates of synonymous substitutions per site (d(S)) were not significantly different between the framework regions (FRs) and complementarity determining regions (CDRs), whereas the rates of nonsynonymous substitutions per site (d(N)) were significantly lower in the FRs than in CDRs. Interestingly, the d(N) values of the CDRs were greater for TRBV than TRAV. These results suggested that after the divergence of Catarrhini from Platyrrhini, amino acid substitutions were decreased in the FRs by purifying selection and occurred more frequently in CDRbeta than in CDRalpha by positive selection, probably depending on structural and functional constraints. This study provides not only useful information facilitating the investigation of adaptive immunity using the marmoset model but also new insight into the molecular evolution of the TCR heterodimer in primate species.

Macrophages are essential immune cells in the cochlea that contribute to inflammation, tissue repair, and homeostasis. They also play an important role in local cochlear immunity. The developmental immigration and maturation of macrophages in the cochlea have been investigated and are considered essential for normal hearing acquisition. Most of our current knowledge regarding cochlear development is based on rodent models because of the ethical challenges of using human fetal samples for research. However, inter-species differences between rodents and humans have been reported. In this study, we used a primate animal model to investigate the distributions of macrophages in the developing cochlea. The common marmoset (Callithrix jacchus), a small monkey species that inhabits the New World, was used as the model. We investigated the distribution of macrophages in the developing cochlea of the common marmoset by performing immunohistochemical analyses of cochlear tissue from common marmoset embryos at different development stages. We revealed detailed distribution changes in the macrophages of a primate animal model cochlea. This observation indicates that most of the changes in the general distribution of macrophages were well preserved between rodents and this primate. The distribution changes observed in the common marmoset were also compatible with observations in the human fetus; although, observations in the human fetus are limited. Our observations in this study also revealed several differences between common marmosets and rodents. The time course of immunological development and maturations established in this study will aid in the study of the primate-specific developmental biology of the inner ear. These observations may eventually lead to new therapeutic strategies for hearing loss in humans. In addition, understanding the immunological steady-state of the cochlea may help in the study of age- and genetic-induced hearing loss and in the design of regenerative therapies.

A descriptive study was conducted to find out physical, social problems & emotional stress of the mothers of the babies who are admitted in NICU/SNCU of selected government hospital. The objectives of the study were to find out physical, social problems & emotional stress of the mothers, to identify the relationship between emotional stress & physical problems, emotional stress & social problems, to identify the association between physical, social problems, emotional stress with selected socio- demographic variables. The conceptual framework was adopted for this study was Holistic care model. Non-experimental research approach & descriptive survey research design was adopted for this study. One ninety-five (195) mothers of babies admitted in NICU/SNCU of R. G. Kar Medical College & Hospital were selected as sample through non-probability purposive sampling technique. The instruments used for data collection were structured interview schedule, record analysis proforma, Semi-structured interview schedule & structured assessment tool (Likert scale). The findings of the study revealed that 55.89% mothers were found with physical problems. Out of them, 55.05% had sleeping disturbances, 30.27% had breast engorgement, 18.34% had constipation, 9.17% had headache, 8.26% had extreme tiredness, 7.34% had loss of appetite, and 7.34% had heartburn, 1.83% had fever. In social problems, family members blamed to 10.77% mothers, superstition present for 18.97% of mothers, 67.18% mothers had financial problems in the family, 100% mothers didn’t receive any financial help from any organization, 2.56% mothers had lack of support person in the family & for 100% mothers’ family bonding with the newborn child affected. Child’s admission to NICU/SNCU induces moderate stress, mild stress & severe stress to 45.13%, 27.18% & 24.62% mothers respectively. A significant relationship found between social problems & emotional stress (r = 0.201). There was a significant association between age & physical problems of mother [χ2 df (1) =4.634, p < 0.05], gravida & physical problem of mothers [χ2 df (1) =29.221, p < 0.05], NICU admission duration of baby & physical problems of mothers [χ2 df (2) =15.257, p < 0.05], religion & social problems of mothers [χ2 df(1) =41.679, p < 0.05], area of living & social problems of mothers [χ2 df(1) = 56.231, p < 0.05], socioeconomic status & social problems of mothers [χ2 df (1) = 66.087, p < 0.05], baby’s NICU admission duration & emotional stress of mothers [χ2 df (2)= 63.564, p < 0.05]. It can be concluded that mothers of NICU/SNCU admitted babies face different physical, social problems & emotional stress. The finding of the study has several implications in nursing practice, education, administration & research. A similar study can be conducted with large sample size & random sampling & the study can be done to identify both the physical, social problems & emotional stress of mothers & its contributing factors.

Takotsubo syndrome (broken-heart syndrome) is considered a cardiac disorder typically associated with exposure to severe psychological or physical stress, and it clinically resembles acute coronary syndrome. The literature indicates its association with elevated levels of anxiety and depression among patients, in addition to the potential impairment of cognitive functions. This study aims to identify the differences in psychological indicators (anxiety & depression) and cognitive functions between patients with Takotsubo syndrome (TTS) and healthy Controls. A case-control cross-sectional design was employed. The study sample consisted of twenty patients who were selected from the Health Insurance Hospital in Zagazig, Al-Sharqia Governorate, aged (35.8 ± 8.4) years, and twenty healthy Controls aged (36 ± 9.7) years, who were matched with the patient group in terms of demographic characteristics, including gender, age, educational level, and mental state variables. The study instruments included an initial clinical interview for data collection, the Perceived Stress Scale (PSS-10), Raven's Progressive Matrices Test, the Hospital Anxiety and Depression Scale (HADS), and the Montreal Cognitive Assessment (MoCA). The study revealed a significant increase in anxiety and depression levels, along with cognitive impairment in patients with TTS compared to healthy controls, manifested particularly in executive functions, memory, and attention, thereby reflecting a unique interaction between the brain and the heart in this syndrome. The findings indicate that the psychological and cognitive indicators in patients with TTS are multifactorial in nature, involving an interplay of Cerebral Hypoperfusion, Neurohormonal alterations, and dysfunction of brain networks.

BackgroundPersecution and conflicts in countries like Vietnam and Myanmar force many to flee their countriesto those with more resources, such as Australia, in search of a better life. However, maternalintegration into the new society is often compounded by the task of nurturing her infant while shenavigates unfamiliar and contrasting socio-cultural norms, ideologies and expectations. Whileglobal data show that child malnutrition due to sub-optimal feeding practices are high in lowerincome countries, there is no recent data that showcase the infant feeding experiences of refugeemothers from Vietnam and Myanmar in Australia or globally. Thus, an understanding of the beliefs,practices and experiences related to infant feeding decisions in their new homeland would helphealthcare and policy sectors focus attention on aspects of maternal infant feeding negotiations thatrequire attention.Research objectivesThis research was designed to understand infant feeding beliefs, practices and experiences, and thecultural meanings of maternal and infant health in Vietnamese and Myanmarese refugee women inAustralia. The objectives were to 1) define the post-birth rituals and its connection with infantfeeding; 2) understand the cultural definition and maternal management of optimal infant health inchanging contexts; 3) explore infant feeding experiences in relation to societal norms, networks andsocial structures pre- and post-resettlement; and 4) examine the embodied experiences of nurturingin traditional and modernistic contexts.MethodologyThis study employed qualitative research methods to explore the infant feeding experiences ofVietnamese and Myanmarese mothers who have resettled in Brisbane, Australia.Phenomenological-, feminism-, and postmodern- informed methodological frameworks were usedto guide data collection through in-depth interviewing and drawing methods. Most mothers had onefollow-up interview and were given the freedom to express their voices through artwork at theirpreferred phase of the interview. Data surrounding infant feeding beliefs, practices, experiences andnegotiations in social spheres were gathered. Verbal and visual data were analysed thematically and using the critical visual analytical framework respectively and later juxtaposed with the interviewthemes. There were thirty-eight participants; 16 from Vietnam and 22 from Myanmar. Half of theVietnamese mothers were recent arrivals (l 10 years), while the remainder arrived in Australia aschildren or teenagers (g 20 years). Participants from Myanmar were all recent arrivals (l 10 years),and from four ethnic groups (Karen, Karenni, Chin and Kachin).Results and discussionsThe findings and discussion of this study were situated within four theories: Liminality; MaternalinfantEmbodiment and Inter-embodiment; Motherhood Risk and Responsibility; and BourdieursTheory of Practice. Four main themes were derived from the data: Infant feeding beliefs; Maternalways of knowing infant health and growth; Negotiations of infant feeding beliefs, practices andexperiences in changing socio-cultural and medicalised contexts; and the embodiment of infantfeeding in changing contexts. Breastfeeding was seen as an embodied behaviour and breast milk asan embodied bodily fluid; both were interdependent of the other. Breast milk was thought to be ofoptimal quality for infant growth and development when the mother, infant and culturalenvironment were in a state of elemental harmony and oneness. Childbirth was thought tocontribute to maternal bodily vulnerability and disharmony, while conformity to heat-enhancingpostpartum rituals established a state of bodily strength and elemental harmony. Maternal ill health,emotional stressors and disconnection from support networks and ritualistic environmentscontributed to the use of alternative feeding methods to protect the infant from health risks that maybe transmitted through breast milk. The vulnerability of mothers who were recent arrivals wasfrequently compounded by negotiations with unfamiliar socio-cultural environments. Issues such asthe medicalisation of infant feeding, negotiating lforeignr healthcare systems, work ideologies thatnecessitate maternal-infant separation, and sexualisation of the breast often instilled feelings ofdoubt about their capacity as nurturers. Often, this contributed to the cession of breastfeeding andsubsequent use of infant formula. Mothers who could communicate in English and those who wereeducated in Australia or had familial support networks were able to integrate into and negotiateAustralian norms while maintaining their identity as breastfeeding mothers. This study providesnew knowledge especially in respect to embodied experiences that were predominantly expressedthrough drawing exercises, since some descriptions are inexpressible with words and many recentarrivals, in particular, struggled to verbalise their life journeys. Conclusion and recommendationsSince infant feeding does not stand alone but is tempered with contextual negotiations, multilevelsocietal interventions would be valuable in supporting breastfeeding practice in the context ofrefugee motherhood. It is suggested that fostering a culturally sensitive, knowledgeable andintegrative healthcare system, educational programs, community support groups and social spaceswould aid maternal integration into a new society.