RESUMO
Background: Obesity is highly stigmatized, with negative obesity-related stereotypes widespread across society. Internalized weight stigma (IWS) is linked to negative outcomes including poor mental health and disordered eating. Previous evidence examining population groups at higher risk of experiencing IWS comes from small, nonrepresentative samples. Here, we re-assess previously reported associations of IWS with demographic, socioeconomic, and wider social factors in a large general population birth cohort study for the first time. Methods: In the Avon Longitudinal Study of Parents and Children (ALSPAC), we explored differences in IWS at age 31 years by sex, ethnicity, socioeconomic factors, sexual orientation, and family and wider social influences, using confounder-adjusted multivariable regression. Findings: In models adjusted for potential confounders and BMI in childhood, adolescence, and adulthood (N = 4060), IWS was higher for females (standardized beta: 0.56, 95% CI: 0.50, 0.61), sexual minorities (0.17 S.D. higher, 95% CI: 0.09, 0.24), and less socioeconomically advantaged individuals (e.g., 0.16 S.D. higher (95% CI: 0.08, 0.24) for participants whose mothers had minimum or no qualifications, compared to a university degree). The social environment during adolescence and young adulthood was important: IWS was higher for people who at age 13 years felt pressure to lose weight from family (by 0.13 S.D., 95% CI: 0.03, 0.23), and the media (by 0.17, 95% CI: 0.10, 0.25), or had experienced bullying (e.g., 0.25 S.D., 95% CI: 0.17, 0.33 for bullying at age 23 years). Interpretation: Internalized weight stigma differs substantially between demographic groups. Risk is elevated for females, sexual minorities, and socioeconomically disadvantaged adults, and this is not explained by differences in BMI. Pressure to lose weight from family and the media in adolescence may have long-lasting effects on IWS. Funding: The ESRC, MRC, NIHR, and Wellcome Trust.
RESUMO
Social bonds influence physiology and behavior, which can shape how individuals respond to physical and affective challenges. Coppery titi monkey (Plecturocebus cupreus) offspring form selective bonds with their fathers, making them ideal for investigating how father-daughter bonds influence juveniles' responses to oxytocin (OT) and arginine-vasopressin (AVP) manipulations. We quantified the expression of father-daughter bond-related behaviors in females (n = 10) and gave acute intranasal treatments of saline, low/medium/high OT, low/high AVP, or an OT receptor antagonist (OTA) to subjects prior to a parent preference test. While females spent more time in proximity to their parents than strangers, we found a large degree of individual variation. Females with greater expression of bonding behaviors responded to OT treatments in a dose-dependent manner. Subjects also spent less time in proximity to strangers when treated with High OT (p = 0.003) and Low OT (p = 0.007), but more time when treated with High AVP (p = 0.007), Low AVP (p = 0.009), and OTA (p = 0.001). Findings from the present study suggest that variation in the expression of bond-related behaviors may alter responsiveness to OT and AVP, increasing engagement with unfamiliar social others. This enhanced sociality with strangers may promote the formation of pair bonds with partners.
Assuntos
Callicebus , Ocitocina , Feminino , Animais , Humanos , Ocitocina/metabolismo , Callicebus/metabolismo , Vasopressinas , Comportamento Social , Arginina VasopressinaRESUMO
Social behavior plays an important role in supporting both psychological and physical health across the lifespan. People's social lives change as they age, and the nature of these changes differ based on whether people are on healthy aging trajectories or are experiencing neurodegenerative diseases that cause dementia, such as Alzheimer's disease and Parkinson's disease. Nonhuman primate models of aging have provided a base of knowledge comparing aging trajectories in health and disease, but these studies rarely emphasize social behavior changes as a consequence of the aging process. What data exist hold particular value, as negative effects of disease and aging on social behavior are likely to have disproportionate impacts on quality of life. In this mini review, we examine the literature on nonhuman primate models of aging with a focus on social behavior, in the context of both health and disease. We propose that adopting a greater focus on social behavior outcomes in nonhuman primates will improve our understanding of the intersection of health, aging and sociality in humans.
Assuntos
Doença de Alzheimer , Primatas , Animais , Humanos , Qualidade de Vida , Envelhecimento , Comportamento SocialRESUMO
Social interactions regulate our behavior and physiology, and strong social bonds can buffer us from stress. Coppery titi monkeys (Plecturocebus cupreus) are socially monogamous South American monkeys that display strong social bonds. Infants form selective bonds with their fathers, making them ideal for studying father-daughter bonds. We established a method for quantifying variability in expression of bond-related behaviors in females (n = 12), and the present study is the second to use this method for explaining titi monkey responses to behavioral tests. We also investigated how manipulations of oxytocin (OT) and vasopressin (AVP) influenced juvenile behavior and physiology. Subjects received acute intranasal treatments of saline, low/medium/high OT, low/high AVP, or OT receptor antagonist (OTA) prior to an acute social separation. General linear mixed-effects model results revealed fathers were significant behavioral and physiological stress buffers for their daughters, as evidenced by fewer distress vocalizations (p < 0.001), less locomotion (p < 0.001), and lower plasma cortisol (p < 0.001) in a social separation paradigm. Females vocalized less if they exhibited greater expression of bond-related behaviors with their fathers as infants (p = 0.01), and this stress-buffering effect remained even when the daughter was separated from the father (p = 0.001). While treatments did not alter behaviors, OTA treatment caused the largest rise in plasma cortisol (p < 0.001), suggesting blockade of OT receptors can inhibit fathers' stress-buffering effects. Remarkably, females with greater expression of father-daughter bond-related behaviors exhibited an overall reduced physiological separation distress response (p = 0.04). Findings from the present study advance current knowledge of the neurobiological mechanisms foundational to female bonds and help inform how social disruptions may differently impact individuals based on expression of bond-related behaviors.
Assuntos
Callicebus , Pitheciidae , Humanos , Animais , Feminino , Masculino , Callicebus/metabolismo , Comportamento Social , Núcleo Familiar , Hidrocortisona , Pitheciidae/metabolismo , Ocitocina , Receptores de Ocitocina/metabolismo , PaiRESUMO
The investigation of neurobiological and neuropathological changes that affect synaptic integrity and function with aging is key to understanding why the aging brain is vulnerable to Alzheimer's disease. We investigated the cellular characteristics in the cerebral cortex of behaviorally characterized marmosets, based on their trajectories of cognitive learning as they transitioned to old age. We found increased astrogliosis, increased phagocytic activity of microglial cells and differences in resting and reactive microglial cell phenotypes in cognitively impaired compared to nonimpaired marmosets. Differences in amyloid beta deposition were not related to cognitive trajectory. However, we found age-related changes in density and morphology of dendritic spines in pyramidal neurons of layer 3 in the dorsolateral prefrontal cortex and the CA1 field of the hippocampus between cohorts. Overall, our data suggest that an accelerated aging process, accompanied by neurodegeneration, that takes place in cognitively impaired aged marmosets and affects the plasticity of dendritic spines in cortical areas involved in cognition and points to mechanisms of neuronal vulnerability to aging.
Assuntos
Peptídeos beta-Amiloides , Callithrix , Animais , Encéfalo , Neurônios , Envelhecimento/fisiologiaRESUMO
Intranasal oxytocin (IN OXT) administration has been proposed as a pharmacological treatment for a range of biomedical conditions including neurodevelopmental disorders. However, studies evaluating the potential long-lasting effects of chronic IN OXT during development are still scarce. Here we conducted a follow-up study of a cohort of adult titi monkeys that received intranasal oxytocin 0.8 IU/kg (n = 15) or saline (n = 14) daily for six months during their juvenile period (12 to 18 months of age), with the goal of evaluating the potential long-lasting behavioral and neural effects one year post-treatment. Subjects were paired with an opposite-sex mate at 30 months of age (one year post-treatment). We examined pair affiliative behavior in the home cage during the first four months and tested for behavioral components of pair bonding at one week and four months post-pairing. We assessed long-term changes in brain glucose uptake using 18FDG positron emission tomography (PET) scans. Our results showed that OXT-treated animals were more affiliative across a number of measures, including tail twining, compared to SAL treated subjects (tail twining is considered the "highest" type of affiliation in titi monkeys). Neuroimaging showed no treatment differences in glucose uptake between SAL and OXT-treated animals; however, females showed higher glucose uptake in whole brain at 23 months, and in both the whole brain and the social salience network at 33 months of age compared to males. Our results suggest that chronic IN OXT administration during development can have long-term effects on adult social behavior.
Assuntos
Callicebus , Ocitocina , Administração Intranasal , Animais , Encéfalo/diagnóstico por imagem , Proteínas de Ligação a DNA , Feminino , Seguimentos , Glucose , Masculino , Ocitocina/farmacologia , Comportamento SocialRESUMO
The Positivity Resonance Theory of coexperienced positive affect describes moments of interpersonal connection characterized by shared positive affect, caring nonverbal synchrony, and biological synchrony. The construct validity of positivity resonance and its longitudinal associations with health have not been tested. The current longitudinal study examined whether positivity resonance in conflict interactions between 154 married couples predicts health trajectories over 13 years and longevity over 30 years. We used couples' continuous ratings of affect during the interactions to capture coexperienced positive affect and continuous physiological responses to capture biological synchrony between spouses. Video recordings were behaviorally coded for coexpressed positive affect, synchronous nonverbal affiliation cues (SNAC), and behavioral indicators of positivity resonance (BIPR). To evaluate construct validity, we conducted a confirmatory factor analysis to test a latent factor of positivity resonance encompassing coexperienced positive affect, coexpressed positive affect, physiological linkage of interbeat heart intervals, SNAC, and BIPR. The model showed excellent fit. To evaluate associations with health and longevity, we used dyadic latent growth curve modeling and Cox proportional hazards modeling, respectively, and found that greater latent positivity resonance predicted less steep declines in health and increased longevity. Associations were robust when accounting for initial health symptoms, sociodemographic characteristics, health-related behaviors, and individually experienced positive affect. We repeated health and longevity analyses, replacing latent positivity resonance with BIPR, and found consistent results. Findings validate positivity resonance as a multimodal construct, support the utility of the BIPR measure, and provide initial evidence for the characterization of positivity resonance as a positive health behavior. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
Assuntos
Longevidade , Cônjuges , Humanos , Estudos LongitudinaisRESUMO
Longitudinal studies are essential to understand healthy and pathological neurocognitive aging such as Alzheimer's Disease, but longitudinal designs are rare in both humans and non-human primate models of aging because of the difficulty of tracking cognitive change in long-lived primates. Common marmosets (Callithrix jacchus) are uniquely suited for aging studies due to their naturally short lifespan (10-12 years), sophisticated cognitive and social abilities and Alzheimer Disease-like neuropathology. We report the first longitudinal study of cognitive aging in marmosets (N = 28) as they transitioned from middle- (â¼5 years) to old age (â¼9 years). We characterized aging trajectories using reversal learning with different stimuli each year. Marmosets initially improved on cognitive performance due to practice, but worsened in the final year, suggesting the onset of age-related decline. Cognitive impairment emerged earlier in females than males and was more prominent for discrimination than for reversal learning. Sex differences in cognitive aging could not be explained by differences in motivation or motor abilities, which improved or remained stable across aging. Likewise, males and females did not differ in aging trajectories of overall behavior or reactivity to a social stressor, with the exception of a progressive decline in the initiation of social behavior in females. Patterns of cognitive aging were highly variable across marmosets of both sexes, suggesting the potential for pathological aging for some individuals. Future work will link individual cognitive trajectories to neuropathology in order to better understand the relationships between neuropathologic burden and vulnerability to age-related cognitive decline in each sex.
Assuntos
Envelhecimento/fisiologia , Envelhecimento/psicologia , Callithrix , Envelhecimento Cognitivo/fisiologia , Caracteres Sexuais , Animais , Comportamento Animal , Cognição , Feminino , Estudos Longitudinais , Masculino , Modelos Animais , Reversão de Aprendizagem , Comportamento Social , Fatores de TempoRESUMO
Aging across the Primate Order is poorly understood because ages of individuals are often unknown, there is a dearth of aged animals available for study, and because aging is best characterized by longitudinal studies which are difficult to carry out in long-lived species. The human population is aging rapidly, and advanced age is a primary risk factor for several chronic diseases and conditions that impact healthspan. As lifespan has increased, diseases and disorders of the central nervous system (CNS) have become more prevalent, and Alzheimer's disease and related dementias have become epidemic. Nonhuman primate (NHP) models are key to understanding the aging primate CNS. This Special Issue presents a review of current knowledge about NHP CNS aging across the Primate Order. Similarities and differences to human aging, and their implications for the validity of NHP models of aging are considered. Topics include aging-related brain structure and function, neuropathologies, cognitive performance, social behavior and social network characteristics, and physical, sensory, and motor function. Challenges to primate CNS aging research are discussed. Together, this collection of articles demonstrates the value of studying aging in a breadth of NHP models to advance our understanding of human and nonhuman primate aging and healthspan.
Assuntos
Disfunção Cognitiva , Primatas , Envelhecimento , Animais , Biologia , Doença Crônica , Estados UnidosRESUMO
Age-related cognitive decline has been extensively studied in humans, but the majority of research designs are cross-sectional and compare across younger and older adults. Longitudinal studies are necessary to capture variability in cognitive aging trajectories but are difficult to carry out in humans and long-lived nonhuman primates. Marmosets are an ideal primate model for neurocognitive aging as their naturally short lifespan facilitates longitudinal designs. In a longitudinal study of marmosets tested on reversal learning starting in middle-age, we found that, on average, the group of marmosets declined in cognitive performance around 8 years of age. However, we found highly variable patterns of cognitive aging trajectories across individuals. Preliminary analyses of brain tissues from this cohort also show highly variable degrees of neuropathology. Future work will tie together behavioral trajectories with brain pathology and provide a window into the factors that predict age-related cognitive decline.
Assuntos
Envelhecimento , Callithrix , Animais , Estudos Transversais , Longevidade , Estudos LongitudinaisRESUMO
BACKGROUND: Clinical assessments for children and young people entering a mental health service help to identify the prevalence of need within that population, support intervention recommendations, and enable service evaluation. Evidence related to the use of standardised measures in an ever-expanding online environment, for the purpose of identifying need, is limited. METHODS: This study explores the reliability of using a standardised measure to detect clinical need in an online therapeutic environment, and the measures assessed are as follows: Strengths and Difficulties Questionnaire (SDQ), Young Person's CORE (YP-CORE) and the Short Warwick and Edinburgh Wellbeing Scale (SWEMWBS). A deep-dive approach is used to inform practitioner assessment of young people, followed by a Weighted Cohen's Kappa (Κw) to measure the interrater reliability between this and the individuals' self-rated outcome. Composite case studies represent the complexities of presentation among the sample population. RESULTS: The interrater reliability between self-rated and practitioner rated assessment varied between Κw = .222 and Κw = 0.446 depending on the measure. High levels of need and low levels of well-being were found among the sample (YP-CORE Avg. = 26.9, SDQ Avg. = 19.56, SWEMWBS Avg. = 18.1). CONCLUSIONS: The findings demonstrate a fair to moderate reliability when assessing concordance between service users and practitioners, which suggests standardised measures are a reliable indicator of need. Higher levels of need were present than those seen previously in general or face-to-face clinical populations, which suggests using such measures in an online therapeutic environment influences the way in which assessments are responded to.
Assuntos
Serviços de Saúde Mental , Adolescente , Criança , Aconselhamento , Humanos , Reprodutibilidade dos TestesRESUMO
Physiological linkage refers to the degree to which peoples' physiological responses change in coordinated ways. Here, we examine whether and how physiological linkage relates to incidents of shared emotion, distinguished by valence. Past research has used an "overall average" approach and characterized how physiological linkage over relatively long time periods (e.g., 10-15 min) reflects psychological and social processes (e.g., marital satisfaction, empathy). Here, we used a "momentary" approach and characterized whether physiological linkage over relatively short time periods (i.e., 15 s) reflects shared positive emotion, shared negative emotion, or both, and whether linkage during shared emotions relates to relational functioning. Married couples (156 dyads) had a 15-min conflict conversation in the laboratory. Using behavioral coding, each second of conversation was classified into 1 of 4 emotion categories: shared positive emotion, shared negative emotion, shared neutral emotion, or unshared emotion. Using a composite of 3 peripheral physiological measures (i.e., heart rate, skin conductance, finger pulse amplitude), we computed momentary in-phase and antiphase linkage to represent coordinated changes in the same or opposite direction, respectively. We found that shared positive emotion was associated with higher in-phase and lower antiphase linkage, relative to the other 3 emotion categories. Greater in-phase physiological linkage during shared positive emotion was also consistently associated with higher-quality interactions and relationships, both concurrently and longitudinally (i.e., 5 to 6 years later). These findings advance our understanding of the nature of physiological linkage, the emotional conditions under which it occurs, and its possible associations with relational functioning. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
Assuntos
Emoções , Casamento , Comunicação , Empatia , Humanos , CônjugesRESUMO
Pair-bonded primates have uniquely enduring relationships and partners engage in a suite of behaviors to maintain these close bonds. In titi monkeys, pair bond formation has been extensively studied, but changes across relationship tenure remain unstudied. We evaluated differences in behavioral indicators of pair bonding in newly formed (~6 months paired, n = 9) compared to well-established pairs (average 3 years paired, n = 8) of titi monkeys (Callicebus cupreus) as well as sex differences within the pairs. We hypothesized that overall males would contribute more to maintenance than females, but that the pattern of maintenance behaviors would differ between newly formed and well-established pairs. Each titi monkey (N = 34) participated in a partner preference test (PPT), where the subject was placed in a middle test cage with grated windows separating the subject from the partner on one side and an opposite-sex stranger on the other side. During this 150-min behavioral test, we quantified four key behaviors: time in proximity to the partner or stranger as well as aggressive displays toward the partner or stranger. Overall, we found different behavioral profiles representing newly formed and well-established pair-bond relationships in titi monkeys and male-biased relationship maintenance. Males spent â¼40% of their time in the PPT maintaining proximity to the female partner, regardless of relationship tenure. Males from well-established bonds spent less time (14%) near the female stranger compared to males from newly formed bonds (21%) at the trend level. In contrast, females from well-established bonds spent less (23%) time near the male partner in the PPT compared to females from newly formed bonds (47%). Aggressive displays were more frequent in newly formed bonds compared to well-established bonds, especially for females. Scan sampling for homecage affiliation showed that newly formed pairs were more likely to be found tail twining than well-established pairs.
Assuntos
Callicebus/fisiologia , Ligação do Par , Comportamento Social , Agressão , Animais , Feminino , Masculino , Caracteres Sexuais , Fatores de TempoRESUMO
Intranasal oxytocin (IN OXT) has been proposed as a treatment for autism spectrum disorder (ASD); however, little is known about the effects of long-term exposure. This is the first study in a non-human primate species to examine how developmental exposure to chronic IN OXT affects juvenile's interactions with family members, social preference for parents versus strangers, anxiety-like behavior, and cerebral glucose metabolism. Titi monkeys are socially monogamous and biparental; their family bonds share important characteristics with human family bonds. Fourteen males and 15 females were treated intranasally with saline (nâ¯=â¯14) or 0.8 IU/kg OXT (nâ¯=â¯15), daily from 12 to 18 months of age. Compared to SAL-treated animals, OXT-treated animals of both sexes spent significantly more time grooming other family members (F1â¯=â¯8.97, pâ¯=â¯0.006). Overall, OXT-treated subjects were more social (F1â¯=â¯8.35, pâ¯=â¯0.005) during preference tests. OXT-treated females displayed an enhanced preference for their parents (tâ¯=â¯2.265, pâ¯=â¯0.026). OXT-treated males had a blunted preference for their parents and an increase in the time spent near unfamiliar pairs (F1â¯=â¯10.89, pâ¯=â¯0.001). During anxiety tests, OXT-treated males refused to complete the task more often than SAL-treated males and had longer latencies (pâ¯<â¯0.0001). Neuroimaging studies revealed that OXT-treated animals had higher glucose uptake across the social salience network as a whole after one month of treatment (F1,9 = 1.07, pâ¯=â¯0.042). Our results suggest moderate prosocial effects of chronic IN OXT, that did not depend on anxiolytic properties. We also found important sex differences that should be considered in a translational context.
Assuntos
Transtorno do Espectro Autista/tratamento farmacológico , Glucose/metabolismo , Ocitocina/farmacologia , Administração Intranasal/métodos , Animais , Ansiedade/fisiopatologia , Comportamento Animal/efeitos dos fármacos , Callicebus/fisiologia , Feminino , Masculino , Modelos Animais , Ocitocina/administração & dosagem , Fatores Sexuais , Comportamento SocialRESUMO
BACKGROUND: Human cytomegalovirus (HCMV) causes a ubiquitous infection which can pose a significant threat for immunocompromised individuals, such as those undergoing solid organ transplant (SOT). Arguably, the most successful vaccine studied to date is the recombinant glycoprotein-B (gB) with MF59 adjuvant which, in 3 Phase II trials, demonstrated 43-50% efficacy in preventing HCMV acquisition in seronegative healthy women or adolescents and reduction in virological parameters after SOT. However, the mechanism of vaccine protection in seronegative recipients remains undefined. METHODS: We evaluated samples from the cohort of seronegative SOT patients enroled in the Phase II glycoprotein-B/MF59 vaccine trial who received organs from seropositive donors. Samples after SOT (0-90 days) were tested by real-time quantitative PCR for HCMV DNA. Anti-gB antibody levels were measured by ELISA. Neutralization was measured as a decrease in infectivity for fibroblast cell cultures revealed by expression of immediate-early antigens. FINDINGS: Serological analyses revealed a more rapid increase in the humoral response against gB post transplant in vaccine recipients than in those randomised to receive placebo. Importantly, a number of patient sera displayed HCMV neutralising responses - neutralisation which was abrogated by pre-absorbing the sera with recombinant gB. INTERPRETATION: We hypothesise that the vaccine primed the immune system of seronegative recipients which, when further challenged with virus at time of transplant, allowed the host to mount rapid immunological humoral responses even under conditions of T cell immune suppression during transplantation.
Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Infecções por Citomegalovirus/prevenção & controle , Citomegalovirus/imunologia , Polissorbatos , Esqualeno , Proteínas do Envelope Viral/imunologia , Vacinas Virais/imunologia , Adjuvantes Imunológicos , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Ensaios Clínicos Fase II como Assunto , Infecções por Citomegalovirus/sangue , Infecções por Citomegalovirus/etiologia , Ensaio de Imunoadsorção Enzimática , Humanos , Imunização Secundária , Hospedeiro Imunocomprometido , Testes de Neutralização , Transplante de Órgãos/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo , Vacinação , Vacinas Virais/administração & dosagem , Viremia/prevenção & controle , Viremia/virologiaRESUMO
Several neurobiological mechanisms are implicated in the formation of selective pair bonds in socially monogamous mammals, however much less is known about the mechanisms that underlie the long-term behavioral maintenance of these bonds. In prairie voles (Microtus ochrogaster), agonistic behavior that contributes to pair bond maintenance are regulated by dopamine activity at D1-like receptors (D1R) within the mesocorticolimbic system. Evidence suggests D1Rs similarly regulate the behavioral components of pair bond maintenance in socially monogamous titi monkeys (Callicebus cupreus); however, evaluation with behavioral pharmacology is necessary to evaluate this hypothesis. In the current study we evaluated the role of D1Rs in behavioral components of pair bond maintenance in captive male titi monkeys (N = 8). We administered two doses of a D1R selective antagonist, SCH23390, (0.1 mg/kg, 0.01 mg/kg) or saline vehicle to male titi monkeys and presented pairs with a simulated intruder monkey via the use of a mirror stimulus. The non-reflective back of the mirror stimulus was used for control sessions. We video recorded responses to the five-minute stimulus presentations and later scored for arousal and agonistic behaviors relevant to mate guarding as well as affiliative behavior between the pair mates. We also conducted a locomotor assessment to evaluate the potential side effect for SCH23390 of impaired locomotion. Finally, we collected blood samples at the end of each session to assay for plasma cortisol responses. We found evidence of locomotor impairment only with the high dose of SCH23390, and therefore analyses were conducted comparing only test sessions where low dose SCH23390 and saline were administered. With saline administration, males displayed more agonistic behavior via back arching and tail lashing as well as restraining their female partners when viewing the mirror compared to the back of the mirror. D1R antagonist treatment attenuated these agonistic behaviors indicative of mate guarding when males viewed the mirror. Results also indicated that this reduction in agonistic behavior occurred without evidence of overall behavioral blunting or generally reduced social interest. Likewise changes in agonistic behavior were not driven by differences in HPA activity across testing sessions. Mate-directed affiliative behavior, including lip smacks and approaches to female partners, were not altered by D1R antagonist treatment. Dyadic social contact was higher with D1R antagonist treatment, but this was due to a reduction in contact termination by the treated males, which was typically followed by an approach or arousal display to the simulated intruder. These results provide further evidence that D1R activity regulates mate guarding behaviors in titi monkeys and suggests that the dopamine system plays a similar role in the agonistic behavioral components of pair bond maintenance behavior in non-human primates and rodents.
Assuntos
Ligação do Par , Receptores de Dopamina D1/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Benzazepinas/farmacologia , Callicebus/metabolismo , Dopamina/metabolismo , Feminino , Hidrocortisona/análise , Hidrocortisona/sangue , Masculino , Comportamento SocialRESUMO
BACKGROUND: Human cytomegalovirus (HCMV) can be managed by monitoring HCMV DNA in the blood and giving valganciclovir when viral load exceeds a defined value. We hypothesised that such pre-emptive therapy should occur earlier than the standard 3000 genomes/ml (2520 IU/ml) when a seropositive donor transmitted virus to a seronegative recipient (D+R-) following solid organ transplantation (SOT). METHODS: Our local protocol was changed so that D+R- SOT patients commenced valganciclovir once the viral load exceeded 200 genomes/ml; 168 IU/ml (new protocol). The decision point remained at 3000 genomes/ml (old protocol) for the other two patient subgroups (D+R+, D-R+). Virological outcomes were assessed three years later, when 74 D+R- patients treated under the old protocol could be compared with 67 treated afterwards. The primary outcomes were changes in peak viral load, duration of viraemia and duration of treatment in the D+R- group. The secondary outcome was the proportion of D+R- patients who developed subsequent viraemia episodes. FINDINGS: In the D+R- patients, the median values of peak viral load (30,774 to 11,135 genomes/ml, p<0.0215) were significantly reduced on the new protocol compared to the old, but the duration of viraemia and duration of treatment were not. Early treatment increased subsequent episodes of viraemia from 33/58 (57%) to 36/49 (73%) of patients (p< 0.0743) with a significant increase (p = 0.0072) in those episodes that required treatment (16/58; 27% versus 26/49; 53%). Median peak viral load increased significantly (2,103 to 3,934 genomes/ml, p<0.0249) in the D+R+ but not in the D-R+ patient subgroups. There was no change in duration of viraemia or duration of treatment for any patient subgroup. INTERPRETATION: Pre-emptive therapy initiated at the first sign of viraemia post-transplant significantly reduced the peak viral load but increased later episodes of viraemia, consistent with the hypothesis of reduced antigenic stimulation of the immune system.
Assuntos
Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/transmissão , Citomegalovirus/efeitos dos fármacos , Transplante de Órgãos/efeitos adversos , Carga Viral/efeitos dos fármacos , Adulto , Antivirais/uso terapêutico , Protocolos Clínicos , Citomegalovirus/genética , Infecções por Citomegalovirus/virologia , DNA Viral/sangue , DNA Viral/genética , Feminino , Humanos , Transplante de Rim/efeitos adversos , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Recidiva , Prevenção Secundária , Doadores de Tecidos , Valganciclovir/uso terapêutico , Carga Viral/genética , Viremia/tratamento farmacológico , Viremia/virologiaRESUMO
[This corrects the article DOI: 10.1371/journal.pone.0163722.].
RESUMO
BACKGROUND: To help decide when to start and when to stop pre-emptive therapy for cytomegalovirus infection, we conducted two open-label randomized controlled trials in renal, liver and bone marrow transplant recipients in a single centre where pre-emptive therapy is indicated if viraemia exceeds 3000 genomes/ml (2520 IU/ml) of whole blood. METHODS: Patients with two consecutive viraemia episodes each below 3000 genomes/ml were randomized to continue monitoring or to immediate treatment (Part A). A separate group of patients with viral load greater than 3000 genomes/ml was randomized to stop pre-emptive therapy when two consecutive levels less than 200 genomes/ml (168 IU/ml) or less than 3000 genomes/ml were obtained (Part B). For both parts, the primary endpoint was the occurrence of a separate episode of viraemia requiring treatment because it was greater than 3000 genomes/ml. RESULTS: In Part A, the primary endpoint was not significantly different between the two arms; 18/32 (56%) in the monitor arm had viraemia greater than 3000 genomes/ml compared to 10/27 (37%) in the immediate treatment arm (p = 0.193). However, the time to developing an episode of viraemia greater than 3000 genomes/ml was significantly delayed among those randomized to immediate treatment (p = 0.022). In Part B, the primary endpoint was not significantly different between the two arms; 19/55 (35%) in the less than 200 genomes/ml arm subsequently had viraemia greater than 3000 genomes/ml compared to 23/51 (45%) among those randomized to stop treatment in the less than 3000 genomes/ml arm (p = 0.322). However, the duration of antiviral treatment was significantly shorter (p = 0.0012) in those randomized to stop treatment when viraemia was less than 3000 genomes/ml. DISCUSSION: The results illustrate that patients have continuing risks for CMV infection with limited time available for intervention. We see no need to alter current rules for stopping or starting pre-emptive therapy.
RESUMO
Partner preference, or the selective social preference for a pair mate, is a key behavioral indicator of social monogamy. Standardized partner preference testing has been used extensively in rodents but a single test has not been standardized for primates. The goal of this study was to develop a partner preference test with socially monogamous titi monkeys (Callicebus cupreus) adapted from the widely used rodent test. In Experiment 1, we evaluated the test with pairs of titi monkeys (N = 12) in a three-chambered apparatus for 3 hr. The subject was placed in the middle chamber, with grated windows separating it from its partner on one side and an opposite sex stranger on the other side. Subjects spent a greater proportion of time in proximity to their partners' windows than the strangers', indicating a consistent preference for the partner over the stranger. Touching either window did not differ between partners and strangers, suggesting it was not a reliable measure of partner preference. Subjects chose their partner more than the stranger during catch and release sessions at the end of the test. In Experiment 2, we compared responses of females with current partners (N = 12) in the preference test with other relationship types representing former attachment bonds (N = 13) and no attachment bond (N = 8). Only females from established pair bonds spent significantly more time near their partner's window compared to the stranger's indicating that this measure of preference was unique to current partners. Other measures of preference did not differentiate behavior toward a current partner and other relationship types. This test reproduces behavioral patterns found in previous studies in titi monkeys highlighting the accuracy of this new partner preference test. This test can be used as a standardized measure of partner preference in titi monkeys to quantitatively study pair bonding and evaluate factors influencing partner preference.