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1.
BMC Womens Health ; 23(1): 503, 2023 09 21.
Artículo en Inglés | MEDLINE | ID: mdl-37735400

RESUMEN

BACKGROUND: Induced abortion in Costa Rica is illegal in all cases except to save the life of the pregnant person. Despite severe restrictions to legal abortion, individuals in Costa Rica still induce abortions outside of the formal healthcare system. These individuals and those with spontaneous abortions, also known as miscarriages, occasionally need medical care for complications. In Costa Rica, an estimated 41% of unintended pregnancies end in abortion, yet there is very little published literature exploring the perspectives of healthcare providers on abortion in Costa Rica. METHODS: We interviewed ten obstetrician-gynecologist clinicians and five obstetrician-gynecologist medical residents in San José, Costa Rica about their beliefs and practices related to extra-legal abortion and post-abortion care (PAC) using a Spanish language in-depth semi-structured interview guide. After transcription and translation into English, analysis team pairs used a combination of deductive and inductive coding to identify themes and sub-themes within the data. RESULTS: Obstetrician-gynecologist clinicians and medical residents were aware of the presence of extra-legal abortion, and particularly, medication abortion, in their communities, but less familiar with dosing for induction. They expressed the desire to provide non-judgmental care and support their patients through extra-legal abortion and PAC journeys. Study participants were most familiar with providing care to individuals with spontaneous abortions. When discussing PAC, they often spoke about a policy of reporting individuals who seek PAC following an extra-legal abortion, without commenting on whether or not they followed the guidance. CONCLUSIONS: This study contributes to a gap in research about the knowledge, attitudes, and practices of Costa Rican obstetrician-gynecologist clinicians and medical residents around extra-legal abortion and PAC. The results reveal an opportunity to train these healthcare providers as harm reduction experts, who are able to accurately counsel individuals who are seeking abortion services outside of the healthcare system, and to provide training to improve care for individuals needing PAC.


Asunto(s)
Aborto Espontáneo , Internado y Residencia , Femenino , Embarazo , Humanos , Aborto Legal , Costa Rica , Ginecólogos , Conocimientos, Actitudes y Práctica en Salud , Obstetras , Personal de Salud
2.
Behav Brain Sci ; 45: e37, 2022 02 10.
Artículo en Inglés | MEDLINE | ID: mdl-35139962

RESUMEN

In his target article, Yarkoni prescribes descriptive research as a potential antidote for the generalizability crisis. In our commentary, we offer four guiding principles for conducting descriptive research that is generalizable and enduring: (1) prioritize context over control; (2) let naturalistic observations contextualize structured tasks; (3) operationalize the target phenomena rigorously and transparently; and (4) attend to individual data.

3.
Child Dev ; 92(4): 1337-1353, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33475164

RESUMEN

Pre-mobile infants and caregivers spontaneously engage in a sequence of contingent facial expressions and vocalizations that researchers have referred to as a social "dance." Does this dance continue when both partners are free to move across the floor? Locomotor synchrony was assessed in 13- to 19-month-old infant-mother dyads (N = 30) by tracking each partner's step-to-step location during free play. Although infants moved more than mothers, dyads spontaneously synchronized their locomotor activity. For 27 dyads, the spatiotemporal path of one partner uniquely identified the path of the other. Clustering analyses revealed two patterns of synchrony (mother-follow and yo-yo), and infants were more likely than mothers to lead the dance. Like face-to-face synchrony, locomotor synchrony scaffolds infants' interactions with the outside world.


Asunto(s)
Relaciones Madre-Hijo , Madres , Cuidadores , Expresión Facial , Femenino , Humanos , Lactante , Conducta del Lactante
4.
Dev Psychobiol ; 61(1): 29-42, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30447002

RESUMEN

What happens to early acquired but later abandoned motor skills? To investigate effects of disuse on early-developing motor skills, we examined crawling in two groups of habitual crawlers (34 6-12-month-old infants and five adults with Uner Tan Syndrome) and two groups of rusty crawlers (27 11-12-year-old children and 13 college-aged adults). Habitual crawlers showed striking similarities in gait patterns, limbs supporting the body, and crawling speed, despite dramatic differences in crawling practice, posture, and body size. Habitual crawlers trotted predominantly, whereas rusty crawlers showed a variety of gait patterns. Within sequences, habitual crawlers and children showed more switches in gait patterns than young adults. Children crawled faster and kept fewer limbs on the grounds than the other groups. Old crawling patterns were retained despite disuse, but new ones were also added. Surprisingly, results indicate that nothing was lost with disuse, but some features of crawling were gained or altered.


Asunto(s)
Fenómenos Biomecánicos/fisiología , Ataxia Cerebelosa/fisiopatología , Desarrollo Humano/fisiología , Locomoción/fisiología , Destreza Motora/fisiología , Adulto , Niño , Femenino , Humanos , Lactante , Masculino , Adulto Joven
5.
J Acoust Soc Am ; 156(5): R11-R12, 2024 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-39485105
6.
Dev Sci ; 21(4): e12615, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29057555

RESUMEN

Researchers can study complex developmental phenomena with all the inherent noise and complexity or simplify behaviors to hone in on the essential aspects of a phenomenon. We used the development of walking as a model system to compare the costs and benefits of simplifying a complex, noisy behavior. Traditionally, researchers simplify infant walking by recording gait measures as infants take continuous, forward steps along straight paths. Here, we compared the traditional straight-path task with spontaneous walking during 20 minutes of free play in 97 infants (10.75-19.99 months of age). We recorded infants' footfalls on an instrumented floor to calculate gait measures in the straight-path and free-play tasks. In addition, we scored videos for other critical aspects of spontaneous walking-steps per bout, shape of walking path, and step direction. Studying infant walking during free play incurred no cost compared with the straight-path task, but considerable benefits. Straight-path gait was highly correlated with spontaneous gait and both sets of measures improved with walking age, validating use of the straight-path task as an index of development. However, a large proportion of free-play bouts were too short to permit standard gait measures, and most bouts were curved with omnidirectional steps. The high prevalence of these "non-canonical" bouts was constant over development. We propose that a focus on spontaneous walking, the phenomenon we ostensibly wish to explain, yields important insights into the problems infants solve while learning to walk. Other areas of developmental research may also benefit from retaining the complexity of complex phenomena.


Asunto(s)
Marcha , Aprendizaje/fisiología , Caminata/fisiología , Femenino , Humanos , Lactante , Masculino
7.
Dev Psychobiol ; 58(3): 341-54, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26497472

RESUMEN

Adults primarily walk to reach a new location, but why do infants walk? Do infants, like adults, walk to travel to a distant goal? We observed 30 13-month-old and 30 19-month-old infants during natural walking in a laboratory playroom. We characterized the bout structure of walking-when infants start and stop walking-to examine why infants start and stop walking. Locomotor activity was composed largely of brief spurts of walking. Half of 13-month-olds' bouts and 41% of 19-month-olds' bouts consisted of three or fewer steps-too few to carry infants to a distant goal. Most bouts ended in the middle of the floor, not at a recognizable goal. Survival analyses of the distribution of steps per bout indicated that the probability of continuing to walk was independent of the length of the ongoing bout; infants were just as likely to stop walking after five steps as after 50 steps and they showed no bias toward bouts long enough to carry them across the room to a goal. However, 13-month-olds showed an increased probability of stopping after 1-3 steps, and they did not initiate walking more frequently to compensate for their surfeit of short bouts. We propose that infants' natural walking is not intentionally directed at distant goals; rather, it is a stochastic process that serves exploratory functions. Relations between the bout structure of walking and other measures of walking suggest that locomotor exploration is constrained by walking skill in younger infants, but not in older infants.


Asunto(s)
Desarrollo Infantil/fisiología , Objetivos , Conducta del Lactante/fisiología , Caminata/fisiología , Femenino , Humanos , Lactante , Masculino
8.
Pediatr Phys Ther ; 27(4): 403-12, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26397087

RESUMEN

PURPOSE: To describe behavior of children with periventricular brain injury (PBI) in a tethered-kicking intervention. METHODS: Sixteen infants with PBI were randomly assigned to exercise or no-training in a longitudinal pilot study. Frequencies of leg movements and interlimb coordination were described from videos at 2 and 4 months' corrected age (CA). RESULTS: Eight of the 13 children (62%) with longitudinal data increased the frequency of leg movements while tethered to a mobile between 2 and 4 months' CA. Movement frequency was correlated with scores on the Test of Infant Motor Performance, but no differences between experimental groups were found. Children with typical development at 12 months' CA increased the proportion of leg movements that were synchronous between 2 and 4 months, as did a child with cerebral palsy in the experimental group. CONCLUSIONS: The tethered-kicking intervention facilitates movement in infants with PBI, but effects on development remain to be demonstrated.


Asunto(s)
Lesiones Encefálicas/rehabilitación , Ventrículos Cerebrales , Movimiento/fisiología , Femenino , Cabeza/fisiopatología , Humanos , Lactante , Pierna/fisiopatología , Estudios Longitudinales , Masculino , Proyectos Piloto
9.
Exp Brain Res ; 225(3): 309-19, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23411672

RESUMEN

We examined several factors that affect people's ability to perceive possibilities for action. In Experiment 1, 24 participants crossed expanses of various sizes in three conditions: leaping, a familiar, launching action system; arm-swinging on monkey bars, an unpracticed skill that uses the arms rather than the legs; and crawling on hands and knees, a disused skill that involves all four limbs. Before and after performing each action, participants gave verbal judgments about the largest gap they could cross. Participants scaled initial judgments to their actual abilities in all three conditions. But they considerably underestimated their abilities for leaping, a launching action, and for arm-swinging when it was performed as a launching action; judgments about crawling, a non-launching action, and arm-swinging when it was performed as a non-launching action were more accurate. Thus, launching actions appear to produce a deficit in perceiving affordances that is not ameliorated by familiarity with the action. However, after performing the actions, participants partially corrected for the deficiency and more accurately judged their abilities for launching actions-suggesting that even brief action experience facilitates the perception of affordances. In Experiment 2, we confirmed that the deficit was due to the launching nature of the leaping and arm-swinging actions in Experiment 1. We asked an additional 12 participants to cross expanses using two non-launching actions using the legs (stepping across an expanse) and the arms (reaching across an expanse). Participants were highly accurate when judging affordances for these actions, supporting launching as the cause of the underestimation reported in Experiment 1.


Asunto(s)
Juicio/fisiología , Locomoción/fisiología , Destreza Motora/fisiología , Percepción/fisiología , Adolescente , Femenino , Humanos , Masculino , Destreza Motora/clasificación , Adulto Joven
10.
Integr Comp Biol ; 63(3): 653-663, 2023 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-37355781

RESUMEN

Infants of all species learn to move in the midst of tremendous variability and rapid developmental change. Traditionally, researchers consider variability to be a problem for development and skill acquisition. Here, we argue for a reconsideration of variability in early life, taking a developmental, ecological, systems approach. Using the development of walking in human infants as an example, we argue that the rich, variable experiences of infancy form the foundation for flexible, adaptive behavior in adulthood. From their first steps, infants must cope with changes in their bodies, skills, and environments. Rapid growth spurts and a continually expanding environment of surfaces, elevations, and obstacles alter the biomechanical constraints on balance and locomotion from day to day and moment to moment. Moreover, infants spontaneously generate a variable practice regimen for learning to walk. Self-initiated locomotion during everyday activity consists of immense amounts of variable, time-distributed, error-filled practice. From infants' first steps and continuing unabated over the next year, infants walk in short bursts of activity (not continual steps), follow curved (not straight) paths, and take steps in every direction (not only forward)-all the while, accompanied by frequent falls as infants push their limits (rather than a steady decrease in errors) and explore their environments. Thus, development ensures tremendous variability-some imposed by physical growth, caregivers, and a changing environment outside infants' control, and some self-generated by infants' spontaneous behavior. The end result of such massive variability is a perceptual-motor system adept at change. Thus, infants do not learn fixed facts about their bodies or environments or their level of walking skill. Instead, they learn how to learn-how to gauge possibilities for action, modify ongoing movements, and generate new movements on the fly from step to step. Simply put, variability in early development is a feature, not a bug. It provides a natural training regimen for successfully navigating complex, ever-changing environments throughout the lifespan. Moreover, observations of infants' natural behavior in natural, cluttered environments-rather than eliciting adult-like behaviors under artificial, controlled conditions-yield very different pictures of what infants of any species do and learn. Over-reliance on traditional tasks that artificially constrain variability therefore risks distorting researchers' understanding of the origins of adaptive behavior.


Asunto(s)
Desarrollo Infantil , Aprendizaje , Animales , Humanos , Caminata , Locomoción , Conducta del Lactante
11.
J Exp Psychol Gen ; 152(11): 3243-3265, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37535540

RESUMEN

Researchers routinely infer learning and other unobservable psychological functions based on observable behavior. But what behavioral changes constitute evidence of learning? The standard approach is to infer learning based on a single behavior across individuals, including assumptions about the direction and magnitude of change (e.g., everyone should avoid falling repeatedly on a treacherous obstacle). Here we illustrate the benefits of an alternative "multiexpression, relativist, agnostic, individualized" approach. We assessed infant learning from falling based on multiple behaviors relative to each individual's baseline, agnostic about the direction and magnitude of behavioral change. We tested infants longitudinally (10.5-15 months of age) over the transition from crawling to walking. At each session, infants were repeatedly encouraged to crawl or walk over a fall-inducing foam pit interspersed with no-fall baseline trials on a rigid platform. Our approach revealed two learning profiles. Like adults in previous work, "pit-avoid" infants consistently avoided falling. In contrast, "pit-go" infants fell repeatedly across trials and sessions. However, individualized comparisons to baseline across multiple locomotor, exploratory, and social-emotional behaviors showed that pit-go infants also learned at every session. But they treated falling as an unimpactful "pratfall" rather than an aversive "pitfall." Pit-avoid infants displayed enhanced learning across sessions and partial transfer of learning from crawling to walking, whereas pit-go infants displayed neither. Thus, reliance on a predetermined, "one-size-fits-all" behavioral expression of a psychological function can obscure different behavioral profiles and lead to erroneous inferences. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Asunto(s)
Accidentes por Caídas , Locomoción , Adulto , Humanos , Lactante , Caminata , Afecto , Conducta del Lactante
12.
Psychol Sci ; 23(11): 1387-94, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23085640

RESUMEN

A century of research on the development of walking has examined periodic gait over a straight, uniform path. The current study provides the first corpus of natural infant locomotion derived from spontaneous activity during free play. Locomotor experience was immense: Twelve- to 19-month-olds averaged 2,368 steps and 17 falls per hour. Novice walkers traveled farther faster than expert crawlers, but had comparable fall rates, which suggests that increased efficiency without increased cost motivates expert crawlers to transition to walking. After walking onset, natural locomotion improved dramatically: Infants took more steps, traveled farther distances, and fell less. Walking was distributed in short bouts with variable paths--frequently too short or irregular to qualify as periodic gait. Nonetheless, measures of periodic gait and of natural locomotion were correlated, which indicates that better walkers spontaneously walk more and fall less. Immense amounts of time-distributed, variable practice constitute the natural practice regimen for learning to walk.


Asunto(s)
Desarrollo Infantil/fisiología , Aprendizaje/fisiología , Locomoción/fisiología , Práctica Psicológica , Desempeño Psicomotor/fisiología , Femenino , Humanos , Lactante , Masculino , Destreza Motora/fisiología , Caminata/fisiología
13.
Dev Sci ; 15(6): 783-90, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23106732

RESUMEN

In light of cross-cultural and experimental research highlighting effects of childrearing practices on infant motor skill, we asked whether wearing diapers, a seemingly innocuous childrearing practice, affects infant walking. Diapers introduce bulk between the legs, potentially exacerbating infants' poor balance and wide stance. We show that walking is adversely affected by old-fashioned cloth diapers, and that even modern disposable diapers - habitually worn by most infants in the sample - incur a cost relative to walking naked. Infants displayed less mature gait patterns and more missteps and falls while wearing diapers. Thus, infants' own diapers constitute an ongoing biomechanical perturbation while learning to walk. Furthermore, shifts in diapering practices may have contributed to historical and cross-cultural differences in infant walking.


Asunto(s)
Desarrollo Infantil/fisiología , Pañales Infantiles/efectos adversos , Marcha/fisiología , Caminata/fisiología , Factores de Edad , Humanos , Lactante
14.
Neurocase ; 18(1): 66-74, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22026916

RESUMEN

Proprioception is the sense of the position of one's own body. Here, we present a case study of an individual with proprioceptive loss in one limb consequent to stroke. The patient indicated that merely touching his impaired arm with his unimpaired arm temporarily restored his proprioception. We examined this claim and the effects of imagined touch by the unimpaired arm. Assessments were made using three-dimensional tracking of reaching trajectories towards targets in conditions of light and darkness. Both actual and imagined touching significantly reduced movement error and jerk, specifically for targets located in regions that both hands would be able to reach.


Asunto(s)
Propiocepción/fisiología , Trastornos de la Sensación/fisiopatología , Tacto/fisiología , Anciano , Humanos , Masculino , Movimiento/fisiología , Desempeño Psicomotor/fisiología , Trastornos de la Sensación/rehabilitación , Extremidad Superior/fisiología
15.
Infancy ; 24(4): 547-569, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31244556

RESUMEN

Manual skills such as reaching, grasping, and exploring objects appear months earlier in infancy than locomotor skills such as walking. To what extent do infants incorporate an old skill (manual actions on objects) into the development of a new skill (walking)? We video recorded 64 sessions of infants during free play in a laboratory playroom. Infants' age (12.7-19.5 months), walking experience (0.5-10.3 months), and walking proficiency (speed, step length, etc.) varied widely. We found that the earlier developing skills of holding and exploring objects are immediately incorporated into the later developing skill of walking. Although holding incurred a reliable cost to infants' gait patterns, holding and exploring objects in hand were relatively common activities, and did not change with development. Moreover, holding objects was equally common in standing and walking. However, infants did not interact with objects indiscriminately: Object exploration was more frequent while standing than walking, and infants selectively chose lighter objects to carry and explore. Findings suggest that the earlier appearance of some skills may serve to motivate and enrich later appearing skills.

16.
JBMR Plus ; 3(9): e10199, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31667455

RESUMEN

Aging is associated with significant bone loss and increased fracture risk, which has been attributed to a diminished response to anabolic mechanical loading. In adults, skeletal progenitors proliferate and differentiate into bone-forming osteoblasts in response to increasing mechanical stimuli, though the effects of aging on this response are not well-understood. Here we show that both adult and aged mice exhibit load-induced periosteal bone formation, though the response is significantly attenuated with age. We also show that the acute response of adult bone to loading involves expansion of Sca-1+Prrx1+ and Sca-1-Prrx1+ cells in the periosteum. On the endosteal surface, loading enhances proliferation of both these cell populations, though the response is delayed by 2 days relative to the periosteal surface. In contrast to the periosteum and endosteum, the marrow does not exhibit increased proliferation of Sca-1+Prrx1+ cells, but only of Sca-1-Prrx1+ cells, underscoring fundamental differences in how the stem cell niche in distinct bone envelopes respond to mechanical stimuli. Notably, the proliferative response to loading is absent in aged bone even though there are similar baseline numbers of Prrx1 + cells in the periosteum and endosteum, suggesting that the proliferative capacity of progenitors is attenuated with age, and proliferation of the Sca-1+Prrx1+ population is critical for load-induced periosteal bone formation. These findings provide a basis for the development of novel therapeutics targeting these cell populations to enhance osteogenesis for overcoming age-related bone loss. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

17.
Trends Cogn Sci ; 22(8): 699-711, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-30032744

RESUMEN

Although a fundamental goal of developmental science is to identify general processes of change, developmental scientists rarely generalize beyond their specific content domains. As a first step toward a more unified approach to development, we offer 15 suggestions gleaned from a century of research on infant walking. These suggestions collectively address the multi-leveled nature of change processes, cascades of real-time and developmental events, the diversity of developmental trajectories, inter- and intraindividual variability, starting and ending points of development, the natural input for learning, and the roles of body, environment, and sociocultural context. We argue that these 15 suggestions are not limited to motor development, and we encourage researchers to consider them within their own areas of research.


Asunto(s)
Desarrollo Infantil , Caminata , Humanos , Lactante , Modelos Teóricos , Proyectos de Investigación , Caminata/fisiología
18.
Infant Behav Dev ; 37(3): 305-14, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24857934

RESUMEN

The stability of a system affects how it will handle a perturbation: The system may compensate for the perturbation or not. This study examined how 14-month-old infants-notoriously unstable walkers-and adults cope with a perturbation to walking. We attached a platform to one of participants' shoes, forcing them to walk with one elongated leg. At first, the platform shoe caused both age groups to slow down and limp, and caused infants to misstep and fall. But after a few trials, infants altered their gait to compensate for the platform shoe whereas adults did not; infants recovered symmetrical gait whereas adults continued to limp. Apparently, adult walking was stable enough to cope with the perturbation, but infants risked falling if they did not compensate. Compensation depends on the interplay of multiple factors: The availability of a compensatory response, the cost of compensation, and the stability of the system being perturbed.


Asunto(s)
Adaptación Fisiológica , Desarrollo Infantil/fisiología , Marcha/fisiología , Pierna/fisiología , Caminata/fisiología , Adulto , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Equilibrio Postural , Zapatos , Adulto Joven
19.
PLoS One ; 9(7): e101758, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25029457

RESUMEN

Since 2005, an extensive literature documents individuals from several families afflicted with "Uner Tan Syndrome (UTS)," a condition that in its most extreme form is characterized by cerebellar hypoplasia, loss of balance and coordination, impaired cognitive abilities, and habitual quadrupedal gait on hands and feet. Some researchers have interpreted habitual use of quadrupedalism by these individuals from an evolutionary perspective, suggesting that it represents an atavistic expression of our quadrupedal primate ancestry or "devolution." In support of this idea, individuals with "UTS" are said to use diagonal sequence quadrupedalism, a type of quadrupedal gait that distinguishes primates from most other mammals. Although the use of primate-like quadrupedal gait in humans would not be sufficient to support the conclusion of evolutionary "reversal," no quantitative gait analyses were presented to support this claim. Using standard gait analysis of 518 quadrupedal strides from video sequences of individuals with "UTS", we found that these humans almost exclusively used lateral sequence-not diagonal sequence-quadrupedal gaits. The quadrupedal gait of these individuals has therefore been erroneously described as primate-like, further weakening the "devolution" hypothesis. In fact, the quadrupedalism exhibited by individuals with UTS resembles that of healthy adult humans asked to walk quadrupedally in an experimental setting. We conclude that quadrupedalism in healthy adults or those with a physical disability can be explained using biomechanical principles rather than evolutionary assumptions.


Asunto(s)
Marcha/fisiología , Primates , Caminata/fisiología , Adulto , Animales , Niño , Evolución Molecular , Femenino , Humanos , Lactante , Masculino , Postura/fisiología , Síndrome
20.
J Bone Joint Surg Am ; 95(14): 1278-88, 2013 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-23864176

RESUMEN

BACKGROUND: Age-related fatty degeneration of the bone marrow contributes to delayed fracture-healing and osteoporosis-related fractures in the elderly. The mechanisms underlying this fatty change are unknown, but they may relate to the level of Wnt signaling within the aged marrow cavity. METHODS: Transgenic mice were used in conjunction with a syngeneic bone-graft model to follow the fates of cells involved in the engraftment. Immunohistochemistry along with quantitative assays were used to evaluate Wnt signaling and adipogenic and osteogenic gene expression in bone grafts from young and aged mice. Liposomal Wnt3a protein (L-Wnt3a) was tested for its ability to restore osteogenic potential to aged bone grafts in critical-size defect models created in mice and in rabbits. Radiography, microquantitative computed tomography (micro-CT) reconstruction, histology, and histomorphometric measurements were used to quantify bone-healing resulting from L-Wnt3a or a control substance (liposomal phosphate-buffered saline solution [L-PBS]). RESULTS: Expression profiling of cells in a bone graft demonstrated a shift away from an osteogenic gene profile and toward an adipogenic one with age. This age-related adipogenic shift was accompanied by a significant reduction (p < 0.05) in Wnt signaling and a loss in osteogenic potential. In both large and small animal models, osteogenic competence was restored to aged bone grafts by a brief incubation with the stem-cell factor Wnt3a. In addition, liposomal Wnt3a significantly reduced cell death in the bone graft, resulting in significantly more osseous regenerate in comparison with controls. CONCLUSIONS: Liposomal Wnt3a enhances cell survival and reestablishes the osteogenic capacity of bone grafts from aged animals. CLINICAL RELEVANCE: We developed an effective, clinically applicable, regenerative medicine-based strategy for revitalizing bone grafts from aged patients.


Asunto(s)
Regeneración Ósea/efectos de los fármacos , Trasplante Óseo/métodos , Osteogénesis/efectos de los fármacos , Proteína Wnt3A/farmacología , Adipogénesis/efectos de los fármacos , Adipogénesis/fisiología , Animales , Regeneración Ósea/fisiología , Expresión Génica , Ratones , Ratones Transgénicos , Osteogénesis/fisiología , Conejos , Transducción de Señal
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