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1.
Am J Perinatol ; 2023 Nov 10.
Article in English | MEDLINE | ID: mdl-37769696

ABSTRACT

OBJECTIVE: Antenatal corticosteroid (ACS) administration is standard practice for pregnant individuals delivering in the late preterm period, though no guidelines are in place for those with diabetes. This study aims to characterize the prevalence of neonatal hypoglycemia after ACS administration in pregnant individuals with diabetes delivering in the late preterm period. STUDY DESIGN: This is a retrospective, single-center, case-control study of individuals with diabetes who delivered between 340/7 and 366/7 weeks' gestation at a large academic medical center from 2016 to 2021. A total of 169 individuals were included in the analysis; 87 received corticosteroids and 82 did not. The proportion of neonates with hypoglycemia, neonatal intensive care unit (NICU) admission, respiratory distress syndrome, and hyperbilirubinemia were compared between parents who received ACSs versus those who did not. RESULTS: The prevalence of neonatal hypoglycemia (40.2 vs. 23.2%, p = 0.027), requiring treatment (40.3 vs. 22.4%, p = 0.041), and hyperbilirubinemia (35.6 vs 18.5%, p = 0.018) was greater for neonates born to individuals with diabetes who received late preterm ACSs compared with those who did not. There was no difference in NICU admission and respiratory distress between the groups. These results remained unchanged after controlling for confounders including gestational age at delivery and birth weight. CONCLUSION: This study demonstrates that late preterm corticosteroid administration to pregnant individuals with diabetes increases the risk for neonatal hypoglycemia without changing the rates of respiratory morbidity. KEY POINTS: · Late preterm ACS in diabetic patients resulted in higher rates of neonatal hypoglycemia.. · There are no differences in rates of respiratory distress syndrome and transient tachypnea of the newborn between the ACS group and control group.. · There was no noted difference in rate of NICU admission and length of stay between the two groups..

2.
Elife ; 112022 12 01.
Article in English | MEDLINE | ID: mdl-36453722

ABSTRACT

The spine provides structure and support to the body, yet how it develops its characteristic morphology as the organism grows is little understood. This is underscored by the commonality of conditions in which the spine curves abnormally such as scoliosis, kyphosis, and lordosis. Understanding the origin of these spinal curves has been challenging in part due to the lack of appropriate animal models. Recently, zebrafish have emerged as promising tools with which to understand the origin of spinal curves. Using zebrafish, we demonstrate that the urotensin II-related peptides (URPs), Urp1 and Urp2, are essential for maintaining spine morphology. Urp1 and Urp2 are 10-amino acid cyclic peptides expressed by neurons lining the central canal of the spinal cord. Upon combined genetic loss of Urp1 and Urp2, adolescent-onset planar curves manifested in the caudal region of the spine. Highly similar curves were caused by mutation of Uts2r3, an URP receptor. Quantitative comparisons revealed that urotensin-associated curves were distinct from other zebrafish spinal curve mutants in curve position and direction. Last, we found that the Reissner fiber, a proteinaceous thread that sits in the central canal and has been implicated in the control of spine morphology, breaks down prior to curve formation in mutants with perturbed cilia motility but was unaffected by loss of Uts2r3. This suggests a Reissner fiber-independent mechanism of curvature in urotensin-deficient mutants. Overall, our results show that Urp1 and Urp2 control zebrafish spine morphology and establish new animal models of spine deformity.


The backbone, or spine, is an integral part of the human body, providing support to our torsos so that we can sit, stand, bend and twist. If this structure does not form correctly, it can lead to pain, neurologic problems, and mobility issues. The spine normally has curves, but these can become deformed for many reasons, including genetic and muscular factors. There are also cases in which the cause of a spine distortion is unknown, such as in scoliosis (where the spine twists to the side), lordosis (where the lower part of the spine curves excessively), and kyphosis (where the upper part of the spine shows extreme curvature). The structure of the spine is laid out during embryonic development and maintained throughout life. Experiments in zebrafish have shown that a crucial element in preserving the shape of the spine is the flow of cerebrospinal fluid or CSF. Propelled by the movement of little 'hairs' at the surface of specialized cells, this liquid runs through our central nervous system along a cavity lined with neurons. These nerve cells produce Urp1 and Urp2, two short molecules (or peptides) built from the same components as proteins. In zebrafish embryos, lowering the levels of these peptides had previously been shown to cause early body deformities. But what role, if any, do Urp1 and Urp2 play in maintaining the shape of the spine in adult zebrafish? Bearce et al. set out to answer this question. First, they generated mutant zebrafish which did not carry either Urp1, Urp2 or both peptides. Contrary to previous findings, all three of these mutants developed normally as embryos. Once they were adults, zebrafish lacking Urp1 exhibited normal spines, while those lacking Urp2 had slightly deformed curves. However, zebrafish lacking both peptides had prominent curves in the tail-region of their spines, somewhat akin to lordosis in humans. This indicates that both peptides are necessary for adult spine structure, but work in a semi-redundant manner. Interestingly, the defects observed first appeared in adolescent fish and gradually worsened as they grew; many forms of human spinal abnormalities follow a similar trajectory. Bearce et al. also tested the role of the protein Uts2r3, a receptor for peptides which belong to the urotensin family (such as Urp1 and Urp2). Fish lacking this protein showed normal spine structure as embryos, but distorted spinal curves as adults, suggesting that Urp1 and Urp2 might control spine morphology by signaling via the Uts2r3 receptor. Together, Bearce et al.'s observations show that disturbing urotensin signaling leads to a lordosis-like condition in adult zebrafish, with evident deformities in the tail-region of the spine. Considering the broad similarities in structures between the zebrafish and the human spine, these results point to a possible involvement of urotensin signaling in spine distortion in humans. More studies using zebrafish will likely provide further insights into the principles that control the shape of the spine and what goes wrong when it breaks down.


Subject(s)
Scoliosis , Urotensins , Animals , Urotensins/genetics , Zebrafish/genetics , Spine
3.
Sleep Med ; 100: 49-55, 2022 12.
Article in English | MEDLINE | ID: mdl-36007431

ABSTRACT

INTRODUCTION: Although 80% of cancer survivors report symptoms of insomnia, only 28-43% meet DSM-5 criteria for this diagnosis. We sought to characterize the association between patient-reported insomnia symptoms, patient outcomes, and supportive care variables, as well as explore clinically meaningful insomnia thresholds in a sample of women diagnosed with breast and gynecologic cancers. METHODS: From July 2018-March 2019, all breast and gynecologic cancer survivors seen at the Stanford Women's Cancer Center were approached and invited to participate in the study (15% declined). Of those who consented, 273 survivors completed an online survey related to their sleep (ISI), quality of life (FACT-G), distress (PHQ-4), supportive care needs (SCNS-SF34), and symptom severity (MDASI). Survivors who scored <8 on ISI were categorized as "good sleepers," survivors with ISI ≥8 were categorized as "bad sleepers." RESULTS: 126 (46.2%) of survivors were "good sleepers," 147 (53.8%) were "bad sleepers." Good sleepers were older than bad sleepers (p < .05) but did not differ in any other demographic or any medical variables. Using hierarchical linear regression models, we found that good sleep (ISI <8) was associated with higher quality of life, lower psychological distress, increased social support, lower symptom severity, and lower supportive care needs, after accounting for demographic, medical, and treatment variables. The findings were largely replicated with an ISI cut off of 15. CONCLUSIONS: Among women treated for breast and gynecologic cancers, survivors who were good sleepers had better psychosocial outcomes, fewer supportive care needs, and lower symptom severity compared to those who reported insomnia symptoms. Results also indicate that degree of sleep impairment, whether mild or severe, has similarly poor associations with most aspects of patient functioning and symptomatic burden. Further research is needed to determine causality of these findings.


Subject(s)
Breast Neoplasms , Sleep Initiation and Maintenance Disorders , Female , Humans , Quality of Life , Survivorship , Survivors/psychology , Surveys and Questionnaires
4.
Front Nutr ; 9: 917880, 2022.
Article in English | MEDLINE | ID: mdl-35942169

ABSTRACT

Objectives: In utero glycemia is an important determinant of fetal growth. Women with gestational diabetes are more likely to deliver large-for-gestational age babies that are at increased risk for obesity. The maternal nutritional state modulates the development of offspring biological systems during the critical periods of gestation and lactation. Carbohydrate typically contributes most of the dietary energy, however, there are very few mechanistic studies investigating the effects of maternal dietary carbohydrate quality on fetal and offspring outcomes. Therefore, we sought to investigate the direct effects of maternal carbohydrate quality on sex-specific offspring metabolic programming. Methods: Female C57BL/6 mice were fed one of five isocaloric diets: four high-sugar diets based on glucose, sucrose, isomaltulose or fructose (all containing 60% energy as carbohydrate), or a standard, minimally processed, chow diet, and were mated with chow-fed males. Half of the dams were sacrificed for fetus dissection and placental collection, with the remaining giving live birth. All dams were metabolically profiled before and during pregnancy, and pups were similarly profiled at 12 weeks of age. Results: Overall, glucose-fed dams were heavier and fatter than chow or isomaltulose-fed dams. Female fetuses from glucose and isomaltulose-fed mothers weighed less and had smaller livers, than those from chow-fed mothers, with isomaltulose-fed female fetuses also having decreased placental mass. In contrast, male fetuses responded differently to the maternal diets, with heart mass being significantly increased when their mothers were fed fructose-containing diets, that is, sucrose, isomaltulose and fructose. High-sugar fed female offspring weighed the same, but were significantly fatter, than chow-fed offspring at 12 weeks of age, while glucose and isomaltulose-fed male pups displayed a similar phenotype to their mothers'. Conclusion: While both glucose and isomaltulose diets constrained fetal growth in females, only placentas from isomaltulose-fed dams were significantly smaller than those from chow-fed mothers, suggesting the mechanisms through which fetal growth is reduced may be different. Female fetuses of isomaltulose-fed mothers were also lighter than sucrose-fed fetuses suggesting the glycemic index, or rate of glucose digestion and absorption, may be an important factor in determining nutrient availability to the growing fetus.

5.
Semin Oncol Nurs ; 38(6): 151316, 2022 12.
Article in English | MEDLINE | ID: mdl-35902337

ABSTRACT

OBJECTIVES: This study evaluated breast and gynecologic cancer patients' sexual function, unmet needs related to sexuality, and distress. DATA SOURCES: Secondary analyses of a cross-sectional survey study evaluated measures of sexual function (Female Sexual Function Index [FSFI]), unmet needs (Supportive Care Needs Scale), and distress (Patient Health Questionnaire). χ2 test, t tests, and analysis of variances (ANOVAs) tested bivariate relationships. Subgroup comparisons were made based on the Female Sexual Function Index sexual dysfunction diagnostic cut-off score (<26.55; lower scores indicate greater dysfunction). A regression model tested associations between sexual function and unmet needs with distress as the outcome variable. CONCLUSION: Clinically significant sexual dysfunction was common in this cohort of women. In multivariate modeling, worse sexual function and greater unmet sexuality needs related to greater distress. Future work should explore reasons behind the high levels of sexual dysfunction and unmet needs in female survivors. IMPLICATIONS FOR NURSING PRACTICE: It is important to routinely screen for sexual health concerns among female cancer survivors at all phases of the cancer trajectory including years posttreatment.


Subject(s)
Cancer Survivors , Genital Neoplasms, Female , Sexual Dysfunction, Physiological , Sexual Health , Female , Humans , Cross-Sectional Studies , Quality of Life , Survivors , Sexual Dysfunction, Physiological/epidemiology , Sexual Dysfunction, Physiological/etiology , Genital Neoplasms, Female/complications , Genital Neoplasms, Female/therapy
6.
Health Psychol ; 41(6): 389-395, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35604702

ABSTRACT

OBJECTIVE: This study aimed to examine the association between mindsets-established, but mutable beliefs that a person holds-and health-related quality of life in survivors of breast and gynecologic cancer. METHOD: A cross-sectional survey study was conducted with breast and gynecologic cancer survivors. Measures included the Illness Mindset Questionnaire and Functional Assessment of Cancer Therapy-General (FACT-G). RESULTS: Two hundred seventy-three survivors (74% breast/26% gynecologic) who were on average 3.9 years post-diagnosis (SD = 4.2), Mage 55 (SD = 12) completed the survey (response rate 80%). Of the survivors, 20.1% (N = 55) endorsed ("agree" or "strongly agree") that Cancer is a Catastrophe, 52.4% (N = 143) endorsed that Cancer is Manageable, and 65.9% (N = 180) endorsed that Cancer can be an Opportunity (not mutually exclusive). Those who endorsed a maladaptive mindset (Cancer is a Catastrophe) reported lower health-related quality of life (HRQOL) compared with those who did not hold this belief (p < .001). Alternatively, those who endorsed more adaptive mindsets (Cancer is Manageable or Cancer can be an Opportunity) reported better HRQOL compared with those who disagreed (all p-values < .05). All three mindsets were independent correlates of HRQOL, explaining 6-15% unique variance in HRQOL, even after accounting for demographic and medical factors. CONCLUSIONS: Mindsets about illness are significantly associated with HRQOL in cancer survivors. Our data come from a one-time evaluation of cancer survivors at a single clinic and provide a foundation for future longitudinal studies and RCTs on the relationship between mindsets and psychosocial outcomes in cancer survivors. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Subject(s)
Cancer Survivors , Neoplasms , Cancer Survivors/psychology , Cross-Sectional Studies , Female , Humans , Quality of Life , Surveys and Questionnaires , Survivors
7.
Psychooncology ; 31(1): 9-20, 2022 01.
Article in English | MEDLINE | ID: mdl-34224603

ABSTRACT

BACKGROUND: Financial toxicity includes distress and burden from cancer-related costs. Women are more likely to experience worse cancer-related financial outcomes than men. This study evaluated breast and gynecologic cancer patients' subjective experiences of financial toxicity and associations with distress and quality of life (QOL). METHODS: A cross-sectional survey study included measures of financial toxicity (Comprehensive Score for Financial Toxicity [COST] Version 2), distress (Patient Health Questionnaire), and QOL (Functional Assessment of Cancer Therapy). Chi-square, t-tests, and ANOVAs examined bivariate relationships. Two regression models tested associations between financial toxicity and distress and QOL, controlling for covariates. Financial toxicity subgroups were compared based on a validated grading system. RESULTS: Participants (N = 273; 74% breast cancer) averaged 54.65 years (SD = 12.08), were 3.42 years (SD = 4.20) post-diagnosis, and 33% reported cancer-related change in employment status. Financial toxicity was "mild" overall (COST M = 26.11, SD = 11.14); 32% worried about cancer-related financial problems (quite a bit/very much; item-level analysis). Worse financial toxicity related to younger age (p < 0.001), identifying as a non-Asian minority (p = 0.03) or Hispanic (p = 0.01), being single (p < 0.001), lower education (p = 0.004), lower income (p < 0.001), late-stage disease (p = 0.001), recurrent disease (p = 0.004), and active treatment (p < 0.001). In separate multivariable models, greater financial toxicity related to greater distress (ß = -0.45 p < 0.001) and worse QOL (ß = 0.58, p < 0.001). Financial toxicity subgroups reported clinically significant differences in distress and QOL (p's < 0.05). CONCLUSIONS: Cancer-related financial burden is associated with pervasive negative effects and may impact subgroups differently. Future research should explore financial experiences across subgroups, aiming to better identify those at risk and build targeted interventions.


Subject(s)
Cancer Survivors , Neoplasms , Cross-Sectional Studies , Female , Financial Stress , Humans , Male , Quality of Life , Survivors
8.
Cancer ; 127(23): 4492-4503, 2021 Dec 01.
Article in English | MEDLINE | ID: mdl-34357593

ABSTRACT

BACKGROUND: Breast cancer survivors often have persisting headache. In a secondary analysis of the Brief Behavioral Therapy for Cancer-Related Insomnia (BBT-CI) clinical trial (ClinicalTrials.gov identifier NCT02165839), the authors examined the effects of BBT-CI on headache outcomes in patients with breast cancer. METHODS: Patients with breast cancer who were receiving chemotherapy were randomly assigned to receive either the BBT-CI intervention or the Healthy EAting Education Learning for healthy sleep (HEAL) control intervention, and both were delivered over 6 weeks by trained staff. Headache outcomes and heart rate variability (HRV) were measured at baseline, 6 weeks, 6 months, and 12 months. Mixed-effects models were used to examine longitudinal headache outcomes in the groups according to the intention to treat. Principal component analysis and agglomerative hierarchical clustering were conducted to reduce 16 variables for data-driven phenotyping. RESULTS: Patients in the BBT-CI arm (n = 73) exhibited a significant reduction in headache burden over time (P = .02; effect size [Cohen d] = 0.43), whereas the reduction was not significant among those in the HEAL arm (n = 66). The first principal component was positively loaded by headache, sleep, fatigue, and nausea/vomiting and was negatively loaded by cognitive, physical, and emotional functioning. Agglomerative hierarchical clustering revealed 3 natural clusters. Cluster I (n = 58) featured the highest burden of headache, insomnia, and nausea/vomiting; cluster II (n = 50) featured the lowest HRV despite a low burden of headache and insomnia; and cluster III (n = 31) showed an inverse relation between HRV and headache-insomnia, signifying autonomic dysfunction. CONCLUSIONS: BBT-CI is efficacious in reducing headache burden in breast cancer survivors. Patient phenotyping demonstrates a headache type featuring sleep disturbance, nausea/vomiting, and low physical functioning-revealing similarities to migraine. LAY SUMMARY: Breast cancer survivors often have persisting headache symptoms. In patients with cancer, treatment of chronic headache disorders using daily medications may be challenging because of drug interactions with chemotherapy and other cancer therapies as well as patients' reluctance to add more drugs to their medicine list. Headache and sleep disorders are closely related to each other. This study demonstrates that a sleep behavioral therapy reduced headache burden in breast cancer survivors. In addition, the majority of headache sufferers had a headache type with similarities to migraine-featuring sleep disturbance, nausea/vomiting, and low physical functioning.


Subject(s)
Breast Neoplasms , Cancer Survivors , Cognitive Behavioral Therapy , Sleep Initiation and Maintenance Disorders , Behavior Therapy , Breast Neoplasms/drug therapy , Breast Neoplasms/therapy , Cancer Survivors/psychology , Female , Headache/etiology , Headache/therapy , Humans , Sleep/physiology , Sleep Initiation and Maintenance Disorders/complications , Sleep Initiation and Maintenance Disorders/therapy , Treatment Outcome
9.
J Cancer Surviv ; 15(5): 677-684, 2021 10.
Article in English | MEDLINE | ID: mdl-33161562

ABSTRACT

PURPOSE: We sought to characterize the use of social media (SM) among breast and gynecologic cancer survivors, as well as associations between patterns of SM use and psychosocial outcomes. METHODS: Two hundred seventy-three breast and gynecologic cancer survivors recruited at the Stanford Women's Cancer Center completed the study. Participants completed questionnaires to measure quality of life (FACT-G), functional social support (Duke-UNC FSSQ), distress (PHQ-4), decision regret (DRS), and SM use. RESULTS: In total, 75.8% of the sample reported using SM. There was no difference in quality of life (QOL), functional social support (FSS), distress, or decision regret between SM users and non-users. SM users indicated using SM for social support (34.3%) and loneliness (24.6%) more than for information-seeking (15.9%), coping (18.8%), or self-disclosure (14%). SM use for coping was associated with lower QOL (p < .001), lower FSS (p < .001), and higher decision regret (p = .029). Use for social support was associated with lower FSS (p = .029). Use for information seeking was associated with lower QOL (p = .012). Use of SM when lonely was associated with lower QOL (p < .001), higher distress (p = .007), lower FSS (p < .001), and higher decision regret (p = .020). CONCLUSIONS: Associations between SM use and psychosocial outcomes are nuanced and dependent on motivation for use. Further research is needed to better characterize SM use and associations with psychosocial outcomes among cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: SM is an important potential avenue for understanding and addressing the psychosocial effects associated with cancer survivorship.


Subject(s)
Breast Neoplasms , Cancer Survivors , Genital Neoplasms, Female , Social Media , Female , Humans , Quality of Life , Social Support , Surveys and Questionnaires , Survivors
10.
ACS Photonics ; 7(5): 1096-1103, 2020 May 20.
Article in English | MEDLINE | ID: mdl-32596415

ABSTRACT

We present a novel design for an ultracompact, passive light source capable of generating ultraviolet and X-ray radiation, based on the interaction of free electrons with the magnetic near-field of a ferromagnet. Our design is motivated by recent advances in the fabrication of nanostructures, which allow the confinement of large magnetic fields at the surface of ferromagnetic nanogratings. Using ab initio simulations and a complementary analytical theory, we show that highly directional, tunable, monochromatic radiation at high frequencies could be produced from relatively low-energy electrons within a tabletop design. The output frequency is tunable in the extreme ultraviolet to hard X-ray range via electron kinetic energies from 1 keV to 5 MeV and nanograting periods from 1 µm to 5 nm. The proposed radiation source can achieve the tunability and monochromaticity of current free-electron-driven sources (free-electron lasers, synchrotrons, and laser-driven undulators), yet with a significantly reduced scale, cost, and complexity. Our design could help realize the next generation of tabletop or on-chip X-ray sources.

11.
Curr Opin Support Palliat Care ; 14(2): 120-126, 2020 06.
Article in English | MEDLINE | ID: mdl-32332211

ABSTRACT

PURPOSE OF REVIEW: The current review outlines the existing research on the impact of circadian rhythm on gastrointestinal toxicity associated with cancer treatment and explores clinical evidence for utilizing circadian-based approaches in addressing gastrointestinal symptoms such as nausea, vomiting, diarrhea, mucositis, and hepatotoxicity. RECENT FINDINGS: Recent evidence highlights circadian control of gastrointestinal physiology of appetite, digestion, nutrient absorption, and cellular proliferation in the digestive system. In addition, animal models support the mechanistic rationale of using chronotherapy (a type of anticancer therapy delivered at specific times with the goal of producing less toxicity and greater treatment response) to minimize gastrointestinal-impact of systemic cancer treatments. In addition, earlier research demonstrates that many chemotherapeutic agents are responsive to circadian timing in animals. On the contrary, clinical trials focused on minimizing gastrointestinal toxicity using chronotherapy have been limited in recent years and have not yielded the efficacy initially hoped for. Instead, researchers focused on understanding circadian rhythm's influence on the gastrointestinal system at a mechanistic level as well as measuring circadian rhythm at an individual level. SUMMARY: Although using circadian timing is a promising target for reducing gastrointestinal toxicity, recent evidence suggests that more research is needed to understand circadian rhythm before circadian-based interventions can be developed that will result in lessening of gastrointestinal toxicity.


Subject(s)
Antineoplastic Agents/adverse effects , Circadian Rhythm/physiology , Gastrointestinal Diseases/chemically induced , Gastrointestinal Diseases/prevention & control , Neoplasms/drug therapy , Antineoplastic Agents/administration & dosage , Appetite/physiology , Cell Proliferation/physiology , Circadian Clocks/physiology , Digestion/physiology , Drug Chronotherapy , Humans , Suprachiasmatic Nucleus/metabolism
12.
Cognition ; 197: 104187, 2020 04.
Article in English | MEDLINE | ID: mdl-31981883

ABSTRACT

Items with special histories (e.g. celebrity owners) or qualities (e.g. limited editions) are more valuable than similar "inauthentic" items. Typically developing (TD) children privilege authenticity and are particularly influenced by who objects belong to. Here, we explore why children and adults over-value items with special ownership histories and examine how autism spectrum disorder (ASD) affects object valuation. In Studies 1 and 2, TD children perceived items belonging to famous owners (with "good" or "bad" reputations) to be more valuable than similar items belonging to non-famous owners. However, they ascribed significantly higher values to items belonging to famous heroes than infamous villains when compared. Children with ASD did not over-value objects with special ownership histories, but their valuations were moderated by qualities unrelated to ownership (e.g. rarity). In Study 3, adults with ASD assigned high values to authentic items with special ownership histories but were more likely to keep inauthentic objects than neurotypical adults. Our findings show that association with a famous owner is sufficient to increase an item's value for TD children and adults (with and without ASD). The degree of added value may be determined by the famous owner's character for TD children, but not adults. By contrast, children with ASD value objects via a different strategy that prioritizes material qualities over ownership history. However, the awareness of authenticity displayed by adults with ASD suggests that the emergence of ownership history as an important influence on object evaluation may be developmentally delayed in ASD, rather than completely absent.


Subject(s)
Autism Spectrum Disorder , Autistic Disorder , Adult , Child , Humans , Ownership
13.
Cell Rep ; 30(4): 1164-1177.e7, 2020 01 28.
Article in English | MEDLINE | ID: mdl-31995756

ABSTRACT

Neuronal migration, axon fasciculation, and axon guidance need to be closely coordinated for neural circuit assembly. Spinal motor neurons (MNs) face unique challenges during development because their cell bodies reside within the central nervous system (CNS) and their axons project to various targets in the body periphery. The molecular mechanisms that contain MN somata within the spinal cord while allowing their axons to exit the CNS and navigate to their final destinations remain incompletely understood. We find that the MN cell surface protein TAG-1 anchors MN cell bodies in the spinal cord to prevent their emigration, mediates motor axon fasciculation during CNS exit, and guides motor axons past dorsal root ganglia. TAG-1 executes these varied functions in MN development independently of one another. Our results identify TAG-1 as a key multifunctional regulator of MN wiring that coordinates neuronal migration, axon fasciculation, and axon guidance.


Subject(s)
Axon Guidance/genetics , Cell Movement/genetics , Contactin 2/metabolism , Fasciculation/metabolism , Motor Neurons/metabolism , Neurogenesis/genetics , Animals , Axon Guidance/physiology , Axons/metabolism , COS Cells , Cell Line , Chlorocebus aethiops , Contactin 2/genetics , Fasciculation/genetics , Ganglia, Spinal/cytology , Ganglia, Spinal/metabolism , Gene Expression Regulation, Developmental/genetics , Mice , Mice, Inbred C57BL , Mice, Knockout , Signal Transduction/genetics , Spinal Cord/metabolism
14.
J Autism Dev Disord ; 48(8): 2714-2726, 2018 08.
Article in English | MEDLINE | ID: mdl-29512018

ABSTRACT

This study investigated whether children with autism spectrum disorder (ASD) and typically developing children matched on receptive language share resources fairly and reciprocally. Children completed age-appropriate versions of the Ultimatum and Dictator Games with real stickers and an interactive partner. Both groups offered similar numbers of stickers (preferring equality over self-interest), offered more stickers in the Ultimatum Game, and verbally referenced 'fairness' at similar rates. However, children with ASD were significantly more likely to accept unfair offers and were significantly less likely to reciprocate the puppet's offers. Failure to reciprocate fair sharing may significantly impact on social cohesion and children's ability to build relationships. These important differences may be linked to broader deficits in social-cognitive development and potentially self-other understanding.


Subject(s)
Autism Spectrum Disorder/psychology , Comprehension , Interpersonal Relations , Child , Female , Games, Experimental , Humans , Male , Play and Playthings
15.
Cognition ; 172: 26-36, 2018 03.
Article in English | MEDLINE | ID: mdl-29216519

ABSTRACT

Ownership has a unique and privileged influence on human psychology. Typically developing (TD) children judge their objects to be more desirable and valuable than similar objects belonging to others. This 'ownership effect' is due to processing one's property in relation to 'the self'. Here we explore whether children with autism spectrum disorder (ASD) - a population with impaired self-understanding - prefer and over-value property due to ownership. In Experiment 1, we discovered that children with ASD did not favour a randomly endowed toy and frequently traded for a different object. By contrast, TD children showed a clear preference for their randomly endowed toy and traded infrequently. Both populations also demonstrated highly-accurate tracking of owner-object relationships. Experiment 2 showed that both TD children and children with ASD over-value their toys if they are self-selected and different from other-owned toys. Unlike TD children, children with ASD did not over-value their toys in comparison to non-owned identical copies. This finding was replicated in Experiment 3, which also established that mere ownership elicited over-valuation of randomly endowed property in TD children. However, children with ASD did not consistently regard their randomly endowed toys as the most valuable, and evaluated property irrespective of ownership. Our findings show that mere ownership increases preferences and valuations for self-owned property in TD children, but not children with ASD. We propose that deficits in self-understanding may diminish ownership effects in ASD, eliciting a more economically-rational strategy that prioritises material qualities (e.g. what a toy is) rather than whom it belongs to.


Subject(s)
Autism Spectrum Disorder/physiopathology , Child Behavior/physiology , Child Development/physiology , Ownership , Self Concept , Child , Female , Humans , Male
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