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The early development of infant siblings of children with autism spectrum disorder: Characteristics of sibling interactions.
PubMed
Bontinck, Chloè; Warreyn, Petra; Van der Paelt, Sara; Demurie, Ellen; Roeyers, Herbert
2018-01-01
Although sibling interactions play an important role in children's early development, they are rarely studied in very young children with an older brother or sister with autism spectrum disorder (ASD). This study used a naturalistic, observational method to compare interactions between 18-month-old infants and their older sibling with ASD (n = 22) with a control group of 18-month-old infants and their typically developing (TD) older sibling (n = 29). In addition, role (a)symmetry and the influence of gender were evaluated. Sibling interactions in ASD-dyads were characterized by higher levels of negativity. Although somewhat less pronounced in ASD-dyads, role asymmetry was present in both groups, with the older child taking the dominant position. Finally, siblings pairs with an older sister were characterized by more positive behaviours. Since differences in sibling interactions may alter the developmental trajectories of both siblings, these early relationships should be taken into account in future ASD research and interventions.
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Early Head Growth in Infants at Risk of Autism: A Baby Siblings Research Consortium Study
PubMed Central
Zwaigenbaum, Lonnie; Young, Gregory S.; Stone, Wendy L.; Dobkins, Karen; Ozonoff, Sally; Brian, Jessica; Bryson, Susan E.; Carver, Leslie J.; Hutman, Ted; Iverson, Jana M.; Landa, Rebecca J.; Messinger, Daniel
2014-01-01
Objective: While early brain overgrowth is frequently reported in autism spectrum disorder (ASD), the relationship between ASD and head circumference (HC) is less clear, with inconsistent findings from longitudinal studies that include community controls. Our aim was to examine whether head growth in the first 3 years differed between children with ASD from a high-risk (HR) sample of infant siblings of children with ASD (by definition, multiplex), HR siblings not diagnosed with ASD, and low-risk (LR) controls. Method: Participants included 442 HR and 253 LR infants from 12 sites of the international Baby Siblings Research Consortium. Longitudinal HC data were obtained prospectively, supplemented by growth records. Random effects non-linear growth models were used to compare HC in HR infants and LR infants. Additional comparisons were conducted with the HR group stratified by diagnostic status at age 3: ASD (n=77), developmental delay (DD; n=32), and typical development (TD; n=333). Nonlinear growth models were also developed for height to assess general overgrowth associated with ASD. Results: There was no overall difference in head circumference growth over the first 3 years between HR and LR infants, although secondary analyses suggested possible increased total growth in HR infants, reflected by the model asymptote. Analyses stratifying the HR group by 3-year outcomes did not detect differences in head growth or height between HR infants who developed ASD and those who did not, nor between infants with ASD and LR controls. Conclusion: Head growth was uninformative as an ASD risk marker within this HR cohort. PMID:25245349
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Immature Spinal Locomotor Output in Children with Cerebral Palsy.
PubMed
Cappellini, Germana; Ivanenko, Yury P; Martino, Giovanni; MacLellan, Michael J; Sacco, Annalisa; Morelli, Daniela; Lacquaniti, Francesco
2016-01-01
Detailed descriptions of gait impairments have been reported in cerebral palsy (CP), but it is still unclear how maturation of the spinal motoneuron output is affected. Spatiotemporal alpha-motoneuron activation during walking can be assessed by mapping the electromyographic activity profiles from several, simultaneously recorded muscles onto the anatomical rostrocaudal location of the motoneuron pools in the spinal cord, and by means of factor analysis of the muscle activity profiles. Here, we analyzed gait kinematics and EMG activity of 11 pairs of bilateral muscles with lumbosacral innervation in 35 children with CP (19 diplegic, 16 hemiplegic, 2-12 years) and 33 typically developing (TD) children (1-12 years). TD children showed a progressive reduction of EMG burst durations and a gradual reorganization of the spatiotemporal motoneuron output with increasing age. By contrast, children with CP showed very limited age-related changes of EMG durations and motoneuron output, as well as of limb intersegmental coordination and foot trajectory control (on both sides for diplegic children and the affected side for hemiplegic children). Factorization of the EMG signals revealed a comparable structure of the motor output in children with CP and TD children, but significantly wider temporal activation patterns in children with CP, resembling the patterns of much younger TD infants. A similar picture emerged when considering the spatiotemporal maps of alpha-motoneuron activation. Overall, the results are consistent with the idea that early injuries to developing motor regions of the brain substantially affect the maturation of the spinal locomotor output and consequently the future locomotor behavior.
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Immature Spinal Locomotor Output in Children with Cerebral Palsy
PubMed Central
Cappellini, Germana; Ivanenko, Yury P.; Martino, Giovanni; MacLellan, Michael J.; Sacco, Annalisa; Morelli, Daniela; Lacquaniti, Francesco
2016-01-01
Detailed descriptions of gait impairments have been reported in cerebral palsy (CP), but it is still unclear how maturation of the spinal motoneuron output is affected. Spatiotemporal alpha-motoneuron activation during walking can be assessed by mapping the electromyographic activity profiles from several, simultaneously recorded muscles onto the anatomical rostrocaudal location of the motoneuron pools in the spinal cord, and by means of factor analysis of the muscle activity profiles. Here, we analyzed gait kinematics and EMG activity of 11 pairs of bilateral muscles with lumbosacral innervation in 35 children with CP (19 diplegic, 16 hemiplegic, 2–12 years) and 33 typically developing (TD) children (1–12 years). TD children showed a progressive reduction of EMG burst durations and a gradual reorganization of the spatiotemporal motoneuron output with increasing age. By contrast, children with CP showed very limited age-related changes of EMG durations and motoneuron output, as well as of limb intersegmental coordination and foot trajectory control (on both sides for diplegic children and the affected side for hemiplegic children). Factorization of the EMG signals revealed a comparable structure of the motor output in children with CP and TD children, but significantly wider temporal activation patterns in children with CP, resembling the patterns of much younger TD infants. A similar picture emerged when considering the spatiotemporal maps of alpha-motoneuron activation. Overall, the results are consistent with the idea that early injuries to developing motor regions of the brain substantially affect the maturation of the spinal locomotor output and consequently the future locomotor behavior. PMID:27826251
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Toddle temporal-spatial deviation index: Assessment of pediatric gait.
PubMed
Cahill-Rowley, Katelyn; Rose, Jessica
2016-09-01
This research aims to develop a gait index for use in the pediatric clinic as well as research, that quantifies gait deviation in 18-22 month-old children: the Toddle Temporal-spatial Deviation Index (Toddle TDI). 81 preterm children (≤32 weeks) with very-low-birth-weights (≤1500g) and 42 full-term TD children aged 18-22 months, adjusted for prematurity, walked on a pressure-sensitive mat. Preterm children were administered the Bayley Scales of Infant Development-3rd Edition (BSID-III). Principle component analysis of TD children's temporal-spatial gait parameters quantified raw gait deviation from typical, normalized to an average(standard deviation) Toddle TDI score of 100(10), and calculated for all participants. The Toddle TDI was significantly lower for preterm versus TD children (86 vs. 100, p=0.003), and lower in preterm children with <85 vs. ≥85 BSID-III motor composite scores (66 vs. 89, p=0.004). The Toddle TDI, which by design plateaus at typical average (BSID-III gross motor 8-12), correlated with BSID-III gross motor (r=0.60, p<0.001) and not fine motor (r=0.08, p=0.65) in preterm children with gross motor scores ≤8, suggesting sensitivity to gross motor development. The Toddle TDI demonstrated sensitivity and specificity to gross motor function in very-low-birth-weight preterm children aged 18-22 months, and has been potential as an easily-administered, revealing clinical gait metric. Copyright © 2016 Elsevier B.V. All rights reserved.
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Vaccination of adults 65 years of age and older with tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Boostrix(®)): results of two randomized trials.
PubMed
Weston, Wayde M; Friedland, Leonard R; Wu, Xiangfeng; Howe, Barbara
2012-02-21
Pertussis can cause significant morbidity in elderly patients, who can also transmit this disease to infants and young children. There is little data available on the use of acellular pertussis vaccines in recipients ≥65 years of age. Two studies examined the safety and immunogenicity of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine (Boostrix(®)) in healthy ≥65 year olds. In Study A subjects received single doses of Tdap and seasonal influenza vaccine either co-administered or given one month apart. In Study B subjects received either Tdap or tetanus-diphtheria (Td) vaccine. Antibodies were measured before and one month after vaccination. Reactogenicity and safety were actively assessed using diary cards. A total of 1104 subjects 65 years of age and older received a Tdap vaccination in the two studies. In study A, no differences in immune responses to Tdap or influenza vaccine were observed between co-administered or sequentially administered vaccines. In study B, Tdap was non-inferior to Td with respect to diphtheria and tetanus seroprotection, and anti-pertussis GMCs were non-inferior to those observed in infants following a 3-dose diphtheria, tetanus and acellular pertussis (DTaP) primary vaccination series, in whom efficacy against pertussis was demonstrated. Reports of adverse events were similar between Tdap and Td groups. Tdap was found to be immunogenic in subjects ≥65 years, with a safety profile comparable to US-licensed Td vaccine. Tdap and influenza vaccine may be co-administered without compromise of either the reactogenicity or immunogenicity profiles of the two vaccines. Copyright © 2012 Elsevier Ltd. All rights reserved.
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School-age outcomes of infants at risk for autism spectrum disorder.
PubMed
Miller, Meghan; Iosif, Ana-Maria; Young, Gregory S; Hill, Monique; Phelps Hanzel, Elise; Hutman, Ted; Johnson, Scott; Ozonoff, Sally
2016-06-01
Studies of infants at risk for autism spectrum disorder (ASD) have proliferated, but few of these samples have been followed longer-term. We conducted a follow-up study, at age 5.5-9 years, of younger siblings of children with ASD (high-risk group, n = 79) or typical development (low-risk group, n = 60), originally recruited as infants. Children with ASD were excluded because of the focus on understanding the range of non-ASD outcomes among high-risk siblings. Using examiner ratings, parent ratings, and standardized assessments, we evaluated differences in clinical outcomes, psychopathology symptoms, autism symptoms, language skills, and nonverbal cognitive abilities. After adjusting for covariates, the high-risk group had increased odds of any clinically elevated/impaired score across measures relative to the low-risk group (43% vs. 12%, respectively). The high-risk group also had increased odds of examiner-rated Clinical Concerns (CC) outcomes (e.g., ADHD concerns, broader autism phenotype, speech-language difficulties, anxiety/mood problems, learning problems) relative to the low-risk group (38% vs. 13%, respectively). The high-risk group with CC outcomes had higher parent-reported psychopathology and autism symptoms, and lower directly-assessed language skills, than the Low-Risk Typically Developing (TD) and High-Risk TD groups, which did not differ. There were no differences in nonverbal cognitive skills. For some in the high-risk group, clinical concerns persisted from early childhood, whereas for others clinical concerns were first evident at school-age. Results suggest continued vulnerability in at least a subgroup of school-age children with a family history of ASD and suggest that this population may benefit from continued screening and monitoring into the school-age years. Autism Res 2016, 9: 632-642. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
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Cognitive Delay and Behavior Problems Prior to School Age
PubMed Central
Palta, Mari; Kotelchuck, Milton; Poehlmann, Julie; Witt, Whitney P.
2014-01-01
OBJECTIVE: To investigate the relationship between cognitive delay (CD) and behavior problems between ages 9 months and 5 years, while adjusting for covariates related to CD. METHODS: Data were from 4 waves of the Early Childhood Longitudinal Study, Birth Cohort (n = 8000). Children were classified as typically developing (TD) or as having resolved, newly developed, or persistent CD between 9 and 24 months, based on scores from the Bayley Short Form-Research Edition below or above the 10th percentile. Child behavior was measured by using the Infant/Toddler Symptom Checklist (ages 9 and 24 months) and the Preschool and Kindergarten Behavior Scales (ages 4 and 5 years); children in the top 10th percentile were considered to have a behavior problem. Hierarchical linear modeling estimated the effect of CD status on children’s behavioral trajectories, adjusted for confounders. RESULTS: CD resolved for 80.3% of children between 9 and 24 months. Behavior problems at 24 months were detected in 19.3%, 21.8%, and 35.5% of children with resolved, newly developed, and persistent CD, respectively, versus 13.0% of TD children. Behavior problems increased among children with CD over time, and more so among children with persistent CD. By age 5, children with persistent CD had behavior scores moderately (0.59 SD) higher than TD children. CONCLUSIONS: Behavior problems among children with CD are slightly higher at 9 months, clearly evident by 24 months, and increase as children move toward school age. Efforts to promote the earliest identification, evaluation, and service referral may be necessary to improve outcomes for these children. PMID:25113290
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Ordering human CD34+CD10−CD19+ pre/pro-B-cell and CD19− common lymphoid progenitor stages in two pro-B-cell development pathways
PubMed Central
Sanz, Eva; Muñoz-A., Norman; Monserrat, Jorge; Van-Den-Rym, Ana; Escoll, Pedro; Ranz, Ismael; Álvarez-Mon, Melchor; de-la-Hera, Antonio
2010-01-01
Studies here respond to two long-standing questions: Are human “pre/pro-B” CD34+CD10−CD19+ and “common lymphoid progenitor (CLP)/early-B” CD34+CD10+CD19− alternate precursors to “pro-B” CD34+CD19+CD10+ cells, and do the pro-B cells that arise from these progenitors belong to the same or distinct B-cell development pathways? Using flow cytometry, gene expression profiling, and Ig VH-D-JH sequencing, we monitor the initial 10 generations of development of sorted cord blood CD34highLineage− pluripotential progenitors growing in bone marrow S17 stroma cocultures. We show that (i) multipotent progenitors (CD34+CD45RA+CD10−CD19−) directly generate an initial wave of Pax5+TdT− “unilineage” pre/pro-B cells and a later wave of “multilineage” CLP/early-B cells and (ii) the cells generated in these successive stages act as precursors for distinct pro-B cells through two independent layered pathways. Studies by others have tracked the origin of B-lineage leukemias in elderly mice to the mouse B-1a pre/pro-B lineage, which lacks the TdT activity that diversifies the VH-D-JH Ig heavy chain joints found in the early-B or B-2 lineage. Here, we show a similar divergence in human B-cell development pathways between the Pax5+TdT− pre/pro-B differentiation pathway that gives rise to infant B-lineage leukemias and the early-B pathway. PMID:20231472
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Intergroup cannibalism in the European Early Pleistocene: the range expansion and imbalance of power hypotheses.
PubMed
Saladié, Palmira; Huguet, Rosa; Rodríguez-Hidalgo, Antonio; Cáceres, Isabel; Esteban-Nadal, Montserrat; Arsuaga, Juan Luis; Bermúdez de Castro, José María; Carbonell, Eudald
2012-11-01
In this paper, we compare cannibalism in chimpanzees, modern humans, and in archaeological cases with cannibalism inferred from evidence from the Early Pleistocene assemblage of level TD6 of Gran Dolina (Sierra de Atapuerca, Spain). The cannibalism documented in level TD6 mainly involves the consumption of infants and other immature individuals. The human induced modifications on Homo antecessor and deer remains suggest that butchering processes were similar for both taxa, and the remains were discarded on the living floor in the same way. This finding implies that a group of hominins that used the Gran Dolina cave periodically hunted and consumed individuals from another group. However, the age distribution of the cannibalized hominins in the TD6 assemblage is not consistent with that from other cases of exo-cannibalism by human/hominin groups. Instead, it is similar to the age profiles seen in cannibalism associated with intergroup aggression in chimpanzees. For this reason, we use an analogy with chimpanzees to propose that the TD6 hominins mounted low-risk attacks on members of other groups to defend access to resources within their own territories and to try and expand their territories at the expense of neighboring groups. Copyright © 2012 Elsevier Ltd. All rights reserved.
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Preventing tetanus, diphtheria, and pertussis among adults: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine recommendations of the Advisory Committee on Immunization Practices (ACIP) and recommendation of ACIP, supported by the Healthcare Infection Control Practices Advisory Committee (HICPAC), for use of Tdap among health-care personnel.
PubMed
Kretsinger, Katrina; Broder, Karen R; Cortese, Margaret M; Joyce, M Patricia; Ortega-Sanchez, Ismael; Lee, Grace M; Tiwari, Tejpratap; Cohn, Amanda C; Slade, Barbara A; Iskander, John K; Mijalski, Christina M; Brown, Kristin H; Murphy, Trudy V
2006-12-15
On June 10, 2005, a tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Tdap) formulated for use in adults and adolescents was licensed in the United States for persons aged 11-64 years (ADACEL, manufactured by sanofi pasteur, Toronto, Ontario, Canada). Prelicensure studies demonstrated safety and efficacy, inferred through immunogenicity, against tetanus, diphtheria, and pertussis when Tdap was administered as a single booster dose to adults. To reduce pertussis morbidity among adults and maintain the standard of care for tetanus and diphtheria prevention and to reduce the transmission of pertussis to infants and in health-care settings, the Advisory Committee on Immunization Practices (ACIP) recommends that: 1) adults aged 19-64 years should receive a single dose of Tdap to replace tetanus and diphtheria toxoids vaccine (Td) for booster immunization against tetanus, diphtheria, and pertussis if they received their last dose of Td >or=10 years earlier and they have not previously received Tdap; 2) intervals shorter than 10 years since the last Td may be used for booster protection against pertussis; 3) adults who have or who anticipate having close contact with an infant aged <12 months (e.g., parents, grandparents aged <65 years, child-care providers, and health-care personnel) should receive a single dose of Tdap to reduce the risk for transmitting pertussis. An interval as short as 2 years from the last Td is suggested; shorter intervals can be used. When possible, women should receive Tdap before becoming pregnant. Women who have not previously received Tdap should receive a dose of Tdap in the immediate postpartum period; 4) health-care personnel who work in hospitals or ambulatory care settings and have direct patient contact should receive a single dose of Tdap as soon as feasible if they have not previously received Tdap. An interval as short as 2 years from the last dose of Td is recommended; shorter intervals may be used. These recommendations for use of Tdap in health-care personnel are supported by the Healthcare Infection Control Practices Advisory Committee (HICPAC). This statement 1) reviews pertussis, tetanus and diphtheria vaccination policy in the United States; 2) describes the clinical features and epidemiology of pertussis among adults; 3) summarizes the immunogenicity, efficacy, and safety data of Tdap; and 4) presents recommendations for the use of Tdap among adults aged 19-64 years.
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Pathophysiological analyses of periventricular nodular heterotopia using gyrencephalic mammals.
PubMed
Matsumoto, Naoyuki; Hoshiba, Yoshio; Morita, Kazuya; Uda, Natsu; Hirota, Miwako; Minamikawa, Maki; Ebisu, Haruka; Shinmyo, Yohei; Kawasaki, Hiroshi
2017-03-15
Although periventricular nodular heterotopia (PNH) is often found in the cerebral cortex of people with thanatophoric dysplasia (TD), the pathophysiology of PNH in TD is largely unknown. This is mainly because of difficulties in obtaining brain samples of TD patients and a lack of appropriate animal models for analyzing the pathophysiology of PNH in TD. Here we investigate the pathophysiological mechanisms of PNH in the cerebral cortex of TD by utilizing a ferret TD model which we recently developed. To make TD ferrets, we electroporated fibroblast growth factor 8 (FGF8) into the cerebral cortex of ferrets. Our immunohistochemical analyses showed that PNH nodules in the cerebral cortex of TD ferrets were mostly composed of cortical neurons, including upper layer neurons and GABAergic neurons. We also found disorganizations of radial glial fibers and of the ventricular lining in the TD ferret cortex, indicating that PNH may result from defects in radial migration of cortical neurons along radial glial fibers during development. Our findings provide novel mechanistic insights into the pathogenesis of PNH in TD. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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Peak alpha frequency is a neural marker of cognitive function across the autism spectrum.
PubMed
Dickinson, Abigail; DiStefano, Charlotte; Senturk, Damla; Jeste, Shafali Spurling
2018-03-01
Cognitive function varies substantially and serves as a key predictor of outcome and response to intervention in autism spectrum disorder (ASD), yet we know little about the neurobiological mechanisms that underlie cognitive function in children with ASD. The dynamics of neuronal oscillations in the alpha range (6-12 Hz) are associated with cognition in typical development. Peak alpha frequency is also highly sensitive to developmental changes in neural networks, which underlie cognitive function, and therefore, it holds promise as a developmentally sensitive neural marker of cognitive function in ASD. Here, we measured peak alpha band frequency under a task-free condition in a heterogeneous sample of children with ASD (N = 59) and age-matched typically developing (TD) children (N = 38). At a group level, peak alpha frequency was decreased in ASD compared to TD children. Moreover, within the ASD group, peak alpha frequency correlated strongly with non-verbal cognition. As peak alpha frequency reflects the integrity of neural networks, our results suggest that deviations in network development may underlie cognitive function in individuals with ASD. By shedding light on the neurobiological correlates of cognitive function in ASD, our findings lay the groundwork for considering peak alpha frequency as a useful biomarker of cognitive function within this population which, in turn, will facilitate investigations of early markers of cognitive impairment and predictors of outcome in high risk infants. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
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Development of Hot and Cold Executive Function in Boys and Girls With ADHD.
PubMed
Skogli, Erik Winther; Andersen, Per Normann; Hovik, Kjell Tore; Øie, Merete
2017-02-01
To investigate the development of executive function with pronounced emotional salience (hot EF) and less pronounced emotional salience (cold EF) in boys and girls with ADHD relative to typically developing (TD) children. Seventy-five children with ADHD and 47 TD children were assessed with hot and cold EF tests at baseline and after 2 years. Despite considerable maturation, the ADHD group remained impaired on all cold EF tests relative to TD children after 2 years. There was no effect of gender on cold EF test results. Females with ADHD outperformed TD counterparts on hot EF at baseline. Females with ADHD showed deteriorating hot EF performance, while TD counterparts showed improved hot EF performance across time. Enduring cold EF impairments after 2 years may reflect stable phenotypic traits in children with ADHD. Results indicate divergent developmental trajectories of hot EF in girls with ADHD relative to TD counterparts.
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Distinct age-related differences in temporal discounting and risk taking in adolescents and young adults.
PubMed
de Water, Erik; Cillessen, Antonius H N; Scheres, Anouk
2014-01-01
Age-related differences in temporal discounting (TD) and risk taking, and their association, were examined in adolescents and young adults (n = 337) aged 12-27 years. Since monetary rewards are typically used in TD and risk-taking tasks, the association between monetary reward valuation and age and decision making in these tasks was explored as well. TD declined linearly with age, with a particularly sharp decline from 15 to 16 years. In contrast, risk taking was not correlated with age and TD. Reward valuation was not associated with TD and risk taking, and age-related differences in TD remained significant after controlling for reward valuation. Together, these findings suggest that risk taking and TD are two separate constructs with distinct age-related differences in adolescence and young adulthood. © 2014 The Authors. Child Development © 2014 Society for Research in Child Development, Inc.
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Resourcing the Training and Development Function. IES Report.
ERIC Educational Resources Information Center
Carter, A.; Hirsh, W.; Aston, J.
A study explored current practice in organizing and resourcing training and development (T&D) using survey responses from over 100 major private and public sector employers and case studies of T&D functions in 6 organizations. Business drivers for T&D were senior management as customers; diagnosis of training as "the…
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Oral Wild-Type Salmonella Typhi Challenge Induces Activation of Circulating Monocytes and Dendritic Cells in Individuals Who Develop Typhoid Disease.
PubMed
Toapanta, Franklin R; Bernal, Paula J; Fresnay, Stephanie; Darton, Thomas C; Jones, Claire; Waddington, Claire S; Blohmke, Christoph J; Dougan, Gordon; Angus, Brian; Levine, Myron M; Pollard, Andrew J; Sztein, Marcelo B
2015-06-01
A new human oral challenge model with wild-type Salmonella Typhi (S. Typhi) was recently developed. In this model, ingestion of 104 CFU of Salmonella resulted in 65% of subjects developing typhoid fever (referred here as typhoid diagnosis -TD-) 5-10 days post-challenge. TD criteria included meeting clinical (oral temperature ≥38°C for ≥12 h) and/or microbiological (S. Typhi bacteremia) endpoints. One of the first lines of defense against pathogens are the cells of the innate immune system (e.g., monocytes, dendritic cells -DCs-). Various changes in circulating monocytes and DCs have been described in the murine S. Typhimurium model; however, whether similar changes are present in humans remains to be explored. To address these questions, a subset of volunteers (5 TD and 3 who did not develop typhoid despite oral challenge -NoTD-) were evaluated for changes in circulating monocytes and DCs. Expression of CD38 and CD40 were upregulated in monocytes and DCs in TD volunteers during the disease days (TD-0h to TD-96h). Moreover, integrin α4β7, a gut homing molecule, was upregulated on monocytes but not DCs. CD21 upregulation was only identified in DCs. These changes were not observed among NoTD volunteers despite the same oral challenge. Moreover, monocytes and DCs from NoTD volunteers showed increased binding to S. Typhi one day after challenge. These monocytes showed phosphorylation of p38MAPK, NFkB and Erk1/2 upon stimulation with S. Typhi-LPS-QDot micelles. In contrast, monocytes from TD volunteers showed only a moderate increase in S. Typhi binding 48 h and 96 h post-TD, and only Erk1/2 phosphorylation. This is the first study to describe different activation and migration profiles, as well as differential signaling patterns, in monocytes and DCs which relate directly to the clinical outcome following oral challenge with wild type S. Typhi.
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Valbenazine for the treatment of tardive dyskinesia.
PubMed
Seeberger, Lauren C; Hauser, Robert A
2017-08-01
Tardive dyskinesia (TD) is a hyperkinetic movement disorder that may result from treatment with antipsychotics or other dopamine receptor blocking agents. Underlying pathophysiology is incompletely understood but since the 1970s dopamine depleting agents have been used to reduce involuntary movements. The search for safe, effective treatments for TD is ongoing. Valbenazine, a novel VMAT2 inhibitor, has recently been FDA approved for treatment of TD. Areas covered: An overview of TD, unmet medical needs and current treatment guidelines are presented. The background, chemistry and clinical development of valbenazine to treat TD is detailed. A competitive market is developing as the treatment gap is identified and potential therapies are discussed in context of a broader market overview. Expert opinion: Antipsychotic use is growing among adults and children in the U.S. Consequently, prevalence of TD is expected to rise. Cessation of antipsychotics is often not possible as the psychiatric condition may deteriorate. Increasing doses of an antipsychotic to suppress involuntary movements is not sustainable long term as underlying TD worsens and movements typically recur. There were no FDA approved treatments for TD. The approval of valbenazine to treat TD is a critical step in addressing this gap in neurologic care.
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ERP correlates of object recognition memory in Down syndrome: Do active and passive tasks measure the same thing?
PubMed
Van Hoogmoed, A H; Nadel, L; Spanò, G; Edgin, J O
2016-02-01
Event related potentials (ERPs) can help to determine the cognitive and neural processes underlying memory functions and are often used to study populations with severe memory impairment. In healthy adults, memory is typically assessed with active tasks, while in patient studies passive memory paradigms are generally used. In this study we examined whether active and passive continuous object recognition tasks measure the same underlying memory process in typically developing (TD) adults and in individuals with Down syndrome (DS), a population with known hippocampal impairment. We further explored how ERPs in these tasks relate to behavioral measures of memory. Data-driven analysis techniques revealed large differences in old-new effects in the active versus passive task in TD adults, but no difference between these tasks in DS. The group with DS required additional processing in the active task in comparison to the TD group in two ways. First, the old-new effect started 150 ms later. Second, more repetitions were required to show the old-new effect. In the group with DS, performance on a behavioral measure of object-location memory was related to ERP measures across both tasks. In total, our results suggest that active and passive ERP memory measures do not differ in DS and likely reflect the use of implicit memory, but not explicit processing, on both tasks. Our findings highlight the need for a greater understanding of the comparison between active and passive ERP paradigms before they are inferred to measure similar functions across populations (e.g., infants or intellectual disability). Copyright © 2016 Elsevier Ltd. All rights reserved.
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Influence of a National Cancer Institute transdisciplinary research and training initiative on trainees' transdisciplinary research competencies and scholarly productivity.
PubMed
Vogel, Amanda L; Feng, Annie; Oh, April; Hall, Kara L; Stipelman, Brooke A; Stokols, Daniel; Okamoto, Janet; Perna, Frank M; Moser, Richard; Nebeling, Linda
2012-12-01
Over the past several decades, there has been burgeoning interest and investment in large transdisciplinary (TD) team science initiatives that aim to address complex societal problems. Despite this trend, TD training opportunities in the health sciences remain limited, and evaluations of these opportunities are even more uncommon due to funding constraints. We had the unique opportunity to conduct an exploratory study to examine the potential outcomes and impacts of TD training in a National Cancer Institute-supported initiative for TD research and training-the Transdisciplinary Research on Energetics and Cancer I (TREC I) initiative. This study used a retrospective mixed-methods approach leveraging secondary analysis of existing data sources to learn about TREC trainees' experiences with TREC training, TD research competencies, changes in scholarly productivity, and the associations among these domains. Results indicated that, on average, TREC trainees were satisfied with their TREC mentoring experiences and believed that TREC training processes were effective, in general. Participation in TREC training was associated with TD research competencies, including TD research orientation, positive general attitude toward TD training, development of scientific skills for TD research, and intrapersonal/interpersonal competencies for collaboration. There was also a significant increase in trainees' scholarly productivity from before to after starting in TREC training, as indicated by average annual number of publications and presentations and average number of coauthors per publication. Perceived effectiveness of TREC training was positively correlated with change in average annual number of research presentations from before to after starting in TREC training (r = 0.65, p < 0.05, N = 12), as well as TD research orientation (r = 0.36, p < 0.05), general attitude toward TD training (0.39, p < 0.05), scientific skills for TD research (r = 0.45-0.48, p < 0.05), and perceived collaborative productivity at one's TREC center (r = 0.47, p < 0.01). Finally, a significant positive correlation was observed between multi-mentoring experiences and both TD research orientation (r = 0.58, p < 0.05) and perceived collaborative productivity at one's TREC center (r = 0.44, p < 0.05). This exploratory study had methodological constraints including the absence of a comparison group and cross-sectional rather than longitudinal data related to TD research competencies. Despite these limitations, the study provided an opportunity to use existing data sources to explore potential outcomes and impacts of TD training and inform development of future rigorous evaluations of TD training. Overall, findings suggest that TD training in the context of a TD research initiative can provide satisfying training opportunities that support the development of TD research competencies and promote scholarly productivity.