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1.
Brain Behav Immun ; 118: 510-520, 2024 May.
Article in English | MEDLINE | ID: mdl-38431237

ABSTRACT

Prenatal exposure to inflammation is related to the risk for cognitive impairment in offspring. However, mechanisms underlying the link between inflammatory cytokines at the maternal-fetal interface and human cognitive development are largely unknown. This study addressed this research gap by examining whether i) cytokines within the placenta are associated with different domains of neurocognitive development during infancy, and ii) if DHEA-S in cord blood mediates these associations. We also explored the role of early-life socioeconomic status (SES) in moderating the effect of fetal adrenal steroids on cognitive development in low- and middle-income country contexts. A cohort of 242 mother-infant dyads in Leyte, the Philippines participated in the study and all of them were followed from early pregnancy until 12-months. Concentrations of pro- and anti-inflammatory cytokines in the placenta, and DHEA-S in cord blood collected at delivery were evaluated. The multifactorial aspects of the infant's cognitive functioning were assessed based on the Bayley Scales of Infant Development, third edition (BSID-III). We used Structural Equation Modelling (SEM) with an orthogonal rotation to examine associated paths among latent variables of pro- and anti-inflammatory cytokines in the placenta, fetal neuroendocrine factors, and cognitive development. Pathway analyses showed that both pro- and anti-inflammatory cytokines in the placenta were indirectly related to cognitive (p < 0.05) and language developmental outcomes (p < 0.1) via DHEA-S in cord blood among the low SES group. Yet, we found no statistically significant indirect effect of pro- or anti-inflammatory cytokines on neurocognitive development among the high SES sub-sample. This study extends our understanding of how early-life socioeconomic conditions modify biological pathways underlying the relationship between prenatal factors and postpartum cognitive development.


Subject(s)
Cytokines , Placenta , Infant , Child , Humans , Pregnancy , Female , Placental Circulation , Philippines , Cognition , Dehydroepiandrosterone , Anti-Inflammatory Agents
2.
J Pediatr ; 269: 113977, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38401788

ABSTRACT

OBJECTIVE: To assess the impact and potential mechanistic pathways of prenatal alcohol exposure (PAE) on longitudinal growth and nutritional status in early childhood. STUDY DESIGN: A cohort of 296 mother-infant dyads (32% with PAE vs 68% unexposed) were recruited in Leyte, the Philippines, and followed from early gestation through 24 months of age. PAE was assessed using serum phosphatidylethanol (PEth) captured twice prenatally and in cord blood and supplemented with self-reported alcohol consumption. Linear mixed models were used to examine longitudinal effects of PAE on growth from birth through 2 years including key potential mediating factors (placental histopathology, and infant serum leptin and Insulin-like Growth Factor 1 [IGF-1]). RESULTS: After adjusting for potential confounders, we found that PAE was significantly associated with a delayed blunting of linear growth trajectories (height-for-age z-score, body length) and weight (weight-for-age z-score, body weight) that manifested between 4 and 6 months and continued through 12-24 months. PAE was also associated with a decreased rate of mid-upper-arm circumference growth from birth to 12 months, and a lower mean IGF-1 levels at birth and 6 months. CONCLUSION: This study demonstrates a delayed impact of PAE on growth that manifested around 6 months of age, underscoring the importance of routine clinical monitoring in early childhood. Furthermore, the findings supported prior animal model findings that suggest a mechanistic role for IGF-1 in PAE-induced growth delay.


Subject(s)
Insulin-Like Growth Factor I , Nutritional Status , Prenatal Exposure Delayed Effects , Humans , Insulin-Like Growth Factor I/metabolism , Insulin-Like Growth Factor I/analysis , Female , Philippines/epidemiology , Pregnancy , Infant , Male , Infant, Newborn , Longitudinal Studies , Child, Preschool , Alcohol Drinking/adverse effects , Child Development/drug effects , Adult , Fetal Blood/metabolism , Fetal Blood/chemistry , Glycerophospholipids/blood , Insulin-Like Peptides
3.
Int J Gynaecol Obstet ; 164(2): 750-757, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37589399

ABSTRACT

OBJECTIVE: Poor intrauterine growth has negative impacts for child growth and development and disproportionately affects children living in low-resource settings. In the present study, we investigated relationships between placental pathologies and indicators of poor intrauterine growth. METHODS: We enrolled a longitudinal cohort of 279 mother-infant pairs from Leyte, the Philippines. Placental measures included characteristics, pathological findings, and immunohistochemistry. At birth, intrauterine growth was assessed using anthropometric measures, weight-for-gestational age, and the clinical assessment of nutritional status score (CANSCORE) for determining fetal malnutrition. Multivariate linear regression and log-binomial regression models were applied, controlling for potential confounding factors. RESULTS: Maternal vascular malperfusion (MVM) was related to reduced birthweight (P < 0.0001), birth length (P = 0.002), head circumference (P = 0.001), and weight-to-length ratio (P = 0.016). MVM increased the risk for preterm delivery (P = 0.0005) and small for gestational age (SGA) (P = 0.016). Acute chorioamnionitis (P = 0.013) and MVM (P = 0.021) both led to an increased risk for fetal malnutrition defined by CANSORE<25. Villous tissue activated caspase-3 was associated with lower birth length (P = 0.0006), higher weight-to-length ratio (P = 0.004), reduced risks for SGA (P = 0.011) and low weight-to-length ratio for gestational age (P = 0.004). CONCLUSION: The present study applied comprehensive measures for intrauterine growth and demonstrates that low placental weight and placental pathology, chiefly MVM, contribute to poor intrauterine growth. A better understanding of the mechanistic role of specific placental pathologies on adverse newborn outcomes will provide opportunities for reducing incidence of poor intrauterine growth and associated long-term morbidities.


Subject(s)
Fetal Nutrition Disorders , Placenta , Infant, Newborn , Child , Pregnancy , Female , Humans , Placenta/blood supply , Pregnancy Outcome/epidemiology , Mothers , Fetal Nutrition Disorders/pathology , Philippines/epidemiology , Retrospective Studies , Fetal Growth Retardation/epidemiology , Fetal Growth Retardation/etiology
4.
Res Child Adolesc Psychopathol ; 52(3): 369-383, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37922002

ABSTRACT

The Proposed Specifiers for Conduct Disorder (PSCD; Salekin in Pers Disord: Theory Res Treat 7:180-191, 2016) scale was designed to assess interrelated psychopathic trait domains in conjunction with symptoms of Conduct Disorder (CD) in children and adolescents (i.e., grandiose-manipulative, callous-unemotional, daring-impulsive). Variable-centered studies have provided support for a four-factor PSCD structure (Salekin et al. in Psychol Assess 34(10):985-992, 2022) in line with other adolescent and adult studies. The current person-centered study used latent profile analysis of the PSCD domains to examine whether theoretically meaningful and empirically robust PSCD subtypes emerged from a diverse sample (70.9% White, 20.1% Black, 3.6% Hispanic, and 5.4% other) of adolescents (modal age = 17) in a military style residential facility (N = 409; Males = 80.6%). As hypothesized, a four-class solution was best, consistent with adult psychopathy subtyping research (Hare et al. in Handbook of Psychopathy 39-79, 2018; Roy et al. in Pers Disord: Theory Res Treat, in press). The PSCD subtype profiles were uniform across sex and race/ethnicity. Adolescents evincing a psychopathic trait propensity profile (elevated on all four PSCD domains) displayed the greatest number of arrests and higher overall externalizing psychopathology, compared to the other three latent classes, as well as higher internalizing psychopathology compared to adolescents with general delinquency. The PSCD provides a sound measure of psychopathic trait propensities in youth and our results offer investigators and clinicians a means for understanding person-centered psychopathic traits versus antisocial profiles among at-risk adolescents. Taken together, the current results may offer a viable approach for examining specific treatment targets based on PSCD subtype profiles.


Subject(s)
Conduct Disorder , Male , Child , Adult , Humans , Adolescent , Conduct Disorder/diagnosis , Conduct Disorder/psychology , Antisocial Personality Disorder/diagnosis , Antisocial Personality Disorder/psychology , Impulsive Behavior , Psychopathology
5.
Water Res ; 247: 120815, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-37931359

ABSTRACT

Riparian tree canopies are key components of river systems, and influence the provision of many essential ecosystem services. Their management provides the potential for substantial control of the downstream persistence of pollutants. The recent advent of new advances in mass spectrometry to detect a large suite of emerging contaminants, high-frequency observations of water quality and gas exchange (e.g., aquatic eddy covariance), and improved spatial resolution in remote sensing (e.g., hyperspectral measurements and high-resolution imagery), presents new opportunities to understand and more comprehensively quantify the role of riparian canopies as Nature-based Solutions. The paper outlines how we may now couple these advances in observational technologies with developments in water quality modelling to integrate simulation of eutrophication impacts with organic matter dynamics and fate of synthetic toxic compounds. In particular regarding solar radiation drivers, this enables us to scale-up new knowledge of canopy-mediated photodegradation processes at a basin level, and integrate it with ongoing improvements in understanding of thermal control, eutrophication, and ecosystem metabolism.


Subject(s)
Ecosystem , Environmental Monitoring , Environmental Monitoring/methods , Estuaries , Cities , Water Quality
6.
Antioxidants (Basel) ; 12(9)2023 Sep 01.
Article in English | MEDLINE | ID: mdl-37760010

ABSTRACT

Peroxiredoxins play central roles in the detoxification of reactive oxygen species and have been modelled across multiple organisms using a variety of kinetic methods. However, the peroxiredoxin dimer-to-decamer transition has been underappreciated in these studies despite the 100-fold difference in activity between these forms. This is due to the lack of available kinetics and a theoretical framework for modelling this process. Using published isothermal titration calorimetry data, we obtained association and dissociation rate constants of 0.050 µM-4·s-1 and 0.055 s-1, respectively, for the dimer-decamer transition of human PRDX1. We developed an approach that greatly reduces the number of reactions and species needed to model the peroxiredoxin decamer oxidation cycle. Using these data, we simulated horse radish peroxidase competition and NADPH-oxidation linked assays and found that the dimer-decamer transition had an inhibition-like effect on peroxidase activity. Further, we incorporated this dimer-decamer topology and kinetics into a published and validated in vivo model of PRDX2 in the erythrocyte and found that it almost perfectly reconciled experimental and simulated responses of PRDX2 oxidation state to hydrogen peroxide insult. By accounting for the dimer-decamer transition of peroxiredoxins, we were able to resolve several discrepancies between experimental data and available kinetic models.

7.
Redox Biol ; 65: 102802, 2023 09.
Article in English | MEDLINE | ID: mdl-37423162

ABSTRACT

Infectious diseases are a significant health burden for developing countries, particularly with the rise of multidrug resistance. There is an urgent need to elucidate the factors underlying the persistence of pathogens such as Mycobacterium tuberculosis, Plasmodium falciparum and Trypanosoma brucei. In contrast to host cells, these pathogens traverse multiple and varied redox environments during their infectious cycles, including exposure to high levels of host-derived reactive oxygen species. Pathogen antioxidant defenses such as the peroxiredoxin and thioredoxin systems play critical roles in the redox stress tolerance of these cells. However, many of the kinetic rate constants obtained for the pathogen peroxiredoxins are broadly similar to their mammalian homologs and therefore, their contributions to the redox tolerances within these cells are enigmatic. Using graph theoretical analysis, we show that compared to a canonical Escherichia coli redoxin network, pathogen redoxin networks contain unique network connections (motifs) between their thioredoxins and peroxiredoxins. Analysis of these motifs reveals that they increase the hydroperoxide reduction capacity of these networks and, in response to an oxidative insult, can distribute fluxes into specific thioredoxin-dependent pathways. Our results emphasize that the high oxidative stress tolerance of these pathogens depends on both the kinetic parameters for hydroperoxide reduction and the connectivity within their thioredoxin/peroxiredoxin systems.


Subject(s)
Antioxidants , Sulfhydryl Compounds , Animals , Antioxidants/metabolism , Sulfhydryl Compounds/metabolism , Hydrogen Peroxide/metabolism , Oxidation-Reduction , Peroxiredoxins/metabolism , Oxidative Stress , Thioredoxins/metabolism , Mammals/metabolism
8.
J Pers Assess ; 105(4): 508-519, 2023.
Article in English | MEDLINE | ID: mdl-35678638

ABSTRACT

Adolescent personality assessment measures can aid in the identification of traits that are associated with various types of maladjustment. Externalizing personality pathology traits (e.g., antisocial, borderline, and narcissistic personality disorder features) are particularly relevant for many problematic outcomes, yet measures that assess these traits have not been validated extensively in diverse samples. The present study aimed to examine the properties of measures of externalizing personality pathology traits in a sample of White (n = 184) and Black (n = 99) adolescents participating in a residential program for at-risk youth. The fit of the proposed structure for these measures was tested in the sample as a whole and in each racial group separately. Associations between these measures and the count of disciplinary infractions received while in the program were also tested. Measures were found to have less than optimal fit in this sample, especially among Black adolescents. Suggestions for future research and clinical use of these measures are discussed.


Subject(s)
Black or African American , Personality Disorders , White , Adolescent , Humans , Antisocial Personality Disorder , Personality , Personality Disorders/diagnosis
9.
J Child Fam Stud ; 32(1): 110-121, 2023.
Article in English | MEDLINE | ID: mdl-36277326

ABSTRACT

This study investigated the relations of adolescent COVID-19 knowledge, quarantine/lockdown experiences, and social media use with indices of their psychosocial adjustment. The sample consisted of 215 adolescents from throughout the United States, with adolescents ranging from ages 14 to 17. Better knowledge of COVID-19 was related to lower loneliness, stress, anxiety, depression, and fear of missing out (FoMO). Higher parent-reported restrictions during quarantine were associated with these difficulties as well. Further, the lowest anxiety was reported for adolescents with good COVID-19 knowledge who also checked social media relatively less frequently. The findings point to the importance of accurate information about COVID-19 for adolescents and the impact of quarantine/lockdown experiences on their perceived emotional and social adjustment.

10.
J Am Coll Health ; : 1-10, 2022 Nov 17.
Article in English | MEDLINE | ID: mdl-36395063

ABSTRACT

Objective: The present study investigated the association between social media engagement and factors related to well-being (e.g., depression, anxiety, sleep, loneliness, self-esteem). Participants: A sample of 1120 college student-athletes (338 males, 777 females, 5 identified as non-binary) from nine universities participated in this study. Method: Data were collected through self-report measures and screen shots of participants' screen time in the previous week. Results: Overall screen time taken from devices was not associated with self-reported well-being, whereas use of social media during daily activities was related to worse well-being across domains (e.g., lower self-esteem, higher fear of missing out, stress, anxiety, depression). In addition, student-athlete perceptions that social media interfere with their lives were related to worse well-being. Conclusions: The implications of these findings, including the possibility of using protective behavioral strategies (PBS) to reduce negative impacts of social media in college students, are discussed.

11.
Psychol Assess ; 34(10): 985-992, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35925738

ABSTRACT

The Proposed Specifiers for Conduct Disorder scale (PSCD; Salekin & Hare, 2016) is a new scale for the assessment of psychopathic characteristic domains in children and adolescents. The four domains are Grandiose-manipulative (GM), Callous-unemotional (CU), Daring-impulsive (DI), and Conduct Disorder (CD). We examined the properties of the self-report version of the PSCD in a large sample of adolescents (n = 409; age = 16-19; 80.6% male) in a military-style residential facility. Factor analytic results supported a four-factor model consistent with other PSCD research (e.g., López-Romero et al., 2019; Luo et al., 2021). Structural equation model (SEM) indicated a superordinate PSCD factor accounted for significant variance in self-reported delinquency history. The PSCD had good internal consistency and strong convergent and discriminant validity with measures of externalizing and internalizing disorders. The present study provides encouraging data that the PSCD may provide a sound measure of psychopathic propensities in youth. However, additional data are needed to test the stability of the PSCD. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Subject(s)
Conduct Disorder , Adolescent , Adult , Antisocial Personality Disorder/diagnosis , Antisocial Personality Disorder/psychology , Child , Conduct Disorder/diagnosis , Conduct Disorder/psychology , Female , Humans , Male , Psychometrics , Residential Facilities , Schools , Young Adult
12.
Psychol Rep ; : 332941221100459, 2022 Jun 14.
Article in English | MEDLINE | ID: mdl-35699603

ABSTRACT

Adolescents often engage in behaviors such as substance use and risky sexual activity that can lead to negative health and psychological consequences for themselves and others. Accurate measurement of these behaviors in surveys is challenging given that the behaviors are often viewed as undesirable and/or are illegal, so it is important to test the psychometric properties of instruments used to assess adolescent risk behaviors. The current study aimed to assess the test-retest reliability of a widely used measure of youth risk-taking behavior, the Youth Risk Behavior Survey (YRBS). A sample of 156 at-risk adolescents aged 16-18 years (81% male; 61% White) completed the YRBS retrospectively across intervals ranging from 3 to 12 days during their stay in a residential program at which they were under close supervision and had limited ability to engage in new risk behaviors. Participants were asked to complete the YRBS based on their "typical" (pre-program) behavior at both administrations, which were 10-14 weeks into their stay. The reliability of responses was assessed using kappa and weighted kappa analyses. Findings indicate moderate to substantial reliability for nearly all items, suggesting that at-risk youth reliably reported their engagement in health risk behaviors across multiple administrations and supporting the psychometric strength of the YRBS measure for use with this population.

13.
J Infect Dis ; 225(10): 1856-1860, 2022 05 16.
Article in English | MEDLINE | ID: mdl-35091745

ABSTRACT

Hookworm infection is associated with poor nutritional outcomes, anemia, and impaired cognitive performance. We examined the association between maternal hookworm infection and birth outcomes in a cohort of women in Leyte, Philippines. We observed poor intrauterine growth characteristics associated with maternal hookworm only among male offspring, with lower birth weight, head circumference, and placental surface area. Male neonates also had higher insulin-like growth factor 2 (IGF-2) and lower adiponectin in cord blood. These data intriguingly suggest nutritional impacts of maternal hookworm infection during pregnancy may be divergent based on sex of the offspring.


Subject(s)
Hookworm Infections , Placenta , Birth Weight , Female , Fetal Blood , Hookworm Infections/complications , Humans , Infant, Newborn , Insulin-Like Growth Factor I/metabolism , Male , Placenta/metabolism , Pregnancy
14.
Arch Suicide Res ; 26(1): 208-225, 2022.
Article in English | MEDLINE | ID: mdl-32755362

ABSTRACT

OBJECTIVE: This study examines psychopathology and personality correlates of non-suicidal self-injury (NSSI) and suicide-related behavior (SRB) in an understudied sample of adolescents who have exhibited behaviors (e.g., delinquent acts, premature high school termination) that place them at-risk for poor psychosocial outcomes. METHOD: Participants included a predominantly White male sample of 182 adolescents (Mage = 16.82 years). In addition to information about NSSI and SRB histories, participants self-reported various facets of personality and psychopathology on the Personality Assessment Inventory-Adolescent (PAI-A). RESULTS: Logistic regression analyses indicated that the Suicidal Ideation (SUI) scale on the PAI-A was the strongest predictor of both NSSI and SRB history, as it outperformed other relevant PAI-A scales and the Suicide Potential Index (SPI), an aggregate scale that was designed to assess for suicide risk using the PAI for adults. Receiver operating characteristic (ROC) curve analyses were also conducted to determine optimal cutoff scores for significant PAI-A predictors. CONCLUSIONS: Findings from the current study can be used to identify NSSI and SRB risk and target these life-threatening behaviors when working with at-risk adolescents.HighlightsPAI-A SUI outperformed other PAI-A variables in predicting NSSI and SRB risk.PAI SPI did not perform as well in adolescents compared to adult samples.Cutoff scores in the current sample were well below those in the PAI-A manual.


Subject(s)
Self-Injurious Behavior , Suicide Prevention , Adolescent , Adult , Humans , Male , Personality Assessment , Risk Factors , Self-Injurious Behavior/diagnosis , Self-Injurious Behavior/psychology , Suicidal Ideation , Suicide, Attempted/prevention & control , Suicide, Attempted/psychology
15.
Assessment ; 29(8): 1931-1941, 2022 12.
Article in English | MEDLINE | ID: mdl-34388939

ABSTRACT

The Personality Assessment Inventory (PAI) Treatment Process Index (TPI) is a measure of treatment amenability based on an index of factors related to poor treatment outcomes (e.g., hostility, lack of social support, and poor impulse control). In this study, the formula used to calculate the TPI for the adult PAI was applied to PAI-Adolescent (PAI-As) protoocols completed by 372 adolescents (mean age: 16.8 years; 80% male) during a 22-week residential program for at-risk youth. The number of disciplinary infractions received during the program was used as an indicator of the participants' response to the program. Average PAI-A scale scores and TPI scores were higher than those previously reported for community samples, but lower than those found in clinical samples. TPI scores were positively associated with disciplinary infractions, particularly nonaggressive infractions, when controlling for demographic factors and other clinically relevant variables. Results suggest that the the TPI has relevance for adolescents completing the PAI-A.


Subject(s)
Antisocial Personality Disorder , Personality Assessment , Adult , Adolescent , Male , Humans , Female , Personality Disorders
16.
N Engl J Med ; 385(9): 803-814, 2021 08 26.
Article in English | MEDLINE | ID: mdl-34379916

ABSTRACT

BACKGROUND: Additional interventions are needed to reduce the morbidity and mortality caused by malaria. METHODS: We conducted a two-part, phase 1 clinical trial to assess the safety and pharmacokinetics of CIS43LS, an antimalarial monoclonal antibody with an extended half-life, and its efficacy against infection with Plasmodium falciparum. Part A of the trial assessed the safety, initial side-effect profile, and pharmacokinetics of CIS43LS in healthy adults who had never had malaria. Participants received CIS43LS subcutaneously or intravenously at one of three escalating dose levels. A subgroup of participants from Part A continued to Part B, and some received a second CIS43LS infusion. Additional participants were enrolled in Part B and received CIS43LS intravenously. To assess the protective efficacy of CIS43LS, some participants underwent controlled human malaria infection in which they were exposed to mosquitoes carrying P. falciparum sporozoites 4 to 36 weeks after administration of CIS43LS. RESULTS: A total of 25 participants received CIS43LS at a dose of 5 mg per kilogram of body weight, 20 mg per kilogram, or 40 mg per kilogram, and 4 of the 25 participants received a second dose (20 mg per kilogram regardless of initial dose). No safety concerns were identified. We observed dose-dependent increases in CIS43LS serum concentrations, with a half-life of 56 days. None of the 9 participants who received CIS43LS, as compared with 5 of 6 control participants who did not receive CIS43LS, had parasitemia according to polymerase-chain-reaction testing through 21 days after controlled human malaria infection. Two participants who received 40 mg per kilogram of CIS43LS and underwent controlled human malaria infection approximately 36 weeks later had no parasitemia, with serum concentrations of CIS43LS of 46 and 57 µg per milliliter at the time of controlled human malaria infection. CONCLUSIONS: Among adults who had never had malaria infection or vaccination, administration of the long-acting monoclonal antibody CIS43LS prevented malaria after controlled infection. (Funded by the National Institute of Allergy and Infectious Diseases; VRC 612 ClinicalTrials.gov number, NCT04206332.).


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal/therapeutic use , Antimalarials/therapeutic use , Malaria, Falciparum/prevention & control , Adult , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal/pharmacokinetics , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/pharmacokinetics , Antibodies, Protozoan/blood , Antimalarials/administration & dosage , Antimalarials/adverse effects , Antimalarials/pharmacokinetics , Dose-Response Relationship, Drug , Healthy Volunteers , Humans , Infusions, Intravenous/adverse effects , Injections, Subcutaneous/adverse effects , Middle Aged , Plasmodium falciparum/immunology , Plasmodium falciparum/isolation & purification
17.
PLoS Negl Trop Dis ; 15(4): e0009328, 2021 04.
Article in English | MEDLINE | ID: mdl-33861768

ABSTRACT

In areas endemic to schistosomiasis, fetal exposure to schistosome antigens prime the offspring before potential natural infection. Praziquantel (PZQ) treatment for Schistosoma japonicum infection in pregnant women has been demonstrated to be safe and effective. Our objectives were to evaluate whether maternal PZQ treatment modifies the process of in utero sensitization to schistosome antigens potentially impacting later risk of infection, as well as immune response to S. japonicum. We enrolled 295 children at age six, born to mothers with S. japonicum infection who participated in a randomized control trial of PZQ versus placebo given at 12-16 weeks gestation in Leyte, The Philippines. At enrollment, we assessed and treated current S. japonicum infection and measured serum cytokines. During a follow-up visit four weeks later, we assessed peripheral blood mononuclear cell (PBMC) cytokine production in response to soluble worm antigen preparation (SWAP) or soluble egg antigen (SEA). Associations between maternal treatment group and the child's S. japonicum infection status and immunologic responses were determined using multivariate linear regression analysis. PZQ treatment during pregnancy did not impact the prevalence (P = 0.12) or intensity (P = 0.59) of natural S. japonicum infection among children at age six. Among children with infection at enrollment (12.5%) there were no significant serum cytokine concentration differences between maternal treatment groups. Among children with infection at enrollment, IL-1 production by PBMCs stimulated with SEA was higher (P = 0.03) in the maternal PZQ group compared to placebo. Among children without infection, PBMCs stimulated with SEA produced greater IL-12 (P = 0.03) and with SWAP produced less IL-4 (P = 0.01) in the maternal PZQ group compared to placebo. Several cytokines produced by PBMCs in response to SWAP and SEA were significantly higher in children with S. japonicum infection irrespective of maternal treatment: IL-4, IL-5, IL-10, and IL-13. We report that maternal PZQ treatment for S. japonicum shifted the PBMC immune response to a more inflammatory signature but had no impact on their offspring's likelihood of infection or serum cytokines at age six, further supporting the safe use of PZQ in pregnant women. Trial Registration: ClinicalTrials.gov NCT00486863.


Subject(s)
Cytokines/metabolism , Immunity, Maternally-Acquired , Praziquantel/administration & dosage , Pregnancy Complications, Parasitic/drug therapy , Schistosomiasis japonica/drug therapy , Animals , Antiprotozoal Agents/administration & dosage , Child , Cohort Studies , Cytokines/blood , Double-Blind Method , Female , Humans , Leukocytes, Mononuclear/immunology , Linear Models , Male , Multivariate Analysis , Philippines , Pregnancy , Pregnancy Complications, Parasitic/immunology , Schistosoma japonicum/drug effects , Schistosomiasis japonica/immunology , Treatment Outcome
18.
PLoS Comput Biol ; 17(3): e1008778, 2021 03.
Article in English | MEDLINE | ID: mdl-33647016

ABSTRACT

Human pluripotent stem cells hold significant promise for regenerative medicine. However, long differentiation protocols and immature characteristics of stem cell-derived cell types remain challenges to the development of many therapeutic applications. In contrast to the slow differentiation of human stem cells in vitro that mirrors a nine-month gestation period, mouse stem cells develop according to a much faster three-week gestation timeline. Here, we tested if co-differentiation with mouse pluripotent stem cells could accelerate the differentiation speed of human embryonic stem cells. Following a six-week RNA-sequencing time course of neural differentiation, we identified 929 human genes that were upregulated earlier and 535 genes that exhibited earlier peaked expression profiles in chimeric cell cultures than in human cell cultures alone. Genes with accelerated upregulation were significantly enriched in Gene Ontology terms associated with neurogenesis, neuron differentiation and maturation, and synapse signaling. Moreover, chimeric mixed samples correlated with in utero human embryonic samples earlier than human cells alone, and acceleration was dose-dependent on human-mouse co-culture ratios. The altered gene expression patterns and developmental rates described in this report have implications for accelerating human stem cell differentiation and the use of interspecies chimeric embryos in developing human organs for transplantation.


Subject(s)
Chimerism , Human Embryonic Stem Cells , Neurogenesis , Pluripotent Stem Cells , Animals , Cells, Cultured , Computational Biology , Human Embryonic Stem Cells/cytology , Human Embryonic Stem Cells/physiology , Humans , Mice , Neurogenesis/genetics , Neurogenesis/physiology , Pluripotent Stem Cells/cytology , Pluripotent Stem Cells/physiology , Species Specificity , Transcriptome/genetics
19.
J Pers Assess ; 103(1): 48-56, 2021.
Article in English | MEDLINE | ID: mdl-31899957

ABSTRACT

This study examines the validity of the Personality Assessment Inventory-Adolescent (PAI-A; Morey) in assessing callous-unemotional (CU) traits within two independent samples of at-risk adolescents from a residential intervention program. The study tests the extent to which CU traits are represented within PAI-A scales with respect to empirically- or theoretically-related indicators, such as antisociality, aggression, low warmth, low social connectedness, and subdued internalizing psychopathology. The PAI-A substantive scales statistically accounted for an average of 55.0% of the variance in total scores on the Inventory of Callous-Unemotional Traits (ICU; Frick) across samples. Broadly, PAI-A substantive scales evinced theoretically-consistent relations with CU traits. Consistent with expectations, CU traits were broadly related to PAI-A-assessed constructs of antisocial features, aggression, low warmth and social disconnection, but not to subdued internalizing symptoms. Moreover, some of the PAI-A clinical, treatment consideration, and interpersonal scales or subscales demonstrated differential relations across the traits. Implications for assessment of CU traits using the PAI framework are discussed. Overall, this research adds to the literature on CU traits in broadband personality assessment and provides a foundation for future research on CU traits using the PAI-A.


Subject(s)
Aggression/psychology , Antisocial Personality Disorder/psychology , Conduct Disorder/psychology , Defense Mechanisms , Juvenile Delinquency/psychology , Adolescent , Female , Humans , Male , Personality Assessment , Young Adult
20.
Assessment ; 28(1): 116-127, 2021 01.
Article in English | MEDLINE | ID: mdl-31522513

ABSTRACT

The purpose of this study was to evaluate the factor structure and measurement invariance of the Barratt Impulsiveness Scale-Brief version (BIS-Brief) in an archival sample of 315 adolescents (81% male; 63.5% Caucasian; Mage = 16.7 years) participating in a military-style residential program for at-risk youths. Additionally, correlations between BIS scores and external measures of impulsivity-related behaviors were examined. Results showed support for a previously described two-dimensional structure for the BIS-Brief, which was invariant across racial groups. Additionally, the BIS-Brief performed similarly to the total BIS-11 score in relation to external measures of impulsivity-related behaviors. However, the two dimensions exhibited some significant differences in their associations with other measures. This study supports the utility of the BIS-Brief as a brief measure of impulsivity and suggests that the dimensions of the BIS-Brief may be useful in distinguishing how different aspects of impulsivity relate to problem behaviors such as binge drinking and self-injury.


Subject(s)
Impulsive Behavior , White People , Adolescent , Female , Humans , Male , Psychometrics
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