Predictive Validity of the Whole Child Assessment in a Generally Healthy Pediatric Cohort.

BACKGROUND: Adverse childhood experience (ACE) exposure is associated with increased risk of poor health outcomes. Several tools to identify ACEs during pediatric practice exist, but few include all 10 ACEs from the original ACE study and none have established predictive validity. OBJECTIVES: Assess predictive validity of the ACE score reported during routine pediatric practice using the Whole Child Assessment (WCA). METHODS: This retrospective cohort study included children ages 3 to 8 years presenting for well-child care at a low-income resident clinic between May 25, 2016 and March 31, 2018, and ages 5 to 8 years presenting for well-child care at a private insurance clinic between November 1, 2017 and March 31, 2018. Patients with chronic health problems were excluded to prevent confounding by preexisting health problems. The charts of children with 0 to 1 ACEs (lower risk) and 2+ ACEs (higher risk) at baseline were reviewed to collect data on health and psychosocial outcomes at follow-up from diagnoses documented in the medical record and parent-reported outcomes on the WCA. Logistic regression models adjusted for age, gender, and clinic were used to analyze differences in outcomes. We hypothesized that children in the higher risk group at baseline would have more health and psychosocial problems at follow-up. RESULTS: The initial cohort (n = 907) had 669 children with 0 to 1 ACEs and 238 children with 2+ ACEs. At follow-up (mean 718 days, range 329-1155 days), children in the higher risk group had statistically significantly higher rates of ADHD/ADD, school failure/learning problem, and other behavioral/mental problems. Parents of these children also reported on the WCA higher rates of children being nervous or afraid, feeling sad or unhappy, having trouble paying attention or staying still, getting angry or into fights, bullying, poor sleep, and healthcare utilization. There were no statistically significant differences in various physical health concerns measured. CONCLUSION: This study supports the predictive validity of the WCA to identify subpopulations at risk of developing poor mental health and social-emotional outcomes. While more research is needed to facilitate translation into pediatric practice, these results highlight the strong influence of ACEs on mental health outcomes.

Enhancing component-specific trust with consumer automated systems through humanness design.

Consumer automation is a suitable venue for studying the efficacy of untested humanness design methods for promoting specific trust in multi-component systems. Subjective (trust, self-confidence) and behavioural (use, manual override) measures were recorded as 82 participants interacted with a four-component automation-bearing system in a simulated smart home task for two experimental blocks. During the first block all components were perfectly reliable (100%). During the second block, one component became unreliable (60%). Participants interacted with a system containing either a single or four simulated voice assistants. In the single-assistant condition, the unreliable component resulted in trust changes for every component. In the four-assistant condition, trust decreased for only the unreliable component. Across agent-number conditions, use decreased between blocks for only the unreliable component. Self-confidence and overrides exhibited ceiling and floor effects, respectively. Our findings provide the first evidence of effectively using humanness design to enhance component-specific trust in consumer systems.Practitioner summary: Participants interacted with simulated smart-home multi-component systems that contained one or four voiced assistants. In the single-voice condition, one component's decreasing reliability coincided with trust changes for all components. In the four-voice condition, trust decreased for only the decreasingly reliable component. The number of voices did not influence use strategies.Abbreviations: ACC: adaptive cruise control; CST: component-specific trust; SWT: system-wide trust; UAV: unmanned aerial vehicle; CPRS: complacency potential rating scale; MANOVA: multivariate analysis of variance.

Use of the Whole Child Assessment to identify children at risk of poor outcomes.

BACKGROUND: Screening for Adverse Childhood Experiences (ACEs) in pediatric patients has the potential to prevent poor health outcomes associated with ACEs. Only a limited number of tools screen for all ten ACEs in all pediatric age groups, and none of these have demonstrated robust validity to date. OBJECTIVE: In order to evaluate the validity of the Whole Child Assessment, we examined associations between poor outcomes in pediatric patients and responses to questions about exposure to and risk of ACEs. METHODS: This cross-sectional study used medical record data from 499 children ages 5-11 years old who received care at one of two university-affiliated clinics in California. All Child-ACE measures were included on the Whole Child Assessment, which caregivers completed when they brought their child to a well-child visit. Medical charts were reviewed for current diagnoses and problems, current or past history of any developmental delay, and health care utilization. RESULTS: Compared to lower risk patients (0-1 reported ACE exposure), patients with 2 or more reported exposures were statistically significantly more likely to experience sadness, anger, sleep problems, bullying, school problems, and enuresis. The directionality of effects and the number of statistically significant associations improved when adding questions about risk of ACEs to the total Child-ACE score. CONCLUSION: We found strong relationships between Child-ACEs reported on the Whole Child Assessment and odds of poor child health and psychosocial outcomes in pediatric patients age 5-11 years old, which supports the validity of using the Whole Child Assessment at well-child visits.

Catching more than pocket monsters: Pokémon Go's social and psychological effects on players.

The augmented reality mobile game Pokémon Go has reached unprecedented popularity since its release in 2016. The game has received intense media attention, but scientific inquiry into its popularity and the effects of play are in the early stages. Previous work has used secondary data or simple correlational analysis to draw early conclusions. A seven-day diary study was conducted to investigate potential health, psychological, and social outcomes of daily gameplay. Daily time spent playing Pokémon Go was related to higher scores of life satisfaction, vitality, and greater social interactions and conversation with both friends and strangers, but not with increased daily exercise. Increased total gameplay across the week was associated with increased interaction and conversations along with more exercise. Future directions for this unique type of game along with the need for theoretical development for unique style of games are discussed.

Magnitude and Functionality of the NS1-Specific Antibody Response Elicited by a Live-Attenuated Tetravalent Dengue Vaccine Candidate.

BACKGROUND: Dengue virus (DENV) can cause life-threatening disease characterized by endothelial dysfunction and vascular leakage. DENV nonstructural protein 1 (NS1) induces human endothelial hyperpermeability and vascular leak in mice, and NS1 vaccination confers antibody-mediated protective immunity. We evaluated the magnitude, cross-reactivity, and functionality of NS1-specific IgG antibody responses in sera from a phase 2 clinical trial of Takeda's live-attenuated tetravalent dengue vaccine candidate (TAK-003). METHODS: We developed an enzyme-linked immunosorbent assay to measure anti-DENV NS1 IgG in sera from DENV-naive or preimmune subjects pre- and postvaccination with TAK-003 and evaluated the functionality of this response using in vitro models of endothelial permeability. RESULTS: TAK-003 significantly increased DENV-2 NS1-specific IgG in naive individuals, which cross-reacted with DENV-1, -3, and -4 NS1 to varying extents. NS1-induced endothelial hyperpermeability was unaffected by prevaccination serum from naive subjects but was variably inhibited by serum from preimmune subjects. After TAK-003 vaccination, all samples from naive and preimmune vaccinees completely abrogated DENV-2 NS1-induced hyperpermeability and cross-inhibited hyperpermeability induced by DENV-1, -3, and -4 NS1. Inhibition of NS1-induced hyperpermeability correlated with NS1-specific IgG concentrations. Postvaccination sera also prevented NS1-induced degradation of endothelial glycocalyx components. CONCLUSION: We provide evidence for functional NS1-specific IgG responses elicited by a candidate dengue vaccine. CLINICAL TRIALS REGISTRATION: NCT01511250.

In Depth Breadth Analyses of Human Blockade Responses to Norovirus and Response to Vaccination.

To evaluate and understand the efficacy of vaccine candidates, supportive immunological measures are needed. Critical attributes for a norovirus vaccine are the strength and breadth of antibody responses against the many different genotypes. In the absence of suitable neutralization assays to test samples from vaccine clinical trials, blockade assays offer a method that can measure functional antibodies specific for many of the different norovirus strains. This paper describes development and optimization of blockade assays for an extended panel of 20 different norovirus strains that can provide robust and reliable data needed for vaccine assessment. The blockade assays were used to test a panel of human clinical samples taken before and after vaccination with the Takeda TAK-214 norovirus vaccine. Great variability was evident in the repertoire of blocking antibody responses prevaccination and postvaccination among individuals. Following vaccination with TAK-214, blocking antibody levels were enhanced across a wide spectrum of different genotypes. The results indicate that adults may have multiple exposures to norovirus and that the magnitude and breadth of the complex preexisting antibody response can be boosted and expanded by vaccination.

Interoceptive accuracy moderates the response to a glucose load: a test of the predictive coding framework.

Recently, interoception and homeostasis have been described in terms of predictive coding and active inference. Afferent signals update prior predictions about the state of the body, and stimulate the autonomic mediation of homeostasis. Performance on tests of interoceptive accuracy (IAc) may indicate an individual's ability to assign precision to interoceptive signals, thus determining the relative influence of ascending signals and the descending prior predictions. Accordingly, individuals with high IAc should be better able to regulate during the postprandial period. One hundred females were allocated to consume glucose, an artificially sweetened drink, water or no drink. Before, and 30 min after a drink, IAc, heart rate (HR) and blood glucose (BG) were measured, and participants rated their hunger, thirst and mood. A higher IAc was related to lower BG levels, a decline in anxiety and a higher HR, after consuming glucose. A higher IAc also resulted in a larger decline in hunger if they consumed either glucose or sucralose. These data support the role of active inference in interoception and homeostasis, and suggest that the ability to attend to interoceptive signals may be critical to the maintenance of physical and emotional health.

Observation study showed that the continuity of skin-to-skin contact with low-birthweight infants in Uganda was suboptimal.

AIM: Kangaroo mother care (KMC) is a safe and effective method of reducing neonatal mortality in resource-limited settings, but there has been a lack of data on the duration of skin-to-skin contact (SSC) in busy, low-resource newborn units. Previous studies of intermittent KMC suggest the duration of SSC ranged from 10 minutes to 17 hours per day. METHODS: This was an observational study of newborn infants born weighing less than 2000 g, which collected quantitative data on SSC over the first week after birth. The study took place in July 2016 in the newborn unit of a low-resource facility in Uganda. RESULTS: The mean daily duration of SSC over the first week after birth was three hours. This differed significantly from the World Health Organization recommendation of at least 20 hours of SSC per day. SSC was provided by mothers most of the time (73.5%), but other family members also took part, especially on the day of birth. CONCLUSION: Our study found a disappointingly low daily duration of SSC in this Ugandan newborn unit. However, advocacy and community education of SSC may help to decrease the stigma of KMC, improve overall acceptance and reduce the age at SSC initiation.

Is the link between depressed mood and heart rate variability explained by disinhibited eating and diet?

Consistently it has been reported that a depressed mood and low heart rate variability (HRV) are linked. However, studies have not considered that the association might be explained by dietary behaviour. The resting inter-beat interval data of 266 adults (Study 1: 156 (51M), Study 2: 112 (38M)) were recorded for six minutes and quantified using linear (HF power: 0.15-0.4Hz) and nonlinear indices (Sample entropy). Participants also completed the Profile of Mood States and the Three Factor Eating questionnaires. The Alternative Healthy Eating Index was used to quantify diet quality. In study 1 mood was associated with HRV; an effect partially mediated by diet. Study 2 replicated the finding: disinhibited eating (the tendency to lose control over one's eating) and diet sequentially mediated the association between mood and HRV. Diet plays a role in the link between mood and HRV and studies should consider the influence of this factor.

Eating disinhibition and vagal tone moderate the postprandial response to glycemic load: a randomised controlled trial.

Reducing the glycemic load (GL) of the diet may benefit appetite control but its utility is complicated by psychological influences on eating. Disinhibited behaviour, a risk factor for overconsumption, is characterized by reduced prefrontal cortex activity, which in turn modulates vagal tone; a phenomenon associated with glucoregulation. This double blind randomised controlled trial explored for the first time the influence of disinhibited eating and vagal tone (heart rate variability (HRV)) on hunger and the postprandial response to GL. Blood glucose (BG) and hunger were measured 30 and 150 min after consumption of water, glucose or isomaltulose (low glycemic sugar). After consuming glucose, independently of BMI or habitual diet, those with the highest levels of disinhibition had higher BG levels after thirty minutes (B = 0.192, 95% CI LL. 086, UL 0.297), and lower BG after one hundred and fifty minutes (B = -0.240, 95% CI LL -0.348, UL -0.131). BG was related to hunger but only in low disinhibited eaters. Disinhibited eaters were characterised by a reduced HRV which was related to greater BG excursions (B = 0.407, 95% CI LL 0.044, UL 1.134). These findings highlight novel mechanisms by which disinhibited eating leads to obesity and insulin resistance. This trial was registered at clinicaltrials.gov NCT02827318.

Minor degree of hypohydration adversely influences cognition: a mediator analysis.

BACKGROUND: Because the assumption that small changes in hydration status are readily compensated by homeostatic mechanisms has been little studied, the influence of hypohydration on cognition was examined. OBJECTIVES: We assessed whether a loss of <1% of body mass due to hypohydration adversely influenced cognition, and examined the possible underlying mechanisms. DESIGN: A total of 101 individuals were subjected to a temperature of 30°C for 4 h and randomly either did or did not consume 300 mL H2O during that period. Changes in body mass, urine osmolality, body temperature, and thirst were monitored. Episodic memory, focused attention, mood, and the perceived difficulty of tasks were measured on 3 occasions. The data were analyzed with the use of a regression-based approach whereby we looked for variables that mediated the influence of hypohydration on psychological functioning. RESULTS: Drinking water improved memory and focused attention. In the short-term, thirst was associated with poorer memory. Later, a greater loss of body mass was associated with poorer memory and attention (mean loss: 0.72%). At 90 min, an increase in thirst was associated with a decline in subjective energy and increased anxiety and depression, effects that were reduced by drinking water. At 180 min, subjects found the tests easier if they had consumed water. CONCLUSIONS: Drinking water was shown, for the first time to our knowledge, to benefit cognitive functioning when there was a loss of <1% body mass at levels that may occur during everyday living. Establishing the variables that generate optimal fluid consumption will help to tailor individual advice, particularly in clinical situations. This trial was registered at clinicaltrials.gov as NCT02671149.

Chlamydia trachomatis polymorphic membrane protein D is a virulence factor involved in early host-cell interactions.

Chlamydia trachomatis is an obligate intracellular mucosotropic pathogen of significant medical importance. It is the etiological agent of blinding trachoma and bacterial sexually transmitted diseases, infections that afflict hundreds of millions of people globally. The C. trachomatis polymorphic membrane protein D (PmpD) is a highly conserved autotransporter and the target of broadly cross-reactive neutralizing antibodies; however, its role in host-pathogen interactions is unknown. Here we employed a targeted reverse genetics approach to generate a pmpD null mutant that was used to define the role of PmpD in the pathogenesis of chlamydial infection. We show that pmpD is not an essential chlamydial gene and the pmpD null mutant has no detectable deficiency in cultured murine cells or in a murine mucosal infection model. Notably, however, the pmpD null mutant was significantly attenuated for macaque eyes and cultured human cells. A reduction in pmpD null infection of human endocervical cells was associated with a deficiency in chlamydial attachment to cells. Collectively, our results show that PmpD is a chlamydial virulence factor that functions in early host-cell interactions. This study is the first of its kind using reverse genetics to evaluate the contribution of a C. trachomatis gene to disease pathogenesis.

Antibody signature of spontaneous clearance of Chlamydia trachomatis ocular infection and partial resistance against re-challenge in a nonhuman primate trachoma model.

BACKGROUND: Chlamydia trachomatis is the etiological agent of trachoma the world's leading cause of infectious blindness. Here, we investigate whether protracted clearance of a primary infection in nonhuman primates is attributable to antigenic variation or related to the maturation of the anti-chlamydial humoral immune response specific to chlamydial antigens. METHODOLOGY/PRINCIPAL FINDINGS: Genomic sequencing of organisms isolated throughout the protracted primary infection revealed that antigenic variation was not related to the inability of monkeys to efficiently resolve their infection. To explore the maturation of the humoral immune response as a possible reason for delayed clearance, sera were analyzed by radioimmunoprecipitation using intrinsically radio-labeled antigens prepared under non-denaturing conditions. Antibody recognition was restricted to the antigenically variable major outer membrane protein (MOMP) and a few antigenically conserved antigens. Recognition of MOMP occurred early post-infection and correlated with reduction in infectious ocular burdens but not with infection eradication. In contrast, antibody recognition of conserved antigens, identified as PmpD, Hsp60, CPAF and Pgp3, appeared late and correlated with infection eradication. Partial immunity to re-challenge was associated with a discernible antibody recall response against all antigens. Antibody recognition of PmpD and CPAF was destroyed by heat treatment while MOMP and Pgp3 were partially affected, indicating that antibody specific to conformational epitopes on these proteins may be important to protective immunity. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that delayed clearance of chlamydial infection in NHP is not the result of antigenic variation but rather a consequence of the gradual maturation of the C. trachomatis antigen-specific humoral immune response. However, we cannot conclude that antibodies specific for these proteins play the primary role in host protective immunity as they could be surrogate markers of T cell immunity. Collectively, our results argue that an efficacious subunit trachoma vaccine might require a combination of these antigens delivered in their native conformation.

Chlamydia trachomatis plasmid-encoded Pgp4 is a transcriptional regulator of virulence-associated genes.

Chlamydia trachomatis causes chronic inflammatory diseases of the eye and genital tract and has global medical importance. The chlamydial plasmid plays an important role in the pathophysiology of these diseases, as plasmid-deficient organisms are highly attenuated. The cryptic plasmid carries noncoding RNAs and eight conserved open reading frames (ORFs). To understand plasmid gene function, we generated plasmid shuttle vectors with deletions in each of the eight ORFs. The individual deletion mutants were used to transform chlamydiae and the transformants were characterized phenotypically and at the transcriptional level. We show that pgp1, -2, -6, and -8 are essential for plasmid maintenance, while the other ORFs can be deleted and the plasmid stably maintained. We further show that a pgp4 knockout mutant exhibits an in vitro phenotype similar to its isogenic plasmidless strain, in terms of abnormal inclusion morphology and lack of glycogen accumulation. Microarray and qRT-PCR analysis revealed that Pgp4 is a transcriptional regulator of plasmid-encoded pgp3 and multiple chromosomal genes, including the glycogen synthase gene glgA, that are likely important in chlamydial virulence. Our findings have major implications for understanding the plasmid's role in chlamydial pathogenesis at the molecular level.

Distance communication of sexual status in the crayfish Orconectes quinebaugensis: female sexual history mediates male and female behavior.

Chemical communication plays an important role in mediating social interactions of many taxa, particularly arthropods. Many individuals communicate information about their reproductive status to potential mates through distance and/or contact pheromones, an ability that may be advantageous to both signalers and receivers. In this paper, we describe tests of two hypotheses on the role of distance communication in the reproductive behaviors of crayfish (Orconectes quinebaugensis). First, we hypothesized that male crayfish would show stronger attraction towards virgin females (females with no viable sperm) than towards non-virgin females because of the fitness costs (to males) associated with sperm competition. Second, we hypothesized that female crayfish should show differential responses to mature male signals depending on their own sexual history: virgin females should be more strongly attracted to male signals than should non-virgin females because they must mate at least once to be able to fertilize eggs in the spring. Data from two Y-maze experiments yielded support for both hypotheses: males were attracted to signals from virgin females, but not to signals from non-virgins. Likewise, virgin females were attracted to signals from males, but non-virgin females were not. We discuss our data in the context of the potential costs and benefits of mate searching and suggest that distance chemical communication of sexual status may be particularly advantageous when the costs of mate searching are high.

CCL28 effects on periodontal pathogens.

BACKGROUND: Chemokines are small proteins that signal to and attract cells of the immune system; they are vital components in the modulation of immunity and wound healing. A newly described chemokine was reported to have antibacterial and antifungal activity. This chemokine, chemokine (C-C motif) ligand 28 (CCL28; also called mucosae-associated epithelial chemokine), is secreted by mucosal epithelial cells and is found in saliva and in breast milk. The objective of this study was to test whether CCL28 has antibacterial activity against two anaerobic periodontal pathogens: Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans. METHODS: We used a bacterial viability test, in which two fluorescent dyes are bound differentially to living and killed bacteria. We tested the bacteria at concentrations of 2 x 10(7)/ml, exposing them to CCL28 at concentrations from 0.04 to 10 microM. RESULTS: CCL28 was effective at killing both organisms. After 1 hour of exposure to the chemokine under appropriate oxygen conditions, the percentage of living organisms was reduced significantly for each species. We estimated the 50% effective concentration to be approximately 0.7 microM for P. gingivalis and approximately 2.0 microM for A. actinomycetemcomitans (N = five experiments each). We confirmed these observations using standard bacterial plating methods. CONCLUSION: Because this chemokine is secreted into the saliva, a reduction in salivary flow (as in xerostomia) may diminish the oral self-defense mechanisms by also reducing the exposure of bacteria to the antibacterial action of CCL28.