Screening for Anxiety and Depression Symptoms Using Concussion Symptom Scales Among Varsity Athletes.

OBJECTIVE: This study examined associations between Sport Concussion Assessment Tool-5 (SCAT-5) symptom reporting and gold-standard measures of anxiety and depression, and explored the utility SCAT-5 symptom subscales to identify anxiety and depression symptomology. DESIGN: Prospective cross-sectional study. SETTING: York University in Toronto, Canada. PARTICIPANTS: Preseason data were collected for varsity athletes (N = 296) aged between 17 and 25 years ( M = 20.01 years, SD = 1.69 years; 52% male). MAIN OUTCOME MEASURES: The SCAT-5 symptom evaluation scale was used to assess baseline symptoms. The Generalized Anxiety Disorder Index-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) were used to assess symptoms of anxiety and depression, respectively. RESULTS: Endorsement of SCAT-5 symptoms of feeling anxious, sadness, irritability, and feeling more emotional had the strongest correlations with the GAD-7 ( r' s > 0.400; P' s < 0.001). Sadness, trouble falling asleep, concentration problems, feeling slowed down, anxious, irritability, mental fog, fatigue, and memory problems had the highest correlations with the PHQ-9 ( r' s >0 .400; P' s < 0.001). The Emotional subscale from the SCAT-5 predicted mild to severe anxiety on the GAD-7 ( P < 0.001). The Sleep, Cognitive, and Emotional subscales predicted mild to severe depression on the PHQ-9 ( P' s < 0.05). CONCLUSIONS: These findings provide better delineation of symptoms endorsed on the SCAT-5 symptoms that aid in identification of athletes with symptoms of anxiety or depression who may be at risk for developing a clinical disorder or experiencing persistent symptoms after a concussion.

A Measure of Caregivers' Distress-Promoting Behaviors During Toddler Vaccination: Validation of the OUCHIE-RV.

OBJECTIVE: The current study discusses the development and preliminary validation of an observational measure of caregivers' distress-promoting behavior (OUCHIE-RV) in the context of toddler routine vaccination. METHODS: Measure validation was based on a sample of caregiver-toddler dyads (N = 223) from a longitudinal cohort-sequential study who were observed during toddlers' 12-, 18-, or 24-month routine vaccinations. Validity was assessed using correlations and cross-lagged path analysis and associations were tested between OUCHIE-RV composite scores and toddlers' pain-related distress as well as caregivers' state anxiety, soothing behaviors, heart rate, and heart rate variability. Interrater reliability was examined using intraclass correlations (ICC) and kappa coefficients. RESULTS: Results of a cross-lagged path analysis indicated positive concurrent (ß = .27 to ß = .37) and cross-lagged predictive associations (ß = .01 to ß = .34) between OUCHIE-RV composite scores (reflecting the frequency and intensity of caregivers' distress-promoting behavior) and toddlers' pain-related distress. OUCHIE-RV composite scores were negatively associated with caregivers' concurrent use of physical comfort (r = -.34 to -.24) and rocking (r = -.36 to -.19) and showed minimal associations with caregivers' use of verbal reassurance (r = .06 to .12), state anxiety (r = -.02 to r = .09), heart rate (r = -.15 to r = .05), and heart rate variability (r = -.04 to r = .13). Interrater reliability was strong (Cohen's k = .86 to .97, ICC = .77 to .85). CONCLUSIONS: Findings provide support for the validity and reliability of the OUCHIE-RV as a research tool for measuring caregiver behaviors that promote toddlers' pain-related distress during routine vaccinations and contribute to a better understanding of the dynamics of caregiver-toddler interaction in acute pain contexts.

Sex difference of pre- and post-natal exposure to six developmental neurotoxicants on intellectual abilities: a systematic review and meta-analysis of human studies.

BACKGROUND: Early life exposure to lead, mercury, polychlorinated biphenyls (PCBs), polybromide diphenyl ethers (PBDEs), organophosphate pesticides (OPPs), and phthalates have been associated with lowered IQ in children. In some studies, these neurotoxicants impact males and females differently. We aimed to examine the sex-specific effects of exposure to developmental neurotoxicants on intelligence (IQ) in a systematic review and meta-analysis. METHOD: We screened abstracts published in PsychINFO and PubMed before December 31st, 2021, for empirical studies of six neurotoxicants (lead, mercury, PCBs, PBDEs, OPPs, and phthalates) that (1) used an individualized biomarker; (2) measured exposure during the prenatal period or before age six; and (3) provided effect estimates on general, nonverbal, and/or verbal IQ by sex. We assessed each study for risk of bias and evaluated the certainty of the evidence using Navigation Guide. We performed separate random effect meta-analyses by sex and timing of exposure with subgroup analyses by neurotoxicant. RESULTS: Fifty-one studies were included in the systematic review and 20 in the meta-analysis. Prenatal exposure to developmental neurotoxicants was associated with decreased general and nonverbal IQ in males, especially for lead. No significant effects were found for verbal IQ, or postnatal lead exposure and general IQ. Due to the limited number of studies, we were unable to analyze postnatal effects of any of the other neurotoxicants. CONCLUSION: During fetal development, males may be more vulnerable than females to general and nonverbal intellectual deficits from neurotoxic exposures, especially from lead. More research is needed to examine the nuanced sex-specific effects found for postnatal exposure to toxic chemicals.

A Benchmark Dose Analysis for Maternal Pregnancy Urine-Fluoride and IQ in Children.

As a guide to establishing a safe exposure level for fluoride exposure in pregnancy, we applied benchmark dose modeling to data from two prospective birth cohort studies. We included mother-child pairs from the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) cohort in Mexico and the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort in Canada. Maternal urinary fluoride concentrations (U-F, in mg/L, creatinine-adjusted) were measured in urine samples obtained during pregnancy. Children were assessed for intelligence quotient (IQ) at age 4 (n = 211) and between six and 12 years (n = 287) in the ELEMENT cohort, and three to four years (n = 407) in the MIREC cohort. We calculated covariate-adjusted regression coefficients and their standard errors to assess the association of maternal U-F concentrations with children's IQ measures. Assuming a benchmark response of 1 IQ point, we derived benchmark concentrations (BMCs) and benchmark concentration levels (BMCLs). No deviation from linearity was detected in the dose-response relationships, but boys showed lower BMC values than girls. Using a linear slope for the joint cohort data, the BMC for maternal U-F associated with a 1-point decrease in IQ scores was 0.31 mg/L (BMCL, 0.19 mg/L) for the youngest boys and girls in the two cohorts, and 0.33 mg/L (BMCL, 0.20 mg/L) for the MIREC cohort and the older ELEMENT children. Thus, the joint data show a BMCL in terms of the adjusted U-F concentrations in the pregnant women of approximately 0.2 mg/L. These results can be used to guide decisions on preventing excess fluoride exposure in pregnant women.

Critical windows of fluoride neurotoxicity in Canadian children.

BACKGROUND: Fluoride has been associated with IQ deficits during early brain development, but the period in which children are most sensitive is unknown. OBJECTIVE: We assessed effects of fluoride on IQ scores across prenatal and postnatal exposure windows. METHODS: We used repeated exposures from 596 mother-child pairs in the Maternal-Infant Research on Environmental Chemicals pregnancy and birth cohort. Fluoride was measured in urine (mg/L) collected from women during pregnancy and in their children between 1.9 and 4.4 years; urinary fluoride was adjusted for specific gravity. We estimated infant fluoride exposure (mg/day) using water fluoride concentration and duration of formula-feeding over the first year of life. Intelligence was assessed at 3-4 years using the Wechsler Preschool and Primary Scale of Intelligence-III. We used generalized estimating equations to examine the associations between fluoride exposures and IQ, adjusting for covariates. We report results based on standardized exposures given their varying units of measurement. RESULTS: The association between fluoride and performance IQ (PIQ) significantly differed across prenatal, infancy, and childhood exposure windows collapsing across child sex (p = .001). The strongest association between fluoride and PIQ was during the prenatal window, B = -2.36, 95% CI: -3.63, -1.08; the association was also significant during infancy, B = -2.11, 95% CI: -3.45, -0.76, but weaker in childhood, B = -1.51, 95% CI: -2.90, -0.12. Within sex, the association between fluoride and PIQ significantly differed across the three exposure windows (boys: p = .01; girls: p = .01); among boys, the strongest association was during the prenatal window, B = -3.01, 95% CI: -4.60, -1.42, whereas among girls, the strongest association was during infancy, B = -2.71, 95% CI: -4.59, -0.83. Full-scale IQ estimates were weaker than PIQ estimates for every window. Fluoride was not significantly associated with Verbal IQ across any exposure window. CONCLUSION: Associations between fluoride exposure and PIQ differed based on timing of exposure. The prenatal window may be critical for boys, whereas infancy may be a critical window for girls.

Fluoride exposure and duration and quality of sleep in a Canadian population-based sample.

BACKGROUND: Fluoride from dietary and environmental sources may concentrate in calcium-containing regions of the body such as the pineal gland. The pineal gland synthesizes melatonin, a hormone that regulates the sleep-wake cycle. We examined associations between fluoride exposure and sleep outcomes among older adolescents and adults in Canada. METHODS: We used population-based data from Cycle 3 (2012-2013) of the Canadian Health Measures Survey. Participants were aged 16 to 79 years and 32% lived in communities supplied with fluoridated municipal water. Urinary fluoride concentrations were measured in spot samples and adjusted for specific gravity (UFSG; n = 1303) and water fluoride concentrations were measured in tap water samples among those who reported drinking tap water (n = 1016). We used multinomial and ordered logistic regression analyses (using both unweighted and survey-weighted data) to examine associations of fluoride exposure with self-reported sleep outcomes, including sleep duration, frequency of sleep problems, and daytime sleepiness. Covariates included age, sex, ethnicity, body mass index, chronic health conditions, and household income. RESULTS: Median (IQR) UFSG concentration was 0.67 (0.63) mg/L. Median (IQR) water fluoride concentration was 0.58 (0.27) mg/L among participants living in communities supplied with fluoridated municipal water and 0.01 (0.06) mg/L among those living in non-fluoridated communities. A 0.5 mg/L higher water fluoride level was associated with 34% higher relative risk of reporting sleeping less than the recommended duration for age [unweighted: RRR = 1.34, 95% CI: 1.03, 1.73; p = .026]; the relative risk was higher, though less precise, using survey-weighted data [RRR = 1.96, 95% CI: 0.99, 3.87; p = .05]. UFSG was not significantly associated with sleep duration. Water fluoride and UFSG concentration were not significantly associated with frequency of sleep problems or daytime sleepiness. CONCLUSIONS: Fluoride exposure may contribute to sleeping less than the recommended duration among older adolescents and adults in Canada.

Investigating convergence of cardiac and behavioral indicators of distress during routine vaccinations over the second year of life.

There is considerable variability regarding the convergence between behavioral and biological aspects of distress responses in toddlerhood, and little research has investigated the convergence of these measures in high distress. The aim of the current study was to describe patterns of distress responses to vaccinations as indexed by both pain-related behavioral distress and heart rate (HR) at 12 and 18 months. Caregiver-toddler dyads were part of an ongoing longitudinal cohort observed during 12- (N = 158) and 18-month (N = 122) well-baby vaccinations. Parallel-process growth mixture models discerned two distinct groups at 12 months and three distinct groups at 18 months. All groups had comparable pain-related behavioral distress and HR responses post-vaccination, with most participants displaying high arousal and regulation to baseline levels following the vaccination. However, at 18 months, an important minority had a blunted response or did not regulate to a low level of distress by 3 min post-needle. Post hoc analyses revealed that higher baseline pain-related behavioral distress predicted membership in the majority groups at 12 and 18 months. These results highlight the developmental differences and variability in behavioral and cardiac indicators of distress regulation across the second year of life.

Evaluating Equivalence Testing Methods for Measurement Invariance.

Measurement Invariance (MI) is often concluded from a nonsignificant chi-square difference test. Researchers have also proposed using change in goodness-of-fit indices ([Formula: see text]GOFs) instead. Both of these commonly used methods for testing MI have important limitations. To combat these issues, To combat these issues, it was proposed using an equivalence test (EQ) to replace the chi-square difference test commonly used to test MI. Due to concerns with the EQ's power, and adjusted version (EQ-A) was created, but provides little evaluation of either procedure. The current study evaluated the Type I error and power of both the EQ and EQ-A, and compared their performance to that of the traditional chi-square difference test and [Formula: see text]GOFs. The EQ was the only procedure that maintained empirical error rates below the nominal alpha level. Results also highlight that the EQ requires larger sample sizes than traditional difference-based approaches or using equivalence bounds based on larger than conventional RMSEA values (e.g., > .05) to ensure adequate power rates. We do not recommend the proposed adjustment (EQ-A) over the EQ.

Trajectories of BMI and internalizing symptoms: Associations across adolescence.

The present study examined the longitudinal relations between body mass index (BMI) and internalizing symptoms among youth ages 10-17. Adolescents were selected from Statistics Canada's National Longitudinal Survey of Children and Youth (NLSCY). Latent growth curve modeling was used to investigate: 1) whether initial level (at age 10) or change in BMI were associated with changes in internalizing symptoms; and, 2) whether initial level or change in internalizing symptoms were associated with changes in BMI across adolescence. Associations between trajectories differed for boys and girls. Boys who started out with higher BMI experienced more internalizing symptoms across early- to mid-adolescence, but not more depressive symptoms at ages 16 and 17. For girls, there was a bidirectional relation between BMI and internalizing symptoms which persisted into later adolescence. Results suggest the bidirectional relation between BMI and internalizing symptoms is more salient for girls than for boys.

Irreversible sortase A-mediated ligation driven by diketopiperazine formation.

Sortase A (SrtA)-mediated ligation has emerged as an attractive tool in bioorganic chemistry attributing to the remarkable specificity of the ligation reaction and the physiological reaction conditions. However, the reversible nature of this reaction limits the efficiency of the ligation reaction and has become a significant constraint to its more widespread use. We report herein a novel set of SrtA substrates (LPETGG-isoacyl-Ser and LPETGG-isoacyl-Hse) that can be irreversibly ligated to N-terminal Gly-containing moieties via the deactivation of the SrtA-excised peptide fragment through diketopiperazine (DKP) formation. The convenience of the synthetic procedure and the stability of the substrates in the ligation buffer suggest that both LPETGG-isoacyl-Ser and LPETGG-isoacyl-Hse are valuable alternatives to existing irreversible SrtA substrate sequences.

Age of onset as a moderator of cognitive decline in pediatric-onset multiple sclerosis.

Cognitive impairment is often reported in pediatric-onset multiple sclerosis (MS). Using serial cognitive data from 35 individuals with pediatric-onset MS, this study examined how age at disease-onset and proxies of cognitive reserve may impact cognitive maturation over the course of childhood and adolescence. Neuropsychological evaluations were conducted at baseline and up to four more assessments. Of the 35 participants, 7 completed only one assessment, 5 completed two assessments, 13 completed three assessments, 10 completed four or more assessments. Growth curve modeling was used to assess longitudinal trajectories on the Trail Making Test-Part B (TMT-B) and the Symbol Digit Modalities (SDMT; oral version) and to examine how age at disease onset, baseline Full Scale IQ, and social status may moderate rate of change on these measures. Mean number of evaluations completed per patient was 2.8. Younger age at disease onset was associated with a greater likelihood of cognitive decline on both the TMT-B (p=.001) and SDMT (p=.005). Baseline IQ and parental social status did not moderate any of the cognitive trajectories. Findings suggest that younger age at disease-onset increases the vulnerability for disrupted performance on measures of information processing, visual scanning, perceptual/motor speed, and working memory. Proxies of cognitive reserve did not protect against the progression of decline on these measures. Young patients with MS should be advised to seek follow-up cognitive evaluation to assess cognitive maturation and to screen for the potential late emergence of cognitive deficits. (JINS, 2014, 20, 1-9).

Infant pain-related negative affect at 12 months of age: early infant and caregiver predictors.

OBJECTIVES: To examine the predictive relationships of early infant and caregiver variables on expressed pain-related negative affect duration at the 12-month immunization. METHODS: Infants and their caregivers (N = 255) were followed during immunization appointments over the first year of life. Latent growth curve modeling in a structural equation modeling context was used. RESULTS: Higher levels of initial infant pain reactivity at 2 months and caregiver emotional availability averaged across 2, 4, and 6 months of age were related to larger decreases in the duration of infant negative affect over the first 6 months of life. Longer duration of infant negative affect at 2 months and poorer regulation of infant negative affect over the first 6 months of life predicted longer durations of infant negative affect by 12 months. CONCLUSIONS: Infant negative affect at 12 months was a function of both infant factors and the quality of caregiver interactive behaviors (emotional availability) in early infancy.

A synthetic route to human insulin using isoacyl peptides.

The chemical synthesis of insulin has been a longstanding challenge, mainly because of the notorious hydrophobicity of the A chain and the complicated topology of this 51-mer peptide hormone consisting of two chains and three disulfide bonds. Reported herein is a new synthetic route utilizing the isoacyl peptide approach to address the hydrophobicity problems. The incorporation of isoacyl dipeptide segments into both A and B chains greatly improved their preparation and purification, and the RP-HPLC recovery of the chain ligation intermediates. The new route affords human insulin with a yield of 68 % based on the starting purified A chain and an overall yield of 24 % based on the substitution of the resin used for the preparation of A chain. To the best of our knowledge, this represents the most efficient route of human insulin chemical synthesis reported to date.

The Impact of Measurement Model Misspecification on Coefficient Omega Estimates of Composite Reliability.

Coefficient omega indices are model-based composite reliability estimates that have become increasingly popular. A coefficient omega index estimates how reliably an observed composite score measures a target construct as represented by a factor in a factor-analysis model; as such, the accuracy of omega estimates is likely to depend on correct model specification. The current paper presents a simulation study to investigate the performance of omega-unidimensional (based on the parameters of a one-factor model) and omega-hierarchical (based on a bifactor model) under correct and incorrect model misspecification for high and low reliability composites and different scale lengths. Our results show that coefficient omega estimates are unbiased when calculated from the parameter estimates of a properly specified model. However, omega-unidimensional produced positively biased estimates when the population model was characterized by unmodeled error correlations or multidimensionality, whereas omega-hierarchical was only slightly biased when the population model was either a one-factor model with correlated errors or a higher-order model. These biases were higher when population reliability was lower and increased with scale length. Researchers should carefully evaluate the feasibility of a one-factor model before estimating and reporting omega-unidimensional.

Parents' physiological reactivity to child distress and associations with parenting behaviour: A systematic review.

This systematic review and narrative synthesis characterized parents' physiological stress responses to child distress and how parents' physiological and behavioural responses relate. The review was pre-registered with PROSPERO (#CRD42021252852). In total, 3607 unique records were identified through Medline, Embase, PsycINFO, and CINAHL. Fifty-five studies reported on parents' physiological stress responses during their young child's (0-3 years) distress and were included in the review. Results were synthesized based on the biological outcome and distress context used and risk of bias was evaluated. Most studies examined cortisol or heart rate variability (HRV). Small to moderate decreases in parents' cortisol levels from baseline to post-stressor were reported across studies. Studies of salivary alpha amylase, electrodermal activity, HRV, and other cardiac outcomes reflected weak or inconsistent physiological responses or a paucity of relevant studies. Among the studies that examined associations between parents' physiological and behavioural responses, stronger associations emerged for insensitive parenting behaviours and during dyadic frustration tasks. Risk of bias was a significant limitation across studies and recommendations for future research are discussed.

Understanding the concurrent and predictive relations between child-led emotion regulation behaviors and pain during vaccination in toddlerhood.

ABSTRACT: The purpose of this study was to further our understanding of early childhood pain-related distress regulation. Concurrent and predictive relations between child-led emotion regulation (ER) behaviors and pain-related distress during vaccination were examined at 2 different ages using autoregressive cross-lagged path analyses. Toddlers were video-recorded at the 12- and 18-month routine vaccination appointments (12-month-old [N = 163]; 18-month-old [N = 149]). At 1, 2, and 3 minutes postneedle, videos were coded for 3 clusters of child-led ER behaviors (disengagement of attention, parent-focused behaviors, and physical self-soothing) and pain-related distress. The concurrent and predictive relations between child-led ER behaviors and pain-related distress behaviors were assessed using 6 models (3 emotion regulation behaviors by 2 ages). At 18 months, disengagement of attention was significantly negatively related to pain-related distress at 1 minute postneedle, and pain-related distress at 1 minute postneedle was significantly related to less disengagement of attention at 2 minutes postneedle. Parent-focused behaviors had significant positive relations with pain-related distress at both ages, with stronger magnitudes at 18 months. Physical self-soothing was significantly related to less pain-related distress at both ages. Taken together, these findings suggest that disengagement of attention and physical self-soothing may serve more of a regulatory function during toddlerhood, whereas parent-focused behaviors may serve more of a function of gaining parent support for regulation. This study is the first to assess these relations during routine vaccination in toddlerhood and suggests that toddlers in the second year of life are beginning to play a bigger role in their own regulation from painful procedures than earlier in infancy.

Distinct trajectories of caregiver-toddler physiological attunement during routine vaccinations.

Introduction: Toddlers rely on their caregivers for regulatory support when faced with pain-related distress. The caregiver's ability to support their toddler relies on their capacity to regulate their own distress and respond effectively to the child's need for support. The aim of the current study was to describe patterns of caregiver-toddler physiological co-regulatory patterns, also known as attunement, during routine vaccinations across the second year of life. Methods: Caregiver-toddler dyads (N = 189) were part of a longitudinal cohort observed at either 12-, 18-, or 24-month well-baby vaccinations. Parallel-process growth-mixture modeling was used to examine patterns of dyadic physiological co-regulatory responses, indexed by high-frequency heart rate variability (HF-HRV). Results: Three groups of dyads were discerned. The largest group (approximately 80%) demonstrated physiological attunement, with a stable and parallel regulatory pattern of HF-HRV from baseline to postneedle. The second group (7.9%) had parallel regulatory trajectories but with notably lower (ie, less regulated) HF-HRV values, which indicates independent regulatory responses (ie, a lack of attunement among dyad members). The third group (11.1%) showed diverging regulatory trajectories: Caregivers showed a stable regulatory trajectory, but toddlers demonstrated a steep decrease followed by an increase in HF-HRV values that surpassed their baseline levels by the third minute postneedle. Post hoc analyses with the HF-HRV groupings explored heart rate patterns and potential predictors. Conclusions: These findings elucidate potential adaptive and maladaptive co-regulatory parasympathetic patterns in an acute pain context.