Three novel genetic variants in NRF2 signaling pathway genes are associated with pancreatic cancer risk.

Pancreatic cancer (PanC) is one of the most lethal solid malignancies, and metastatic PanC is often present at the time of diagnosis. Although several high- and low-penetrance genes have been implicated in PanC, their roles in carcinogenesis remain only partially elucidated. Because the nuclear factor erythroid2-related factor2 (NRF2) signaling pathway is involved in human cancers, we hypothesize that genetic variants in NRF2 pathway genes are associated with PanC risk. To test this hypothesis, we assessed associations between 31 583 common single nucleotide polymorphisms (SNP) in 164 NRF2-related genes and PanC risk using three published genome-wide association study (GWAS) datasets, which included 8474 cases and 6944 controls of European descent. We also carried out expression quantitative trait loci (eQTL) analysis to assess the genotype-phenotype correlation of the identified significant SNP using publicly available data in the 1000 Genomes Project. We found that three novel SNP (ie, rs3124761, rs17458086 and rs1630747) were significantly associated with PanC risk (P = 5.17 × 10-7 , 5.61 × 10-4 and 5.52 × 10-4 , respectively). Combined analysis using the number of unfavorable genotypes (NUG) of these three SNP suggested that carriers of two to three NUG had an increased risk of PanC (P < 0.0001), compared with those carrying zero to one NUG. Furthermore, eQTL analysis showed that both rs3124761 T and rs17458086 C alleles were associated with increased mRNA expression levels of SLC2A6 and SLC2A13, respectively (P < 0.05). In conclusion, genetic variants in NRF2 pathway genes could play a role in susceptibility to PanC, and further functional exploration of the underlying molecular mechanisms is warranted.

Initiation of Human Papillomavirus Vaccination Among Predominantly Minority Female and Male Adolescents at Inner-City Community Health Centers.

OBJECTIVES: We examined the prevalence and correlates of human papillomavirus (HPV) vaccine initiation among adolescents in low-income, urban areas. METHODS: The study consisted of electronic health record data on HPV vaccination for 3180 adolescents (aged 10-20 years) at a multisite community health center in 2011. RESULTS: Only 27% initiated the HPV vaccine. The adjusted odds ratio (AOR) of HPV vaccination was lower among older adolescents (AOR = 0.552; 95% confidence interval [CI] = 0.424, 0.718) and those seen by nonpediatric health care providers (HCPs; AOR = 0.311; 95% CI = 0.222, 0.435), and higher among non-English speakers (AOR = 1.409; 95% CI = 1.134, 1.751) and those seen at 2 site locations (AOR = 1.890; 95% CI = 1.547, 2.311). Insurance status was significant only among female and Hispanic adolescents. Language was not a predictor among Hispanic adolescents. Across all analyses, the interaction of age and HCP specialty was associated with HPV vaccination. Dramatically lower HPV vaccination rates were found among older adolescents seen by nonpediatric HCPs (3%-5%) than among other adolescents (23%-45%). CONCLUSIONS: Improving HPV vaccination initiation in low-income urban areas is critical to reducing disparities in cervical and other HPV-related cancer, especially among Black, Hispanic, and low-income populations.

HPV Vaccination Completion and Compliance with Recommended Dosing Intervals Among Female and Male Adolescents in an Inner-City Community Health Center.

Human papillomavirus (HPV) vaccination continues to lag behind other adolescent vaccines, especially in areas with pervasive disparities in HPV-related cancers. The purpose of this study was to examine HPV vaccine completion and dosing intervals among low-income adolescents in urban areas. The study included electronic health record data on HPV vaccination for 872 adolescents who received at least one dose of the HPV vaccine. Only 28.4% completed the 3-dose series. For the whole sample, HPV vaccine completion was higher for non-English speakers and among adolescents seen at Newark-South and East Orange sites. Completion was higher among non-English speaking female and Hispanic adolescents, females seen in Newark-South and East Orange sites, and insured Black adolescents. Completion was also dramatically lower among non-English speaking Black adolescents seen at Newark-North, Irvington, and Orange sites (12.5%) compared to other Black adolescents (22.0-44.4%). The mean dosing intervals were 5.5 months (SD = 4.6) between dose 1 and 2 and 10 months (SD = 6.1) between dose 1 and 3. Longer durations between vaccine doses were found among uninsured adolescents and those seen at Newark-North, Irvington, and Orange sites. Non-English speakers had longer duration between dose 1 and 3. Further, durations between dose 1 and 3 were dramatically longer among insured adolescents seen at Newark-North, Irvington, and Orange locations for the whole sample (M = 11.70; SD = 7.12) and among Hispanic adolescents (M = 13.45; SD = 8.54). Understanding how the study predictors facilitate or impede HPV vaccination is critical to reducing disparities in cervical and other HPV-related cancer, especially among Black, Hispanic, and low-income populations.

Externalizing problems in late childhood as a function of prenatal cocaine exposure and environmental risk.

OBJECTIVE: To examine whether prenatal cocaine exposure (PCE) predicts externalizing problems in late childhood. METHODS: Externalizing problems were assessed using caregiver, teacher, and child ratings and a laboratory task when children (N = 179; 74 cocaine exposed) were aged 8-10 years. PCE, environmental risk, sex, neonatal health, other prenatal exposures, and foster care history were examined as predictors of externalizing problems. RESULTS: Multiple regression analyses indicated that PCE, environmental risk, and male sex explained significant variance in externalizing problems in late childhood. Models varied by source of information. PCE predicted externalizing problems for child laboratory behavior and interacted with sex because males with PCE reported more externalizing problems. PCE did not predict caregiver or teacher ratings of externalizing problems. CONCLUSIONS: The effect of PCE on externalizing problems may persist into late childhood. The findings highlight the potential importance of including child-based measures of externalizing problems in studies of prenatal exposure.

Self representation in children with and without Autism Spectrum Disorders.

In order to examine the roles of mental age, social interaction, and communication in self-representation abilities, typically-developing children were compared with children with Autism Spectrum Disorders. Typically-developing children (TD, n = 66) and children with Autism Spectrum Disorders (ASD, n = 20), including subgroups of autistic disorder and pervasive developmental disorder-not otherwise specified, were assessed on self-representation ability, which was measured by mirror recognition, other-directed pretend play, and use of personal pronouns. More TD children (100%) showed mirror recognition than ASD children (55%). TD children were more likely to show other-directed pretense (80%) than the ASD group (35%). Personal pronouns were used more by TD children (83%) than by ASD children (63%). Self-representation ability appears to be underdeveloped in some children with ASD. Self-representation ability in children with ASD was related to the Social Interaction subscale of the Autism Diagnostic Observation Schedule such that greater self representation ability was associated with better Social Interaction scores, although it was not related to the Communication scores of the ADOS-G. The mental age of the children with ASD was at least 2 years; therefore, the deficits in self representation in children with ASD cannot be explained by mental age alone.

Factors that Influence Healthcare Provider Recommendation of HPV Vaccination.

Purpose: This study examined factors associated with healthcare providers' (HCPs') recommendation of HPV vaccination for younger and older adolescents. Methods: This is a cross-sectional study, using web-based survey of HCPs in New Jersey in 2018. The study outcome was a dichotomous measure of HCPs' recommendation of the HPV vaccine. The study predictors included practice characteristics (i.e., proportions of race/ethnicity, age groups, insurance type, and VFC recipients) and HCP's characteristics (i.e., specialty and perceived knowledge, effectiveness, concerns, parent- and system-related barriers, and facilitators). Data analysis included logistic regression models using separate blocks for practice and provider characteristics, followed by a backward stepwise approach to determine the surviving predictors. Results: Respondents (N=390) included physicians (75%) and nurse practitioners (25%), specialized in pediatrics (62%), family medicine (20%), and women's health (18%). The HCPs' recommendation rates for HPV vaccination were 56% for younger adolescents (11-13 years old) and 73% for older adolescents (14-17 years old). For younger adolescents, the recommendation rates were significantly higher in practices with higher proportions of younger adolescent, Black and Hispanic patients; among pediatric providers; and with HCPs' higher levels of knowledge and lower levels of concern about the vaccine. For older adolescents, the rates were significantly higher in practices with higher proportions patients who are Hispanic, privately insured, and VFC recipients; among pediatric providers; and with HCPs' higher levels of knowledge and lower levels of concern about the vaccine as well as higher levels of facilitators for recommending the HPV vaccine. Conclusions: Interventions targeting HCPs need to focus on improving their knowledge regarding the vaccine, reduce their concerns around its safety, and utilize facilitators strategies, particularly among non-pediatric providers.

Regional white matter development in children with autism spectrum disorders.

In this pilot study the severity of autism spectrum disorders (ASD) was associated with alterations in white matter development. Children with ASD and without ASD were assessed by magnetic resonance imaging (MRI) for their myelination development on a regional basis. Measures were obtained in medial frontal cortex, temporal poles, and temporo-parietal junction in both left and right hemispheres. Children with ASD showed myelination that was greater than expected for their age in both left and right medial frontal cortex and showed myelination that was less than expected in left temporo-parietal junction. The severity of ASD symptoms, as assessed by the Autism Diagnostic Observation Schedule-Generic, was associated more with left hemisphere alterations than right hemisphere.

How neglect and punitiveness influence emotion knowledge.

To explore whether punitive parenting styles contribute to early-acquired emotion knowledge deficits observable in neglected children, we observed 42 preschool children's emotion knowledge, expression recognition time, and IQ. The children's mothers completed the Parent-Child Conflict Tactics Scales to assess the recent use of three types of discipline strategies (nonviolent, physically punitive, and psychological aggression), as well as neglectful parenting. Fifteen of the children were identified as neglected by Child Protective Services (CPS) reports; 27 children had no record of CPS involvement and served as the comparison group. There were no differences between the neglect and comparison groups in the demographic factors of gender, age, home language, minority status, or public assistance, nor on IQ. Hierarchical multiple regression modeling showed that neglect significantly predicted emotion knowledge. The addition of IQ contributed a significant amount of additional variance to the model and maintained the fit. Adding parental punitiveness in the final stage contributed little additional variance and did not significantly improve the fit. Thus, deficits in children's emotion knowledge may be due primarily to lower IQ or neglect. IQ was unrelated to speed of emotion recognition. Punitiveness did not directly contribute to emotion knowledge deficits but appeared in exploratory analysis to be related to speed of emotion recognition.

Traumatic brain injury rehabilitation: QEEG biofeedback treatment protocols.

Interventions for improvement of cognitive problems in patients with traumatic brain injury (TBI) include electroencephalography biofeedback, also known as neurofeedback. Quantitative electroencephalography (QEEG) patterns are assessed in TBI patients and then compared to a database obtained from a normative population. Deviations in QEEG patterns from the normative group are the basis for an intervention plan. While QEEG patterns, obtained under an eyes closed, resting condition, provide information about deviations at rest, QEEG patterns obtained while the patient engages in cognitive tasks reflect specific deficiencies in brain functioning. This paper reviews and assesses QEEG patterns collected under both resting conditions as well as cognitive tasks. The article provides a theoretical and empirical base for QEEG interventions with TBI.

History of Childhood Abuse and Risk for Cervical Cancer Among Women in Low-Income Areas.

PURPOSE: The purpose of this study was to examine pathways through which childhood abuse increases the risk of cervical cancer, including smoking, stress, risky sexual behavior, and not having a Papanicolaou (Pap) test. MATERIALS AND METHODS: This is a descriptive, correlational study. The sample included 410 women, recruited from a large, multisite women's health center that serves low-income communities in New Jersey. Data were analyzed using path models and conditional regression analysis. RESULTS: Overall, 15% and 12% of the women in the study reported history of physical and sexual childhood abuse, respectively. There was a significant association between child abuse history and failure to receive a Pap test (χ2 = 5.34, p = 0.021). History of childhood abuse was associated with 44% lower odds of having a Pap test. The findings indicate a significant association between child abuse history and cervical cancer risk (χ2 = 7.65, p = 0.006, Cramer's V = 0.138). History of childhood abuse was associated with 96% higher odds of being at risk of cervical cancer. Both physical and sexual abuses were associated with higher levels of smoking, risky sexual behavior, perceived stress, and cervical cancer risk. In the conditional regression analysis, the effect of risky sexual behavior on the likelihood of cervical cancer risk showed an increased risk with higher risky sexual behavior scores only for those with a history of childhood abuse. CONCLUSION: Childhood abuse increases the risk of cervical cancer in adulthood, through failure to receive a Pap test and higher levels of smoking, perceived stress, and most importantly, risky sexual behavior. More importantly, the combination of childhood abuse and risky sexual behavior plays a greater role in increasing cervical cancer risk.

Substance craving changes in university students receiving heart rate variability biofeedback: A longitudinal multilevel modeling approach.

BACKGROUND: Previously published findings from a study of university students living in substance use disorder (SUD) recovery housing showed an eight-session heart rate variability biofeedback (HRVB) intervention significantly reduced craving. That study, however, uncovered pronounced inter-participant variability in craving change patterns through the course of HRVB that warranted further exploration. The purpose of the current investigation was to examine how within- and between-person factors may have differentially influenced craving changes. METHODS: A longitudinal multilevel modeling approach was used with time at level-1 nested within persons at level-2. Multilevel models of change were estimated to model craving trajectories and predictor relationships over time as a function of age, sex, length of abstinence, daily HRVB practice, anxiety, depression, and stress. RESULTS: A quadratic pattern of craving reductions was found, indicating that craving reductions accelerated over time for some participants. Daily HRVB practice of >12 min and older age significantly enhanced craving reductions over time. Increases in depressive symptoms attenuated the effects of HRVB on craving. The other predictors were not significantly associated with craving in this study. The true R2 for the final model indicated that 20.5% of the variance in craving was explained by older age, daily HRVB >12 min, and within-person changes in depression. CONCLUSIONS: HRVB shows promise as an accessible, scalable, and cost-effective complementary anti-craving intervention. Healthcare providers may help persons recovering from SUD to better manage substance craving by the routine and strategic use of HRVB practice.

Acculturation stress and allostatic load among Mexican immigrant women. / Estresse de aculturação e carga alostática entre mulheres imigrantes mexicanas.

OBJECTIVES: this case-control study compared levels of stress and allostatic load (AL) among Mexican women in the US ( n =19) and Mexico ( n = 40). METHOD: measures of stress included the Perceived Stress Scale (PSS) and the Hispanic Women's Social Stressor Scale (HWSSS). A composite measure of 8 indicators of AL (systolic and diastolic blood pressure, body mass index (BMI), waist-to-hip ratio, total cholesterol, glycated hemoglobin (hemoglobin A1C), triglycerides and C-reactive protein) was calculated. RESULTS: there were no significant group differences in AL between Mexican and Mexican immigrant women ( t = 1.55, p = .126). A principal component factor analysis was conducted on the 8 AL indicators; a 2-factor solution explained 57% of the variance. Group differences in the two AL factors were analyzed using MANOVA. BMI and waist-to-hip ratios were lower, but blood pressure and triglycerides were higher in the US group and were mediated by time in the US. Greater acculturation stress was significantly related to increased waist-to-hip ratio ( r = .57, p = .02). FINAL REMARKS: findings suggest some measures of AL increased with time in the US, and acculturation stress may be a significant factor.

Perceived Impact of Incentives for Chronic Disease Prevention.

INTRODUCTION: This study evaluates the effect of program and incentive characteristics on satisfaction with incentives and perceived impact of incentives on behavior change among Medicaid beneficiaries who participated in the Centers for Medicare and Medicaid Services Medicaid Incentives for Prevention of Chronic Diseases program. METHODS: In 2014-2015, an English- and Spanish-language survey was administered to Medicaid Incentives for Prevention of Chronic Diseases program participants about their satisfaction with incentives and perceived impact of incentives. Completed surveys were received from 2,276 eligible sample members (response rate=52.7%). In 2016-2017, multilevel, multivariable, ordinal logistic regression models were performed to examine program characteristics that predict outcomes, while controlling for respondent characteristics. RESULTS: Medicaid Incentives for Prevention of Chronic Diseases participants were satisfied with program incentives. Most survey respondents strongly agreed that they liked getting incentives for taking care of their health (78%), they were happy with the incentives overall (75%), the incentives were fair (73%), and they liked how often they received incentives (67%). Participants in programs delivered by telephone reported higher satisfaction with incentives compared with those in programs delivered in person. However, participants in programs delivered both in person and by telephone were more likely to perceive a positive impact of incentives. Incentive form was a significant predictor of satisfaction with incentives but not of incentive impact. Dollar amount of incentives influenced satisfaction with incentives and impact of incentives. CONCLUSIONS: Program delivery method, incentive form, and incentive magnitude are important characteristics to consider when designing incentive programs. Incentive programs can consider providing modest incentive amounts to achieve self-reported impact on behavior change.

Self-representation and brain development.

This study examined the relation between self-representation and brain development in infants and young children. Self-representation was assessed by mirror recognition, personal pronoun use, and pretend play. Structural brain images were obtained from magnetic resonance imaging (MRI). Brain development was assessed by a quantitative measure of maturation of the temporo-parietal junction, temporal pole, medial frontal cortex, and occipital cortex. Fifteen children (15 to 30 months of age; 3 girls) without MRI abnormalities were assessed. Only maturation of the left temporo-parietal junction was related to self-representation after controlling for age. These findings provide some evidence that brain maturation is related to the emergence of a representation of self in the human child.

Approach-related emotion, toddlers' persistence, and negative reactions to failure.

Approach behavior, defined as differences in behavior to an incentive event and anger at its removal, was assessed during contingency learning in 87 5-month-olds was related to maternal ratings of mastery behaviors at two years. Mothers reported on infants' concurrent temperament, as well as the occurrence of anger and tantrums, and their own anger at 12 months. Approach behavior was expected to predict persistence with objects and persistent motor behavior, but not negative reactions to failure. Negative reactions to failure were expected to be mediated by a distress-prone temperament. The moderating effect of maternal anger on these relations was also explored using conditional process regression models. Controlling for soothability, early approach behavior predicted toddlers' persistence, especially gross motor persistence, moderated by maternal anger. With more maternal anger, approach behavior and toddler's persistence were more strongly related. Distress to limits, infant anger at 12 months, and maternal anger were significantly correlated, but only infant anger was related to negative reactions to failure. Prior to six months, goal-directed behavior is related to later behavioral persistence, but maternal responses to child anger are an important contributor to this relation and by 12 months, infant anger directly predicts mastery frustration at two years.

Current Evidence on Heart Rate Variability Biofeedback as a Complementary Anticraving Intervention.

BACKGROUND: The limited success of conventional anticraving interventions encourages research into new treatment strategies. Heart rate variability biofeedback (HRVB), which is based on slowed breathing, was shown to improve symptom severity in various disorders. HRVB, and certain rates of controlled breathing (CB), may offer therapeutic potential as a complementary drug-free treatment option to help control substance craving. METHODS: This review evaluated current evidence on the effectiveness of HRVB and CB training as a complementary anticraving intervention, based on guidelines from the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. Studies that assessed a cardiorespiratory feedback or CB intervention with substance craving as an outcome were selected. Effect sizes were calculated for each study. The Scale for Assessing Scientific Quality of Investigations in Complementary and Alternative Medicine was used to evaluate the quality of each study reviewed. RESULTS: A total of eight articles remained for final review, including controlled studies with or without randomization, as well as noncontrolled trials. Most studies showed positive results with a variety of methodological quality levels and effect size. Current HRVB studies rated moderately on methodological rigor and showed inconsistent magnitudes of calculated effect size (0.074-0.727) across populations. The largest effect size was found in a nonclinical college population of high food cravers utilizing the most intensive HRVB training time of 240 min. CONCLUSIONS: Despite the limitations of this review, there is beginning evidence that HRVB and CB training can be of significant therapeutic potential. Larger clinical trials are needed with methodological improvements such as longer treatment duration, adequate control conditions, measures of adherence and compliance, longitudinal examination of craving changes, and more comprehensive methods of craving measurement.

Brief report: brain activation to social words in a sedated child with autism.

A functional magnetic resonance imaging (fMRI) study was performed on a 4-year-old girl with autism. While sedated, she listened to three utterances (numbers, hello, her own first name) played through headphones. Based on analyses of the fMRI data, the amount of total brain activation varied with the content of the utterance. The greatest volume of overall activation was in response to numbers, followed by the word 'hello', with the least activation to her name. Frontal cortex activation was greatest in response to her name, with less activation for numbers, and the least for the word 'hello.' These findings indicate that fMRI can identify and quantify the brain regions that are activated in response to words in children with autism under sedation.

Prescribers' Knowledge and Skills for Interpreting Research Results: A Systematic Review.

INTRODUCTION: Appropriate medication prescribing may be influenced by a prescriber's ability to understand and interpret medical research. The objective of this review was to synthesize the research related to prescribers' critical appraisal knowledge and skills-defined as the understanding of statistical methods, biases in studies, and relevance and validity of evidence. METHODS: We searched PubMed and other databases from January 1990 through September 2015. Two reviewers independently screened and selected studies of any design conducted in the United States, the United Kingdom, or Canada that involved prescribers and that objectively measured critical appraisal knowledge, skills, understanding, attitudes, or prescribing behaviors. Data were narratively synthesized. RESULTS: We screened 1204 abstracts, 72 full-text articles, and included 29 studies. Study populations included physicians. Physicians' extant knowledge and skills were in the low to middle of the possible score ranges and demonstrated modest increases in response to interventions. Physicians with formal education in epidemiology, biostatistics, and research demonstrated higher levels of knowledge and skills. In hypothetical scenarios presenting equivalent effect sizes, the use of relative effect measures was associated with greater perceptions of medication effectiveness and intent to prescribe, compared with the use of absolute effect measures. The evidence was limited by convenience samples and study designs that limit internal validity. DISCUSSION: Critical appraisal knowledge and skills are limited among physicians. The effect measure used can influence perceptions of treatment effectiveness and intent to prescribe. How critical appraisal knowledge and skills fit among the myriad of influences on prescribing behavior is not known.

Brain activation when hearing one's own and others' names.

Using functional magnetic resonance imaging, brain activation patterns were examined in response to hearing one's own first name in contrast to hearing the names of others. There are several regions in the left hemisphere that show greater activation to one's own name, including middle frontal cortex, middle and superior temporal cortex, and cuneus. These findings provide evidence that hearing one's own name has unique brain functioning activation specific to one's own name in relation to the names of others.

Electroencephalogram biofeedback for reading disability and traumatic brain injury.

The application of electroencephalogram (EEG) biofeedback with reading disability and traumatic brain injury (TBI) is relatively recent. There are many studies regarding the effectiveness (improving attention and IQ scores) of EEG biofeedback in patients with attention deficit hyperactivity disorder, who are known to have a high rate of comorbidity for learning disabilities. This suggests the possibility that EEG biofeedback specifically aimed at remediating reading disability and TBI would be effective. This article provides strong initial support for this idea and provides reason to believe that assessment and training under task conditions are likely to be fruitful. Given the significance of these problems and the absence of very effective alternatives for remediation of these conditions, efforts to complete the needed research seem warranted. Clinical use of this intervention seems to be warranted with informed consent.