BACKGROUND:Fetal alcohol spectrum disorders (FASD) encompass a range of phenotypes in offspring exposed to ethanol via maternal consumption during pregnancy. In a series of studies, our laboratory identified deleterious effects of prenatal ethanol exposure (PrEE) in our FASD mouse model. The first filial generation (F1) of PrEE offspring exhibited abnormal neocortical gene expression, ectopic intraneocortical connectivity, altered neuroanatomy, and disrupted behavior. Our results suggest that PrEE can induce transgenerational transmission of the abnormal phenotypes, potentially via epigenetic modifications. METHODS:Here, we investigated brain and behavioral development in the F1 (directly exposed), F2 (indirectly exposed), and F3 (non-exposed) generations of our PrEE model. Comparative analyses of body weight, brain weight, cortical length, thalamic nuclear areas, hippocampal structures, and corpus callosa were evaluated in control, F1, F2, and F3 newborn mice, with behavioral differences examined at wean age. RESULTS:All generations of PrEE newborns had decreased body weights, brain weights, and neocortical lengths compared with controls. Quantitative measures in F1, F2, and F3 newborn PrEE mice demonstrated altered neocortical thickness in F1 prelimbic, visual, and auditory cortices. Additionally, a transgenerational reduction was also observed in the auditory cortex in F3 mice when compared to controls. When compared to controls, all generations of PrEE mice demonstrated significant reductions in hippocampal CA3 thickness. While no control cases demonstrated corpus callosal agenesis, a majority of F1 cases did, as well as a lower but present percentage of F2 and F3 cases. Finally, we found that disrupted sensorimotor integration, motor control, and anxiety-like behavior persisted to at least the F2 generation. CONCLUSIONS:Our data suggest that PrEE can result in abnormal brain and behavioral development with heritable effects that persist transgenerationally.

Abstract Background Autism spectrum disorder (ASD) is currently diagnosed in approximately 1 in 44 children in the United States, based on a wide array of symptoms, including sensory dysfunction and abnormal language development. Boys are diagnosed ~ 3.8 times more frequently than girls. Auditory temporal processing is crucial for speech recognition and language development. Abnormal development of temporal processing may account for ASD language impairments. Sex differences in the development of temporal processing may underlie the differences in language outcomes in male and female children with ASD. To understand mechanisms of potential sex differences in temporal processing requires a preclinical model. However, there are no studies that have addressed sex differences in temporal processing across development in any animal model of ASD. Methods To fill this major gap, we compared the development of auditory temporal processing in male and female wildtype (WT) and Fmr1 knock-out (KO) mice, a model of Fragile X Syndrome (FXS), a leading genetic cause of ASD-associated behaviors. Using epidural screw electrodes, we recorded auditory event related potentials (ERP) and auditory temporal processing with a gap-in-noise auditory steady state response (ASSR) paradigm at young (postnatal (p)21 and p30) and adult (p60) ages from both auditory and frontal cortices of awake, freely moving mice. Results The results show that ERP amplitudes were enhanced in both sexes of Fmr1 KO mice across development compared to WT counterparts, with greater enhancement in adult female than adult male KO mice. Gap-ASSR deficits were seen in the frontal, but not auditory, cortex in early development (p21) in female KO mice. Unlike male KO mice, female KO mice show WT-like temporal processing at p30. There were no temporal processing deficits in the adult mice of both sexes. Conclusions These results show a sex difference in the developmental trajectories of temporal processing and hypersensitive responses in Fmr1 KO mice. Male KO mice show slower maturation of temporal processing than females. Female KO mice show stronger hypersensitive responses than males later in development. The differences in maturation rates of temporal processing and hypersensitive responses during various critical periods of development may lead to sex differences in language function, arousal and anxiety in FXS.

Autism Spectrum Disorders (ASD) encompass a wide array of debilitating symptoms, including severe sensory deficits and abnormal language development. Sensory deficits early in development may lead to broader symptomatology in adolescents and adults. The mechanistic links between ASD risk genes, sensory processing and language impairment are unclear. There is also a sex bias in ASD diagnosis and symptomatology. The current study aims to identify the developmental trajectory and genotype- and sex-dependent differences in auditory sensitivity and temporal processing in a Pten-deletion (phosphatase and tensin homolog missing on chromosome 10) mouse model of ASD. Auditory temporal processing is crucial for speech recognition and language development and deficits will cause language impairments. However, very little is known about the development of temporal processing in ASD animal models, and if there are sex differences. To address this major gap, we recorded epidural electroencephalography (EEG) signals from the frontal (FC) and auditory (AC) cortex in developing and adult Nse-cre PTEN mice, in which Pten is deleted in specific cortical layers (layers III-V) (PTEN conditional knock-out (cKO). We quantified resting EEG spectral power distribution, auditory event related potentials (ERP) and temporal processing from awake and freely moving male and female mice. Temporal processing is measured using a gap-in-noise-ASSR (auditory steady state response) stimulus paradigm. The experimental manipulation of gap duration and modulation depth allows us to measure cortical entrainment to rapid gaps in sounds. Temporal processing was quantified using inter-trial phase clustering (ITPC) values that account for phase consistency across trials. The results show genotype differences in resting power distribution in PTEN cKO mice throughout development. Male and female cKO mice have significantly increased beta power but decreased high frequency oscillations in the AC and FC. Both male and female PTEN cKO mice show diminished ITPC in their gap-ASSR responses in the AC and FC compared to control mice. Overall, deficits become more prominent in adult (p60) mice, with cKO mice having significantly increased sound evoked power and decreased ITPC compared to controls. While both male and female cKO mice demonstrated severe temporal processing deficits across development, female cKO mice showed increased hypersensitivity compared to males, reflected as increased N1 and P2 amplitudes. These data identify a number of novel sensory processing deficits in a PTEN-ASD mouse model that are present from an early age. Abnormal temporal processing and hypersensitive responses may contribute to abnormal development of language function in ASD.

ObjectivesThe religious influence on the construction of emotions like love and hate have lacked empirical attention. This study sought to address this issue by exploring the influence of culture and religion on love and hate using both quantitative and qualitative measures.MethodSamples from Japan (n = 397), Thailand (n = 258), the U.S. (n = 198), and Sweden (n = 80) took an online survey on either love or hate. Quantitative measures were used to assess either positive or negative attitudes towards love and hate while qualitative measures were used to assess differences in the concepts of love and hate.ResultsQuantitative measures revealed that cultures (Japan and Thailand) with stronger Buddhist influence tend to have more moderate views of love and hate, while cultures with stronger Christian (Sweden and the U.S.) influence tend to have more polarized views of love and hate. Qualitative measures revealed that although the universal presence of love and hate share similar qualities across cultures, there are unique elements of both that may be lost when measuring love and hate.ConclusionsThese findings demonstrate a need to consider the religious influence on emotions. Especially when it comes to emotions like love and hate which have considerable influence over relationships, formation of family, and dissolution of alliances, religion may have a significantly broader influence than currently considered in the empirical literature.

It is well documented that prenatal ethanol exposure via maternal consumption of alcohol during pregnancy alters brain and behavioral development in offspring. Thus, the Centers for Disease Control (CDC) advises against maternal alcohol consumption during pregnancy. However, little emphasis has been placed on educating new parents about alcohol consumption while breastfeeding. This is partly due to a paucity of research on lactational ethanol exposure (LEE) effects in children; although, it has been shown that infants exposed to ethanol via breast milk frequently present with reduced body mass, low verbal IQ scores, and altered sleeping patterns. As approximately 36% of breastfeeding mothers in the US consume alcohol, continued research in this area is critical. Our study employed a novel murine LEE model, where offspring were exposed to ethanol via nursing from postnatal day (P) 6 through P20, a period correlated with infancy in humans. Compared to controls, LEE mice had reduced body weights and neocortical lengths at P20 and P30. Brain weights were also reduced in both ages in males, and at P20 for females, however, female brain weights recovered to control levels by P30. We investigated neocortical features and found that frontal cortex thickness was reduced in LEE males compared to controls. Analyses of dendritic spines in the prelimbic subdivision of medial prefrontal cortex revealed a trend of reduced densities in LEE mice. Results of behavioral tests suggest that LEE mice engage in higher risk-taking behavior, show abnormal stress regulation, and exhibit increased hyperactivity. In summary, our data describe potential adverse brain and behavioral developmental outcomes due to LEE. Thus, women should be advised to refrain from consuming alcohol during breastfeeding until additional research can better guide recommendations of safe maternal practices in early infancy.

BackgroundAutism spectrum disorders (ASD) encompass a wide array of debilitating symptoms, including sensory dysfunction and delayed language development. Auditory temporal processing is crucial for speech perception and language development. Abnormal development of temporal processing may account for the language impairments associated with ASD. Very little is known about the development of temporal processing in any animal model of ASD.MethodsIn the current study, we quantify auditory temporal processing throughout development in the Fmr1 knock-out (KO) mouse model of Fragile X Syndrome (FXS), a leading genetic cause of intellectual disability and ASD-associated behaviors. Using epidural electrodes in awake and freely moving wildtype (WT) and KO mice, we recorded auditory event related potentials (ERP) and auditory temporal processing with a gap-in-noise auditory steady state response (gap-ASSR) paradigm. Mice were recorded at three different ages in a cross sectional design: postnatal (p)21, p30 and p60. Recordings were obtained from both auditory and frontal cortices. The gap-ASSR requires underlying neural generators to synchronize responses to gaps of different widths embedded in noise, providing an objective measure of temporal processing across genotypes and age groups.ResultsWe present evidence that the frontal, but not auditory, cortex shows significant temporal processing deficits at p21 and p30, with poor ability to phase lock to rapid gaps in noise. Temporal processing was similar in both genotypes in adult mice. ERP amplitudes were larger in Fmr1 KO mice in both auditory and frontal cortex, consistent with ERP data in humans with FXS.ConclusionsThese data indicate cortical region-specific delays in temporal processing development in Fmr1 KO mice. Developmental delays in the ability of frontal cortex to follow rapid changes in sounds may shape language delays in FXS, and more broadly in ASD.

Abstract Background Depression can impact both the administration and efficacy of vaccines. Identifying social factors that contribute to depression, especially during a pandemic, is important for both current and future public health issues. Publicly available data can help identify key social factors contributing to depression. Method For each US state, information regarding their change in depression as measured by the Patient Health Questionnaire 2, predominant political affiliation, coronavirus disease 19 cases/100k, and lockdown severity were gathered. Structural equation modeling using latent change scores was conducted to assess the longitudinal relationships among depression, cases/100k, and state social restrictions. Results Higher initial levels of lockdown severity and depression predicted rank-order decreases in themselves over time. Correlations among the latent change variables reveal that changes in lockdown severity are negatively related to changes in cases/100k and changes in lockdown severity are positively related to changes in depression after controlling for the other variables. Conclusion Significant rank-order decreases in depression from T1 to T2 in blue states (who tend to vote for Democrats) vs red states (who tend to vote for Republicans) suggest that decreases in depression may be impacted by the population density and/or political views of that state. Rank-order increases in lockdown measures were negatively associated with rank-order increases in COVID-19 infections, demonstrating strong evidence that lockdown measures do help decrease the spread of COVID-19. Political affiliation and/or population density should be measured and assessed to help facilitate future public health efforts.

Introduction: Reports of mental health issues increased nationally in the USA during the COVID-19 pandemic, often attributed to the effects of quarantine, isolation, and restriction of travel. Given that Hawaiʻi State’s population is unique in its largely ethnic minority population, geographic isolation, and economic dependence on tourism, it is important to document if similar mental health outcomes have occurred during the beginning of the COVID-19 pandemic. Methods: This study compares Hawaiʻi’s rates of depression using data from the National Center for Health Statistics collected in 2020 and the Hawaiʻi Behavioral Risk Factor Surveillance System collected in 2016. Results: Hawaiʻi’s rate of depression, like the rest of the nation, increased significantly during the first wave. A chi-square test of independence was conducted, and the results were significant, χ2 (1, n = 20,261.42) = 582.48, p < .001. Before COVID-19, typical rates of depression were at 11.03%, 95% CI [10.51%, 11.55%]. During the COVID-19 pandemic, reports of depression increased to 24.23%, 95% CI [23.16%, 25.31%]. Conclusion: Depressive symptoms doubled during the early stages of the pandemic in Hawaiʻi. Evidence-based strategies should be developed now to help prevent future possible mental health related issues that are attributable to pandemic related safety protocols.

The prenatal period in human development reflects a time when the embryo or fetus is particularly sensitive to environmental insult from maternal experiences. Therefore, pregnant women should have a clear understanding of what toxins, or teratogens may be present in their environment and how unhealthy exposures can be avoided. Unfortunately, many teratogens go unnoticed in food and water supplies, which increases risk to fetal health and offspring outcome. Teratogens like Methylmercury (MeHg), Polychlorinated Biphenyls (PCBs), and Bisphenol-A (BPA) are hidden, or disguised, in seemingly healthy foods like fish or canned peaches; as well as polybrominated diphenyl ethers (PBDEs) found in seafood, soil, and flame retardants used in household items such as furniture and electronics. Other teratogens—such as nicotine, caffeine, cannabis, and alcohol—are not hidden, but their safety is disputed among physicians and in the media. This article highlights several disguised and disputed teratogens and describes how they may impact brain development, behavior, and mental health.

The preference for animal companionship over human companionship may be predicted by attitudes about pet ownership. We hypothesized that pet attitudes could predict preferences for relationships with pets over humans. We sampled 182 people who named a person and a pet they love and care about. Participants rated their feelings of love, time spent, enjoyment, and equity in both their human and pet relationships. We also presented seven hypothetical negative event scenarios that involve both the pet and human and asked participants to predict their feelings and reactions based on these events. The Pet Attitudes Scale (Templer et al., 1981) was used to assess attitudes towards pets. People had similar positive feelings about their pet-human and human-human relationships. However, people were more likely to react negatively towards a human compared to a pet. Positive pet attitudes predicted more positive and less negative reactions to pets. Positive pet attitudes can predict preference for pet relationships over human relationships and may help researchers identify what relationships work best depending on a personʻs pet attitudes.

Depression is currently ranked as the third leading contributor to global disease burden, and it is estimated that it will be number one by 2030. Care coordination models have been shown to help improve patient outcomes and reduce costs. Yet evidence-based standards for successfully contacting and engaging patients through care coordination are lacking. This study examines Integrated Health Hawaii's engagement-focused care coordination model to provide evidence for the most effective utilization of care coordination with those suffering from depression in a diverse population. The current standard of making a "good effort," three attempts, may only be reaching 60% of patients. To reach at least 75% of patients, seven attempts should be made; and to reach 95% of patients, 10 attempts should be made. These attempts can be made within a 2-week period, and the outcomes prevented are substantial in terms of alleviating symptoms, reducing Patient Health Questionnaire-9 scores, and preventing more costly care, including ER visits and self-harm.

Background: Fetal alcohol spectrum disorders (FASD) represent a leading cause of non-genetic neuropathologies. Recent preclinical evidence from suggests that prenatal ethanol exposure (PrEE), like other environmental exposures, may have a significant, transgenerational impact on the offspring of directly exposed animals, including altered neocortical development at birth and behavior in peri-pubescent mice. How these adverse behavioral outcomes are manifested within the brain at the time of behavioral disruption remains unknown. Methods: A transgenerational mouse model of FASD was used to generate up to a third filial generation of offspring to study. Using a multi-modal battery of behavioral assays, we assessed motor coordination/function, sensorimotor processing, risk-taking behavior, and depressive-like behavior in postnatal day (P) 20 pre-pubescent mice. Additionally, sensory neocortical area connectivity using dye tracing, neocortical gene expression using in situ RNA hybridization, and spine density of spiny stellate cells in the somatosensory cortex using Golgi-Cox staining were examined in mice at P20. Results: We found that PrEE induces behavioral abnormalities including abnormal sensorimotor processing, increased risk-taking behavior, and increased depressive-like behaviors that extend to the F3 generation in 20-day old mice. Assessment of both somatosensory and visual cortical connectivity, as well as cortical RZRβ expression in pre-pubescent mice yielded no significant differences among any experimental generations. In contrast, only directly-exposed F1 mice displayed altered cortical expression of Id2 and decreased spine density among layer IV spiny stellate cells in somatosensory cortex at this pre-pubescent, post weaning age. Conclusion: Our results suggest that robust, clinically-relevant behavioral abnormalities are passed transgenerationally to the offspring of mice directly exposed to prenatal ethanol. Additionally, in contrast to our previous findings in the newborn PrEE mouse, a lack of transgenerational findings within the brain at this later age illuminates the critical need for future studies to attempt to discover the link between neurological function and the described behavioral changes. Overall, our study suggests that multi-generational effects of PrEE may have a substantial impact on human behavior as well as health and well-being and that these effects likely extend beyond early childhood.

BACKGROUND:Presenteeism, the act of going to work while sick, is associated with increases in medication errors, patient falls, diminished quality of care, and higher costs. To date, presenteeism has not been described among nursing students.PURPOSE:This study described presenteeism in nursing students from 3 different international nursing programs.METHOD:A self-administered survey with open-ended responses was used.RESULTS:While nearly all student respondents believed going to class and clinical experiences put their classmates and patients at risk, the overall presenteeism rate was 85.5% for class and 69.5% for clinical experiences. Although there were significant differences between universities for reasons for presenteeism, a lack of opportunity for making up missed lecture or clinical time predominated.CONCLUSION:Nursing students in 3 culturally different cities reported going to class and clinical experiences while sick despite recognizing the safety risk.

Background Presenteeism, the act of going to work while sick, is associated with increases in medication errors, patient falls, diminished quality of care, and higher costs. To date, presenteeism has not been described among nursing students. Purpose This study described presenteeism in nursing students from 3 different international nursing programs. Method A self-administered survey with open-ended responses was used. Results While nearly all student respondents believed going to class and clinical experiences put their classmates and patients at risk, the overall presenteeism rate was 85.5% for class and 69.5% for clinical experiences. Although there were significant differences between universities for reasons for presenteeism, a lack of opportunity for making up missed lecture or clinical time predominated. Conclusion Nursing students in 3 culturally different cities reported going to class and clinical experiences while sick despite recognizing the safety risk.

It is well-accepted that eyewitness identification decisions based on relative judgments are less accurate than identification decisions based on absolute judgments. However, the theoretical foundation for this view has not been established. In this study relative and absolute judgments were compared through simulations of the WITNESS model (Clark, Appl Cogn Psychol 17:629-654, 2003) to address the question: Do suspect identifications based on absolute judgments have higher probative value than suspect identifications based on relative judgments? Simulations of the WITNESS model showed a consistent advantage for absolute judgments over relative judgments for suspect-matched lineups. However, simulations of same-foils lineups showed a complex interaction based on the accuracy of memory and the similarity relationships among lineup members.