Parent-Child Nativity, Race, Ethnicity, and Common Mental Health Conditions Among United States Children and Adolescents.

OBJECTIVE: To examine associations between race, ethnicity, and parent-child nativity, and common mental health conditions among U.S. children and adolescents. METHODS: Data were from 2016 to 2019 National Survey of Children's Health, a US population-based, serial cross-sectional survey, and restricted to children who had access to health care. We used weighted multivariable logistic regression to examine the associations between race and ethnicity (Asian, Black, Hispanic, White, Other-race); mental health outcomes (depression, anxiety, and behavior/conduct problems) stratified by household generation; and between household generation and outcomes stratified by race and ethnicity, adjusting for demographics (age, sex, family income to poverty ratio, parental education), and an adverse childhood experience (ACE) score. RESULTS: When stratifying by household generation, racial and ethnic minority children generally had similar to lower odds of outcomes compared with White children, with the exception of higher odds of behavior/conduct problems among third + -generation Black children. When stratifying by race and ethnicity, third + generation children had increased odds of depression compared to their first-generation counterparts. Third + generation, racial and ethnic minority children had increased odds of anxiety and behavior/conduct problems compared with their first-generation counterparts. The associations generally remained significant after adjusting for the ACE score. CONCLUSIONS: Lower odds of common mental health conditions in racial and ethnic minority children could be due to factors such as differential reporting, and higher estimates, including those in third + generation children, could be due to factors including discrimination; systemic racism; and other factors that vary by generation and need further investigation to advance health equity.

Financial hardship during the COVID-19 pandemic and increased receipt of commercial tobacco discount coupons among US adults who use commercial tobacco.

INTRODUCTION: Many individuals experienced financial hardship during the COVID-19 pandemic; yet commercial tobacco (CT) sales increased in the USA. We examined how experiencing financial hardships relates to increased CT discount coupon reception during the pandemic. METHODS: A nationally representative sample of 1700 US adults who used CT during the 12 months prior to the survey were surveyed online during January to February 2021. Participants reported if they had received more discount coupons for various CT products during (compared with before) the pandemic. They also reported whether they experienced six different types of financial hardships since the pandemic, and the total number of hardships experienced was counted. Weighted multivariable logistic regressions were used to examine the associations between financial hardships and increased coupon reception, adjusting for demographics and CT product use. RESULTS: During the first 10-11 months of the pandemic, 21.3% of US adults who used CT during the 12 months prior to the survey reported receiving more CT discount coupons. Experiencing financial hardship during the pandemic was associated with higher odds of receiving more coupons for all types of CT products: every additional count of financial hardship was associated with higher odds of increased reception of discount coupons for all CT products (adjusted odds ratios ranging from 1.13 to 1.23 across products). CONCLUSIONS: Over one-fifth of US adults who used CT received more discount coupons during the pandemic. Those facing financial hardships had higher discount coupon reception, suggesting potential targeted marketing to financially vulnerable individuals by the tobacco industry.

Financial challenges and hardship during the COVID-19 pandemic and tobacco expenditure minimizing strategies among U.S. adult commercial tobacco users.

INTRODUCTION: Commercial tobacco (CT) users employ tobacco expenditure minimizing strategies (TEMS) to manage their CT expenditures. We examined how financial challenges and hardships during the COVID-19 pandemic relate to increases in TEMS use. METHODS: Data from a nationally representative sample of 1,700 U.S. adult recent former and current CT users were collected from an online panel during January-February 2021. Participants reported if they had increased use of eight TEMS to save money on CT since the pandemic, and experienced financial challenges (e.g., losing a job) and hardships (e.g., not having enough money to pay for food). The number of financial hardships experienced was counted (range: 0-6). Weighted multivariable logistic regression models were used to examine the associations between financial challenges and hardships and increased TEMS use, adjusting for demographics. RESULTS: Since the COVID-19 pandemic, three TEMS showed the largest increase in use by U.S. adult current and recent former CT users: cutting back (22.4%), finding less expensive places to purchase (15.6%), and buying by bulk (15.5%). Many financial challenges and hardships were consistently associated with increased uses of TEMS. Furthermore, every additional count of financial hardships was associated with higher odds of increasing use of each TEMS (AORs ranging between 1.12 and 1.23). CONCLUSIONS: Many CT users increased TEMS use to manage their CT expenditures when facing financial challenges and hardships during the pandemic. This could hinder CT cessation and promote relapse. Prohibiting certain TEMS (e.g., discount coupon and price promotions) may promote CT cessation among this financially vulnerable group.

Parent-Child Nativity, Race, Ethnicity, and Adverse Childhood Experiences Among U.S. Children.

We examined the relationship between parent-child nativity, race/ethnicity, and adverse childhood experiences (ACEs) among US children. We found that a high proportion of Black/Hispanic children experienced ACEs, with variation by generation for Hispanic but not Black children, and a lower but increasing proportion of White children experienced ACEs by generation.

Parenting a Child with a Neurodevelopmental Disorder during the Early Stage of the COVID-19 Pandemic: Quantitative and Qualitative Cross-Cultural Findings.

Research during the COVID-19 pandemic has shown a strong relationship between child symptoms, parental stress, and mental health challenges. The pandemic has changed family routines, worsening child symptomatology and parental burden. The aim of this study was to investigate how the magnitude of the perceived changes in child externalizing behavior, parental stress, and discontinuity of therapy-from before to during the COVID-19 pandemic-affected parental mental health during the pandemic. Moreover, we sought to compare these aspects cross-culturally between European countries and the USA. To these purposes, we asked Italian, Spanish, and U.S. parents of children with neurodevelopmental disabilities (NDD) to complete an online survey. Quantitative results showed that increased parental stress may have contributed to a worsening in parental psychological distress, regardless of culture. Moreover, they suggested an indirect effect of child externalizing behaviors on parents' psychological distress via parental stress. Qualitative analyses highlighted that the lack, or discontinuity, of therapeutic activities may have been one of the key contributors to parenting burden during the COVID-19 pandemic. Finally, qualitative results highlighted resilience factors that could have decreased the risk of psychological problems during the pandemic, such as a strong sense of parental efficacy and the ability to adapt to changing family dynamics.

Adverse Childhood Experiences Predict Common Neurodevelopmental and Behavioral Health Conditions among U.S. Children.

OBJECTIVE: Adverse childhood experiences (ACEs) can have a significant but variable effect on childhood neurodevelopment. The purpose of this study was to quantify and compare the associations between "household challenge" ACEs and common childhood neurodevelopmental and behavioral health conditions, using nationally representative U.S. METHOD: This study used data from the 2016-2019 National Survey of Children's Health, a nationwide, population-based, cross-sectional survey. Seven household challenge ACEs (not including child maltreatment) were reported by parents/guardians: parental death, incarceration, divorce/separation, family violence, mental illness, substance abuse, and poverty. Logistic regression with sample weights was used to estimate the odds ratio (OR) for 15 parent-reported neurodevelopmental and behavioral health conditions, by the number of reported ACEs. A dose-response relationship was examined by applying tests of orthogonal polynomial contrasts to fitted logistic regression models. RESULTS: Down syndrome, Tourette syndrome and cerebral palsy were not associated with household challenge ACEs, whereas behavior/conduct problems, depression, and substance abuse were strongly associated, with adjusted ORs ranging from 6.36 (95% confidence interval (CI) 5.53, 7.32) to 9.19 (95% CI 7.79, 10.84). Other neurodevelopmental conditions not traditionally associated with childhood adversity showed moderate yet robust associations with ACEs, including autism (adjusted OR 2.15, 95% CI 1.64, 2.81), learning disability (adjusted OR 3.26, 95% CI 2.80, 3.80), and attention deficit hyperactivity disorder (adjusted OR 3.95, 95% CI 3.44, 4.53). The ORs increased with the number of ACEs, showing significant positive linear trends. CONCLUSION: We found significant dose-dependent or cumulative associations between ACEs and multiple neurodevelopmental and behavioral conditions.

Toll-like receptor 4 and myeloid differentiation factor 88 are required for gastric bypass-induced metabolic effects.

BACKGROUND: Toll-like receptor 4 (TLR4) has been suggested as one of the forefront cross-communicators between the intestinal bacteria and the host to regulate inflammatory signals and energy homeostasis. High-fat diet-induced inflammation is mediated by changes in gut microbiota and requires a functional TLR-4, the deficiency of which renders mice resistant to diet-induced obesity and its associated metabolic dysfunction. Furthermore, gut microbiota was suggested to play a key role in the beneficial effects of Roux-en-Y gastric bypass (RYGB), a commonly performed bariatric procedure. OBJECTIVES: To explore whether TLR4, myeloid differentiation factor 8 (MyD88; 1 of its key downstream signaling regulators) and gut microbiota play an integrative role in RYGB-induced metabolic outcomes. SETTING: Animal- based study. METHOD: We performed RYGB in TLR4 and MyD88 knock-out (KO) mice and used fecal microbiota transplant (FMT) from RYGB-operated animals to these genetic mouse models to address our questions. RESULTS: We demonstrate that RYGB reduces TLR4 expression explicitly in the small and large intestine of C57Blc/6J mice. We also show that TLR4 KO mice have an attenuated glucoregulatory response to RYGB. In addition, we reveal that MyD88 KO mice fail to respond to all RYGB-induced metabolic effects. Finally, fecal microbiota transplant from RYGB-operated mice into TLR4 KO and MyD88 KO naïve recipients fails to induce a metabolic phenotype similar to that of the donors, as it does in wild-type recipients. CONCLUSION: TLR4 and MyD88 are required for RYGB-induced metabolic response that is likely mediated by gut microbiome.

Bispectral EEG (BSEEG) quantifying neuro-inflammation in mice induced by systemic inflammation: A potential mouse model of delirium.

Most of the animal studies using inflammation-induced cognitive change have relied on behavioral testing without objective and biologically solid methods to quantify the severity of cognitive disturbances. We have developed a bispectral EEG (BSEEG) method using a novel algorithm in clinical study. This method effectively differentiates between patients with and without delirium, and predict long-term mortality. In the present study, we aimed to apply our bispectral EEG (BSEEG) method, which can detect patients with delirium, to a mouse model of delirium with systemic inflammation induced by lipopolysaccharides (LPS) injection. We recorded EEG after LPS injection using wildtype early adulthood mice (2~3-month-old) and aged mice (18-19-month-old). Animal EEG recordings were converted for power spectral density to calculate BSEEG score using the similar BSEEG algorithm previously developed for our human study. The BSEEG score was relatively stable and slightly high during the day. Alternatively, the BSEEG score was erratic and low in average during the night. LPS injection increased the BSEEG score dose-dependently and diminished the diurnal changes. The mean BSEEG score increased much more in the aged mice group as dosage increased. Our results suggest that BSEEG method can objectively "quantify" level of neuro-Inflammation induced by systemic inflammation (LPS), and that this BSEEG method can be useful as a model of delirium in mice.

Nationwide efforts for trauma-informed care implementation and workforce development in healthcare and related fields: a systematic review.

There is building evidence that Adverse Childhood Experiences without early and proper intervention leads to subsequent short- and long-term behavioral, social, physical and mental health problems. Practitioners, researchers, and healthcare systems have been implementing trauma-informed care (TIC) in a variety of health and human services settings, resulting in improvements in clinical care and prevention of illness by identifying high risk populations. This has led to positive health outcomes including improved compliance, better access to mental health services and reduced health care costs. A systematic review was conducted of studies that focused on TIC implementation in healthcare settings, statewide TIC implementation, impact of adverse childhood experiences on health outcomes, impact of TIC on health outcomes, and evaluation of TIC implementation. A search was conducted in March 2019 to identify studies in PubMed, Medline, and other online literature. We limited our search to articles published in English after 2000. This article aims to review the components of TIC phases of implementation in healthcare settings, success stories across the nation to help the readers understand the importance of a paradigm shift to improve healthcare delivery and health outcomes and to prevent illness starting from childhood with a family centered care perspective.

Mimic for Child Physical Abuse: Biochemical and Genetic Evidence of Hypophosphatasia without Classic Radiologic Findings.

Infants presenting with multiple fractures without a plausible accident history need to be evaluated for child abuse or underlying predisposing conditions such as osteogenesis imperfecta and hypophosphatasia. We present a case of infantile hypophosphatasia with multiple unexplained fractures but otherwise normal radiographs in the setting of biochemical and genetic evidence of hypophosphatasia. Standard screening tests for hypophosphatasia include serum alkaline phosphatase level and genetic testing. Despite the presented case's positive biochemical and genetic testing, the case did not have any other radiologic finding suggesting infantile hypophosphatasia, such as severe bone mineralization deficits and rickets. While patients with hypophosphatasia can have increased bone fragility, this has been reported in the context of radiologic abnormalities of the skeleton. Thus, this case is potentially the first reported infantile hypophosphatasia case presenting with no findings of rickets on radiographs, raising concern that the fractures and especially the radius head dislocation might be due to physical abuse.

Endocannabinoid Receptor-1 and Sympathetic Nervous System Mediate the Beneficial Metabolic Effects of Gastric Bypass.

The exact mechanisms underlying the metabolic effects of bariatric surgery remain unclear. Here, we demonstrate, using a combination of direct and indirect calorimetry, an increase in total resting metabolic rate (RMR) and specifically anaerobic RMR after Roux-en-Y gastric bypass (RYGB), but not sleeve gastrectomy (SG). We also show an RYGB-specific increase in splanchnic sympathetic nerve activity and "browning" of visceral mesenteric fat. Consequently, selective splanchnic denervation abolishes all beneficial metabolic outcomes of gastric bypass that involve changes in the endocannabinoid signaling within the small intestine. Furthermore, we demonstrate that administration of rimonabant, an endocannabinoid receptor-1 (CB1) inverse agonist, to obese mice mimics RYGB-specific effects on energy balance and splanchnic nerve activity. On the other hand, arachidonoylethanolamide (AEA), a CB1 agonist, attenuates the weight loss and metabolic signature of this procedure. These findings identify CB1 as a key player in energy regulation post-RYGB via a pathway involving the sympathetic nervous system.

Bispectral EEG (BSEEG) to assess arousal after electro-convulsive therapy (ECT).

OBJECTIVES: Postictal confusion is encountered among most patients following electro-convulsive therapy (ECT). This study aimed to test the capabilities of a point-of-care electroencephalography (EEG) method to quantitatively measure and monitor postictal confusion immediately following ECT. We evaluated whether a two-channel frontal EEG device may provide a purely quantitative measure of the postictal state that could aid in the continuous, clinical monitoring of patients following ECT. METHODS: 50 patients receiving ECT at the University of Iowa Hospitals and Clinics were recruited for this study. Subsequently, we obtained 5 min of frontal bispectral EEG (BSEEG) recording from a hand-held EEG device at baseline and 10-20 min following ECT. We performed power spectral density analysis to yield a "BSEEG" score and to capture the difference between patients at baseline and after ECT. RESULTS: The BSEEG score was demonstrated to be a significant indicator of postictal confusion compared to baseline. For 5 patients, we also obtained continuous EEG recordings following ECT to determine the time course required for a patient's BSEEG score to return to baseline. In this subset of patients, it took between 2 and 3 h in duration for the BSEEG score to return to the baseline range. CONCLUSIONS: In this pilot study, we showed that BSEEG score was able to distinguish between baseline condition and postictal confusion in patients treated with ECT, and assess the duration for recovery from postictal confusion following ECT. BSEEG may provide a more sensitive measure of arousal in patients following ECT compared to traditional survey-based methods.

Microbiota Analysis Using Two-step PCR and Next-generation 16S rRNA Gene Sequencing.

The human gut is colonized by trillions of bacteria that support physiologic functions such as food metabolism, energy harvesting, and regulation of the immune system. Perturbation of the healthy gut microbiome has been suggested to play a role in the development of inflammatory diseases, including multiple sclerosis (MS). Environmental and genetic factors can influence the composition of the microbiome; therefore, identification of microbial communities linked with a disease phenotype has become the first step towards defining the microbiome's role in health and disease. Use of 16S rRNA metagenomic sequencing for profiling bacterial community has helped in advancing microbiome research. Despite its wide use, there is no uniform protocol for 16S rRNA-based taxonomic profiling analysis. Another limitation is the low resolution of taxonomic assignment due to technical difficulties such as smaller sequencing reads, as well as use of only forward (R1) reads in the final analysis due to low quality of reverse (R2) reads. There is need for a simplified method with high resolution to characterize bacterial diversity in a given biospecimen. Advancements in sequencing technology with the ability to sequence longer reads at high resolution have helped to overcome some of these challenges. Present sequencing technology combined with a publicly available metagenomic analysis pipeline such as R-based Divisive Amplicon Denoising Algorithm-2 (DADA2) has helped advance microbial profiling at high resolution, as DADA2 can assign sequence at the genus and species levels. Described here is a guide for performing bacterial profiling using two-step amplification of the V3-V4 region of the 16S rRNA gene, followed by analysis using freely available analysis tools (i.e., DADA2, Phyloseq, and METAGENassist). It is believed that this simple and complete workflow will serve as an excellent tool for researchers interested in performing microbiome profiling studies.

Identification of Patients With High Mortality Risk and Prediction of Outcomes in Delirium by Bispectral EEG.

BACKGROUND: Delirium is common and dangerous, yet underdetected and undertreated. Current screening questionnaires are subjective and ineffectively implemented in busy hospital workflows. Electroencephalography (EEG) can objectively detect the diffuse slowing characteristic of delirium, but it is not suitable for high-throughput screening due to size, cost, and the expertise required for lead placement and interpretation. This study hypothesized that an efficient and reliable point-of-care EEG device for high-throughput screening could be developed. METHODS: This prospective study, which measured bispectral EEG (BSEEG) from elderly inpatients to assess their outcomes, was conducted at the University of Iowa Hospitals and Clinics from January 2016 to October 2017. A BSEEG score was defined based on the distribution of 2,938 EEG recordings from the 428 subjects who were assessed for delirium; primary outcomes measured were hospital length of stay, discharge disposition, and mortality. RESULTS: A total of 274 patients had BSEEG score data available for analysis. Delirium and BSEEG score had a significant association (P < .001). Higher BSEEG scores were significantly correlated with length of stay (P < .001 unadjusted, P = .001 adjusted for age, sex, and Charlson Comorbidity Index [CCI] score) as well as with discharge not to home (P < .01). Hazard ratio for survival controlling for age, sex, CCI score, and delirium status was 1.35 (95% CI,1.04 to 1.76; P = .025). CONCLUSIONS: In BSEEG, an efficient and reliable device that provides an objective measurement of delirium status was developed. The BSEEG score is significantly associated with pertinent clinical outcomes of mortality, hospital length of stay, and discharge disposition. The BSEEG score better predicts mortality than does clinical delirium status. This study identified a previously unrecognized subpopulation of patients without clinical features of delirium who are at increased mortality risk.

Prevotella histicola, A Human Gut Commensal, Is as Potent as COPAXONE® in an Animal Model of Multiple Sclerosis.

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system. We and others have shown that there is enrichment or depletion of some gut bacteria in MS patients compared to healthy controls (HC), suggesting an important role of the gut bacteria in disease pathogenesis. Thus, specific gut bacteria that are lower in abundance in MS patients could be used as a potential treatment option for this disease. In particular, we and others have shown that MS patients have a lower abundance of Prevotella compared to HC, whereas the abundance of Prevotella is increased in patients that receive disease-modifying therapies such as Copaxone® (Glatiramer acetate-GA). This inverse correlation between the severity of MS disease and the abundance of Prevotella suggests its potential for use as a therapeutic option to treat MS. Notably we have previously identified a specific strain, Prevotella histicola (P. histicola), that suppresses disease in the animal model of MS, experimental autoimmune encephalomyelitis (EAE) compared with sham treatment. In the present study we analyzed whether the disease suppressing effects of P. histicola synergize with those of the disease-modifying drug Copaxone® to more effectively suppress disease compared to either treatment alone. Treatment with P. histicola was as effective in suppressing disease as treatment with Copaxone®, whereas the combination of P. histicola plus Copaxone® was not more effective than either individual treatment. P. histicola-treated mice had an increased frequency and number of CD4+FoxP3+ regulatory T cells in periphery as well as gut and a decreased frequency of pro-inflammatory IFN-γ and IL17-producing CD4 T cells in the CNS, suggesting P. histicola suppresses disease by boosting anti-inflammatory immune responses and inhibiting pro-inflammatory immune responses. In conclusion, our study indicates that the human gut commensal P. histicola can suppress disease as efficiently as Copaxone® and may provide an alternative treatment option for MS patients.

Delirium detection by a novel bispectral electroencephalography device in general hospital.

AIM: Delirium is common and dangerous among elderly inpatients; yet, it is underdiagnosed and thus undertreated. This study aimed to test the diagnostic characteristics of a noninvasive point-of-care device with two-channel (bispectral) electroencephalography (EEG) for the screening of delirium in the hospital. METHODS: Patients admitted to the University of Iowa Hospitals and Clinics were assessed for the presence of delirium with a clinical assessment, the Confusion Assessment Method for Intensive Care Unit and Delirium Rating Scale. Subsequently, we obtained a 10-min bispectral EEG (BSEEG) recording from a hand-held electroencephalogram device during hospitalization. We performed power spectral density analysis to differentiate between those patients with and without delirium. RESULTS: Initially 45 subjects were used as a test dataset to establish a cut-off. The BSEEG index was determined to be a significant indicator of delirium, with sensitivity 80% and specificity 87.7%. An additional independent validation dataset with 24 patients confirmed the validity of the approach, with a sensitivity of 83.3% and specificity of 83.3%. CONCLUSION: In this pilot study, the BSEEG method was able to distinguish delirious patients from non-delirious patients. Our data showed the feasibility of this technology for mass screening of delirium in the hospital.

Sonic hedgehog antagonists reduce size and alter patterning of the frog inner ear.

Sonic hedgehog (Shh) signaling plays a major role in vertebrate development, from regulation of proliferation to the patterning of various organs. In amniotes, Shh affects dorsoventral patterning in the inner ear but affects anteroposterior patterning in teleost ears. It remains unknown how altered function of Shh relates to morphogenetic changes that coincide with the evolution of limbs and novel auditory organs in the ear. In this study, we used the tetrapod, Xenopus laevis, to test how increasing concentrations of the Shh signal pathway antagonist, Vismodegib, affects ear development. Vismodegib treatment dose dependently alters the development of the ear, hypaxial muscle, and indirectly the Mauthner cell through its interaction with the inner ear afferents. Together, these phenotypes have an effect on escape response. The altered Mauthner cell likely contributes to the increased time to respond to a stimulus. In addition, the increased hypaxial muscle in the trunk likely contributes to the subtle change in animal C-start flexion angle. In the ear, Vismodegib treatment results in decreasing segregation between the gravistatic sensory epithelia as the concentration of Vismodegib increases. Furthermore, at higher doses, there is a loss of the horizontal canal but no enantiomorphic transformation, as in bony fish lacking Shh. Like in amniotes, Shh signaling in frogs affects dorsoventral patterning in the ear, suggesting that auditory sensory evolution in sarcopterygians/tetrapods evolved with a shift of Shh function in axis specification. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1385-1400, 2017.

A method for detailed movement pattern analysis of tadpole startle response.

Prolonged space flight, specifically microgravity, presents a problem for space exploration. Animal models with altered connections of the vestibular ear, and thus altered gravity sensation, would allow the examination of the effects of microgravity and how various countermeasures can establish normal function. We describe an experimental apparatus to monitor the effects of ear manipulations to generate asymmetric gravity input on the tadpole escape response. To perform the movement pattern analysis, an imaging apparatus was developed that uses a high-speed camera to obtain time-resolved, high-resolution images of tadpole movements. Movements were recorded in a temperature-controlled test chamber following mechanical stimulation with a solenoid actuator, to elicit a C-start response. Temperature within the test cell was controlled with a recirculating water bath. Xenopus laevis embryos were obtained using a standard fertilization technique. Tadpole response to a controlled perturbation was recorded in unprecedented detail and the approach was validated by describing the distinct differences in response between normal and one-eared tadpoles. The experimental apparatus and methods form an important element of a rigorous investigation into the response of the tadpole vestibular system to mechanical and biochemical manipulations, and can ultimately contribute to improved understanding of the effects of altered gravity perception on humans.