Neighborhood disadvantage and pediatric inpatient opioid prescription patterns.

BACKGROUND: To explore the role of children's residential environment on opioid prescribing patterns in a predominantly Latinx sample. METHODS: We connected geocoded data from electronic medical records in a diverse sample of pediatric patients to neighborhood environments constructed using latent profile modeling techniques. We then estimated a series of multilevel models to determine whether opioid prescribing patterns vary by residential context. RESULTS: A stepwise pattern exists between neighborhood disadvantage and pediatric opioid prescription patterns, such that higher levels of disadvantage associate with a greater likelihood of opioid prescription, independent of the patient's individual profile. CONCLUSION: In a largely Latinx sample of children, the neighborhood in which a child lives influences whether or not they will receive opioids. Considering the differences in patient residential environment may reduce variation in opioid dispensing rates among pediatric patients.

Deconstructing sex differences in C-reactive protein trends over time.

OBJECTIVES: Heightened inflammatory state, as measured by circulating C-reactive protein (CRP) levels, can promote inflammation-mediated disease risk. It is important to account for population fluctuation and sex variation in serum CRP concentrations on overall time trends. METHODS: Using the National Health and Nutrition Examination Survey data, we specify linear and algebraic decomposition models separately by sex to identify the drivers of the changing trends in the distribution of CRP values in the population. RESULTS: We found a nonsignificant overall increase in CRP, but a significant decrease among women and increase among men, over a 10-year period. We then used linear and algebraic decomposition techniques to identify the sources of change in CRP over time, separately for women and men. CRP increased among men mainly because lifestyle/health characteristics worsened over time, and because the size of socioeconomic/demographic groups with higher CRP increased and the size of groups with lower CRP decreased. The downward shift in CRP among women occurred because the typical woman across all cohorts had lower CRP levels. CONCLUSIONS: We identified two fundamentally different processes of change driving the decline and rise in CRP values among women and men, respectively.

Pediatric obesity in the United States: Age-period-cohort analysis.

The rates of obesity among American children aged 2-5 years has reached a historic high. It is crucial to identify the putative sources of population-level increases in obesity prevalence among preschool-aged children because early childhood is a critical window for obesity prevention and thus reduction of future incidence. We used the National Health and Nutrition Examination Survey data and hierarchical age-period-cohort analysis to examine lifecycle (i.e., age), historical (i.e., period), and generational (i.e., cohort) distribution of age- and sex-specific body mass index z-scores (zBMI) among 2-5-year-olds in the U.S. from 1999 to 2018. Our current findings indicate that period effects, rather than differences in groups born at a specific time (i.e., cohort effects), account for almost all of the observed changes in zBMI. We need a broad socioeconomic, cultural, and environmental strategy to counteract the current obesogenic environment that influences children of all ages and generations in order to reach large segments of preschoolers and achieve population-wide improvement.

Obesity Heterogeneity by Neighborhood Context in a Largely Latinx Sample.

Neighborhood socioeconomic context where Latinx children live may influence body weight status. Los Angeles County and Orange County of Southern California both are on the list of the top ten counties with the largest Latinx population in the USA. This heterogeneity allowed us to estimate differential impacts of neighborhood environment on children's body mass index z-scores by race/ethnicity using novel methods and a rich data source. We geocoded pediatric electronic medical record data from a predominantly Latinx sample and characterized neighborhoods into unique residential contexts using latent profile modeling techniques. We estimated multilevel linear regression models that adjust for comorbid conditions and found that a child's place of residence independently associates with higher body mass index z-scores. Interactions further reveal that Latinx children living in Middle-Class neighborhoods have higher BMI z-scores than Asian and Other Race children residing in the most disadvantaged communities. Our findings underscore the complex relationship between community racial/ethnic composition and neighborhood socioeconomic context on body weight status during childhood.

Imatinib methanesulfonate reduces hippocampal amyloid-ß and restores cognitive function following repeated endotoxin exposure.

Alzheimer's disease (AD) is characterized, in part, by atrophy of the adult brain and increased presence of extracellular amyloid-beta (Aß) plaques. Previous studies in our lab have shown that peripheral inflammation can lead to increased central Aß and deficits in learning and memory. In order to determine whether Aß accumulation in the brain is responsible for the learning deficits, we attempted to decrease peripheral production of Aß in order to reduce central Aß accumulation. It has previously been shown that Aß is produced in large quantities in the liver, and is transferred across the blood-brain barrier (BBB). Recent research has shown that peripheral treatment with imatinib methanesulfonate salt (IM), known to interfere with the interaction between gamma (γ)-secretase and the γ-secretase activating protein (GSAP), decreases the cleavage of peripheral amyloid precursor protein into Aß. Because IM poorly penetrates the BBB, we hypothesized that co-administration of IM with LPS would decrease peripheral production of Aß in the presence of LPS-induced inflammation, leading to a decrease in Aß accumulation in the hippocampus. We show that peripheral IM treatment eliminates hippocampal Aß elevation that follows LPS-induced peripheral inflammation. Importantly, IM also eliminates the cognitive impairment seen following seven consecutive days of LPS administration, implicating Aß peptides as a likely cause of these cognitive deficits.

Explaining adult obesity, severe obesity, and BMI: Five decades of change.

Obesity rates have increased across all segments of society since the late 1970s, but the reason behind population-level increases in body weight remains unclear. We used the 1971-2020 NHANES data to examine whether the observed trend in obesity prevalence is attributable to changing public health behaviors (i.e., intracohort change) or changing publics (i.e., cohort replacement). We partitioned total change in mean BMI, and rates of obesity and severe obesity, into its IC and CR components using linear and algebraic decomposition methods. We found that the IC mechanism (i.e., broad sectors of individuals changing) plays a dominant role in the overall increase in mean BMI, and obesity and severe obesity prevalence. Birth cohort membership (i.e., the CR mechanism) is also influencing mean BMI, and rates of obesity and severe obesity, but in differing ways. Specifically, the large positive IC and the small positive CR effects are amplifying one another, thus creating a steep increase in the observed rates of severe obesity. Conversely, the large positive IC effect is offset by a small negative CR effect, which created a more gradual rise in mean BMI and rates of obesity. Furthermore, we computed total change for models that entered separately sociodemographic, lifestyle, nutritional, and physical activity measures to estimate differences in mean BMI, and rates of obesity and severe obesity, among cohorts and time periods. Adjustment for all the compositional differences among the cohorts during the study period indicate that a combination of a more pronounced IC and a less pronounced CR drove the observed increase in mean BMI, and rates of obesity and severe obesity. Thus, "universal prevention" (i.e., entire community) strategies for healthy weight promotion may need to be combined with "selective prevention" (i.e., at-risk groups) and/or "targeted prevention" (i.e., at-risk individuals) approaches in order to reverse the obesity epidemic.

Peripheral bacterial endotoxin administration triggers both memory consolidation and reconsolidation deficits in mice.

Peripherally administered inflammatory stimuli, such as lipopolysaccharide (LPS), induce the synthesis and release of proinflammatory cytokines and chemokines in the periphery and the central nervous system, and trigger a variety of neurobiological responses. Indeed, prior reports indicate that peripheral LPS administration in rats disrupts contextual fear memory consolidation processes, potentially due to elevated cytokine expression. We used a similar, but partially olfaction-based, contextual fear conditioning paradigm to examine the effects of LPS on memory consolidation and reconsolidation in mice. Additionally, interleukin-1ß (IL-1ß), brain-derived neurotrophic factor (BDNF), and zinc finger (Zif)-268 mRNA expression in the hippocampus and the cortex, along with peripheral cytokines and chemokines, were assessed. As hypothesized, LPS administered immediately or 2 h, but not 12 h, post-training impaired memory consolidation processes that support the storage of the conditioned contextual fear memory. Additionally, as hypothesized, LPS administered immediately following the fear memory trace reactivation session impaired memory reconsolidation processes. Four hours post-injection, both central cytokine and peripheral cytokine and chemokine levels were heightened in LPS-treated animals, with a simultaneous decrease in BDNF, but not Zif-268, mRNA. Collectively, these data reinforce prior work showing LPS- and cytokine-related effects on memory consolidation, and extend this work to memory reconsolidation.

County-Level Factors That Influenced the Trajectory of COVID-19 Incidence in the New York City Area.

More than a century of research has shown that sociodemographic conditions affect infectious disease transmission. In the late spring and early summer of 2020, reports of the effects of sociodemographic variables on the spread of COVID-19 were used in the media with minimal scientific proof attached. With new cases of COVID-19 surging in the United States at that time, it became essential to better understand how the spread of COVID-19 was varying across all segments of the population. We used hierarchical exponential growth curve modeling techniques to examine whether community socioeconomic characteristics uniquely influence the incidence of reported COVID-19 cases in the urban built environment. We show that as of July 19, 2020, confirmed coronavirus infections in New York City and surrounding areas-one of the early epicenters of the COVID-19 pandemic in the United States-were concentrated along demographic and socioeconomic lines. Furthermore, our data provides evidence that after the onset of the pandemic, timely enactment of physical distancing measures such as school closures was essential to limiting the extent of the coronavirus spread in the population. We conclude that in a pandemic, public health authorities must impose physical distancing measures early on as well as consider community-level factors that associate with a greater risk of viral transmission.

Decomposing Differences in Coronavirus disease 2019-related Case-Fatality Rates across Seventeen Nations.

As of 1 November 2020, estimated case-fatality rates associated with coronavirus disease 2019 are not uniformly patterned across the world and differ substantially in magnitude. Given the global spatial heterogeneity in case-fatality rates, we applied the Blinder-Oaxaca regression decomposition technique to identify how putative sociodemographic, structural, and environmental sources influence variation in case-fatality rates. We show that compositional and associational differences in country-level risk factors explain a substantial proportion of the coronavirus disease 2019-related case-fatality rate gap across nations. Asian countries fair better vis-à-vis case-fatality rate differences mainly due to variation in returns to sociodemographic, structural, and environmental sources among their citizens, relative to those who share similar attributes but live in Europe or North America. The variation in case-fatality rate is driven by Asian populations being better able to buffer the harmful effects of the very risk factors purported to exacerbate the risk of coronavirus disease 2019-related death. The dire circumstances in which we find ourselves demand better understanding of how preexisting conditions across countries contribute to observed disparities in case-fatality rates.

Surgical Patients' Hospital Experience Scores: Neighborhood Context Conceptual Framework.

Objective: Through geocoding the physical residential address included in the electronic medical record to the census tract level, we present a novel model for concomitant examination of individual patient-related and residential context-related factors that are associated with patient-reported experience scores. Summary Background Data: When assessing patient experience in the surgical setting, researchers need to examine the potential influence of neighborhood-level characteristics on patient experience-of-care ratings. Methods: We geocoded the residential address included in the electronic medical record (EMR) from a tertiary care facility to the census tract level of Orange County, CA. We then linked each individual record to the matching census tract and use hierarchical regression analyses to test the impact of distinct neighborhood conditions on patient experience. This approach allows us to estimate how each neighborhood characteristic uniquely influences Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) scores. Results: Individuals residing in communities characterized by high levels of socioeconomic disadvantage have the highest experience ratings. Accounting for individual patient's characteristics such as age, gender, race/ethnicity, primary language spoken at home, length of stay, and average pain levels during their hospital stay, neighborhood-level characteristics such as proportions of people receiving public assistance influence the ratings of hospital experience (0.01, P < 0.05) independent of, and beyond, these individual-level factors. Conclusions: This manuscript is an example of how geocoding could be used to analyze surgical patient experience scores. In this analysis, we have shown that neighborhood-level characteristics influence the ratings of hospital experience independent of, and beyond, individual-level factors.

Peripheral administration of poly I:C leads to increased hippocampal amyloid-beta and cognitive deficits in a non-transgenic mouse.

Alzheimer's disease (AD) is a progressive disorder characterized by neuronal and behavioral deterioration. Two hallmark pathologies of AD are amyloid-beta (Aß) plaques and neurofibrillary tangles, and the presence of such pathology can limit cell-to-cell communication, leading to cognitive deficits, and neuronal cell death. Although Aß plaques were originally thought to cause the cognitive deficits, more simple forms of Aß, such as monomers, dimers, tetramers and oligomers, have also been shown to be neurotoxic. Moreover, chronic inflammation has also been implicated in the onset and progression of these AD-related pathologies. The current study was designed to further our understanding of peripheral inflammation-induced AD-like pathology, by administering polyinosinic:polycytidylic acid (poly I:C), a viral mimetic. Mice were administered intraperitoneal injections of poly I:C or saline once daily for 7 consecutive days. Hippocampal tissue from animals receiving poly I:C contained significantly higher levels of the Aß1₋42 peptide. Even after ensuring that potential sickness behavior could not confound cognitive testing, we found that animals administered poly I:C displayed significant cognitive deficits in the hippocampus-dependent contextual fear conditioning paradigm. These results confirm our hypothesis that peripheral inflammation can lead to increased levels of hippocampal-Aß and associated cognitive deficits.

Peripheral administration of D-cycloserine rescues memory consolidation following bacterial endotoxin exposure.

In the current study, the partial NMDA receptor agonist D-cycloserine (DCS) rescued memory consolidation following systemic bacterial endotoxin exposure. DCS failed, however, to restore hippocampal BDNF mRNA levels that were diminished following a systemic administration of LPS, and did not alter NR1 or NR2C NMDA receptor subunit expression. These results extend prior research into the role of DCS in neural-immune interactions, and indicate that the detrimental effects of peripheral LPS administration on consolidation of contextual fear memory may be ameliorated with DCS treatment, though the mechanisms underlying these effects are currently unclear.

Peripheral administration of poly I:C disrupts contextual fear memory consolidation and BDNF expression in mice.

In the current study, administration of poly I:C induced a deficit in contextual, but not auditory-cue, fear memory consolidation. This memory deficit coincided with a decrease in hippocampal and cortical BDNF mRNA expression. These results extend prior work, and suggest that a single peripheral injection of poly I:C disrupts contextual fear memory consolidation processes in adult mice, and that these deficits may potentially be mediated by diminished BDNF expression.

Age exacerbates sickness behavior following exposure to a viral mimetic.

Poly I:C, a viral mimetic, is a synthetic double-stranded RNA that is known to cause activation of the innate immune system, resulting in the emergence of sickness behaviors in otherwise healthy adult mice. However, the way in which such effects of poly I:C manifest themselves in aged mice are not currently known. We hypothesized that poly I:C administration would lead to burrowing deficits, but that these deficits would be exaggerated in aged subjects (19-months old) compared to young subjects (4-months old) that received the same dose. In order to associate these behavioral decrements with inflammatory factors, we measured mRNA expression of IL-1ß and IL-6 in the hippocampus and parietal cortex and peripheral protein expression of IL-6, TNF-α, MCP-1, MIP-1α, and IL-1ß in the serum. After exposure to poly I:C, aged subjects demonstrated significant impairments in their burrowing behavior, compared to younger subjects administered the same dose. These behavioral decrements coincided with increased expression of IL-6 among animals exposed to poly I:C and increased expression of IL-1ß among aged animals in the hippocampus and cortex. Furthermore, we observed an increase in peripheral poly I:C-induced IL-6, TNF-α, MCP-1, and MIP-1α, but not IL-1ß. These results indicate that virus-mediated immune activation in the aging body can lead to increased sickness behavior. Furthermore, these data indicated a possible dissociation between the effects of poly I:C on sickness behaviors in aged mice, with central expression of IL-1ß potentially playing a role in age-related impairments.

Prolonged elevation in hippocampal Aß and cognitive deficits following repeated endotoxin exposure in the mouse.

Alzheimer's disease (AD) is characterized by neuronal cell death and atrophy in regions of the adult brain, including the hippocampus and cortex, due to formation of amyloid beta (Aß) plaques and neurofibrillary tangles. The presence of these pathologies can limit normal signaling properties and ultimately lead to learning and memory deficits. Chronic inflammation has been implicated in the onset and progression of these AD-related pathologies. Our study was designed to assess the effects of peripheral inflammation on pathologies associated with AD by using the bacterial endotoxin lipopolysaccharide (LPS). C57BL/6J mice were given intraperitoneal injections of LPS or saline for 1, 3, or 7 consecutive days. Hippocampal tissue from animals receiving LPS contained significantly higher levels of Aß1-42, a peptide component of AD plaques, than did those from saline control animals. Central and peripheral pro-inflammatory cytokine levels were increased following a single injection of LPS, but retuned to baseline levels before cognitive testing began. We show that one injection of LPS leads to sickness behavior, but 7 consecutive days does not, indicating tolerance to the endotoxin. Cognitive testing was then conducted to determine if whether deficits from increased Aß1-42 was evident. Results from both Morris water maze and contextual fear conditioning revealed cognitive deficits in LPS-treated mice. In summary, multiple injections of LPS resulted in increased Aß1-42 in the hippocampus and cognitive deficits in mice.

The effects of age on lipopolysaccharide-induced cognitive deficits and interleukin-1ß expression.

An acute LPS challenge immediately following day 1 of shuttlebox training triggered exacerbated central IL-1ß production and disrupted memory consolidation and/or further acquisition of the task in 18-month-old mice, compared to 4-month-old controls. These deficits cannot be attributed to alterations in sickness behavior. The findings suggest that age and immune activation combine to impair learning and memory consolidation processes, and that increased central IL-1ß production may play a role.