Comparison of digital recruitment strategies for Alzheimer's disease patients.

Objectives: Clinical trials studying Alzheimer's Disease (AD) face the challenge of recruiting participants with significant barriers to entering research studies. The objective of this study is to compare digital recruitment strategies' ability to recruit older adults with cognitive impairment (CI). Methods: Older adults with CI were recruited for a clinical trial studying vestibular therapy in reducing falls and improving balance and cognition in older adults with CI. Potential participants were recruited via two different digital recruitment methods, a direct messaging campaign using established patient records and a social media campaign. Potential participants then filled out surveys to determine eligibility for the study. Results: The direct messaging campaign contacted 3060 potential participants and the social media campaign resulted in 8265 instances of unique engagement. Of the number of people reached, the direct messaging campaign had a higher percentage of people who submitted the survey compared to the social media campaign (8.3% vs. 1.2%, p < 0.001). There was no significant difference in age, race, ethnicity, education, household income, and insurance status between the recruitment groups (p > 0.05). Direct messaging recruitment proved more cost-effective at $21.74 per eligible participant compared to the social media campaign at $859.58 per eligible participant. Conclusion: This study found that direct messaging recruitment using established patient records was more cost-effective compared to social media recruitment for this clinical trial. In this sample size, similar demographics were reached by both recruitment methods. Future studies should continue to explore the use of social media and alternative methods to recruit representative participant populations for ongoing AD research.

Assessing attitudes towards pediatric research participation across diverse populations: Psychometric properties of a novel tool.

BACKGROUND: Clinical trials play a crucial role in advancing medical knowledge and improving health outcomes. However, there is a recognized need for greater representation of marginalized groups to ensure that research findings can be generalized and effectively applied to all individuals. While the Pediatric Research Participation Questionnaire (PRPQ) was developed to assist pediatric clinical trials research by identifying benefits and barriers to research participation among children with chronic medical conditions, there is still limited insight into the structure of the PRPQ when administered in diverse samples, including the general pediatric population. Therefore, the current study examined the factor structure of the PRPQ in a general pediatric population to investigate whether rural-urban differences exist in the PRPQ factor structure. METHODS: Caregivers (N = 600) of children under age 18 completed the PRPQ in a population-based survey in Mississippi. Sampling was stratified to ensure equal representation in rural (n = 300) and urban areas (n = 300). Exploratory and confirmatory factor analyses were conducted to determine the factor structure of the PRPQ. RESULTS: A five-factor structure was identified, compromising: social pressure, direct benefit, reasons for participation, mistrust in research/researchers, reasons against participation. While results were similar among urban participants, a three-factor structure emerged for rural participants. CONCLUSIONS: This study contributes to the broader understanding of research participation among underrepresented groups. The findings suggest that clinical researchers should consider tailoring recruitment strategies to increase clinical trial participation among children in rural areas. Understanding factors that influence pediatric research participation, particularly among marginalized communities, is crucial for developing effective recruitment and retention strategies.

A Molecular Basis of Human Brain Connectivity.

Neuroimaging is commonly used to infer human brain connectivity, but those measurements are far-removed from the molecular underpinnings at synapses. To uncover the molecular basis of human brain connectivity, we analyzed a unique cohort of 98 individuals who provided neuroimaging and genetic data contemporaneous with dendritic spine morphometric, proteomic, and gene expression data from the superior frontal and inferior temporal gyri. Through cellular contextualization of the molecular data with dendritic spine morphology, we identified hundreds of proteins related to synapses, energy metabolism, and RNA processing that explain between-individual differences in functional connectivity and structural covariation. By integrating data at the genetic, molecular, subcellular, and tissue levels, we bridged the divergent fields of molecular biology and neuroimaging to identify a molecular basis of brain connectivity. One-Sentence Summary: Dendritic spine morphometry and synaptic proteins unite the divergent fields of molecular biology and neuroimaging.

County incidence and geospatial trends of early-onset hypertensive disorders of pregnancy in Kentucky, 2008-2017.

BACKGROUND: Early-onset hypertensive disorders of pregnancy (eHDP) are associated with more severe maternal and infant outcomes than later-onset disease. However, little has been done to evaluate population-level trends. Therefore, in this paper, we seek to address this understudied area by describing the geospatial and temporal patterns of county-level incidence of eHDP and assessing county-level demographics that may be associated with an increased incidence of eHDP. METHODS: Employing Kentucky certificates of live and stillbirth from 2008-2017, this ecological study detected county-level clusters of early-onset hypertensive disorders of pregnancy using SaTScan, calculated average annual percent change (AAPC) with a join point analysis, and identified county-level covariates (% of births to women ≥ 35 years of age, % with BMI ≥ 30 kg/m2, % currently smoking, % married, and % experienced eHDP) with a fixed-effects negative binomial regression model for longitudinal data with an autoregressive (AR) correlation structure offset with the natural log of the number of births in each county and year. RESULTS: County-level incidence of eHDP had a non-statistically significant increase of almost 3% (AAPC: 2.84, 95% CI: -4.26, 10.46), while maternal smoking decreased by almost 6% over the study period (AAPC:-5.8%, 95%CI: -7.5, -4.1), Risk factors for eHDP such as pre-pregnancy BMI ≥ 30 and proportion of births to women ≥ 35 years of age increased by 2.3% and 3.4% respectively (BMI AAPC:2.3, 95% CI: 0.94, 3.7; ≥ 35 years AAPC:3.4, 95% CI: 0.66, 6.3). After adjusting for race, county-level proportions of college attainment, and maternal smoking throughout pregnancy, counties with the highest proportion of births to women with BMI ≥ 30 kg/m2 reported an eHDP incidence 20% higher than counties with a lower proportion of births to mothers with a BMI ≥ 30 kg/m2 and a 20% increase in eHDP incidence (aRR = 1.20, 95% CI: 1.00, 1.44). We also observed that counties with the highest proportion vs. the lowest of mothers ≥ 35 years old (> 6.1%) had a 26% higher incidence of eHDP (RR = 1.26, 95%CI: 1.04, 1.50) compared to counties with the lowest incidence (< 2.5%). We further identified two county-level clusters of elevated eHDP rates. We also observed that counties with the highest vs. lowest proportion of mothers ≥ 34 years old (> 6.1% vs. < 2.5%) had a 26% increase in the incidence of eHDP (RR = 1.26, 95% CI: 1.04, 1.50). We further identified two county-level clusters of elevated incidence of eHDP. CONCLUSIONS: This study identified two county-level clusters of eHDP, county-level covariates associated with eHDP, and that while increasing, the average rate of increase for eHDP was not statistically significant. This study also identified the reduction in maternal smoking over the study period and the concerning increase in rates of elevated pre-pregnancy BMI among mothers. Further work to explore the population-level trends in this understudied pregnancy complication is needed to identify community factors that may contribute to disease and inform prevention strategies.

Quantitative vestibular assessment: The development and validation of a novel, remote video head impulse test against in-clinic measurements.

Objectives: To develop a novel remote head impulse test (rHIT), and to provide preliminary data validating the rHIT vestibular-ocular reflex (VOR) gains against the in-clinic vHIT. Methods: A convenience sample of 10 patients referred for vestibular assessment at our institution was recruited. In-clinic vHIT was used to quantify lateral VOR gains. Patients subsequently underwent an rHIT protocol, whereby patients performed active, lateral head rotations while their eyes and heads were recorded using a laptop camera and video-conferencing software. The vHIT and rHIT VOR gains were compared using paired t-tests, and a Pearson correlation coefficient between the gains was calculated. Absolute accuracy, sensitivity, and specificity of the rHIT were additionally calculated. Results: Of the 10 patients recruited, 4 were male, and the average ± standard deviation (SD) age was 61.4 ± 15.3 years. As determined by the vHIT, 2 patients had normal bilateral VOR gains, 6 with unilateral vestibular hypofunction, and 2 with bilateral vestibular hypofunction. The correlation between the rHIT and vHIT gains was 0.73 (p < .001). The rHIT exhibited an absolute accuracy of 75.0%, sensitivity of 70.0%, and specificity of 80.0%. When ears had a vHIT VOR gain less than 0.40, the rHIT exhibited 100.0% accuracy. Conversely, 60.0% of deficient ears with vHIT VOR gains greater than 0.40 were incorrectly categorized by the rHIT. Conclusion: The rHIT may be better suited for detecting more severe vestibular deficiencies. Future iterations of the rHIT should aim to increase the video frame-rate capabilities to detect subtler VOR impairments. Level of Evidence: 4.

Endogenous recapitulation of Alzheimer's disease neuropathology through human 3D direct neuronal reprogramming.

Alzheimer's disease (AD) is a neurodegenerative disorder that primarily affects elderly individuals, and is characterized by hallmark neuronal pathologies including extracellular amyloid-ß (Aß) plaque deposition, intracellular tau tangles, and neuronal death. However, recapitulating these age-associated neuronal pathologies in patient-derived neurons has remained a significant challenge, especially for late-onset AD (LOAD), the most common form of the disorder. Here, we applied the high efficiency microRNA-mediated direct neuronal reprogramming of fibroblasts from AD patients to generate cortical neurons in three-dimensional (3D) Matrigel and self-assembled neuronal spheroids. Our findings indicate that neurons and spheroids reprogrammed from both autosomal dominant AD (ADAD) and LOAD patients exhibited AD-like phenotypes linked to neurons, including extracellular Aß deposition, dystrophic neurites with hyperphosphorylated, K63-ubiquitin-positive, seed-competent tau, and spontaneous neuronal death in culture. Moreover, treatment with ß- or γ-secretase inhibitors in LOAD patient-derived neurons and spheroids before Aß deposit formation significantly lowered Aß deposition, as well as tauopathy and neurodegeneration. However, the same treatment after the cells already formed Aß deposits only had a mild effect. Additionally, inhibiting the synthesis of age-associated retrotransposable elements (RTEs) by treating LOAD neurons and spheroids with the reverse transcriptase inhibitor, lamivudine, alleviated AD neuropathology. Overall, our results demonstrate that direct neuronal reprogramming of AD patient fibroblasts in a 3D environment can capture age-related neuropathology and reflect the interplay between Aß accumulation, tau dysregulation, and neuronal death. Moreover, miRNA-based 3D neuronal conversion provides a human-relevant AD model that can be used to identify compounds that can potentially ameliorate AD-associated pathologies and neurodegeneration.

Per-pathogen virulence of HIV-1 subtypes A, C and D.

HIV-1 subtypes differ in their clinical manifestations and the speed in which they spread. In particular, the frequency of subtype C is increasing relative to subtypes A and D. We investigate whether HIV-1 subtypes A, C and D differ in their per-pathogen virulence and to what extend this explains the difference in spread between these subtypes. We use data from the hormonal contraception and HIV-1 genital shedding and disease progression among women with primary HIV infection study. For each study participant, we determine the set-point viral load value, CD4+ T cell level after primary infection and CD4+ T cell decline. Based on both the CD4+ T cell count after primary infection and CD4+ T cell decline, we estimate the time until AIDS. We then obtain our newly introduced measure of virulence as the inverse of the estimated time until AIDS. After fitting a model to the measured virulence and set-point viral load values, we tested if this relation varies per subtype. We found that subtype C has a significantly higher per-pathogen virulence than subtype A. Based on an evolutionary model, we then hypothesize that differences in the primary length of infection period cause the observed variation in the speed of spread of the subtypes.

Cross-Platform Synaptic Network Analysis of Human Entorhinal Cortex Identifies TWF2 as a Modulator of Dendritic Spine Length.

Proteomic studies using postmortem human brain tissue samples have yielded robust assessments of the aging and neurodegenerative disease(s) proteomes. While these analyses provide lists of molecular alterations in human conditions, like Alzheimer's disease (AD), identifying individual proteins that affect biological processes remains a challenge. To complicate matters, protein targets may be highly understudied and have limited information on their function. To address these hurdles, we sought to establish a blueprint to aid selection and functional validation of targets from proteomic datasets. A cross-platform pipeline was engineered to focus on synaptic processes in the entorhinal cortex (EC) of human patients, including controls, preclinical AD, and AD cases. Label-free quantification mass spectrometry (MS) data (n = 2260 proteins) was generated on synaptosome fractionated tissue from Brodmann area 28 (BA28; n = 58 samples). In parallel, dendritic spine density and morphology was measured in the same individuals. Weighted gene co-expression network analysis was used to construct a network of protein co-expression modules that were correlated with dendritic spine metrics. Module-trait correlations were used to guide unbiased selection of Twinfilin-2 (TWF2), which was the top hub protein of a module that positively correlated with thin spine length. Using CRISPR-dCas9 activation strategies, we demonstrated that boosting endogenous TWF2 protein levels in primary hippocampal neurons increased thin spine length, thus providing experimental validation for the human network analysis. Collectively, this study describes alterations in dendritic spine density and morphology as well as synaptic proteins and phosphorylated tau from the entorhinal cortex of preclinical and advanced stage AD patients.SIGNIFICANCE STATEMENT Proteomic studies can yield vast lists of molecules that are altered under various experimental or disease conditions. Here, we provide a blueprint to facilitate mechanistic validation of protein targets from human brain proteomic datasets. We conducted a proteomic analysis of human entorhinal cortex (EC) samples spanning cognitively normal and Alzheimer's disease (AD) cases with a comparison of dendritic spine morphology in the same samples. Network integration of proteomics with dendritic spine measurements allowed for unbiased discovery of Twinfilin-2 (TWF2) as a regulator of dendritic spine length. A proof-of-concept experiment in cultured neurons demonstrated that altering Twinfilin-2 protein level induced corresponding changes in dendritic spine length, thus providing experimental validation for the computational framework.

Investigating the Relation between Electronic Cigarette Use and Sleep Duration in Kentucky Using the BRFSS, 2016-2017.

OBJECTIVES: Like traditional cigarettes, electronic cigarettes (e-cigarettes) contain nicotine, which is known to negatively influence sleep quality. Few studies, however, have examined the relation between e-cigarettes and sleep quality using population-based survey data because of the relatively recent appearance of these products on the market. This study investigated the relation between e-cigarette and cigarette use and sleep duration in Kentucky, a state with high rates of nicotine dependence and related chronic diseases. METHODS: Data from two consecutive years of the Behavioral Risk Factor Surveillance System survey-2016 and 2017-were analyzed using χ2 statistics and multivariable Poisson regression analyses to control for socioeconomic and demographic variables, the presence of other chronic diseases, and traditional cigarette use. RESULTS: This study was conducted using responses from 18,907 Kentucky adults aged 18 years and older. Overall, almost 40% reported short (<7 hours) sleep duration. After adjusting for other covariates, including the presence of chronic diseases, those who had currently or formerly used both traditional and e-cigarettes had the highest risk of short sleep duration. Those who currently or formerly smoked only traditional cigarettes also had significantly higher risk, unlike those who had only used e-cigarettes. CONCLUSIONS: Survey respondents who used e-cigarettes were more likely to report short sleep duration, but only if they currently or formerly smoked traditional cigarettes. Those who used both products, regardless of whether current or former, were more likely to report short sleep duration than those who had used just one of these tobacco products.

The Intersectionality between Race, Ethnicity, and Residential-Level Socioeconomic Status in Disparities of Head and Neck Cancer Outcomes: A SEER Study.

BACKGROUND: Head and neck cancer (HNC) mortality differs by race, ethnicity, and socioeconomic status (SES). However, it is unclear whether the relationship between race/ethnicity and HNC-specific mortality varies according to the residence-level SES. METHODS: Data from the Surveillance Epidemiology and End Results database included participants with primary HNC between 2006 and 2017 (followed through 2018) to assess the joint association of race/ethnicity and census-tract level SES Yost-index groups (quintiles) with all-cause and HNC-specific mortalities. Relative survival rates at 1, 5, and 10 years were calculated. Multivariable Cox proportional hazard regression models estimated hazard-ratios and 95% confidence intervals for all-cause mortality, and Fine-Gray subdistribution hazard models for HNC-specific mortality. Cumulative incidence curves for HNC-specific deaths were estimated. RESULTS: 76,095 patients were included in the analysis: 63.2% were <65 years, 73.4% male, and 11.3% non-Hispanic (NH) Black. Most patients (58.3%) were diagnosed at regional or distant stages and 20.6% died of HNC. The five-year relative survival rate increased with SES group, with 51.6% in the lowest SES group, and 74.1% in the highest SES group. NH-Black patients had higher risk of all-cause and HNC-specific mortality than NH-White patients, regardless of the SES group. NH-Asian/Pacific Islander and Hispanic patients had higher risk of HNC-specific mortality in some SES groups. CONCLUSIONS: NH-Black patients of all SES strata had significantly worse outcomes. Other factors, such as healthcare quality, may be associated with persistent disparities. IMPACT: The study highlights the persistence of significant racial disparities in HNC survival across socioeconomic categories. There is need to consider additional factors underlying these disparities.

Parental Discipline During Emerging Adulthood: A Person-Centered Approach.

Although most parental discipline research examines the effects of discipline in children and adolescents, recent research has demonstrated that emerging adults continue to receive parental discipline. Importantly, a newly validated instrument for assessing discipline specifically during emerging adulthood has been created. Scales from this instrument include maternal and paternal approval, disappointment, and abuse, and these scales were associated with other parenting behaviors and psychological outcomes during emerging adulthood. However, a person-centered approach has not been conducted with this instrument. Given that discipline occurs at an idiographic level and that group norms inform such behaviors, a person-centered approach would identify highly informative emerging adult profiles based on patterns of discipline they receive from their parents. Thus, the current study utilized latent profile analysis (LPA) of 1110 participants attending a Southern United States university to identify emerging adult discipline profiles. These groups were then associated with parental and emerging adult psychological problems to gain an understanding of how these factors relate to different patterns of discipline across gender. Results best supported four profiles labeled as approving, distant, disappointed, and abusive. These groups reported increasingly higher parental and personal psychological problems across approving, distant, disappointed, and abusive profiles. Gender moderated some of these effects. Implications and future directions are discussed.

Developmental/behavioral training innovation in a high-need, low-resource state: The child health and development promotion fellowship.

INTRODUCTION: Developmental and behavioral problems are prevalent in early childhood, whereas the workforce available to identify and address early problems is comparatively limited. Beyond workforce shortages, additional barriers to developing and training a highly skilled workforce in this area exist-particularly in rural, high-need, and underserved U.S. states. As the health care landscape emphasizes expertise in interdisciplinary care, training approaches that provide intensive learning opportunities for supporting a skilled early childhood developmental workforce necessitate novel training approaches. This Workforce Catalyst report summarizes the initial conceptualization, development, execution, and evaluation of a Child Health and Development Promotion (CHDP) postgraduate fellowship in a high need, underserved rural area. METHOD: Three cohorts totaling 15 trainees across fields including psychology, pediatric nursing, speech-language pathology, social work, and occupational therapy were recruited and cross-trained in an intensive postgraduate fellowship in early childhood development and behavior. RESULTS: The CHDP fellowship led to experiences across the care continuum and resulted in multiple clinical, educational, and scholarly products. Outcomes revealed a training program aligned with Infant and Early Childhood Mental Health competencies, high in-state retention (71%) and employment (93%) following training, and graduates who report leadership positions and sharing of specialty developmental-behavioral knowledge in organizations focused on early childhood. DISCUSSION: The CHDP Fellowship is a novel, immersive, and interdisciplinary training experience demonstrating positive initial training outcomes in Mississippi. The model and experience may serve as a roadmap for bolstering a skilled early childhood workforce in other underserved and high-need states. Aspects regarding scale of reach, funding, and accreditation are discussed as barriers. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Childhood adversity associated with poorer health: Evidence from the U.S. National Survey of Children's Health.

BACKGROUND: The association between adverse childhood experiences (ACEs) and increased risk of health problems is well established. However, many studies have relied on unrepresentative or high-risk samples and have focused on a narrow range of health problems. Prior research assessing potential age differences in the ACE-health connection is also sparse. OBJECTIVE: To comprehensively examine the extent to which ACEs are associated with physical, mental, and neurodevelopmental health outcomes in childhood and assess whether these associations differ between age groups. PARTICIPANTS & SETTING: Pooled cross-sectional data from the 2016-2019 National Survey of Children's Health (N = 98,732). METHODS: We estimated age-stratified binary logistic regression models examining associations between the number of ACEs and physical, mental, and neurodevelopmental health problems net of sociodemographic and socioeconomic controls. Separate models were estimated for the total population (ages 3-17), early childhood (ages 3-5), middle childhood (ages 6-11), and adolescence (ages 12-17). RESULTS: We observed a dose-response relationship between ACE exposure and childhood physical, mental, and neurodevelopmental health problems in all age groups. The largest disparities exist between children with no ACEs and three or more ACEs. Compared to children without ACEs, children with three or more ACEs had significantly higher adjusted odds of externalizing disorders (OR = 4.40), internalizing disorders (OR = 5.13), neurodevelopmental disorders (OR = 2.40), and physical health problems (OR = 2.08). CONCLUSIONS: Our results add to evidence linking ACEs to childhood health disparities. Further, findings indicate that ACEs have persistent negative effects across age groups and that clinicians should monitor ACEs when assessing children's physical, mental, and neurodevelopmental health at any age.

A cross-sectional examination of the early-onset hypertensive disorders of pregnancy and industrial emissions of toxic metals using Kentucky birth records, 2008-2017.

This cross-sectional study assessed geospatial patterns of early-onset hypertensive disorders of pregnancy (eHDP) in primiparous mothers and exposure to industrial emissions using geocoded residential information from Kentucky live (N = 210,804) and still (N = 1,247) birth records (2008-2017) and census block group estimates of aerosol concentrations of arsenic (As), cadmium (Cd), chromium (Cr), lead (Pb), mercury (Hg), selenium (Se), and zinc (Zi) from the Risk Screening Environmental Indicators (RSEI) model. A latent class analysis allowed for the identification of four district exposure classes-As, Cd, and Pb (12.6%); Se and Zi (21.4%); Pb and Cr (8%); and low or no exposures (57.9%). Women classified as having a high probability of exposure to both Pb and Cr had a statistically significantly greater prevalence of eHDP after adjusting for demographic factors (aPR = 1.22, 95% CI: 1.04, 1.44) relative to those with low or no exposure. Our findings contribute to the emerging literature on the association of metal exposures with pregnancy outcomes.

Maternal proximity to mountain-top removal mining and birth defects in Appalachian Kentucky, 1997-2003.

Extraction of coal through mountaintop removal mining (MTR) alters many dimensions of the landscape. Explosive blasts, exposed rock, and coal washing have the potential to pollute air and water. Previous research suggests that infants born to mothers living in areas with MTR have a higher prevalence of birth defects. In this cross-sectional study, we further examine the relationship between MTR activity and several types of birth defects. Maternal exposure to MTR was assessed using remote sensing data from Skytruth, which captures MTR activity in the Central Appalachian region of the United States. Active MTR area was quantified within a five-kilometer buffer surrounding geocoded maternal address captured on birth records for live births to Appalachian Kentucky mothers between 1997 and 2003 (N = 95,581). We assigned high, medium, and low exposure based on the tertile of total MTR area within 5-km, and births with no MTR within this buffer were assigned zero exposure. The presence or absence of a birth defect grouped into six major organ systems was identified using birth records alone. Finally, we applied conditional multiple imputation for variables with missing values before conducting separate multivariable log-binomial regression models for each birth defect group. Prevalence ratio (PR) estimates were adjusted for individual level covariates from birth records. The prevalence of gastro-intestinal defects was significantly higher in birth records with high and low active MTR exposure compared to records with no exposure. (High exposure: PR = 1.99, 95% CI = 1.14-3.47; low exposure PR = 1.88, 95% CI = 1.06-3.31). This study supports some of the existing findings of previous ecological studies. Research addressing the relationship between gastro-intestinal birth defects and MTR coal mining is warranted but should carefully consider temporal dimensions of exposure.

Comparison of Golgi-Cox and Intracellular Loading of Lucifer Yellow for Dendritic Spine Density and Morphology Analysis in the Mouse Brain.

Dendritic spines are small protrusions on dendrites that serve as the postsynaptic site of the majority of excitatory synapses. These structures are important for normal synaptic transmission, and alterations in their density and morphology have been documented in various disease states. Over 130 years ago, Ramón y Cajal used Golgi-stained tissue sections to study dendritic morphology. Despite the array of technological advances, including iontophoretic microinjection of Lucifer yellow (LY) fluorescent dye, Golgi staining continues to be one of the most popular approaches to visualize dendritic spines. Here, we compared dendritic spine density and morphology among pyramidal neurons in layers 2/3 of the mouse medial prefrontal cortex (mPFC) and pyramidal neurons in hippocampal CA1 using three-dimensional digital reconstructions of (1) brightfield microscopy z-stacks of Golgi-impregnated dendrites and (2) confocal microscopy z-stacks of LY-filled dendrites. Analysis of spine density revealed that the LY microinjection approach enabled detection of approximately three times as many spines as the Golgi staining approach in both brain regions. Spine volume measurements were larger using Golgi staining compared to LY microinjection in both mPFC and CA1. Spine length was mostly comparable between techniques in both regions. In the mPFC, head diameter was similar for Golgi staining and LY microinjection. However, in CA1, head diameter was approximately 50% smaller on LY-filled dendrites compared to Golgi staining. These results indicate that Golgi staining and LY microinjection yield different spine density and morphology measurements, with Golgi staining failing to detect dendritic spines and overestimating spine size.

Geocoding precision of birth records from 2008 to 2017 in Kentucky, USA.

Maternal address information captured on birth records is increasingly used to estimate residential environmental exposures during pregnancy. However, there has been limited assessment of the geocoding precision of birth records, particularly since the adoption of the 2003 standard birth certificate in 2015. To address this gap, this study evaluated the geocoding precision of live and stillbirth records of Kentucky residents over ten years, from 2008 through 2017. This study summarized the demographic characteristics of imprecisely geocoded records and, using a bivariate logistic regression, identified covariates associated with poor geocoding precision among three population density designations-metro, non-metro, and rural. We found that in metro areas, after adjusting for area deprivation, education, and the race, age and education of both parents, records for Black mothers had 48% lower odds of imprecise geocoding (aOR=0.52, 95% CI: 0.48, 0.56), while Black women in rural areas had 96% higher odds of imprecise geocoding (aOr=1.96, 95% CI: 1.68, 2.28). This study also found that over the study period, rural and non-metro areas began with a high proportion of imprecisely geocoded records (38% in rural areas, 19% in non-metro), but both experienced an 8% decline in imprecisely geocoded records over the study period (aOr=0.92, 95% CI: 0.92, 0.94). This study shows that, while geocoding precision has improved in Kentucky, further work is needed to improve geocoding in rural areas and address racial and ethnic disparities.

Retrospective descriptive analysis of a managed care population with obesity.

OBJECTIVES: To reveal the extent of obesity in a single healthcare system and provide a blueprint for other health systems to perform similar analyses, this study describes characteristics and weight change patterns of patients classified with overweight and obesity at a large integrated delivery network (IDN) in the South-Central United States. METHODS: A descriptive, observational, retrospective study was conducted using electronic medical records and claims data. Patients were ≥18 years old, body mass index (BMI) ≥27 kg/m2, and continuously enrolled in the IDN plan for ≥6 months before and ≥12 months after the index date. Demographics, comorbidities, BMI, and weight were collected. Weight changes were assessed annually, and anti-obesity medications (AOM) use was also captured. RESULTS: A total of 36,430 eligible patients were identified. A subset of 22,712 patients was continuously enrolled for the entire study period (mean age: 57.2) and were primarily white (83.3%) and commercially insured (54.3%). Most patients were categorized as overweight (40.1%) or obesity class I (32.5%) at baseline. At years 1 and 4 post-index, patients who maintained index weight (±3%) was 56.2% and 37.0%, respectively, whereas weight gain (≥3% increase) was 23.7% and 33.3%, respectively. AOM use (1.1%) primarily consisted of phentermine-hydrochloride (n = 114, 0.5%) and orlistat (n = 115, 0.5%). CONCLUSIONS: An increasing proportion of patients gained weight over time, combined with low AOM use, emphasizing the need for weight-loss interventions in this population. Findings from this study provide a foundation for health systems to perform similar analyses.

Examining Adult E-cigarette Use in Kentucky and Its Appalachian Region Using the Behavioral Risk Factor Surveillance System, 2016-2017.

OBJECTIVES: Electronic cigarette (e-cigarette) use has increased steadily in the United States, but little research has examined its prevalence in states comprising Appalachia, a rural region known for high rates of tobacco use. This study assessed lifetime and current e-cigarette use among adults by sociodemographic characteristics, geographic region, and cigarette smoking in Kentucky, with a focus on the Appalachian region. METHODS: We used data from the 2016-2017 Behavioral Risk Factor Surveillance System (BRFSS) surveys to calculate the prevalence of lifetime and current e-cigarette use, and we used weighted multivariable logistic regression analyses to examine the relative influence of other factors. RESULTS: Among adults in Kentucky, 5.8% (95% CI, 5.2%-6.4%) were current e-cigarette users and 27.0% (95% CI, 25.9%-28.0%) were lifetime users, compared with state medians of 4.6% (95% CI, 4.0%-5.1%) and 21.4% (95% CI, 19.4%-23.5%) for the United States. Multivariable regression models showed similar patterns for all regions: higher prevalence odds of current e-cigarette use among adults aged 18-24, current conventional smokers, and adults unable to work. Generally, Appalachian residents of Kentucky did not have significantly higher rates of lifetime or current e-cigarette use as compared with other non-Appalachian residents of Kentucky. Hispanic residents of Appalachian Kentucky, however, had higher rates of e-cigarette use than Hispanic residents of other regions of Kentucky. CONCLUSIONS: Rates of e-cigarette use were higher in Kentucky than in the United States but were not further elevated in Kentucky's Appalachian region. High rates of e-cigarette use among Hispanic residents of Appalachia indicate a need to focus future interventions in the region.

Conditional deletion of ROCK2 induces anxiety-like behaviors and alters dendritic spine density and morphology on CA1 pyramidal neurons.

Rho-associated kinase isoform 2 (ROCK2) is an attractive drug target for several neurologic disorders. A critical barrier to ROCK2-based research and therapeutics is the lack of a mouse model that enables investigation of ROCK2 with spatial and temporal control of gene expression. To overcome this, we generated ROCK2fl/fl mice. Mice expressing Cre recombinase in forebrain excitatory neurons (CaMKII-Cre) were crossed with ROCK2fl/fl mice (Cre/ROCK2fl/fl), and the contribution of ROCK2 in behavior as well as dendritic spine morphology in the hippocampus, medial prefrontal cortex (mPFC), and basolateral amygdala (BLA) was examined. Cre/ROCK2fl/fl mice spent reduced time in the open arms of the elevated plus maze and increased time in the dark of the light-dark box test compared to littermate controls. These results indicated that Cre/ROCK2fl/fl mice exhibited anxiety-like behaviors. To examine dendritic spine morphology, individual pyramidal neurons in CA1 hippocampus, mPFC, and the BLA were targeted for iontophoretic microinjection of fluorescent dye, followed by high-resolution confocal microscopy and neuronal 3D reconstructions for morphometry analysis. In dorsal CA1, Cre/ROCK2fl/fl mice displayed significantly increased thin spine density on basal dendrites and reduced mean spine head volume across all spine types on apical dendrites. In ventral CA1, Cre/ROCK2fl/fl mice exhibited significantly increased spine length on apical dendrites. Spine density and morphology were comparable in the mPFC and BLA between both genotypes. These findings suggest that neuronal ROCK2 mediates spine density and morphology in a compartmentalized manner among CA1 pyramidal cells, and that in the absence of ROCK2 these mechanisms may contribute to anxiety-like behaviors.