Spatial analysis of murine microbiota and bile acid metabolism during amoxicillin treatment.

Antibiotics cause collateral damage to resident microbes that is associated with various health risks. To date, studies have largely focused on the impacts of antibiotics on large intestinal and fecal microbiota. Here, we employ a gastrointestinal (GI) tract-wide integrated multiomic approach to show that amoxicillin (AMX) treatment reduces bacterial abundance, bile salt hydrolase activity, and unconjugated bile acids in the small intestine (SI). Losses of fatty acids (FAs) and increases in acylcarnitines in the large intestine (LI) correspond with spatially distinct expansions of Proteobacteria. Parasutterella excrementihominis engage in FA biosynthesis in the SI, while multiple Klebsiella species employ FA oxidation during expansion in the LI. We subsequently demonstrate that restoration of unconjugated bile acids can mitigate losses of commensals in the LI while also inhibiting the expansion of Proteobacteria during AMX treatment. These results suggest that the depletion of bile acids and lipids may contribute to AMX-induced dysbiosis in the lower GI tract.

School-based racial segregation, social support, and late-life cognitive function in the Study of Healthy Aging in African Americans (STAR).

INTRODUCTION: School-based social support for Black students may mediate or modify the association between school segregation and late-life cognition. METHODS: Study of Healthy Aging in African Americans participants (n = 574) reported segregated school attendance and school-based social support. Associations of segregated schooling with domain-specific cognitive outcomes and effect modification or mediation by school-based social support were evaluated with linear mixed models. RESULTS: Segregated school attendance was associated with increased likelihood of school-based social support. Segregated (vs. desegregated in 6th grade) school attendance was associated with lower executive function (ß = -0.18 [-0.34, -0.02]) and semantic memory z-scores (ß = -0.31 [-0.48, -0.13]). Social support did not mediate these associations. Estimates for segregated school attendance were attenuated among those who felt supported, although there was limited evidence of statistically significant effect modification. DISCUSSION: Early-childhood school segregation was associated with poorer cognitive function. Sources of resilience within racialized educational experiences should be further evaluated to bridge inequities. HIGHLIGHTS: School segregation is a form of structural racism that affected the educational experiences of Black youth with potentially lasting consequences for healthy brain aging. Black students who attended a segregated school experienced greater school-based social support, which may highlight a potential source of resilience and resistance against the effects of racism-related stressors on cognitive function. The estimated adverse association between attending a segregated school on cognition was larger for students without an adult at school who cared about them versus those with an adult at school who cared about them, but estimates were imprecise.

School racial composition, effect modification by caring teacher/staff presence, and mid/late-life depressive symptoms: findings from the Study of Healthy Aging among African Americans.

For Black students in the United States, attending schools with a higher proportion of White students is associated with worse mental and physical health outcomes in adolescence/early adulthood. No prior studies evaluate K-12 school racial composition and later-life mental health. In a cohort of Black adults ages 50+ in Northern California who retrospectively self-reported school racial composition for grades 1, 6, 9, and 12, we assessed the association between attending a school with mostly Black students vs. not and mid/late-life depressive symptoms (8-item PROMIS depression score, standardized to US adult population) using age-, sex/gender-, southern US birth-, and parental education-adjusted generalized estimating equations, and assessed effect modification by caring teacher/staff presence. Later-life depressive symptoms were lower among those who attended schools with mostly Black students in grades 1 and 6 (b=-0.12, 95% CI: -0.23, 0.00 and b=-0.11, 95% CI: -0.22, 0.00, respectively). In grade 6, this difference was larger for students without an adult at school who cared about them (b=-0.29, 95% CI: -0.51, -0.07 vs. b=-0.04, 95% CI: -0.17, 0.09). Among Black Americans, attending early school with mostly Black students may have later life mental health benefits; this protective association appears more important for students without caring teachers/staff.

The Association Between Physical Activity and Cognition in a Racially/Ethnically Diverse Cohort of Older Adults: Results From the Kaiser Healthy Aging and Diverse Life Experiences Study.

OBJECTIVE: Most prior research on physical activity (PA) and cognition is based on predominantly white cohorts and focused on associations of PA with mean (average) cognition versus the distribution of cognition. Quantile regression offers a novel way to quantify how PA affects cognition across the entire distribution. METHODS: The Kaiser Healthy Aging and Diverse Life Experiences study includes 30% white, 19% black, 25% Asian, and 26% Latinx adults age 65+ living in Northern California (n = 1600). The frequency of light or heavy PA was summarized as 2 continuous variables. Outcomes were z-scored executive function, semantic memory, and verbal episodic memory. We tested associations of PA with mean cognition using linear regression and used quantile regression to estimate the association of PA with the 10th-90th percentiles of cognitive scores. RESULTS: Higher levels of PA were associated with higher mean semantic memory (b = 0.10; 95% CI: 0.06, 0.14) and executive function (b = 0.05; 95% CI: 0.01, 0.09). Associations of PA across all 3 cognitive domains were stronger at low quantiles of cognition. CONCLUSION: PA is associated with cognition in this racially/ethnically diverse sample and may have larger benefits for individuals with low cognitive scores, who are most vulnerable to dementia.

COVID-19 and Its Potential Impact on Achieving Pediatric Hospital Medicine Board Certification for Established Internal Medicine-Pediatrics (Med-Peds) Hospitalists.

With the onset of the COVID-19 pandemic and the subsequent rise in adult hospitalized patients, many internal medicine and pediatrics (Med-Peds) hospitalists volunteered or were required by their hospital employers to transition their practice to caring for hospitalized adult patients only. Some Med-Peds hospitalists had a disruption in their practice that may affect their board eligibility for the pediatric hospital medicine (PHM) subspecialty exam in 2024. In this editorial, we review the rise of Med-Peds hospitalist careers, the evolution of PHM becoming a subspecialty, and the effect of the COVID-19 pandemic on some Med-Peds hospitalists in their quest to become board certified in PHM via the practice pathway.

Timing and level of educational attainment and late-life cognition in the KHANDLE study.

INTRODUCTION: The timing of educational attainment may modify its effects on late-life cognition, yet most studies evaluate education only at a single time point. METHODS: Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) Study cohort participants (N = 554) reported educational attainment (dichotomized at any college education) at two time points, and we classified them as having low, high, or later-life high educational attainment. Linear mixed-effects models estimated associations between educational attainment change groups and domain-specific cognitive outcomes (z-standardized). RESULTS: Compared to low educational attainment, high (ß= 0.59 SD units; 95% confidence interval [CI]: 0.39, 0.79) and later-life high educational attainment (ß = 0.22; 95% CI: 0.00, 0.44) were associated with higher executive function. Only high educational attainment was associated with higher verbal episodic memory (ß = 0.27; 95% CI: 0.06, 0.48). DISCUSSION: Level and timing of educational attainment are both associated with domain-specific cognition. A single assessment for educational attainment may inadequately characterize protective associations with late-life cognition. HIGHLIGHTS: Few studies have examined both level and timing of educational attainment on cognition. Marginalized populations are more likely to attain higher education in adulthood. Higher educational attainment in late life is also associated with higher cognition.

Race, community disadvantage, and cognitive decline: Findings from KHANDLE and STAR.

INTRODUCTION: Community disadvantage is associated with late-life cognition. Few studies examine its contribution to racial disparities in cognition/cognitive change. METHODS: Inverse probability weighted models estimated expected mean differences in cognition/cognitive change attributed to residing in less advantaged communities, defined as cohort top quintile of Area Deprivation Indices (ADI): childhood 66-100; adulthood ADI 5-99). Interactions by race tested. RESULTS: More Black participants resided in less advantaged communities. Semantic memory would be lower if all participants had resided in less advantaged childhood (b = -0.16, 95% confidence interval [CI] = -0.30, -0.03) or adulthood (b = -0.14, 95% CI = -0.22, -0.04) communities. Race interactions indicated that, among Black participants, less advantaged childhood communities were associated with higher verbal episodic memory (interaction p-value = 0.007) and less advantaged adulthood communities were associated with lower semantic memory (interaction p-value = 0.002). DISCUSSION: Examining racial differences in levels of community advantage and late-life cognitive decline is a critical step toward unpacking community effects on cognitive disparities.

To confirm your appointment, please press one: Examining demographic and health system interface factors that predict missed appointments in a pediatric outpatient neuropsychology clinic.

Objective: Missed patient appointments have a substantial negative impact on patient care, child health and well-being, and clinic functioning. This study aims to identify health system interface and child/family demographic characteristics as potential predictors of appointment attendance in a pediatric outpatient neuropsychology clinic. Method: Pediatric patients (N = 6,976 across 13,362 scheduled appointments) who attended versus missed scheduled appointments at a large, urban assessment clinic were compared on a broad array of factors extracted from the medical record, and the cumulative impact of significant risk factors was examined. Results: In the final multivariate logistic regression model, health system interface factors that significantly predicted more missed appointments included a higher percentage of previous missed appointments within the broader medical center, missing pre-visit intake paperwork, assessment/testing appointment type, and visit timing relative to the COVID-19 pandemic (i.e. more missed appointments prior to the pandemic). Demographic characteristics that significantly predicted more missed appointments in the final model included Medicaid (medical assistance) insurance and greater neighborhood disadvantage per the Area Deprivation Index (ADI). Waitlist length, referral source, season, format (telehealth vs. in-person), need for interpreter, language, and age were not predictive of appointment attendance. Taken together, 7.75% of patients with zero risk factors missed their appointment, while 22.30% of patients with five risk factors missed their appointment. Conclusions: Pediatric neuropsychology clinics have a unique array of factors that impact successful attendance, and identification of these factors can help inform policies, clinic procedures, and strategies to decrease barriers, and thus increase appointment attendance, in similar settings.

Practical adaptive skills in pediatric brain tumor survivors: the contribution of medical factors and social determinants of health.

Pediatric brain tumor survivors demonstrate weaknesses in adaptive functioning, most notably practical adaptive skills; however, the specific areas of weakness within practical skills are unknown. This study examined the aspects of practical adaptive functions that are most impacted in brain tumor survivors, and identified medical and socio-demographic variables that predicted outcomes. The sample included 117 pediatric brain tumor patients seen for a clinical neuropsychological evaluation and whose parents completed the Adaptive Behavior Assessment System, Second or Third Edition. T-tests compared practical adaptive skills to normative means. Correlations examined associations between medical and socio-demographic variables and each of the practical adaptive subscales (Community Use, Home Living, Health & Safety, Self-Care). Significant correlations were entered into linear regression models for each practical adaptive skill. All practical subscales were significantly below the normative mean. Community Use was positively correlated with age at diagnosis and negatively correlated with treatment burden, time since diagnosis, and neighborhood deprivation. Health and Safety was positively correlated with age at diagnosis. Home Living was positively correlated with neighborhood deprivation. Self-Care was positively correlated with age at diagnosis and parental education. Specific medical and socio-demographic factors predicted practical adaptive functioning, highlighting the importance of considering the role of medical and socio-demographic determinants of health on adaptive functioning outcomes in pediatric brain tumors.

What is the association between adverse childhood experiences and late-life cognitive decline? Study of Healthy Aging in African Americans (STAR) cohort study.

OBJECTIVES: Adverse childhood experiences (ACEs) are associated with higher risk of chronic disease, but little is known about the association with late life cognitive decline. We examined the longitudinal association between ACEs and late-life cognitive decline in the Study of Healthy Aging in African Americans (STAR). DESIGN: Linear mixed models with random intercepts and slope examined the association of individual and composite ACEs with cognitive change adjusting for years from baseline (timescale), baseline age, sex, parental education, childhood socioeconomic status and childhood social support. Participants reported whether they had experienced nine types of ACEs. Executive function and verbal episodic memory were measured up to three times over a 3-year period using the Spanish and English Neuropsychological Assessment Scales. SETTINGS: Kaiser Permanente Northern California members living in the Bay Area. PARTICIPANTS: STAR is a cohort study of cognitive ageing launched in 2018 that has enrolled 764 black Americans ages ≥50 years (mean age=67.5; SD=8.5). RESULTS: Twenty-one per cent of participants reported no ACEs, 24% one ACE, 20% two ACEs, 17% three ACEs and 17% four or more ACEs. Compared with no ACEs, two ACEs (ß=0.117; 95% CI 0.052 to 0.182), three ACEs (ß=0.075; 95% CI 0.007 to 0.143) and four or more ACEs (ß=0.089; 95% CI 0.002 to 0.158) were associated with less decline in executive function. There were no significant associations between number of ACEs and baseline or longitudinal verbal episodic memory or between individual ACEs and executive function or verbal episodic memory. CONCLUSION: In this cohort of older black Americans, there was no association between ACEs and baseline cognition or cognitive change in verbal episodic memory; however, experiencing ≥ 2 ACEs was associated with less decline in executive function. These results may indicate that participants who survived to age 50+ and experienced ACEs may have cognitive resilience that warrants further investigation.

Impact of socioeconomic status and chemotherapy on neurocognitive performance in children with brain tumors.

Background: Although the relationship between radiation and neurocognition has been extensively studied in the pediatric brain tumor population, it is increasingly recognized that neurocognitive impairment is multifactorial. Therefore, we quantified the effect of socioeconomic status (SES) and chemotherapy on neurocognitive impairment and decline post-treatment. Methods: Eligible patients included those diagnosed with a brain tumor at < 22 years of age with ≥1 neurocognitive assessment. Neurocognitive impairment was defined as performance 1.5 standard deviations below the normative mean using age-standardized measures of intellectual function. Neurocognitive decline was defined as a negative slope. Neurocognitive outcomes included Wechsler indices of Full-Scale Intelligence Quotient (IQ). Logistic regression identified variables associated with neurocognitive impairment. Longitudinal data was analyzed using linear mixed models. Results: Eligible patients (n = 152, median age at diagnosis = 9.6 years) had a mean neurocognitive follow-up of 50.2 months. After accounting for age and receipt of craniospinal irradiation, patients with public insurance had 8-fold increased odds of impaired IQ compared to private insurance (odds ratio [OR]: 7.59, P < .001). After accounting for age, change in IQ was associated with chemotherapy use (slope: -0.45 points/year with chemotherapy vs. 0.71 points/year without chemotherapy, P = .012). Conclusions: Public insurance, an indicator of low SES, was associated with post-treatment impairment in IQ, highlighting the need to incorporate SES measures into prospective studies. Chemotherapy was associated with change in IQ. Further work is needed to determine whether impairment associated with low SES is secondary to baseline differences in IQ prior to brain tumor diagnosis, brain tumor/therapy itself, or some combination thereof.

ADHD-related sex differences in frontal lobe white matter microstructure and associations with response control under conditions of varying cognitive load and motivational contingencies.

Children with attention-deficit/hyperactivity disorder (ADHD) demonstrate reduced response inhibition, increased response time variability, and atypical frontal lobe white matter microstructure with emerging evidence of sex differences. This study aims to examine whether frontal lobe white matter microstructure is differentially impacted in ADHD by sex and whether this relates to Go/No-Go (GNG) task performance. Diffusion tensor imaging (DTI) from 187 children (8-12 years), including ADHD (n = 94) and typically developing controls (TD; n = 93). Participants completed three GNG tasks with varying cognitive demands and incentives (standard, cognitive, and motivational). Fractional anisotropy (FA) was examined as an index of white matter microstructure within bilateral frontal lobe regions of interest. Children with ADHD showed reduced FA in primary motor (M1) and supplementary motor area (SMA) regardless of sex. Sex-based dissociation for the effect of diagnosis was observed in medial orbitofrontal cortex (mOFC), with higher FA in girls with ADHD and lower FA in boys with ADHD. Both diagnosis and sex contributed to performance on measures of response inhibition and reaction time (RT) variability, with all children with ADHD demonstrating poorer performance on all GNG tasks, but boys with ADHD demonstrating more impulsivity on standard and motivational behavioral paradigms compared to girls with ADHD. Analyses revealed associations between reduced FA in M1, SMA, and mOFC and increased response inhibition and RT variability with some sex-based differences. These findings provide novel insights regarding the brain basis of ADHD and associated impairments in response inhibition and RT variability, and contribute to our understanding of sexual dimorphic behavioral outcomes.

Cognitive disengagement syndrome (sluggish cognitive tempo) and medical conditions: a systematic review and call for future research.

Cognitive disengagement syndrome (CDS, previously referred to as sluggish cognitive tempo) is a unique set of symptoms distinct from ADHD inattentive symptoms that appear to be independently associated with neuropsychological and psychosocial outcomes in community and ADHD-specific samples of youth. However, our understanding of CDS in individuals with chronic or complex medical conditions is limited. The current systematic review is the first to summarize the literature on CDS prevalence rates and associations with neurocognitive and functional outcomes in youth with medical conditions, and to discuss areas of future research to guide clinical intervention. We conducted literature searches across four major databases and included studies assessing prevalence estimates, associations with neuropsychological and/or psychosocial functioning, or predictors of CDS in individuals with chronic or complex medical conditions. Twenty-five studies were identified and retained. Fifteen of sixteen studies reported elevations in CDS symptoms, though findings were mixed in studies comparing mean differences to typically developing youth. Seven studies provided inconsistent evidence for CDS being associated with neuropsychological or academic functioning, with six studies demonstrating consistent effects on psychosocial functioning. Finally, nine studies identified biological and sociodemographic factors associated with CDS, though almost all await replication. CDS symptoms are significantly elevated in youth with medical conditions and appear to be particularly linked with psychosocial functioning. Future research is needed to identify prevalence of CDS across a range of medical conditions, examine associations with neuropsychological and psychosocial functioning, and examine whether CDS impacts self-management.

Association Between Neighborhood Deprivation and Child Cognition in Clinically Referred Youth.

OBJECTIVE: When socioeconomic status is measured at the individual and/or family level, it has long been associated with cognition in children. However, the association between neighborhood deprivation, an index of community-level socioeconomic status, and child cognition is not fully understood. The goal of this study was to investigate (1) the relationship between neighborhood deprivation and child cognitive functioning and (2) whether child age moderates the relationship between cognitive functioning and neighborhood deprivation. METHODS: This study included 9878 children, ages 3 through 17 years (M = 10.4 yrs, SD = 3.4 yrs). Data were gathered from children referred for and evaluated at an urban, outpatient neuropsychology assessment clinic between 2006 and 2022, located in the Mid-Atlantic region of the United States. Neighborhood socioeconomic status was measured at the census block level using the Area Deprivation Index composite. RESULTS: There was a 20-point median difference in overall intelligence between the neighborhoods with the lowest and highest levels of deprivation. Overall intelligence and verbal comprehension, compared with working memory, fluid reasoning, and processing speed, demonstrated the strongest negative association with neighborhood deprivation (all p < 0.05). Older children had lower overall intelligence scores compared with younger children in neighborhoods with high levels of deprivation ( p < 0.01), suggesting a cumulative influence of poverty exposure. CONCLUSION: This study demonstrates the stark disparities in child cognitive functioning across levels of neighborhood deprivation. Findings support the importance of access to early interventions and services that promote intellectual growth and verbal capacity among children who live in neighborhoods with great deprivation.

Adult Inpatient Services in Pediatric Hospitals: A National Mixed Methods Study.

OBJECTIVES: Some pediatric institutions have developed adult inpatient services to enable quality care of hospitalized adults. Our objectives were to understand the characteristics of these adult inpatient services in pediatric hospitals, barriers and facilitators to their creation and sustainability, and patient and system needs they addressed. METHODS: An explanatory mixed methods study was conducted using a distribution of an electronic survey followed by targeted semi-structured interviews of directors (or designates) of adult inpatient services in US pediatric hospitals. The survey identified institutional demographics, service line characteristics, and patient populations. An interview guide was created to explore survey findings and facilitators and barriers in the creation of adult inpatient services. Interviews were conducted after survey completion. A codebook was created using an inductive thematic approach and iteratively refined. Final themes were condensed, and illustrative quotes selected. RESULTS: Ten institutions identified as having an adult inpatient service. Service staffing models varied, but all had dually trained internal medicine and pediatrics physicians. All participants voiced their respective pediatric institutions valued that these services filled a clinical care gap for hospitalized adults adding to whole-person care, patient safety, and health system navigation. CONCLUSIONS: Adult inpatient services in pediatric institutions have been present for >15 years. These services address clinical care gaps for adults hospitalized in pediatric institutions and use specialized internal medicine and pediatrics knowledge. Demonstrating return on investment of these services using a traditional fee for service model is a barrier to creation and sustainability.

Short-Term Dietary Intervention with Whole Oats Protects from Antibiotic-Induced Dysbiosis.

Antibiotic-induced gut microbiome dysbiosis (AID) is known to be influenced by host dietary composition. However, how and when diet modulates gut dysbiosis remains poorly characterized. Thus, here, we utilize a multi-omics approach to characterize how a diet supplemented with oats, a rich source of microbiota-accessible carbohydrates, or dextrose impacts amoxicillin-induced changes to gut microbiome structure and transcriptional activity. We demonstrate that oat administration during amoxicillin challenge provides greater protection from AID than the always oats or recovery oats diet groups. In particular, the group in which oats were provided at the time of antibiotic exposure induced the greatest protection against AID while the other oat diets saw greater effects after amoxicillin challenge. The oat diets likewise reduced amoxicillin-driven elimination of Firmicutes compared to the dextrose diet. Functionally, gut communities fed dextrose were carbohydrate starved and favored respiratory metabolism and consequent metabolic stress management while oat-fed communities shifted their transcriptomic profile and emphasized antibiotic stress management. The metabolic trends were exemplified when assessing transcriptional activity of the following two common gut commensal bacteria: Akkermansia muciniphila and Bacteroides thetaiotaomicron. These findings demonstrate that while host diet is important in shaping how antibiotics effect the gut microbiome composition and function, diet timing may play an even greater role in dietary intervention-based therapeutics. IMPORTANCE We utilize a multi-omics approach to demonstrate that diets supplemented with oats, a rich source of microbiota-accessible carbohydrates, are able to confer protection against antibiotic-induced dysbiosis (AID). Our findings affirm that not only is host diet important in shaping antibiotics effects on gut microbiome composition and function but also that the timing of these diets may play an even greater role in managing AID. This work provides a nuanced perspective on dietary intervention against AID and may be informative on preventing AID during routine antibiotic treatment.