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In this study, we aimed to understand the potential role of the gut microbiome in the development of Alzheimers disease (AD). We took a multi-faceted approach to investigate this relationship. Urine metabolomics were examined in individuals with AD and controls, revealing decreased formate and fumarate concentrations in AD. Additionally, we utilised whole-genome sequencing (WGS) data obtained from a separate group of individuals with AD and controls. This information allowed us to create and investigate host-microbiome personalised whole-body metabolic models. Notably, AD individuals displayed diminished formate microbial secretion in these models. Additionally, we identified specific reactions responsible for the production of formate in the host, and interestingly, these reactions were linked to genes that have correlations with AD. This study suggests formate as a possible early AD marker and highlights genetic and microbiome contributions to its production. The reduced formate secretion and its genetic associations point to a complex connection between gut microbiota and AD. This holistic understanding might pave the way for novel diagnostic and therapeutic avenues in AD management.

Abstract Inferior frontal sulcal hyperintensities (IFSH) observed on fluid-attenuated inversion recovery (FLAIR) MRI have been proposed as indicators of elevated cerebrospinal fluid waste accumulation in cerebral small vessel disease (CSVD). However, to validate IFSH as a reliable imaging biomarker, further replication studies are required. The objective of this study was to investigate associations between IFSH and CSVD, and their potential repercussions, i.e., cognitive impairment and depression. We prospectively recruited 47 patients with CSVD and 29 cognitively normal controls (NC). IFSH were rated visually based on FLAIR MRI. Using different regression models, we explored the relationship between IFSH, group status (CSVD vs. NC), CSVD severity assessed with MRI, cognitive function, and symptoms of depression. Patients with CSVD were more likely to have higher IFSH scores compared to NC (OR 5.64, 95% CI 1.91–16.60), and greater CSVD severity on MRI predicted more severe IFSH (OR 1.47, 95% CI 1.14–1.88). Higher IFSH scores were associated with lower cognitive function (-0.96, 95% CI -1.81 to -0.10), and higher levels of depression (0.33, 95% CI 0.01–0.65). CSVD and IFSH may be tightly linked to each other, and the accumulation of waste products, indicated by IFSH, could have detrimental effects on cognitive function and symptoms of depression.

Background The study's objective was to examine national trends in patterns of under-vaccination in the United States.Research design and methods The National Immunization Survey-Child (NIS-Child) is an annual cross-sectional survey that collects provider-verified vaccination records from a large national probability sample of children. Records from the 2011–2021 NIS-Child were used to assess receipt of the combined 7-vaccine series by age 24 months. Based on prior work, patterns indicative of hesitancy included zero vaccines, not starting ≥1 series, and consistent vaccine-limiting. Patterns indicative of practical issues included starting all series but missing doses. Up-to-date (UTD) was defined as receiving all doses in the combined 7-vaccine series.Results The study population comprised 127,257 children. Over the observation period, patterns indicative of hesitancy significantly decreased (p-trend

Abstract Objective Glial fibrillary acidic protein (GFAP) is expressed in astrocytes and may be a useful marker of non‐active progressive multiple sclerosis (MS). We evaluate serum GFAP (sGFAP) in a large cohort of MS patients to determine if it predicts progression independent of relapse activity (PIRA), future gait aid, and conversion to secondary progressive disease (SPMS). Methods Adults with clinically isolated syndrome or any subtype of MS who were listed in the Brigham MS Center Research Database and had at least one sGFAP result were included. All clinic visits following first sample were analyzed for PIRA, future gait aid, and conversion to SPMS. Future cognitive dysfunction and fatigue were evaluated as secondary outcomes. Results In total, 741 patients were included (average age: 42.3, average disease duration: 3.7 years, median EDSS: 2, and median follow‐up duration: 10.0 years). Of 643 patients (86.8%) without progressive disease at baseline, 15.9% developed SPMS. Among all 741, 50.5% had PIRA and 18.6% developed a gait aid requirement. sGFAP level predicted PIRA, future gait aid, and conversion to SPMS in univariable models (p

BackgroundIn humans, environmental enrichment (EE), as measured by the engagement in a variety of leisure activities, has been associated with larger hippocampal structure and better memory function. The present cross-sectional study assessed whether EE during early life (13–30 years) and midlife (30–65 years) is associated with better preserved memory-related brain activity patterns in older age.MethodsIn total, 372 cognitively unimpaired older adults (aged ≥60 years old) of the DZNE-Longitudinal Study on Cognitive Impairment and Dementia (DELCODE; DRKS00007966) were investigated. EE was operationalized using items of the Lifetime of Experiences Questionnaire (LEQ), which measures the self-reported participation in a variety of leisure activities in early life and midlife. The preservation of memory-related functional brain activity was assessed using single-value scores, which relate older adults’ brain activity patterns in the temporo-parieto-occipital memory network to those of young adults during visual memory encoding (FADE and SAME scores).ResultsEE during early life and midlife was significantly associated with higher SAME scores during novelty processing (n = 372, β = 0.13, p = 0.011). Thus, older participants with higher EE showed greater similarity of functional brain activity patterns during novelty processing with young adults. This positive association was observed most strongly in participants with subjective cognitive decline (SCD, n = 199, β = 0.20, p = 0.006).ConclusionMore frequent participation in a variety of leisure activities in early life and midlife is associated with more successful aging of functional brain activity patterns in the memory network of older adults, including participants at increased risk for dementia. Longitudinal studies are needed to clarify whether higher EE during life could help preserve memory network function in later life.

Young adults experience high coronavirus disease 2019 (COVID-19) incidence yet have the lowest vaccination and booster rates among adults. Understanding the factors influencing their intentions regarding boosters is essential for crafting effective public health strategies. We examined the psychosocial factors (attitudes, norms, perceived behavioral control) associated with their intentions to receive a COVID-19 booster. This cross-sectional study included 292 young adults aged 18–25 residing in Philadelphia who completed an online survey from September 2021 and February 2022 (mean age 21.98, standard deviation 2.25; 51% racial/ethnic minorities). The survey included measures of attitudes, norms, and perceived behavioral control related to COVID-19 vaccination. We employed structural equation modeling analysis to examine the intention of young adults to receive the COVID-19 booster and their vaccine-related attitudes, norms, and perceived behavioral control. Covariates included race/ethnicity and gender. Subjective norms were significantly associated with the intention to receive a COVID-19 booster (standardized β̂ = 0.685, p = .018). Attitudes and perceived behavioral control showed no significant association with intention. Subgroup analyses based on race/ethnicity revealed that attitudes (standardized β̂ = 0.488, p = .004) and subjective norms (standardized β̂ = 0.451, p = .050) were predictors among young adults from racial and ethnic minority backgrounds, while only subjective norms (standardized β̂ = 1.104, p = .002) were significant for non-Hispanic White young adults. Public health efforts should prioritize engaging healthcare providers and peer groups in order to influence subjective norms and promote collective responsibility and acceptance for vaccination. Tailored interventions and diverse communication strategies targeting specific subgroups of young adults may be useful to ensure comprehensive and effective vaccination initiatives.

Abstract Introduction We investigated the agreement between automated and gold‐standard manual transcriptions of telephone chatbot‐based semantic verbal fluency testing. Methods We examined 78 cases from the Screening over Speech in Unselected Populations for Clinical Trials in AD (PROSPECT‐AD) study, including cognitively normal individuals and individuals with subjective cognitive decline, mild cognitive impairment, and dementia. We used Bayesian Bland–Altman analysis of word count and the qualitative features of semantic cluster size, cluster switches, and word frequencies. Results We found high levels of agreement for word count, with a 93% probability of a newly observed difference being below the minimally important difference. The qualitative features had fair levels of agreement. Word count reached high levels of discrimination between cognitively impaired and unimpaired individuals, regardless of transcription mode. Discussion Our results support the use of automated speech recognition particularly for the assessment of quantitative speech features, even when using data from telephone calls with cognitively impaired individuals in their homes. Highlights High levels of agreement were found between automated and gold‐standard manual transcriptions of telephone chatbot‐based semantic verbal fluency testing, particularly for word count. The qualitative features had fair levels of agreement. Word count reached high levels of discrimination between cognitively impaired and unimpaired individuals, regardless of transcription mode. Automated speech recognition for the assessment of quantitative and qualitative speech features, even when using data from telephone calls with cognitively impaired individuals in their homes, seems feasible and reliable.

Objective: Chronic opioid use can lead to detrimental effects on the immune and various organ systems that put individuals prescribed chronic opioid therapy (COT) for pain and those with an opioid use disorder (OUD) at risk for severe COVID-19 disease. We assessed the association of COT and OUD with COVID-19-related hospitalization and death to inform targeted interventions to improve clinical outcomes in COVID-19 patients who use opioids. Methods: We conducted a retrospective cohort study of adults ages ≥ 18 with laboratory-confirmed SARS-CoV-2 infection in 2020 and 2021 from three US health systems. We used Cox proportional hazards regression to estimate the 30-day risk of COVID-19-related hospitalization and death associated with two opioid exposures (COT and OUD) following an infection. Results: The study cohort included 53,123 patients with SARS-CoV-2 infection and a mean (SD) age of 45.1 (16.5), of whom 1,059 (2.0 %) were exposed to COT and 269 (0.5 %) had an OUD diagnosis in the year prior to infection. There were 2,270 observed COVID-19-related hospitalizations or deaths (1.6 per 1,000 person-days, 95 % CI 1.5–1.7). In the fully adjusted model, COT was not associated with increased risk (HR 1.19; 95 % CI, 0.98–1.43), while past-year OUD was independently associated with severe COVID-19 disease (HR 1.82; 95 % CI, 1.18–2.80). Past-year OUD remained associated with increased risk in post-hoc analysis with COVID-19-related hospitalization alone as the outcome (HR 2.00; 95 % CI, 1.30–3.08). Conclusions: Past-year OUD is a potential independent risk factor for severe COVID-19 disease that warrants monitoring to improve the prognosis of patients with COVID-19.

Summary: Metabolic dysfunction-associated steatotic liver disease (MASLD) prevalence is increasing annually and affects over a third of US adults. MASLD can progress to metabolic dysfunction-associated steatohepatitis (MASH), characterized by severe hepatocyte injury, inflammation, and eventual advanced fibrosis or cirrhosis. MASH is predicted to become the primary cause of liver transplant by 2030. Although the etiology of MASLD/MASH is incompletely understood, dysregulated fatty acid oxidation is implicated in disease pathogenesis. Here, we develop a method for estimating hepatic β-oxidation from the metabolism of [D15]octanoate to deuterated water and detection with deuterium magnetic resonance methods. Perfused livers from a mouse model of MASLD reveal dysregulated hepatic β-oxidation, findings that corroborate in vivo imaging. The high-fat-diet-induced MASLD mouse studies indicate that decreased β-oxidative efficiency in the fatty liver could serve as an indicator of MASLD progression. Furthermore, our method provides a clinically translatable imaging approach for determining hepatic β-oxidation efficiency.

Physical activity is important for children's health and well-being. Supportiveness for physical activity of home and neighborhood environments may affect children's PA, but most studies are cross-sectional. We examined environmental predictors of change in children's physical activity over two years. Data were from the longitudinal, observational cohort study, 'Neighborhood Impact on Kids'. Participants were children (initially aged 6-12 years) and their parent/caregiver (n = 727 dyads) living in neighborhoods throughout San Diego County, California and King County (Seattle area), Washington, USA. Children's moderate-to-vigorous physical activity (MVPA) was measured using accelerometers at T1 (Time 1 or baseline, 2007-2009) and T2, the two-year follow-up. At T1, parents survey-reported on physical activity (PA) equipment at home and demographics. Neighborhood environment was measured using spatial data in Geographic Information Systems (intersection density; park availability) and in-person audits (informal play space near home; park-based PA facilities; land use; support for walking/cycling). Generalized additive mixed models estimated total effects, then direct effects, of environmental attributes on MVPA at T1. Two-way moderating effects of child's sex and age were examined at T1. To examine associations of environmental exposures with changes in MVPA, we estimated interaction effects of environmental attributes on the association between time and MVPA. On average, children accumulated 146 min/day (standard deviation or SD = 53) of MVPA at T1, and 113 (SD = 58) min/day at T2. There were no significant total or direct effects of environmental attributes on MVPA at T1, and no significant two-way interaction effects of child's age and sex for T1 MVPA. Having informal play spaces proximal to home with more amenities was associated with less MVPA decline from T1 to T2. Higher residential density, higher land use mix, and higher number of PA facilities in nearby parks were unexpectedly associated with greater MVPA decline. Higher quality informal play spaces close to home may help offset declines in MVPA during middle childhood, as they may promote unstructured active play with opportunities for parental or neighbor surveillance. Unexpectedly, environmental factors consistent with higher walkability were associated with greater declines in children's MVPA. As physical activity differs across the lifespan, so may environmental factors that facilitate it.

To the Editor.--Use of SARS-CoV-2 serology to assess risk of SARS-CoV-2 breakthrough infection (BTI) after COVID-19 vaccination is officially discouraged. (1) Yet some experts suggest that low SARS-CoV-2 anti-spike protein [...]

Drawing on Dewey's critique of the way educators, historically, have tried to promulgate definitive prescriptions for educational practice, this article examines implications of the use of science for supervisory practice and for the field of supervision as a whole. A content analysis of Dewey's "The Sources of a Science of Education" indicates the pervasiveness of the technocratic nature of teaching and supervision. Historical evidence is presented to indicate the degree and manner to which educators have tried to use science to justify inspectional and prescriptive practices of supervision. The significance of Dewey's work is in the realization that science alone should not dictate supervisory practice. Rather, viewing science with more tentativeness and exploration is needed. Lessons from Dewey's work are discussed, as are implications for the field of supervision.

The field of supervision has perennially struggled to define itself and, hence, find a niche within the larger field of education and, more narrowly, even within the field of instructional leadership. A sort of an odd, almost contradictory state exists, one in which precludes, in my opinion, the field of supervision from gaining traction as a field, but also, perhaps more importantly, as an influential practice in schools. Books on supervision seem popular, but only in title. In others words, publishers, for instance, prefer the word "supervision" as part of the title of books they publish on the subject, whereas scholars in the field tend to eschew the term in favor of a term, perhaps, more palatable such as instructional or pedagogical leadership. Scholars in our field have had to grapple with this bifurcation. This essay discusses some of the implications of the intractable nature of supervision theory and practice and its relationship with the emergence of newer, more preferred terms. This essay attempts to clarify the relationships among supervision, instructional leadership, pedagogical leadership, and some other terms bandied about in the field. Are there differences between and among them? What are the implications for the field of supervision, as well as for the world of practice?