Maternal Sleep Quality and Executive Function are Associated with Perceptions of Infant Sleep.

OBJECTIVES: This study examined the associations among maternal sleep quality, executive function, and perceptions of infant sleep in a sample of families recruited from human service and public health systems. METHODS: Seventy-three mothers of infants 5-14 months old were included in the study. Mothers racially and ethnically identified as American Indian/Alaskan Native (4.1%), Asian (4.1%), Black/African American (12.3%), Latina (23.3%), more than one race (12.3%), Pacific Islander (1.4%), and White (42.5%). Mothers completed questionnaires assessing their own sleep (Pittsburgh Sleep Quality Index) and executive function (Behavior Rating Inventory of Executive Function) as well as their perceptions about their infant's sleep (Brief Infant Sleep Questionnaire). RESULTS: Results of the path analysis indicated significant direct effects among maternal sleep quality, executive function, and perceptions of infant sleep. Significant indirect effects were found such that poor maternal sleep quality was linked to poorer perceptions of infant sleep through maternal executive dysfunction, adjusting for infant sleep patterns, infant age, and maternal race and ethnicity. CONCLUSIONS: The current study highlights the potential role of maternal behavioral and cognitive factors in shaping mothers' perceptions about infant sleep. These findings support the need for health professionals and researchers to consider maternal sleep quality and executive function when addressing mothers' concerns about infant sleep.

Translating an intervention to address chronic pain in home care workers: The COMPASS-NP Pilot.

OBJECTIVE: Pilot test the COMmunity of Practice And Safety Support for Navigating Pain (COMPASS-NP) intervention for home care workers (HCWs) experiencing chronic pain. METHODS: HCWs with chronic pain participated (n = 19; 2 groups) in a 10-week online group program focused on workplace safety and pain self-management. Primary outcomes were changes in pain interference with work and life. Other outcomes related to ergonomics, pain levels, opioid misuse risk, mental health, sleep, and physical activity. RESULTS: The intervention produced a large reduction in pain interference with life (d = -0.85) and a moderate reduction in pain interference with work time demands (d = -0.61). Secondary outcomes showed favorable effect sizes, including a substantial increase in the use of ergonomic tools and techniques (d = 1.47). CONCLUSION: Findings were strongly encouraging. The effectiveness of COMPASS-NP will be evaluated in a future randomized controlled trial.

Linking Type and Extent of Head Trauma to Cavum Septum Pellucidum in Older Adults With and Without Alzheimer Disease and Related Dementias.

BACKGROUND AND OBJECTIVES: Cavum septum pellucidum (CSP) is a common but nonspecific MRI finding in individuals with prior head trauma. The type and extent of head trauma related to CSP, CSP features specific to head trauma, and the impact of brain atrophy on CSP are unknown. We evaluated CSP cross-sectionally and longitudinally in healthy and clinically impaired older adults who underwent detailed lifetime head trauma characterization. METHODS: This is an observational cohort study of University of California, San Francisco Memory and Aging Center participants (healthy controls [HCs], those with Alzheimer disease or related dementias [ADRDs], subset with traumatic encephalopathy syndrome [TES]). We characterized traumatic brain injury (TBI) and repetitive head impacts (RHI) through contact/collision sports. Study groups were no RHI/TBI, prior TBI only, prior RHI only, and prior RHI + TBI. We additionally looked within TBI (1, 2, or 3+) and RHI (1-4, 5-10, and 11+ years). All underwent baseline MRI, and 67% completed a second MRI (median follow-up = 5.4 years). CSP measures included grade (0-4) and length (millimeters). Groups were compared on likelihood of CSP (logistic regression, odds ratios [ORs]) and whether CSP length discriminated groups (area under the curve [AUC]). RESULTS: Our sample included 266 participants (N = 160 HCs, N = 106 with ADRD or TES; age 66.8 ± 8.2 years, 45.3% female). Overall, 123 (49.8%) participants had no RHI/TBI, 52 (21.1%) had TBI only, 41 (16.6%) had RHI only, 31 (12.6%) had RHI + TBI, and 20 were classified as those with TES (7.5%). Compared with no RHI/TBI, RHI + TBI (OR 3.11 [1.23-7.88]) and TES (OR 11.6 [2.46-54.8]) had greater odds of CSP. Approximately 5-10 years (OR 2.96 [1.13-7.77]) and 11+ years of RHI (OR 3.14 [1.06-9.31]) had higher odds of CSP. CSP length modestly discriminated participants with 5-10 years (AUC 0.63 [0.51-0.75]) and 11+ years of prior RHI (AUC 0.69 [0.55-0.84]) from no RHI/TBI (cut point = 6 mm). Strongest effects were noted in analyses of American football participation. Longitudinally, CSP grade was unchanged in 165 (91.7%), and length was unchanged in 171 (95.5%) participants. DISCUSSION: Among older adults with and without neurodegenerative disease, risk of CSP is driven more by duration (years) of RHI, especially American football, than number of TBI. CSP length (≥6 mm) is relatively specific to individuals who have had substantial prior RHI. Neurodegenerative disease and progressive atrophy do not clearly influence development or worsening of CSP.

Disentangling tau: One protein, many therapeutic approaches.

The tauopathies encompass over 20 adult neurodegenerative diseases and are characterized by the dysfunction and accumulation of insoluble tau protein. Among them, Alzheimer's disease, frontotemporal dementia, and progressive supranuclear palsy collectively impact millions of patients and their families worldwide. Despite years of drug development using a variety of mechanisms of action, no therapeutic directed against tau has been approved for clinical use. This raises important questions about our current model of tau pathology and invites thoughtful consideration of our approach to nonclinical models and clinical trial design. In this article, we review what is known about the biology and genetics of tau, placing it in the context of current and failed clinical trials. We highlight potential reasons for the lack of success to date and offer suggestions for new pathways in therapeutic development. Overall, our viewpoint to the future is optimistic for this important group of neurodegenerative diseases.

The Tech4Rest Randomized Controlled Trial: Applying the Hierarchy of Controls to Advance the Sleep, Health, and Well-being of Team Truck Drivers.

OBJECTIVE: The aim of the study was to evaluate the effectiveness of interventions to improve sleep, reduce fatigue, and advance the well-being of team truck drivers. METHODS: In a randomized controlled trial ( k = 24 teams; N = 49 drivers; 61.3% of planned sample), intervention teams were exposed to baseline (3-4 weeks), cab enhancements (active suspension seat, therapeutic mattress; 3-4 weeks), and cab enhancements plus a behavioral sleep-health program (1-2 months). Control teams worked as usual during the same period. RESULTS: Trends in sleep-related outcomes favored the intervention. Large and statistically significant intervention effects were observed for objectively measured physical activity (a behavioral program target). The discussion of results addresses effect sizes, statistical power, intervention exposure, and work organization. CONCLUSIONS: Trends, effect sizes, and significant findings in this rare trial provide valuable guidance for future efforts to improve working conditions and outcomes for team drivers.

Tau pathology in neurodegenerative disease: disease mechanisms and therapeutic avenues.

Tauopathies are disorders associated with tau protein dysfunction and insoluble tau accumulation in the brain at autopsy. Multiple lines of evidence from human disease, as well as nonclinical translational models, suggest that tau has a central pathologic role in these disorders, historically thought to be primarily related to tau gain of toxic function. However, a number of tau-targeting therapies with various mechanisms of action have shown little promise in clinical trials in different tauopathies. We review what is known about tau biology, genetics, and therapeutic mechanisms that have been tested in clinical trials to date. We discuss possible reasons for failures of these therapies, such as use of imperfect nonclinical models that do not predict human effects for drug development; heterogeneity of human tau pathologies which may lead to variable responses to therapy; and ineffective therapeutic mechanisms, such as targeting of the wrong tau species or protein epitope. Innovative approaches to human clinical trials can help address some of the difficulties that have plagued our field's development of tau-targeting therapies thus far. Despite limited clinical success to date, as we continue to refine our understanding of tau's pathogenic mechanism(s) in different neurodegenerative diseases, we remain optimistic that tau-targeting therapies will eventually play a central role in the treatment of tauopathies.

COMMunity of Practice And Safety Support for Navigating Pain (COMPASS-NP): study protocol for a randomized controlled trial with home care workers.

BACKGROUND: Chronic pain is a prevalent and costly problem that often has occupational origins. Home care workers (HCWs) are at high risk for work-related injuries, pain, and disability. Current treatments for chronic pain emphasize medications, which are an inadequate stand-alone treatment and can produce significant adverse effects. METHODS: In this translational study, we will adapt an established work-based injury prevention and health promotion program (COMmunity of Practice And Safety Support: COMPASS) to address the needs of HCWs experiencing chronic pain. COMPASS employs peer-led, scripted group meetings that include educational content, activities, goal setting, and structured social support. The translated intervention, named COMPASS for Navigating Pain (COMPASS-NP), will be delivered in an online group format. Safety protections will be strengthened through an ergonomic self-assessment and vouchers for purchasing ergonomic tools. Educational content will integrate a self-management approach to chronic pain using proven cognitive-behavioral therapy (CBT) principles. We will use a mixed-methods hybrid type 2 evaluation approach to assess effectiveness and implementation. A cluster-randomized waitlist control design will involve 14 groups of 10 HCWs (n = 140) recruited from Washington, Oregon, and Idaho. Half of the groups will be randomly selected to complete the intervention during the first 10 weeks, while the waitlist groups serve as controls. During weeks 10-20, the waitlist groups will complete the intervention while the original intervention groups complete a follow-up period without further intervention. Our primary hypothesis is that COMPASS-NP will reduce pain interference with work and life. Secondary outcomes include injury and pain prevention behaviors, pain severity, changes in medication use, risk for opioid misuse, well-being, physical activity, and sleep. Qualitative data, including phone interviews with group facilitators and organizational partners, will evaluate the implementation and guide dissemination. DISCUSSION: The results will advance the use and knowledge of secondary prevention interventions such as ergonomic tools and cognitive behavior therapy, to reduce injury, pain, and disability and to encourage appropriate uses of analgesic medications among HCWs. TRIAL REGISTRATION: ClinicalTrials.gov NCT05492903. Registered on 08 August 2022.

The Development and Validation of Teen Beliefs on Relationship Abuse Measure (TBRAM).

The purpose of this study was to validate an original and innovative survey focused on both teens' personal beliefs and how they perceived their peers' beliefs regarding relationship abuse with four research questions: What are the measured constructs in this survey? Is the hypothesized factor structure of the five types of relationship abuse confirmed? Does the validity of constructs vary among racial/ethnic groups and genders? Are there differences between teens' own beliefs on relationship abuse and their perceptions of peers' beliefs? To address these questions, two confirmatory factor analysis (CFA) models were examined with 591 high school students' responses. The first CFA model was created based on the exploratory factor analysis results and the second CFA model was created based on the theoretically hypothesized model of five types of relationship abuse. The results indicate that the 5-factor, 11-item model based on the theoretical hypothesis is the best fit to the data. The multiple group model analysis demonstrated that the identified CFA measurement model was invariant across different gender and racial/ethnic groups. The validated instrument of Teen Beliefs on Relationship Abuse Measure is a reliable and valid way to measure both teens' personal beliefs and their perceptions of peers' beliefs on five types of relationship abuse including emotional, physical, sexual, stalking, and digital abuses. With the validated model, t-test results indicate that teens' own beliefs are significantly more positive than their perceptions of their peers' beliefs for all the five factors. The measure is useful for researchers, educators, and parents to measure and understand teen perceptions of themselves and their peers on different types of relationship abuses to better support them develop healthy, respectful, and nonviolent relationships.

Mothers' and fathers' parenting attitudes during COVID-19.

Attitudes about parenting are derived from early socialization of gender role norms and often include intensive parenting beliefs, which give mothers an outsized role in parenting. This study examined the differences in intensive parenting beliefs among cisgender mothers and fathers during the United States COVID-19 response. Data from a sample of 1048 mothers and fathers were collected during March and April 2020 to understand parenting beliefs. Results indicated that some demographic factors, including gender and ethnicity, impact intensive parenting beliefs. Additionally, the number of COVID-19 cases in a state, along with school closure length, was related to intensive parenting beliefs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12144-021-01605-x.

Reelin Regulates Neuronal Excitability through Striatal-Enriched Protein Tyrosine Phosphatase (STEP61) and Calcium Permeable AMPARs in an NMDAR-Dependent Manner.

Alzheimer's disease (AD) is a progressive neurodegenerative disease marked by the accumulation of amyloid-ß (Aß) plaques and neurofibrillary tangles. Aß oligomers cause synaptic dysfunction early in AD by enhancing long-term depression (LTD; a paradigm for forgetfulness) via metabotropic glutamate receptor (mGluR)-dependent regulation of striatal-enriched tyrosine phosphatase (STEP61). Reelin is a neuromodulator that signals through ApoE (apolipoprotein E) receptors to protect the synapse against Aß toxicity (Durakoglugil et al., 2009) Reelin signaling is impaired by ApoE4, the most important genetic risk factor for AD, and Aß-oligomers activate metabotropic glutamate receptors (Renner et al., 2010). We therefore asked whether Reelin might also affect mGluR-LTD. To this end, we induced chemical mGluR-LTD using DHPG (Dihydroxyphenylglycine), a selective mGluR5 agonist. We found that exogenous Reelin reduces the DHPG-induced increase in STEP61, prevents the dephosphorylation of GluA2, and concomitantly blocks mGluR-mediated LTD. By contrast, Reelin deficiency increased expression of Ca2+-permeable GluA2-lacking AMPA receptors along with higher STEP61 levels, resulting in occlusion of DHPG-induced LTD in hippocampal CA1 neurons. We propose a model in which Reelin modulates local protein synthesis as well as AMPA receptor subunit composition through modulation of mGluR-mediated signaling with implications for memory consolidation or neurodegeneration.SIGNIFICANCE STATEMENT Reelin is an important neuromodulator, which in the adult brain controls synaptic plasticity and protects against neurodegeneration. Amyloid-ß has been shown to use mGluRs to induce synaptic depression through endocytosis of NMDA and AMPA receptors, a mechanism referred to as LTD, a paradigm of forgetfulness. Our results show that Reelin regulates the phosphatase STEP, which plays an important role in neurodegeneration, as well as the expression of calcium-permeable AMPA receptors, which play a role in memory formation. These data suggest that Reelin uses mGluR LTD pathways to regulate memory formation as well as neurodegeneration.

Sedentary Work and Physiological Markers of Health.

The purpose of this study is to examine associations between objectively measured workplace sedentary behavior and physiological markers of health. We hypothesize that increased sedentary time and more frequent bouts of uninterrupted sitting are associated with increased hemoglobin A1c, increased blood pressure, and impaired endothelial function. Call center employees (N = 241) were enrolled from four worksites in the United States. Participants completed a survey and a physical health assessment. Sedentary behavior and sitting/standing time at work were quantified using an accelerometer. Hemoglobin A1c was measured using a finger-prick and portable analyzer. Blood pressure was measured with an automated cuff, and vascular endothelial function was assessed in a subsample of participants (n = 56) using EndoPAT. We analyzed data with two series of ordinary least squares regressions, first to examine relationships between bouts of uninterrupted sitting and physiological outcomes, and second to examine relationships between physical activity and sitting/standing time at work and physiological outcomes. The sample was primarily female, and on average was obese, prehypertensive, and prediabetic. There were no significant relationships between bouts of uninterrupted sitting or physical activity/sitting/standing time at work and physiological outcomes. In a sample that is predominantly sedentary, at risk for cardiovascular disease, and prediabetic, there are no significant associations between workplace sedentary behavior and physiological markers. The lack of associations could be related to either physiological adaptations or ceiling effects in this sample.

Mycobacterium avium Complex Infection as a Rare Cause of Cerebral Mass Lesion and IRIS in a Patient With AIDS: Case Report and Review of the Literature.

A patient with advanced HIV/AIDS presented with a brain abscess. While brain biopsy culture and pathology were unrevealing, universal broad-range polymerase chain reaction (uPCR) demonstrated Mycobacterium avium complex (MAC). We review the clinicopathologic characteristics of MAC brain abscesses and highlight the effectiveness of uPCR as a diagnostic tool in partially treated infections.

Advancing the Safety, Health, and Well-Being of Commercial Driving Teams Who Sleep in Moving Semi-Trucks: The Tech4Rest Pilot Study.

OBJECTIVE: To test the feasibility, acceptability, and potential effectiveness of engineering and behavioral interventions to improve the sleep, health, and well-being of team truck drivers (dyads) who sleep in moving semi-trucks. METHODS: Drivers (n = 16) were exposed to Condition A: a new innerspring mattress, and Condition B: a novel therapeutic mattress. A subsample of drivers (n = 8) were also exposed to Condition C: use of their preferred mattress (all chose to keep B), switching to an active suspension driver's seat, and completing a behavioral sleep-health program. Primary outcomes were sleep duration, sleep quality, and fatigue. Behavioral program targets included physical activity and sleep hygiene. RESULTS: Self-reported sleep and fatigue improved with mattress A, and improved further with mattress B which altered vibration exposures and was universally preferred and kept by all drivers. Condition C improved additional targets and produced larger effect sizes for most outcomes. CONCLUSIONS: Results support these interventions as promising for advancing team truck drivers' sleep, health, and well-being.

Geographic Association Between Incidence of Acute Appendicitis and Socioeconomic Status.

Importance: Some studies based on proportions of patients with perforated appendicitis (PA) among all patients with acute appendicitis (AA) have found an association between socioeconomic status (SES) and risk of perforation. A potential limitation is their use of proportions, which assumes that incidence of AA is evenly distributed across populations at risk. This assumption may be invalid, and SES may have a more complex association with both AA and PA. Objective: To generate population-based incidences of AA and PA and to examine geographic patterns of incidence alongside geographic patterns of SES. Design, Setting, and Participants: Retrospective study of data from Washington's Comprehensive Hospital Abstract Reporting System and the 2010 US census. Geographic methods were used to identify patterns of age- and sex-standardized incidence in Washington State between 2008 and 2012. The study included all patients discharged with International Classification of Diseases, Ninth Revision codes for AA or PA. Data were analyzed between November 2016 and December 2018. Exposures: Location of primary residence. Main Outcomes and Measures: Age- and sex-standardized incidence for AA and PA was generated for each census tract (CT). Global spatial autocorrelation was examined using Moran index (0.0 = completely random incidence; 1.0 = fully dependent on location). Clusters of low-incidence CTs (cold spots) and high-incidence CTs (hot spots) were identified for AA. Census-based SES data were aggregated for hot spots and cold spots and then compared. Results: Statewide, over the 5-year study period, there were 35 730 patients with AA (including 9780 cases of PA), of whom 16 574 were women (46.4%). Median age of the cohort was 29 years (IQR, 16-48 years). Statewide incidence of AA and PA was 106 and 29 per 100 000 person-years (PY), respectively. Crude incidence was higher within the male population and peaked at age 10 to 19 years. Age- and sex-standardized incidence of AA demonstrated significant positive spatial autocorrelation (Moran index, 0.30; P < .001), but autocorrelation for PA was only half as strong (0.16; P < .001). Median incidence of AA was 118.1 per 100 000 PY among hot spots vs 86.2 per 100 000 PY among cold spots (P < .001). Socioeconomic status was higher in cold spots vs hot spots: mean proportion of college-educated adults was 56% vs 26% (P < .001), and mean per capita income was $44 691 vs $30 027 (P < .001). Conclusions and Relevance: Age- and sex-standardized incidence of appendicitis is not randomly distributed across geographic subunits, and geographic clustering of AA is twice as strong as PA. Socioeconomic advantages, such as higher income and secondary education, are strongly associated with lower incidence of AA. These findings challenge conventional views that AA occurs randomly and has no predisposing characteristics beyond age/sex. Socioeconomic status, and likely other geographically circumscribed factors, are associated with incidence of AA.

Reversal of ApoE4-induced recycling block as a novel prevention approach for Alzheimer's disease.

ApoE4 genotype is the most prevalent and also clinically most important risk factor for late-onset Alzheimer's disease (AD). Available evidence suggests that the root cause for this increased risk is a trafficking defect at the level of the early endosome. ApoE4 differs from the most common ApoE3 isoform by a single amino acid that increases its isoelectric point and promotes unfolding of ApoE4 upon endosomal vesicle acidification. We found that pharmacological and genetic inhibition of NHE6, the primary proton leak channel in the early endosome, in rodents completely reverses the ApoE4-induced recycling block of the ApoE receptor Apoer2/Lrp8 and the AMPA- and NMDA-type glutamate receptors that are regulated by, and co-endocytosed in a complex with, Apoer2. Moreover, NHE6 inhibition restores the Reelin-mediated modulation of excitatory synapses that is impaired by ApoE4. Our findings suggest a novel potential approach for the prevention of late-onset AD.

Rasch Analysis of the Teachers' Knowledge and Use of Data and Assessment (tKUDA) Measure.

Teachers are expected to use data and assessments to drive their instruction. This is accomplished at a classroom level via the assessment process. The teachers Knowledge and Use of Data and Assessment (tKUDA) measure was created to capture teachers' knowledge and use of this assessment process. This paper explores the measure's utility using Rasch analysis. Evidence of reliability and validity was seen for both knowledge and use factors. Scale was used as expected and item analyses demonstrates good spread with a few items identified for future revision. Item difficulty and results are connected back to literature. Findings support use of this measure to identify teachers' knowledge and use of data and assessment in classroom practice.

Evaluation of the Parent-Report Inventory of Callous-Unemotional Traits in a Sample of Children Recruited from Intimate Partner Violence Services: A Multidimensional Rasch Analysis.

OBJECTIVE: Our study applied multidimensional item response theory (MIRT) to compare structural models of the parent-report version of the Inventory of Callous and Unemotional Traits (ICU; English and North American Spanish translations). METHOD: A total of 291 maternal caregivers were recruited from community-based domestic violence services and reported on their children (77.9% ethnic minority; 47% female), who ranged in age from 7 to 12 years (mean = 9.07, standard deviation = 1.64). We compared 9 models that were based on prior psychometric evaluations of the ICU. RESULTS: MIRT analyses indicated that a revised 18-item version comprising 2 factors (callous-unemotional and empathic-prosocial) was more suitable for our sample. Differential item functioning was found for several items across ethnic and language groups, but not for child gender or age. Evidence of construct validity was found. CONCLUSION: We recommend continued research and revisions to the ICU to better assess the presence of callous-unemotional traits in community samples of school-age children.

Building a better blood-brain barrier.

A new three-dimensional model of the blood-brain barrier can be used to study processes that are involved in neurodegenerative diseases.

NGP 555, a γ-Secretase Modulator, Lowers the Amyloid Biomarker, Aß42, in Cerebrospinal Fluid while Preventing Alzheimer's Disease Cognitive Decline in Rodents.

INTRODUCTION: Alzheimer's disease (AD) is defined by the progressive accumulation of amyloid plaques and neurofibrillary tangles in the brain which precedes cognitive decline by years. METHODS: Using amyloid biomarkers, chemical modeling, mouse behavioral models, and drug development techniques we investigate the properties of NGP 555, a clinical-stage γ-secretase modulator. RESULTS: NGP 555 shifts amyloid peptide production to the smaller, non-aggregating forms of amyloid. Our preclinical studies show beneficial effects on amyloid biomarkers, pathology, and cognition. NGP 555 has successfully completed chemistry, pharmacology, toxicity, metabolism, and safety studies. DISCUSSION: Abundant data support Aß42 as a target for prophylactic or early-stage intervention therapies in AD. The γ-secretase modulator, NGP 555 is being actively developed in human clinical trials for the prevention of Alzheimer's disease with the overall aim to achieve an appropriate balance of potency/efficacy on reducing the toxic forms of amyloid versus safety.