The impact of a medically directed student registered nurse anesthesia staffing model on Postprocedural patient outcomes.

STUDY OBJECTIVE: In 2018, the American Society of Anesthesiologists stated that student registered nurse anesthetists (SRNAs) "are not yet fully qualified anesthesia personnel." It remains unclear, however, whether postprocedural outcomes are affected by SRNAs providing anesthesia care under the medical direction of anesthesiologists, as compared with medically directed anesthesiology fellows or residents, or certified registered nurse anesthetists (CRNAs). We therefore aimed to examine whether medically directed SRNAs serving as in-room anesthesia providers impact surgical outcomes. DESIGN: Retrospective, matched-cohort analysis. SETTING: Adult patients (≥18 years old) undergoing inpatient surgery between 2000 and 2017 at a tertiary academic medical center. PATIENTS: 15,365 patients exclusively cared for by medically directed SRNAs were matched to 15,365 cared for by medically directed CRNAs, anesthesiology residents, and/or fellows. INTERVENTIONS: None. MEASUREMENTS: The primary composite outcome was postoperative occurrence of in-hospital mortality and six categories of major morbidities (infectious, bleeding, serious cardiac, gastrointestinal, respiratory, and urinary complications). In-hospital mortality was analyzed as the secondary outcome. MAIN RESULTS: In all, 30,730 cases were matched using propensity score matching to control for potential confounding. The primary outcome was identified in 2295 (7.5%) cases (7.5% with exclusive medically directed SRNAs vs 7.4% with medically directed CRNAs, residents and/or fellows; relative risk, 1.02; 95% CI, 0.94-1.11). Thus, our effort to determine noninferiority (10% difference in relative risk) with other providers was inconclusive (P = .07). However, the medically directed SRNA group (0.8% [118]) was found to be noninferior (P < .001) to the matched group (1.0% [156]) on in-hospital mortality (relative risk, 0.75; 95% CI, 0.59-0.96). CONCLUSIONS: Among 30,730 patients undergoing inpatient surgery at a single hospital, findings were inconclusive regarding whether exclusive medically directed SRNAs as in-room providers were noninferior to other providers. The use of medically directed SRNAs under this staffing model should be subject to further review. Clinical Trial and Registry URL: Not applicable.

Cell Adhesion, Elasticity, and Rupture Forces Guide Microbial Cell Death on Nanostructured Antimicrobial Titanium Surfaces.

Naturally occurring and synthetic nanostructured surfaces have been widely reported to resist microbial colonization. The majority of these studies have shown that both bacterial and fungal cells are killed upon contact and subsequent surface adhesion to such surfaces. This occurs because the presence of high-aspect-ratio structures can initiate a self-driven mechanical rupture of microbial cells during the surface adsorption process. While this technology has received a large amount of scientific and medical interest, one important question still remains: what factors drive microbial death on the surface? In this work, the interplay between microbial-surface adhesion, cell elasticity, cell membrane rupture forces, and cell lysis at the microbial-nanostructure biointerface during adsorptive processes was assessed using a combination of live confocal laser scanning microscopy, scanning electron microscopy, in situ amplitude atomic force microscopy, and single-cell force spectroscopy. Specifically, the adsorptive behavior and nanomechanical properties of live Gram-negative (Pseudomonas aeruginosa) and Gram-positive (methicillin-resistant Staphylococcus aureus) bacterial cells, as well as the fungal species Candida albicans and Cryptococcus neoformans, were assessed on unmodified and nanostructured titanium surfaces. Unmodified titanium and titanium surfaces with nanostructures were used as model substrates for investigation. For all microbial species, cell elasticity, rupture force, maximum cell-surface adhesion force, the work of adhesion, and the cell-surface tether behavior were compared to the relative cell death observed for each surface examined. For cells with a lower elastic modulus, lower force to rupture through the cell, and higher work of adhesion, the surfaces had a higher antimicrobial activity, supporting the proposed biocidal mode of action for nanostructured surfaces. This study provides direct quantification of the differences observed in the efficacy of nanostructured antimicrobial surface as a function of microbial species indicating that a universal, antimicrobial surface architecture may be hard to achieve.

Signed Rhyme and Rhythm With Deaf Children: Early Childhood Teacher Interviews.

Early childhood programs promote language play opportunities due to the well-documented positive influences on cognition, language, and literacy development. This qualitative investigation explores language play through the form of signed rhyme and rhythm among young deaf children. Teachers specializing in deaf education within an early childhood program were interviewed to assess their knowledge and implementation of signed rhyme and rhythm in their pedagogical practices. The results reveal that despite recognizing numerous advantages and deeming signed rhyme and rhythm as essential for deaf children's development, these teachers perceive themselves as lacking adequate knowledge and preparation to effectively incorporate this approach in their classrooms. To address this gap, professional development opportunities should be provided to develop knowledge and confidence in teachers, empowering them to effectively implement signed rhyme and rhythm with deaf children.

DNA methylation differences in noncoding regions in ER negative breast tumors between Black and White women.

Introduction: Incidence of estrogen receptor (ER)-negative breast cancer, an aggressive tumor subtype associated with worse prognosis, is higher among African American/Black women than other US racial and ethnic groups. The reasons for this disparity remain poorly understood but may be partially explained by differences in the epigenetic landscape. Methods: We previously conducted genome-wide DNA methylation profiling of ER- breast tumors from Black and White women and identified a large number of differentially methylated loci (DML) by race. Our initial analysis focused on DML mapping to protein-coding genes. In this study, motivated by increasing appreciation for the biological importance of the non-protein coding genome, we focused on 96 DMLs mapping to intergenic and noncoding RNA regions, using paired Illumina Infinium Human Methylation 450K array and RNA-seq data to assess the relationship between CpG methylation and RNA expression of genes located up to 1Mb away from the CpG site. Results: Twenty-three (23) DMLs were significantly correlated with the expression of 36 genes (FDR<0.05), with some DMLs associated with the expression of single gene and others associated with more than one gene. One DML (cg20401567), hypermethylated in ER- tumors from Black versus White women, mapped to a putative enhancer/super-enhancer element located 1.3 Kb downstream of HOXB2. Increased methylation at this CpG correlated with decreased expression of HOXB2 (Rho=-0.74, FDR<0.001) and other HOXB/HOXB-AS genes. Analysis of an independent set of 207 ER- breast cancers from TCGA similarly confirmed hypermethylation at cg20401567 and reduced HOXB2 expression in tumors from Black versus White women (Rho=-0.75, FDR<0.001). Discussion: Our findings indicate that epigenetic differences in ER- tumors between Black and White women are linked to altered gene expression and may hold functional significance in breast cancer pathogenesis.

An epigenome-wide analysis of socioeconomic position and tumor DNA methylation in breast cancer patients.

BACKGROUND: Disadvantaged socioeconomic position (SEP), including lower educational attainment and household income, may influence cancer risk and outcomes. We hypothesized that DNA methylation could function as an intermediary epigenetic mechanism that internalizes and reflects the biological impact of SEP. METHODS: Based on tumor DNA methylation data from the Illumina 450 K array from 694 breast cancer patients in the Women's Circle of Health Study, we conducted an epigenome-wide analysis in relation to educational attainment and household income. Functional impact of the identified CpG sites was explored in silico using data from publicly available databases. RESULTS: We identified 25 CpG sites associated with household income at an array-wide significance level, but none with educational attainment. Two of the top CpG sites, cg00452016 and cg01667837, were in promoter regions of NNT and GPR37, respectively, with multiple epigenetic regulatory features identified in each region. NNT is involved in ß-adrenergic stress signaling and inflammatory responses, whereas GPR37 is involved in neurological and immune responses. For both loci, gene expression was inversely correlated to the levels of DNA methylation. The associations were consistent between Black and White women and did not differ by tumor estrogen receptor (ER) status. CONCLUSIONS: In a large breast cancer patient population, we discovered evidence of the significant biological impact of household income on the tumor DNA methylome, including genes in the ß-adrenergic stress and immune response pathways. Our findings support biological effects of socioeconomic status on tumor tissues, which might be relevant to cancer development and progression.

Learning a Sign Language Does Not Hinder Acquisition of a Spoken Language.

PURPOSE: The purpose of this study is to determine whether and how learning American Sign Language (ASL) is associated with spoken English skills in a sample of ASL-English bilingual deaf and hard of hearing (DHH) children. METHOD: This cross-sectional study of vocabulary size included 56 DHH children between 8 and 60 months of age who were learning both ASL and spoken English and had hearing parents. English and ASL vocabulary were independently assessed via parent report checklists. RESULTS: ASL vocabulary size positively correlated with spoken English vocabulary size. Spoken English vocabulary sizes in the ASL-English bilingual DHH children in the present sample were comparable to those in previous reports of monolingual DHH children who were learning only English. ASL-English bilingual DHH children had total vocabularies (combining ASL and English) that were equivalent to same-age hearing monolingual children. Children with large ASL vocabularies were more likely to have spoken English vocabularies in the average range based on norms for hearing monolingual children. CONCLUSIONS: Contrary to predictions often cited in the literature, acquisition of sign language does not harm spoken vocabulary acquisition. This retrospective, correlational study cannot determine whether there is a causal relationship between sign language and spoken language vocabulary acquisition, but if a causal relationship exists, the evidence here suggests that the effect would be positive. Bilingual DHH children have age-expected vocabularies when considering the entirety of their language skills. We found no evidence to support recommendations that families with DHH children avoid learning sign language. Rather, our findings show that children with early ASL exposure can develop age-appropriate vocabulary skills in both ASL and spoken English.

Inflammatory myofibroblastic tumor of the mesentery with a SQSTM1::ALK fusion responding to alectinib.

BACKGROUND: Inflammatory myofibroblastic tumor (IMT) is an ultra-rare soft tissue neoplasm associated with fusion proteins encompassing the anaplastic lymphoma kinase (ALK) protein fused to a variety of partner proteins. Data regarding response to ALK-targeting agents based on fusion partner is limited. CASE: A 30-year-old female sought emergency care after onset of abdominal and lower back pain in 2019. Computed tomography (CT) demonstrated a cystic, mesenteric mass within the pelvis measuring up to 8.9 cm. Complete laparoscopic excision of the mass from the mesentery of the right colon and terminal ileum was performed. Pathologic assessment revealed IMT with a fusion between sequestosome 1 and ALK (SQSTM1::ALK), described in only two other cases of IMT. Four months after surgery, CT revealed multi-focal, unresectable disease recurrence. She was referred to the University of Washington/Fred Hutchinson Cancer Center and placed on therapy with alectinib, after which she experienced a partial response. Three years after IMT recurrence, disease remains under control. CONCLUSION: This is the third reported case of IMT associated with the novel SQSTM1::ALK fusion protein, and the second treated with alectinib. Treatment with the ALK inhibitor alectinib appears to be active in this setting.

Influence of Reduced-Gravity Treadmill Running on Sensor-Derived Biomechanics.

BACKGROUND: Reduced gravity treadmills have become increasingly prevalent in clinical settings. The purpose of this study was to assess the influence of manipulated levels of bodyweight during reduced gravity treadmill running on sensor-derived spatiotemporal, kinematic, and kinetic measures. HYPOTHESES: Reduced gravity conditions would result in significantly altered biomechanical measures compared with 100% gravity conditions, with the most pronounced effects anticipated in the 20% condition. STUDY DESIGN: Cross-sectional clinic-based study. METHODS: A total of 16 runners (8 male [M; age, 28.88 ± 5.69 years; body mass index [BMI], 25.08 ± 3.74 kg/m2], 8 female [F; age, 28.75 ± 5.23 years, BMI, 21.05 ± 3.46 kg/m2]) participated in this study. Participants wore commercially available sensors on their shoelaces and ran in a reduced gravity treadmill at a self-selected pace for 5 minutes each at 100%, 80%, 60%, 40%, and 20% bodyweight in a randomized order. The pace remained constant across all conditions, and rating of perceived exertion (RPE) was obtained following each condition. Step-by-step spatiotemporal, kinematic, and kinetic metrics were extracted to calculate mean outcome measures for each bodyweight condition. Repeated measures analyses of variance were conducted to assess the influence of the different bodyweight reduction levels on RPE and runners' biomechanics. RESULTS: Higher pressure creating lower bodyweight conditions resulted in significantly increased stride length and decreased cadence, contact time, impact g, and RPE, along with a shift toward forefoot strike types compared with higher body weight conditions (P < 0.01). All other outcomes were comparable across conditions. CONCLUSION: Reduced bodyweight running significantly altered spatiotemporal measures and reduced the vertical component of loading. CLINICAL RELEVANCE: Our findings offer objective information on expected biomechanical changes across pressure levels that clinicians should consider when incorporating reduced gravity treadmill running into rehabilitation plans.

The Independent Walking for Brain Health Intervention for Older Adults: Protocol for a Pilot Randomized Controlled Trial.

BACKGROUND: Extensive research suggests that physical activity (PA) is important for brain and cognitive health and may help to delay or prevent Alzheimer's disease and related dementias. Most PA interventions designed to improve brain health in older adults have been conducted in laboratory, gym, or group settings that require extensive resources and travel to the study site or group sessions. Research is needed to develop novel interventions that leverage mobile health (mHealth) technologies to help older adults increase their engagement in PA in free-living environments, reducing participant burden and increasing generalizability of research findings. Moreover, promoting engagement in moderate-to-vigorous PA (MVPA) may be most beneficial to brain health; thus, using mHealth to help older adults increase time spent in MVPA in free-living environments may help to offset the burden of Alzheimer's disease and related dementias and improve quality of life in older age. OBJECTIVE: We developed a novel PA intervention that leverages mHealth to help older adults achieve more minutes of MVPA independently. This pilot study was a 12-week randomized controlled trial to investigate the feasibility of providing just-in-time (JIT) feedback about PA intensity during free-living exercise sessions to help older adults meet current PA recommendations (150 minutes per week of MVPA). METHODS: Participants were eligible if they were cognitively healthy English speakers aged between 65 and 80 years without major cardiovascular, neurologic, or mental health conditions; could ambulate independently; and undergo magnetic resonance imaging. Enrollment occurred from October 2017 to March 2020. Participants randomized to the PA condition received an individualized exercise prescription and an mHealth device that provided heart rate-based JIT feedback on PA intensity, allowing them to adjust their behavior in real time to maintain MVPA during exercise sessions. Participants assigned to the healthy aging education condition received a reading prescription consisting of healthy aging topics and completed weekly quizzes based on the materials. RESULTS: In total, 44 participants were randomized to the intervention. A follow-up manuscript will describe the results of the intervention as well as discuss screening, recruitment, adverse events, and participants' opinions regarding their participation in the intervention. CONCLUSIONS: The long-term goal of this intervention is to better understand how MVPA affects brain and cognitive health in the real world and extend laboratory findings to everyday life. This pilot randomized controlled trial was conducted to determine the feasibility of using JIT heart rate zone feedback to help older adults independently increase time spent in MVPA while collecting data on the plausible mechanisms of change (frontal and medial temporal cerebral blood flow and cardiorespiratory fitness) that may affect cognition (memory and executive function) to help refine a planned stage 2 behavioral trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT03058146; https://clinicaltrials.gov/ct2/show/NCT03058146. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/42980.

Recommendations for Identifying Valid Wear for Consumer-Level Wrist-Worn Activity Trackers and Acceptability of Extended Device Deployment in Children.

BACKGROUND: Self-reported physical activity is often inaccurate. Wearable devices utilizing multiple sensors are now widespread. The aim of this study was to determine acceptability of Fitbit Charge HR for children and their families, and to determine best practices for processing its objective data. METHODS: Data were collected via Fitbit Charge HR continuously over the course of 3 weeks. Questionnaires were given to each child and their parent/guardian to determine the perceived usability of the device. Patterns of data were evaluated and best practice inclusion criteria recommended. RESULTS: Best practices were established to extract, filter, and process data to evaluate device wear, r and establish minimum wear time to evaluate behavioral patterns. This resulted in usable data available from 137 (89%) of the sample. CONCLUSIONS: Activity trackers are highly acceptable in the target population and can provide objective data over longer periods of wear. Best practice inclusion protocols that reflect physical activity in youth are provided.

Mask communication: The development of the face covering as a semiotic resource through government public health posters in England and Wales.

This paper will explore the multi-modal semiotic properties of a selection of key public health information posters issued by the UK Westminster government on the use of masks and face coverings during the first year of the COVID-19 pandemic. Using multi-modal critical discourse analysis, we show how the posters featuring masks sustained consistent government-led branding, while drawing upon what we describe as "synthetic personalisation" to manage the orientation of the crisis as the pandemic progressed. Through this analysis, the article will highlight the possible contribution of these posters to an environment characterised by political confusion and enabling of a relatively widespread rejection of mask-wearing as a public health responsibility. Examining this within a broader decline in trust in government, we suggest the various attempts to produce a positive message about mask-wearing contributed instead to the appropriation of masks as symbols of individual alignment within a contested political field.

Physical activity intensity is associated with cognition and functional connectivity in Parkinson's disease.

BACKGROUND: Cognitive impairment is common in Parkinson's disease (PD) and often leads to dementia, with no effective treatment. Aging studies suggest that physical activity (PA) intensity has a positive impact on cognition and enhanced functional connectivity may underlie these benefits. However, less is known in PD. This cross-sectional study examined the relationship between PA intensity, cognitive performance, and resting state functional connectivity in PD and whether PA intensity influences the relationship between functional connectivity and cognitive performance. METHODS: 96 individuals with mild-moderate PD completed a comprehensive neuropsychological battery. Intensity of PA was objectively captured over a seven-day period using a wearable device (ActiGraph). Time spent in light and moderate intensity PA was determined based on standardized actigraphy cut points. Resting-state fMRI was assessed in a subset of 50 individuals to examine brain-wide functional connectivity. RESULTS: Moderate intensity PA (MIPA), but not light PA, was associated with better global cognition, visuospatial function, memory, and executive function. Individuals who met the WHO recommendation of ≥150 min/week of MIPA demonstrated better global cognition, executive function, and visuospatial function. Resting-state functional connectivity associated with MIPA included a combination of brainstem, hippocampus, and regions in the frontal, cingulate, and parietal cortices, which showed higher connectivity across the brain in those achieving the WHO MIPA recommendation. Meeting this recommendation positively moderated the associations between identified functional connectivity and global cognition, visuospatial function, and language. CONCLUSION: Encouraging MIPA, particularly the WHO recommendation of ≥150 min of MIPA/week, may represent an important prescription for PD cognition.

Results and lessons from dual extraction of DNA and RNA from formalin-fixed paraffin-embedded breast tumor tissues for a large Cancer epidemiologic study.

BACKGROUND: The use of archived formalin-fixed paraffin-embedded (FFPE) tumor tissues has become a common practice in clinical and epidemiologic genetic research. Simultaneous extraction of DNA and RNA from FFPE tissues is appealing but can be practically challenging. Here we report our results and lessons learned from processing FFPE breast tumor tissues for a large epidemiologic study. METHODS: Qiagen AllPrep DNA/RNA FFPE kit was adapted for dual extraction using tissue punches or sections from breast tumor tissues. The yield was quantified using Qubit and fragmentation analysis by Agilent Bioanalyzer. A subset of the DNA samples were used for genome-wide DNA methylation assays and RNA samples for sequencing. The QC metrices and performance of the assays were analyzed with pre-analytical variables. RESULTS: A total of 1859 FFPE breast tumor tissues were processed. We found it critical to adjust proteinase K digestion time based on tissue volume to achieve balanced yields of DNA and RNA. Tissue punches taken from tumor-enriched regions provided the most reliable output. A median of 1475 ng DNA and 1786 ng RNA per sample was generated. The median DNA integrity number (DIN) was 3.8 and median DV200 for RNA was 33.2. Of 1294 DNA samples used in DNA methylation assays, 97% passed quality check by qPCR and 92% generated data deemed high quality. Of the 130 RNA samples with DV200 ≥ 20% used in RNA-sequencing, all but 5 generated usable transcriptomic data with a mapping rate ≥ 60%. CONCLUSIONS: Dual DNA/RNA purification using Qiagen AllPrep FFPE extraction protocol is feasible for clinical and epidemiologic studies. We recommend tissue punches as a reliable source material and fine tuning of proteinase K digestion time based on tissue volume. IMPACT: Our protocol and recommendations may be adapted by future studies for successful extraction of archived tumor tissues.

mTOR pathway gene expression in association with race and clinicopathological characteristics in Black and White breast cancer patients.

BACKGROUND: Aberrant activation of the mammalian Target of Rapamycin (mTOR) pathway has been linked to obesity and endocrine therapy resistance, factors that may contribute to Black-White disparities in breast cancer outcomes. We evaluated associations of race and clinicopathological characteristics with mRNA expression of key mTOR pathway genes in breast tumors. METHODS: Surgical tumor tissue blocks were collected from 367 newly diagnosed breast cancer patients (190 Black and 177 White). Gene expression of AKT1, EIF4EBP1, MTOR, RPS6KB2, and TSC1 were quantified by NanoString nCounter. Differential gene expression was assessed using linear regression on log2-transformed values. Gene expression and DNA methylation data from TCGA were used for validation and investigation of race-related differences. RESULTS: Compared to White women, Black women had relative under-expression of AKT1 (log2 fold-change = - 0.31, 95% CI - 0.44, - 0.18) and RPS6KB2 (log2 fold-change = - 0.11, 95% CI - 0.19, - 0.03). Higher vs. lower tumor grade was associated with relative over-expression of EIF4EBP1 and RPS6KB2, but with lower expression of TSC1. Compared to luminal tumors, triple-negative tumors had relative under-expression of TSC1 (log2 fold-change = - 0.42, 95% CI - 0.22, - 0.01). The results were similar in the TCGA breast cancer dataset. Post-hoc analyses identified differential CpG methylation within the AKT1 and RPS6KB2 locus between Black and White women. CONCLUSIONS: Over-expression of RPS6KB2 and EIF4EBP1 and under-expression of TSC1 might be indicators of more aggressive breast cancer phenotypes. Differential expression of AKT1 and RPS6KB2 by race warrants further investigation to elucidate their roles in racial disparities of treatment resistance and outcomes between Black and White women with breast cancer.

Intrinsic foot muscle size and quality in a single leg weight bearing position across foot posture types in individuals with Patellofemoral Pain compared to healthy.

OBJECTIVE: To identify if any differences exist in IFM size and quality in single leg weight bearing position between healthy and PFP participants based on foot posture. DESIGN: Cross-sectional, matched case-comparison study SETTING: University Laboratory Setting PARTICIPANTS: 35 PFP (age:20.46 ± 3.79yrs, mass:73.28 ± 26.58 kg, height:170.80 ± 11.91 cm) and 35 healthy (age:20.40 ± 3.16yrs, mass:64.76 ± 11.52 kg, height:169.55 ± 9.10 cm) participants METHODS: After measuring Foot Posture Index (FPI), ultrasound images (USI) of Abductor Hallucis (AH), Flexor Digitorum Brevis (FDB) and Quadratus Plantae (QP) were taken in a single limb weight bearing position. Cross-sectional area (CSA) and echogenicity were measured on the USI. RESULTS: FPI was not different between groups (PFP:2.34 ± 3.76, Healthy:2.34 ± 3.10, 9 pronated and 26 non-pronated in both groups). AH CSA was smaller in PFP than healthy group (PFP:0.030 ± 0.01 cm (Smith et al., 2018)/kg, Healthy:0.042 ± 0.01 cm (Smith et al., 2018)/kg, P < 0.001) with a large effect (d = -1.20(-1.71, -0.69). There were no other significant group main effects or group-by-FP interactions in AH/FDB/QP CSA or echogenicity. CONCLUSION: AH CSA was smaller in PFP than healthy controls, but no difference in CSA or echogenicity of FDB/QP exist, as well as no difference in foot posture between groups. While single limb weight bearing, the PFP group presented with a smaller IFM which provides eccentric control of medial longitudinal arch, which may have implications up the chain during weight bearing functional tasks.

Daily Level Association of Physical Activity and Performance on Ecological Momentary Cognitive Tests in Free-living Environments: A Mobile Health Observational Study.

BACKGROUND: Research suggests that physical activity (PA) has both acute and chronic beneficial effects on cognitive function in laboratory settings and under supervised conditions. Mobile health technologies make it possible to reliably measure PA and cognition in free-living environments, thus increasing generalizability and reach. Research is needed to determine whether the benefits of PA on cognitive function extend from the laboratory to real-world contexts. OBJECTIVE: This observational study aims to examine the association between daily fluctuations in PA and cognitive performance using mobile health technologies in free-living environments. METHODS: A total of 90 adults (mean age 59, SD 6.3 years; 65/90, 72% men) with various comorbidities (eg, cardiovascular risk and HIV) and different levels of baseline cognition (ranging from cognitively normal to impaired) completed ecological momentary cognitive tests (EMCTs) on a smartphone twice daily while wearing an accelerometer to capture PA levels for 14 days. Linear mixed-effects models examined the daily associations of PA with executive function and verbal learning EMCTs. Moderation analyses investigated whether the relationship between daily PA and daily performance on EMCTs changed as a function of baseline cognition, cardiovascular risk, and functional status (independent vs dependent). RESULTS: Days with greater PA were associated with better (faster) performance on an executive function EMCT after covariate adjustment (estimate -0.013; ß=-.16; P=.04). Moderation analyses (estimate 0.048; ß=.58; P=.001) indicated that days with greater PA were associated with better (faster) executive function performance in individuals who were functionally dependent (effect size -0.53; P<.001) and not in functionally independent adults (effect size -0.01; P=.91). CONCLUSIONS: EMCTs may be a sensitive tool for capturing daily-level PA-related fluctuations in cognitive performance in real-world contexts and could be a promising candidate for tracking cognitive performance in digital health interventions aimed at increasing PA. Further research is needed to determine individual characteristics that may moderate the association between daily PA and EMCT performance in free-living environments.

Objective and subjective sleep measures are associated with neurocognition in aging adults with and without HIV.

Objective: Poor sleep quality is related to worse neurocognition in older adults and in people with HIV (PWH); however, many previous studies have relied only on self-report sleep questionnaires, which are inconsistently correlated with objective sleep measures. We examined relationships between objective and subjective sleep quality and neurocognition in persons with and without HIV, aged 50 and older. Method: Eighty-five adults (PWH n = 52, HIV-negative n = 32) completed comprehensive neuropsychological testing to assess global and domain-specific neurocognition. Objective sleep quality was assessed with wrist actigraphy (total sleep time, efficiency, sleep fragmentation) for five to 14 nights. Subjective sleep quality was assessed with the Pittsburgh Sleep Quality Index. Results: Objective and subjective sleep measures were unrelated (p's > 0.30). Compared to HIV-negative participants, PWH had greater sleep efficiency (80% vs. 75%, p = 0.05) and were more likely to be using prescription and/or over the counter sleep medication (p = 0.04). In the whole sample, better sleep efficiency (p < 0.01) and greater total sleep time (p = 0.05) were associated with better learning. Less sleep fragmentation was associated with better learning (p < 0.01) and recall (p = 0.04). While PWH had slightly stronger relationships between total sleep time and sleep fragmentation, it is not clear if these differences are clinically meaningful. Better subjective sleep quality was associated with better executive function (p < 0.01) and working memory (p = 0.05); this relationship was primarily driven by the HIV-negative group. Conclusions: Objective sleep quality was associated with learning and recall whereas subjective sleep quality was associated with executive function and working memory. Therefore, assessing objective and subjective sleep quality could be clinically useful, as they are both related to important domains of cognition frequently impacted in HIV-associated neurocognitive disorders as well as neurodegenerative disorders associated with aging. Future studies should evaluate if behavioral sleep interventions can improve neurocognition.

Impact of the COVID-19 Pandemic on Objectively Measured Physical Activity and Sedentary Behavior Among Overweight Young Adults: Yearlong Longitudinal Analysis.

BACKGROUND: The COVID-19 pandemic has impacted multiple aspects of daily living, including behaviors associated with occupation, transportation, and health. It is unclear how these changes to daily living have impacted physical activity and sedentary behavior. OBJECTIVE: In this study, we add to the growing body of research on the health impact of the COVID-19 pandemic by examining longitudinal changes in objectively measured daily physical activity and sedentary behavior among overweight or obese young adults participating in an ongoing weight loss trial in San Diego, California. METHODS: Data were collected from 315 overweight or obese (BMI: range 25.0-39.9 kg/m2) participants aged from 18 to 35 years between November 1, 2019, and October 30, 2020, by using the Fitbit Charge 3 (Fitbit LLC). After conducting strict filtering to find valid data on consistent wear (>10 hours per day for ≥250 days), data from 97 participants were analyzed to detect multiple structural changes in time series of physical activity and sedentary behavior. An algorithm was designed to detect multiple structural changes. This allowed for the automatic identification and dating of these changes in linear regression models with CIs. The number of breakpoints in regression models was estimated by using the Bayesian information criterion and residual sum of squares; the optimal segmentation corresponded to the lowest Bayesian information criterion and residual sum of squares. To quantify the changes in each outcome during the periods identified, linear mixed effects analyses were conducted. In terms of key demographic characteristics, the 97 participants included in our analyses did not differ from the 210 participants who were excluded. RESULTS: After the initiation of the shelter-in-place order in California on March 19, 2021, there were significant decreases in step counts (-2872 steps per day; 95% CI -2734 to -3010), light physical activity times (-41.9 minutes; 95% CI -39.5 to -44.3), and moderate-to-vigorous physical activity times (-12.2 minutes; 95% CI -10.6 to -13.8), as well as significant increases in sedentary behavior times (+52.8 minutes; 95% CI 47.0-58.5). The decreases were greater than the expected declines observed during winter holidays, and as of October 30, 2020, they have not returned to the levels observed prior to the initiation of shelter-in-place orders. CONCLUSIONS: Among overweight or obese young adults, physical activity times decreased and sedentary behavior times increased concurrently with the implementation of COVID-19 mitigation strategies. The health conditions associated with a sedentary lifestyle may be additional, unintended results of the COVID-19 pandemic.

Deletion of Foxa1 in the mouse mammary gland results in abnormal accumulation of luminal progenitor cells: a link between reproductive factors and ER-/TNBC breast cancer?

In humans, parity without breastfeeding increases risk of estrogen receptor-negative (ER-) breast cancer and is associated with hypermethylation of FOXA1, a pioneer factor regulating lineage commitment of mammary gland luminal progenitor cells. We postulate that pregnancy-associated repression of FOXA1 results in the accumulation of aberrant, differentiation-arrested luminal progenitor cells which, following additional genetic and epigenetic insults, may give rise to ER- tumors. Consistent with this hypothesis, we show that deletion of Foxa1 in the mouse mammary gland results in a two-fold increase in the proportion of luminal progenitor cells and a reduction in mammary gland epithelial cells that stain positive for ER. These results provide compelling support for the notion that reduced Foxa1 expression is sufficient to alter mammary gland luminal cell fate determination in vivo, which could be a mechanism linking parity with ER- breast cancer.