Evaluation of ATP bioluminescence for rapid determination of farrowing room cleanliness after pressure washing at a commercial sow farm.

Rotavirus and other pathogenic microorganisms are known to cause scours, respiratory infection, and increased mortality, spread from pig to pig via contaminated equipment, insuffcient washing, and improper disinfection processes in farrowing rooms on commercial sow farms. Pig producers have adopted cleaning procedures and biosecurity policies as an attempt to ensure farrowing rooms are free of infectious organisms before the next group of sows is introduced. Adenosine triphosphate (ATP) bioluminescence has been used in other industries to provide real-time feedback on surface cleanliness through the detection of ATP from organic sources. That technology may provide producers a way of objectively characterizing a farrowing room's suitability for a new group of sows to be moved into the farrowing room. Three ATP luminometers (Charm Sciences novaLUM II-X, 3M Clean Trace, and Neogen AccuPoint) were used to estimate relationships between ATP bioluminescence relative light units (RLU) and coliform plate counts (CPC). Five farrowing crate locations and the room entryway floor were swabbed to determine locations within a farrowing crate that can accurately estimate room cleanliness. Coliform plate counts were strongly correlated with Charm novaLUM II-X RLU (r = 0.70, P < 0.01). The Clean-Trace CPCs and RLU (r = 0.48, P < 0.01) were moderately correlated. There was a weak correlation between CPCs and AccuPoint RLU (r = 0.32, P < 0.01). The greatest area of surface contamination was the entryway floor and the sow feeder. Because CPCs and luminometer RLU were correlated, statistical process control charts were developed to provide cleanliness thresholds based on RLU values. Based on an adjusted 3σ from the mean RLU critical limit, 7.7% of crates for the Charm novaLUM II-X, 10.6% of crates for the 3M Clean Trace, and 0% of crates for the Neogen AccuPoint would have failed the critical limit for the sow feeder cleanliness thresholds. Using a similar approach, 11.4% of crates for the Charm novaLUM II-X, 10.5% of crates for the 3M Clean Trace, and 15.2% of crates for the Neogen AccuPoint would have failed the critical limit for the crate sorting bar cleanliness thresholds. These data suggest that ATP bioluminescence may be a reliable method to monitor cleaning effectiveness in farrowing rooms on commercial sow farms. Bioluminescence is a monitoring tool that should be used in conjunction with periodic microbial validation to monitor procedures for cleaning and disinfection.

PrecivityAD2™ Blood Test: Analytical Validation of an LC-MS/MS Assay for Quantifying Plasma Phospho-tau217 and Non-Phospho-tau217 Peptide Concentrations That Are Used with Plasma Amyloid-ß42/40 in a Multianalyte Assay with Algorithmic Analysis for Detecting Brain Amyloid Pathology.

Alzheimer's disease (AD) is a progressive irreversible neurodegenerative disorder that represents a major global public health concern. Traditionally, AD is diagnosed using cerebrospinal fluid biomarker analysis or brain imaging modalities. Recently, less burdensome, more widely available blood biomarker (BBM) assays for amyloid-beta (Aß42/40) and phosphorylated-tau concentrations have been found to accurately identify the presence/absence of brain amyloid plaques and tau tangles and have helped to streamline AD diagnosis. However, few BBMs have been rigorously analytically validated. Herein, we report the analytical validation of a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) multiplex method for quantifying plasma phosphorylated-tau217 (p-tau217) and non-phosphorylated-tau217 (np-tau217) peptide concentrations. We combined the p-tau217/np-tau217 concentrations ratio (%p-tau217) and the previously validated LC-MS/MS multiplex assay for plasma Aß42/40 into a new multianalyte assay with algorithmic analysis (MAAA; PrecivityAD2™ test) that identifies brain amyloid status based on brain amyloid positron emission tomography. We found (a) the %p-tau217 assay is precise, accurate, sensitive, and linear over a wide analytical measurement range, and free from carryover and interference; (b) the pre-analytical specimen collection, processing, storage, and shipping conditions that maintain plasma tau peptide stability; and (c) using the measured analytical imprecision for plasma Aß42/40 and p-tau217/np-tau217 levels in a worst-case scenario model, the PrecivityAD2 test algorithm for amyloid pathology classification changed for only 3.5% of participants from brain amyloid positive to negative, or from negative to positive. The plasma sample preparation and LC-MS/MS methods underlying the PrecivityAD2 test are suitable for use in the clinical laboratory and valid for the test's intended purpose: to aid in the diagnostic evaluation of individuals aged 55 and older with signs or symptoms of mild cognitive impairment or dementia.

Exploring Perspectives on Stroke Standard Set Data Collection: A Qualitative Descriptive Study.

ABSTRACT: BACKGROUND: The International Consortium on Health Outcome Measurement developed a standard set for stroke (SSS) that includes patient-reported outcome measures to help capture patients' perspectives on their poststroke recovery. The objective of this study was to explore the experiences and perspectives of individuals who collected SSS data from patients who were admitted to hospital for a stroke. METHODS: A qualitative descriptive approach was taken. Semistructured, audio-recorded interviews were conducted with individuals employed at 2 acute neurological inpatient units in Southwestern Ontario, Canada. Interviews were transcribed verbatim and written text responses were analyzed directly. Transcripts were coded line by line and then organized into 5 overarching themes: adoption, acceptance, appropriateness, feasibility, and sustainability. RESULTS: Six interviews were conducted with participants from varying roles (eg, nurses, manager, web developer, social worker, medical clerk). Participants reported that patients were receptive to completing the SSS. Follow-up phone calls provided a significant opportunity to monitor patients' recovery postdischarge. Many patients requested medical guidance and help navigating health and social resources for unmet stroke-related needs. Barriers to consistent SSS assessment included high employee turnover and lack of time, space, or capacity for follow-up. To sustain data collection, a dedicated, financially supported neurological nursing role was suggested. CONCLUSION: Participants were supportive of SSS data collection that could provide monitoring, oversight, and follow-up of stroke patients after discharge from acute care. However, the utility of the dataset is heavily dependent on having the data collection process properly resourced.

Developing a system response to health and homelessness: The important role of health leaders.

This article examines the role of health leaders in the early stages of a community response to address health and homelessness in London, Ontario. Specifically, we explore how leaders from large healthcare-providing organizations have influenced the dynamics of the entire community response. We argue that the high level of engagement from health leaders has been a key ingredient in the early successes of the new approach in London, in part because it validated the reframing of homelessness as a healthcare issue-importantly, changing perceptions about who shares the responsibility to address it.

Let-7 restrains an oncogenic epigenetic circuit in AT2 cells to prevent ectopic formation of fibrogenic transitional cell intermediates and pulmonary fibrosis.

Analysis of lung alveolar type 2 (AT2) progenitor stem cells has highlighted fundamental mechanisms that direct their differentiation into alveolar type 1 cells (AT1s) in lung repair and disease. However, microRNA (miRNA) mediated post-transcriptional mechanisms which govern this nexus remain understudied. We show here that the let-7 miRNA family serves a homeostatic role in governance of AT2 quiescence, specifically by preventing the uncontrolled accumulation of AT2 transitional cells and by promoting AT1 differentiation to safeguard the lung from spontaneous alveolar destruction and fibrosis. Using mice and organoid models with genetic ablation of let-7a1/let-7f1/let-7d cluster (let-7afd) in AT2 cells, we demonstrate prevents AT1 differentiation and results in aberrant accumulation of AT2 transitional cells in progressive pulmonary fibrosis. Integration of enhanced AGO2 UV-crosslinking and immunoprecipitation sequencing (AGO2-eCLIP) with RNA-sequencing from AT2 cells uncovered the induction of direct targets of let-7 in an oncogene feed-forward regulatory network including BACH1/EZH2 which drives an aberrant fibrotic cascade. Additional analyses by CUT&RUN-sequencing revealed loss of let-7afd hampers AT1 differentiation by eliciting aberrant histone EZH2 methylation which prevents the exit of AT2 transitional cells into terminal AT1s. This study identifies let-7 as a key gatekeeper of post-transcriptional and epigenetic chromatin signals to prevent AT2-driven pulmonary fibrosis.

The impact of stroke on employment income: A cohort study using hospital and income tax data in Ontario, Canada.

OBJECTIVE: To document the impact of stroke on employment income among people employed at the time of stroke. DESIGN: Population-based cohort study. PARTICIPANTS: People hospitalized for stroke in Ontario, Canada (2010-2014) and people without stroke matched on demographic characteristics. MAIN MEASURES: Robust Poisson regression to estimate the effects of stroke on the probability of reporting employment income on tax returns over 3 years. Quantile regression difference-in-differences to estimate the changes in annual employment income attributable to stroke. RESULTS: Stroke survivors were increasingly less likely to report any employment income poststroke, incidence rate ratios (IRR) 0.87 at 1 year (95% confidence intervals [CI]; 0.85-0.88), 0.82 at 2 years (95% CI; 0.81-0.84) and 0.81 at 3 years (95% CI; 0.79-0.82). IRR for reporting at least 50% of prestroke income levels were 0.76 at 1 year (95% CI; 0.75-0.78), 0.75 at 2 years (95% CI; 0.73-0.77) and 0.73 at 3 years (95% CI; 0.71-0.75). IRR for reporting at least 90% of prestroke income levels were 0.72 at 1 year (95% CI; 0.70-0.74), 0.66 at 2 years (95% CI; 0.64-0.68) and again 0.66 at 3 years (95% CI; 0.64-0.68). Relative changes in annual employment income attributable to stroke varied from a decrease of 13.8% (95% CI; 8.7-18.9) at the 75th income percentile to a decrease of 43.1% (95% CI; 18.7-67.6) at the 25th income percentile. CONCLUSIONS: It is important for healthcare and service providers to recognize the impact of stroke on return to prestroke levels of employment income. Low-income stroke survivors experience a more drastic loss in employment income and may need additional social support.

Evaluation of ATP bioluminescence for rapid determination of cleanliness of livestock trailers after a commercial wash.

Pathogens such as porcine epidemic diarrhea virus (PEDV), porcine reproductive and respiratory syndrome (PRRSV), and E. coli are known to spread by contaminated vehicles and equipment. Pork producers have adopted trailer wash policies where each trailer is washed, disinfected, and dried before it can return to a farm. Cleanliness of livestock trailers after washing is determined by visual inspection rather than any objective method. Adenosine triphosphate (ATP) bioluminescence is used in many industries to provide real-time feedback on surface cleanliness through the detection of ATP from organic sources. That same technology may provide trailer wash facilities a way of objectively characterizing a livestock trailer's suitability to return to a farm after washing. Two ATP luminometers (3M Clean-Trace and Neogen AccuPoint) were used to estimate the correlation between ATP bioluminescence readings and aerobic bacterial plate counts (APCs) from sampled surfaces and to determine locations within a livestock trailer that can accurately estimate surface cleanliness. Five locations in livestock trailers were evaluated. Those locations included the nose access door (NAD), back door flush gate, rear side access door (RSAD), belly flush gate (BFG), and belly side access door (BSAD). There was a positive log-log association between the two luminometers (r = 0.59, P < 0.01). Every log unit increase in one unit, resulted in a 0.42 log increase (P < 0.01) in the other unit. ATP can come from bacteria, yeasts, molds, and manure. There was a poor association (r ≥ 0.10, P ≥ 0.02) between APCs and the ATP luminometers. Still, an increase in relative light units (RLUs) resulted in a corresponding increase in colony-forming units. The greatest area of surface contamination measured by APC was the NAD. RLUs were also greater in the NAD compared to the RSAD, the BFG, and the BSAD (P ≤ 0.01). Because APCs and luminometer RLUs provided similar outcomes, statistical process control charts were developed to determine control limits for RLUs. This provides real-time feedback to trailer wash workers in determining cleanliness outcomes for livestock trailers. These data suggest that ATP bioluminescence can be a reliable method to monitor cleaning effectiveness in livestock trailers. Bioluminescence is a monitoring tool that should be used in conjunction with microbial methods to monitor procedures for cleaning and disinfection.

Three-dimensional printing of wood.

Natural wood has served as a foundational material for buildings, furniture, and architectural structures for millennia, typically shaped through subtractive manufacturing techniques. However, this process often generates substantial wood waste, leading to material inefficiency and increased production costs. A potential opportunity arises if complex wood structures can be created through additive processes. Here, we demonstrate an additive-free, water-based ink made of lignin and cellulose, the primary building blocks of natural wood, that can be used to three-dimensional (3D) print architecturally designed wood structures via direct ink writing. The resulting printed structures, after heat treatment, closely resemble the visual, textural, olfactory, and macro-anisotropic properties, including mechanical properties, of natural wood. Our results pave the way for 3D-printed wooden construction with a sustainable pathway to upcycle/recycle natural wood.

Antinociceptive and adverse effects of morphine:ketamine mixtures in rats.

Prescription opioids are the gold standard for treating moderate to severe pain despite their well-documented adverse effects. Of all prescription medications, opioids are abused most widely, and fatal overdoses have reached epidemic levels. One strategy for improving the margin of safety of opioids is combining them with non-opioid drugs to decrease the opioid dose needed for pain relief, thereby reducing adverse effects that occur with larger doses. The N-methyl-D-aspartate receptor antagonist ketamine has been used safely as an analgesic but only under a very limited range of conditions. The current studies characterized the antinociceptive, behavioral suppressant, and gastrointestinal effects of morphine and ketamine alone and in mixtures to determine their interaction in 24 adult male Sprague-Dawley rats (n = 8 per assay). Given alone, both morphine and ketamine produced antinociception, decreased responding for food, and reduced gastrointestinal transit (i.e. produced constipation). The effects of morphine:ketamine mixtures generally were additive, except for the antinociceptive effects of 1:1 mixtures for which the difference in slope (i.e. non-parallel shift) between the observed and predicted effects suggested synergy at smaller doses and additivity at larger doses. The potency of morphine to produce constipation was not enhanced by administration of morphine:ketamine mixtures with antinociceptive effects. The nature of the interaction between morphine and ketamine for adverse effects such as dependence, withdrawal, abuse, or respiratory depression remains unknown but also might be related to the ratio of each drug in mixtures. It will be important to identify conditions that produce the largest potential therapeutic window in humans.

Clinical validation of the PrecivityAD2 blood test: A mass spectrometry-based test with algorithm combining %p-tau217 and Aß42/40 ratio to identify presence of brain amyloid.

BACKGROUND: With the availability of disease-modifying therapies for Alzheimer's disease (AD), it is important for clinicians to have tests to aid in AD diagnosis, especially when the presence of amyloid pathology is a criterion for receiving treatment. METHODS: High-throughput, mass spectrometry-based assays were used to measure %p-tau217 and amyloid beta (Aß)42/40 ratio in blood samples from 583 individuals with suspected AD (53% positron emission tomography [PET] positive by Centiloid > 25). An algorithm (PrecivityAD2 test) was developed using these plasma biomarkers to identify brain amyloidosis by PET. RESULTS: The area under the receiver operating characteristic curve (AUC-ROC) for %p-tau217 (0.94) was statistically significantly higher than that for p-tau217 concentration (0.91). The AUC-ROC for the PrecivityAD2 test output, the Amyloid Probability Score 2, was 0.94, yielding 88% agreement with amyloid PET. Diagnostic performance of the APS2 was similar by ethnicity, sex, age, and apoE4 status. DISCUSSION: The PrecivityAD2 blood test showed strong clinical validity, with excellent agreement with brain amyloidosis by PET.

50-nm Gas-Filled Protein Nanostructures to Enable the Access of Lymphatic Cells by Ultrasound Technologies.

Ultrasound imaging and ultrasound-mediated gene and drug delivery are rapidly advancing diagnostic and therapeutic methods; however, their use is often limited by the need for microbubbles, which cannot transverse many biological barriers due to their large size. Here, the authors introduce 50-nm gas-filled protein nanostructures derived from genetically engineered gas vesicles(GVs) that are referred to as 50 nmGVs. These diamond-shaped nanostructures have hydrodynamic diameters smaller than commercially available 50-nm gold nanoparticles and are, to the authors' knowledge, the smallest stable, free-floating bubbles made to date. 50 nmGVs can be produced in bacteria, purified through centrifugation, and remain stable for months. Interstitially injected 50 nmGVs can extravasate into lymphatic tissues and gain access to critical immune cell populations, and electron microscopy images of lymph node tissues reveal their subcellular location in antigen-presenting cells adjacent to lymphocytes. The authors anticipate that 50 nmGVs can substantially broaden the range of cells accessible to current ultrasound technologies and may generate applications beyond biomedicine as ultrasmall stable gas-filled nanomaterials.

Phase transition of GvpU regulates gas vesicle clustering in bacteria.

Gas vesicles (GVs) are microbial protein organelles that support cellular buoyancy. GV engineering has multiple applications, including reporter gene imaging, acoustic control and payload delivery. GVs often cluster into a honeycomb pattern to minimize occupancy of the cytosol. The underlying molecular mechanism and the influence on cellular physiology remain unknown. Using genetic, biochemical and imaging approaches, here we identify GvpU from Priestia megaterium as a protein that regulates GV clustering in vitro and upon expression in Escherichia coli. GvpU binds to the C-terminal tail of the core GV shell protein and undergoes a phase transition to form clusters in subsaturated solution. These properties of GvpU tune GV clustering and directly modulate bacterial fitness. GV variants can be designed with controllable sensitivity to GvpU-mediated clustering, enabling design of genetically tunable biosensors. Our findings elucidate the molecular mechanisms and functional roles of GV clustering, enabling its programmability for biomedical applications.

Discussions With End Users to Inform the Vision for a Shared Care Record in Ontario: Qualitative Interview Study.

BACKGROUND: Improving the health outcomes of populations of individuals through population health management requires the use of electronic health records that can exchange real-time digital information using an accurate and complete shared care record that is accessible to health care providers, services, and patients. OBJECTIVE: The aims of this study were to understand end users' (health care providers) experiences, attitudes, and insights using current electronic health records; their expectations of what is required to establish a shared care record; and how they anticipate adapting to the use of a shared care record in daily practice. This work is the result of a quality improvement initiative deemed not to require ethics approval according to the Western research ethics board checklist. METHODS: Clinicians were contacted using voluntary response sampling and interviewed via Zoom (Zoom Video Communications) between June 2022 and July 2022. The participants were from various health care sectors and at various stages of career development. RESULTS: Overall, adaptation to the use of a shared care record was viewed positively by health care providers, highlighting the benefits of a centralized, shared, and accessible location for real-time data, promoting patient continuity of care. The main concerns included the privacy, confidentiality, and security of the record along with patients' ability to interpret their own medical information found in a patient portal. The resources requested by end users included multifaceted ongoing training on the use of a shared care record. CONCLUSIONS: This study provides practical findings that will help emphasize factors that facilitate clinicians' practical use and process of adaptation to the use of a shared care record.

Cytotoxic rhamnolipid micelles drive acute virulence in Pseudomonas aeruginosa.

Pseudomonas aeruginosa is an opportunistic human pathogen that has developed multi- or even pan-drug resistance toward most frontline and last resort antibiotics, leading to increasing frequency of infections and deaths among hospitalized patients, especially those with compromised immune systems. Further complicating treatment, P. aeruginosa produces numerous virulence factors that contribute to host tissue damage and immune evasion, promoting bacterial colonization and pathogenesis. In this study, we demonstrate the importance of rhamnolipid production in host-pathogen interactions. Secreted rhamnolipids form micelles that exhibited highly acute toxicity toward murine macrophages, rupturing the plasma membrane and causing organellar membrane damage within minutes of exposure. While rhamnolipid micelles (RMs) were particularly toxic to macrophages, they also caused membrane damage in human lung epithelial cells, red blood cells, Gram-positive bacteria, and even noncellular models like giant plasma membrane vesicles. Most importantly, rhamnolipid production strongly correlated with P. aeruginosa virulence against murine macrophages in various panels of clinical isolates. Altogether, our findings suggest that rhamnolipid micelles are highly cytotoxic virulence factors that drive acute cellular damage and immune evasion during P. aeruginosa infections.

Timing of Biomarker Changes in Sporadic Alzheimer's Disease in Estimated Years from Symptom Onset.

OBJECTIVE: A clock relating amyloid positron emission tomography (PET) to time was used to estimate the timing of biomarker changes in sporadic Alzheimer disease (AD). METHODS: Research participants were included who underwent cerebrospinal fluid (CSF) collection within 2 years of amyloid PET. The ages at amyloid onset and AD symptom onset were estimated for each individual. The timing of change for plasma, CSF, imaging, and cognitive measures was calculated by comparing restricted cubic splines of cross-sectional data from the amyloid PET positive and negative groups. RESULTS: The amyloid PET positive sub-cohort (n = 118) had an average age of 70.4 ± 7.4 years (mean ± standard deviation) and 16% were cognitively impaired. The amyloid PET negative sub-cohort (n = 277) included individuals with low levels of amyloid plaque burden at all scans who were cognitively unimpaired at the time of the scans. Biomarker changes were detected 15-19 years before estimated symptom onset for CSF Aß42/Aß40, plasma Aß42/Aß40, CSF pT217/T217, and amyloid PET; 12-14 years before estimated symptom onset for plasma pT217/T217, CSF neurogranin, CSF SNAP-25, CSF sTREM2, plasma GFAP, and plasma NfL; and 7-9 years before estimated symptom onset for CSF pT205/T205, CSF YKL-40, hippocampal volumes, and cognitive measures. INTERPRETATION: The use of an amyloid clock enabled visualization and analysis of biomarker changes as a function of estimated years from symptom onset in sporadic AD. This study demonstrates that estimated years from symptom onset based on an amyloid clock can be used as a continuous staging measure for sporadic AD and aligns with findings in autosomal dominant AD. ANN NEUROL 2024;95:951-965.

Expression of Nephronectin in the Descemet's membrane of mouse corneas during development and adult homeostasis.

Nephronectin (Npnt) is an extracellular matrix (ECM) protein with pleiotropic functions during organogenesis, disease, and homeostasis. Although the ECM plays a crucial role during development and homeostasis of the adult cornea, little is known about the expression of Npnt in the mammalian cornea. Here, we investigated the expression of Npnt during early embryonic and postnatal development, and in adult mouse corneas. We combined ultrastructural and immunohistochemical analyses to study the early formation of the Descemet's membrane and how the expression of Npnt relates to key basement membrane proteins. Our section in situ hybridization and immunohistochemical analyses revealed that Npnt mRNA is expressed by the nascent corneal endothelial cells at embryonic day (E) 14.5, whereas the protein is localized in the adjacent extracellular matrix. These expression patterns were maintained in the corneal endothelium and Descemet's membrane throughout development and in adult corneas. Ultrastructural analysis revealed discontinuous electron dense regions of protein aggregates at E18.5 that was separated from the endothelial layer by an electron lucent space. At birth (postnatal day, P0), the Descemet's membrane was a single layer, which continuously thickened throughout P4, P8, P10, and P14. Npnt was localized to the Descemet's membrane by E18.5 and overlapped with Collagens IV and VIII, Laminin, and Perlecan. However, the proteins subsequently shifted and formed distinct layers in the adult cornea, whereby Npnt localized between two Collagen VIII bands and anterior to Collagen IV but overlapped with Laminin and Perlecan. Combined, our results reveal the expression of Npnt in the mouse cornea and define its spatiotemporal localization relative to key basement membrane proteins during the formation of the Descemet's membrane and in the adult cornea. Understanding the spatiotemporal expression of Npnt is important for future studies to elucidate its function in the mammalian cornea.

Associations of sleep duration and daytime sleepiness with plasma amyloid beta and cognitive performance in cognitively unimpaired, middle-aged and older African Americans.

STUDY OBJECTIVES: Given the established racial disparities in both sleep health and dementia risk for African American populations, we assess cross-sectional and longitudinal associations of self-report sleep duration (SRSD) and daytime sleepiness with plasma amyloid beta (Aß) and cognition in an African American (AA) cohort. METHODS: In a cognitively unimpaired sample drawn from the African Americans Fighting Alzheimer's in Midlife (AA-FAiM) study, data on SRSD, Epworth Sleepiness Scale, demographics, and cognitive performance were analyzed. Aß40, Aß42, and the Aß42/40 ratio were quantified from plasma samples. Cross-sectional analyses explored associations between baseline predictors and outcome measures. Linear mixed-effect regression models estimated associations of SRSD and daytime sleepiness with plasma Aß and cognitive performance levels and change over time. RESULTS: One hundred and forty-seven participants comprised the cross-sectional sample. Baseline age was 63.2 ±â€…8.51 years. 69.6% self-identified as female. SRSD was 6.4 ±â€…1.1 hours and 22.4% reported excessive daytime sleepiness. The longitudinal dataset included 57 participants. In fully adjusted models, neither SRSD nor daytime sleepiness is associated with cross-sectional or longitudinal Aß. Associations with level and trajectory of cognitive test performance varied by measure of sleep health. CONCLUSIONS: SRSD was below National Sleep Foundation recommendations and daytime sleepiness was prevalent in this cohort. In the absence of observed associations with plasma Aß, poorer self-reported sleep health broadly predicted poorer cognitive function but not accelerated decline. Future research is necessary to understand and address modifiable sleep mechanisms as they relate to cognitive aging in AA at disproportionate risk for dementia. CLINICAL TRIAL INFORMATION: Not applicable.

Plasma Aß42/Aß40 and phospho-tau217 concentration ratios increase the accuracy of amyloid PET classification in preclinical Alzheimer's disease.

INTRODUCTION: Incorporating blood-based Alzheimer's disease biomarkers such as tau and amyloid beta (Aß) into screening algorithms may improve screening efficiency. METHODS: Plasma Aß, phosphorylated tau (p-tau)181, and p-tau217 concentration levels from AHEAD 3-45 study participants were measured using mass spectrometry. Tau concentration ratios for each proteoform were calculated to normalize for inter-individual differences. Receiver operating characteristic (ROC) curve analysis was performed for each biomarker against amyloid positivity, defined by > 20 Centiloids. Mixture of experts analysis assessed the value of including tau concentration ratios into the existing predictive algorithm for amyloid positron emission tomography status. RESULTS: The area under the receiver operating curve (AUC) was 0.87 for Aß42/Aß40, 0.74 for phosphorylated variant p-tau181 ratio (p-tau181/np-tau181), and 0.92 for phosphorylated variant p-tau217 ratio (p-tau217/np-tau217). The Plasma Predicted Centiloid (PPC), a predictive model including p-tau217/np-tau217, Aß42/Aß40, age, and apolipoprotein E improved AUC to 0.95. DISCUSSION: Including plasma p-tau217/np-tau217 along with Aß42/Aß40 in predictive algorithms may streamline screening preclinical individuals into anti-amyloid clinical trials. CLINICALTRIALS: gov Identifier: NCT04468659 HIGHLIGHTS: The addition of plasma phosphorylated variant p-tau217 ratio (p-tau217/np-tau217) significantly improved plasma biomarker algorithms for identifying preclinical amyloid positron emission tomography positivity. Prediction performance at higher NAV Centiloid levels was improved with p-tau217/np-tau217. All models generated for this study are incorporated into the Plasma Predicted Centiloid (PPC) app for public use.

Atl (atlastin) regulates mTor signaling and autophagy in Drosophila muscle through alteration of the lysosomal network.

ABBREVIATIONS: atl atlastin; ALR autophagic lysosome reformation; ER endoplasmic reticulum; GFP green fluorescent protein; HSP hereditary spastic paraplegia; Lamp1 lysosomal associated membrane protein 1 PolyUB polyubiquitin; RFP red fluorescent protein; spin spinster; mTor mechanistic Target of rapamycin; VCP valosin containing protein.

Filamentous virus-like particles are present in coral dinoflagellates across genera and ocean basins.

Filamentous viruses are hypothesized to play a role in stony coral tissue loss disease (SCTLD) through infection of the endosymbiotic dinoflagellates (Family Symbiodiniaceae) of corals. To evaluate this hypothesis, it is critical to understand the global distribution of filamentous virus infections across the genetic diversity of Symbiodiniaceae hosts. Using transmission electron microscopy, we demonstrate that filamentous virus-like particles (VLPs) are present in over 60% of Symbiodiniaceae cells (genus Cladocopium) within Pacific corals (Acropora hyacinthus, Porites c.f. lobata); these VLPs are more prevalent in Symbiodiniaceae of in situ colonies experiencing heat stress. Symbiodiniaceae expelled from A. hyacinthus also contain filamentous VLPs, and these cells are more degraded than their in hospite counterparts. Similar to VLPs reported from SCTLD-affected Caribbean reefs, VLPs range from ~150 to 1500 nm in length and 16-37 nm in diameter and appear to constitute various stages in a replication cycle. Finally, we demonstrate that SCTLD-affected corals containing filamentous VLPs are dominated by diverse Symbiodiniaceae lineages from the genera Breviolum, Cladocopium, and Durusdinium. Although this study cannot definitively confirm or refute the role of filamentous VLPs in SCTLD, it demonstrates that filamentous VLPs are not solely observed in SCTLD-affected corals or reef regions, nor are they solely associated with corals dominated by members of a particular Symbiodiniaceae genus. We hypothesize that filamentous viruses are a widespread, common group that infects Symbiodiniaceae. Genomic characterization of these viruses and empirical tests of the impacts of filamentous virus infection on Symbiodiniaceae and coral colonies should be prioritized.