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1.
Clin Rehabil ; : 2692155241249345, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38689431

RESUMEN

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.

2.
Transl Anim Sci ; 8: txae052, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38651119

RESUMEN

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.

3.
Alzheimers Dement ; 20(5): 3179-3192, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38491912

RESUMEN

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.


Asunto(s)
Algoritmos , Enfermedad de Alzheimer , Péptidos beta-Amiloides , Biomarcadores , Encéfalo , Espectrometría de Masas , Fragmentos de Péptidos , Tomografía de Emisión de Positrones , Proteínas tau , Humanos , Péptidos beta-Amiloides/sangre , Femenino , Masculino , Proteínas tau/sangre , Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/diagnóstico por imagen , Anciano , Fragmentos de Péptidos/sangre , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Biomarcadores/sangre , Persona de Mediana Edad , Anciano de 80 o más Años , Curva ROC
4.
Sci Adv ; 10(11): eadk3250, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38489368

RESUMEN

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.

5.
Nat Microbiol ; 9(4): 1021-1035, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38553608

RESUMEN

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.


Asunto(s)
Orgánulos , Proteínas , Bacterias
6.
Behav Pharmacol ; 35(2-3): 122-131, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38451024

RESUMEN

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.


Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Ketamina , Adulto , Humanos , Masculino , Ratas , Animales , Morfina/efectos adversos , Ketamina/efectos adversos , Ratas Sprague-Dawley , Analgésicos Opioides/efectos adversos , Dolor/tratamiento farmacológico
7.
Adv Mater ; : e2307123, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38533973

RESUMEN

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.

8.
Online J Public Health Inform ; 16: e51231, 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38412006

RESUMEN

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.

9.
Infect Immun ; 92(3): e0040723, 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38391248

RESUMEN

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.


Asunto(s)
Antineoplásicos , Glucolípidos , Infecciones por Pseudomonas , Humanos , Animales , Ratones , Virulencia , Percepción de Quorum , Pseudomonas aeruginosa , Micelas , Factores de Virulencia/metabolismo
10.
Ann Neurol ; 95(5): 951-965, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38400792

RESUMEN

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.


Asunto(s)
Enfermedad de Alzheimer , Péptidos beta-Amiloides , Biomarcadores , Tomografía de Emisión de Positrones , Humanos , Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/líquido cefalorraquídeo , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/diagnóstico , Femenino , Masculino , Biomarcadores/líquido cefalorraquídeo , Biomarcadores/sangre , Anciano , Péptidos beta-Amiloides/líquido cefalorraquídeo , Péptidos beta-Amiloides/sangre , Persona de Mediana Edad , Fragmentos de Péptidos/líquido cefalorraquídeo , Fragmentos de Péptidos/sangre , Anciano de 80 o más Años , Estudios Transversales , Factores de Tiempo , Edad de Inicio , Estudios de Cohortes , Progresión de la Enfermedad , Proteína 1 Similar a Quitinasa-3/líquido cefalorraquídeo , Proteína 1 Similar a Quitinasa-3/sangre , Disfunción Cognitiva/líquido cefalorraquídeo , Disfunción Cognitiva/sangre , Placa Amiloide/diagnóstico por imagen , Placa Amiloide/patología
11.
Exp Eye Res ; 240: 109797, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38246333

RESUMEN

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.


Asunto(s)
Lámina Limitante Posterior , Células Endoteliales , Proteínas de la Matriz Extracelular , Animales , Ratones , Colágeno Tipo IV/metabolismo , Córnea/metabolismo , Lámina Limitante Posterior/metabolismo , Células Endoteliales/metabolismo , Homeostasis , Laminina/metabolismo , Mamíferos , Proteínas de la Membrana/metabolismo
12.
Autophagy ; 20(1): 131-150, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37649246

RESUMEN

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.


Asunto(s)
Autofagia , Drosophila , Animales , Autofagia/fisiología , Lisosomas/metabolismo , Músculos , Serina-Treonina Quinasas TOR/metabolismo
13.
Sleep ; 47(1)2024 01 11.
Artículo en Inglés | MEDLINE | ID: mdl-38011629

RESUMEN

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.


Asunto(s)
Demencia , Trastornos de Somnolencia Excesiva , Trastornos del Inicio y del Mantenimiento del Sueño , Anciano , Femenino , Humanos , Persona de Mediana Edad , Péptidos beta-Amiloides , Negro o Afroamericano , Cognición , Estudios Transversales , Trastornos de Somnolencia Excesiva/complicaciones , Duración del Sueño , Masculino
14.
Alzheimers Dement ; 20(2): 1214-1224, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37932961

RESUMEN

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.


Asunto(s)
Enfermedad de Alzheimer , Humanos , Enfermedad de Alzheimer/diagnóstico , Péptidos beta-Amiloides , Fragmentos de Péptidos , Amiloide , Proteínas tau , Tomografía de Emisión de Positrones , Biomarcadores
15.
ISME J ; 17(12): 2389-2402, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37907732

RESUMEN

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.


Asunto(s)
Antozoos , Dinoflagelados , Animales , Antozoos/genética , Dinoflagelados/genética , Arrecifes de Coral , Simbiosis , Océanos y Mares
16.
bioRxiv ; 2023 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-37873290

RESUMEN

Pseudomonas aeruginosa is an opportunistic human pathogen that has developed multi- or even pan-drug resistance towards most frontline and last resort antibiotics, leading to increasing 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 towards 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 non-cellular models like giant plasma membrane vesicles. Most importantly, rhamnolipid production strongly correlated to 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.

17.
Alzheimers Dement (N Y) ; 9(3): e12414, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37752907

RESUMEN

Introduction: It is critical to develop more inclusive Alzheimer's disease (AD) research protocols to ensure that historically excluded groups are included in preclinical research and have access to timely diagnosis and treatment. If validated in racialized groups, plasma AD biomarkers and measures of subtle cognitive dysfunction could provide avenues to expand diversity in preclinical AD research. We sought to evaluate the utility of two easily obtained, low-burden disease markers, plasma amyloid beta (Aß)42/40, and intra-individual cognitive variability (IICV), to predict concurrent and longitudinal cognitive performance in a sample of Black adults. Methods: Two hundred fifty-seven Black participants enrolled in the African Americans Fighting Alzheimer's in Midlife (AA-FAIM) study underwent at least one cognitive assessment visit; a subset of n = 235 had plasma samples. Baseline IICV was calculated as the standard deviation across participants' z scores on five cognitive measures: Rey Auditory Verbal Learning Test Delayed Recall, Trail Making Test Parts A and B (Trails A and B), and Boston Naming Test. Using mixed effects regression models, we compared concurrent and longitudinal models to baseline plasma Aß42/40 or IICV by age interactions. PrecivityAD assays quantified baseline plasma Aß42/40. Results: IICV was associated with concurrent/baseline performance on several outcomes but did not modify associations between age and cognitive decline. In contrast, plasma Aß42/40 was unrelated to baseline cognitive performance, but a pattern emerged in interactions with age in longitudinal models of Trails A and B and Rey Auditory Verbal Learning Test total learning trials. Although not significant after correcting for multiple comparisons, low Aß42/40 was associated with faster cognitive declines over time. Discussion: Our results are promising as they extend existing findings to an Black American sample using low-cost, low-burden methods that can be implemented outside of a research center, thus supporting efforts for inclusive AD biomarker research.

18.
Surg Open Sci ; 15: 32-37, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37609369

RESUMEN

Background: The operating room (OR) is a major cost and revenue center for a hospital. One of the few modifiable costs in the OR is single-use, sterile surgical supplies (SUSSS). If SUSSS are opened on the scrub table and not used, then they are wasted. High-fidelity SUSSS usage data is important to strategically implement solutions to reduce waste of SUSSS in the OR. OR waste reduction may decrease health systems' carbon footprints and reduce spending. Methods: A convenience sample of general pediatric surgical cases was observed in summer 2021. HIPAA-free images of the surgical scrub table were acquired every 2 s with minimal impact on pediatric OR workflow. These images were asynchronously analyzed to obtain SUSSS usage data for each case. Results: Image data from three pediatric surgeons performing 41 pediatric surgeries was reviewed. The median cost of unused SUSSS was $13.10 (IQR = $2.73-$47.97) with a range of $0.07 to $489.08 wasted in a single surgery. The mean number of items wasted was 9.3 ± 6.4. The most frequently wasted items were sutures, syringes, towels, paper rulers, and specimen cups. The most expensive sources of waste were laparoscopic trocars, sutures, insufflation needles, drapes, and guidewires. Conclusions: SUSSS that were discarded without being used were successfully identified through the asynchronous analysis of HIPAA-free OR scrub table image data. This may be an opportunity to identify SUSSS waste efficiently without an observer in the OR.

19.
bioRxiv ; 2023 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-37425762

RESUMEN

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 of microbubbles, which cannot transverse many biological barriers due to their large size. Here we introduce 50-nm gas-filled protein nanostructures derived from genetically engineered gas vesicles that we referred to as 50nm GVs. These diamond-shaped nanostructures have hydrodynamic diameters smaller than commercially available 50-nm gold nanoparticles and are, to our knowledge, the smallest stable, free-floating bubbles made to date. 50nm GVs can be produced in bacteria, purified through centrifugation, and remain stable for months. Interstitially injected 50nm GVs 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. We anticipate that 50nm GVs can substantially broaden the range of cells accessible to current ultrasound technologies and may generate applications beyond biomedicine as ultrasmall stable gas-filled nanomaterials.

20.
Healthc Manage Forum ; 36(5): 299-303, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37318024

RESUMEN

Primary care is considered the foundation of any health system. In Ontario, Canada Bills 41 and 74 introduced in 2016 and 2019, respectively, aimed to move towards a primary care-focused and sustainable integrated care approach designed around the needs of local populations. These bills collectively set the stage for integrated care and population health management in Ontario, with Ontario Health Teams (OHTs) introduced as a model of integrated care delivery systems. OHTs aim to streamline patient connectivity through the healthcare system and improve outcomes aligned with the Quadruple Aim. When Ontario released a call for health system partners to apply to become an OHT, providers, administrators, and patient/caregiver partners from the Middlesex-London area were quick to respond. We highlight the critical elements and journey of the Middlesex-London Ontario Health Team since its start.


Asunto(s)
Prestación Integrada de Atención de Salud , Humanos , Ontario , Cuidadores , Grupo de Atención al Paciente
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