Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.175
Filtrar
1.
Heliyon ; 10(17): e37377, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39296142

RESUMEN

Phosphorus (P) is a widespread waterborne pollutant that impairs many waterbodies. However, it is challenging to measure directly, and much research has been dedicated to developing surrogacy models that can repeatedly predict its concentration. Optimal approaches for modeling strategies are often unclear and depend upon local P dynamics and the availability of financial and technical resources. This study presents a schema for developing P surrogacy models at a statewide scale (16 major rivers in Iowa, USA). Specifically, we examined the relationship between particulate phosphorus (Part P) and orthophosphate (OP) and explored the viability of eight potential surrogates in predicting their concentrations using multiple linear regression and power regression methods. We also investigated similarities between surrogate models for Part P and total suspended solids (TSS). At all sites, OP and Part P were not strongly correlated (mean R = 0.20 ± 0.17). Many instances were observed where samples had high concentrations of one form but not the other. Modeling results demonstrated that turbidity was consistently the best predictor (t-statistics >10) of Part P, and adding other surrogates alongside turbidity did little to improve model performance. No surrogates proved useful in estimating OP. Viable power regression models were created using turbidity to predict Part P (mean R2 = 0.69 ± 0.12). These models had a nonlinear form where Part P concentrations leveled off as waters became exceptionally turbid. This contrasted with TSS, which maintained a strong linear relationship across all turbidity levels. Turbidity-based models show promise in quantifying statewide P levels, as they enable high-resolution and real-time Part P estimates.

2.
ACS Synth Biol ; 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39302688

RESUMEN

Terminal deoxynucleotidyl transferase (TdT) is a unique DNA polymerase capable of template-independent extension of DNA. TdT's de novo DNA synthesis ability has found utility in DNA recording, DNA data storage, oligonucleotide synthesis, and nucleic acid labeling, but TdT's intrinsic nucleotide biases limit its versatility in such applications. Here, we describe a multiplexed assay for profiling and engineering the bias and overall activity of TdT variants with high throughput. In our assay, a library of TdTs is encoded next to a CRISPR-Cas9 target site in HEK293T cells. Upon transfection of Cas9 and sgRNA, the target site is cut, allowing TdT to intercept the double-strand break and add nucleotides. Each resulting insertion is sequenced alongside the identity of the TdT variant that generated it. Using this assay, 25,623 unique TdT variants, constructed by site-saturation mutagenesis at strategic positions, were profiled. This resulted in the isolation of several altered-bias TdTs that expanded the capabilities of our TdT-based DNA recording system, Cell HistorY Recording by Ordered InsertioN (CHYRON), by increasing the information density of recording through an unbiased TdT and achieving dual-channel recording of two distinct inducers (hypoxia and Wnt) through two differently biased TdTs. Select TdT variants were also tested in vitro, revealing concordance between each variant's in vitro bias and the in vivo bias determined from the multiplexed high throughput assay. Overall, our work and the multiplex assay it features should support the continued development of TdT-based DNA recorders, in vitro applications of TdT, and further study of the biology of TdT.

3.
medRxiv ; 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39228735

RESUMEN

Importance: In US emergency departments (EDs), empiric antibiotic treatment for gonorrhea (GC) and chlamydia (CT) is common due to the unavailability of immediate test results. Evidence suggests sex-based disparities in treatment practices, with females potentially receiving less empiric treatment than males. Objective: To investigate sex differences in empiric antibiotic treatment for GC and CT in EDs, comparing practices to subsequent laboratory-confirmed results. Design Setting and Participants: This systematic review and meta-analysis included studies from US EDs reporting GC/CT testing and empiric antibiotic treatment from January 2010 to February 2021. A total of 1,644 articles were screened, with 17 studies (n = 31,062 patients) meeting inclusion criteria. Main Outcomes and Measures: The primary outcomes were GC/CT test positivity, empiric antibiotic treatment rates, and discordance between treatment and test results, stratified by sex. Data were analyzed using a random-effects model. Results: Overall GC/CT positivity was 14% (95% CI, 11%-16%): 11% (95% CI, 8%-14%) in females and 25% (95% CI, 23%-26%) in males. Empiric antibiotic treatment was administered in 46% (95% CI, 38%-55%) of cases: 31% (95% CI, 24%-37%) in females and 73% (95% CI, 65%-80%) in males. Among patients without a laboratory-confirmed infection, 38% (95% CI, 30%-47%) received treatment: 27% (95% CI, 20%-34%) of females and 64% (95% CI, 55%-73%) of males. Conversely, 39% (95% CI, 31%-48%) of patients with laboratory-confirmed infections were not treated: 52% (95% CI, 46%-57%) of females and 15% (95% CI, 12%-17%) of males. Conclusions and Relevance: There is significant discordance between ED empiric antibiotic treatment and laboratory-confirmed results, with notable sex-based disparities. Females were 3.5 times more likely than males to miss treatment despite confirmed infection. These findings highlight the need for improved strategies to reduce sex-based disparities and enhance empiric treatment accuracy for GC/CT in ED settings. Key Points: Question: Are there sex-based differences in empiric antibiotic treatment for gonorrhea and chlamydia in US emergency departments (EDs), and how do these practices compare to laboratory-confirmed results?Findings: In this systematic review and meta-analysis of 17 studies with 31,062 patients, females were significantly less likely than males to receive empiric antibiotic treatment for gonorrhea and chlamydia. Additionally, 39% of patients with a laboratory-confirmed infection were not empirically treated, with females 3.5 times more likely to miss treatment than males.Meaning: The findings indicate significant sex disparities in ED empiric antibiotic treatment for sexually transmitted infections, underscoring the need for improved strategies to ensure equitable and accurate treatment across sexes.

4.
Adv Mater ; : e2406600, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39258368

RESUMEN

Thermoset toughness and deconstructability are often opposing features; simultaneously improving both without sacrificing other mechanical properties (e.g., stiffness and tensile strength) is difficult, but, if achieved, could enhance the usage lifetime and end-of-life options for these materials. Here, a strategy that addresses this challenge in the context of photopolymer resins commonly used for 3D printing of glassy, acrylic thermosets is introduced. It is shown that incorporating bis-acrylate "transferinkers," which are cross-linkers capable of undergoing degenerative chain transfer and new strand growth, as additives (5-25 mol%) into homemade or commercially available photopolymer resins leads to photopolymer thermosets with substantially improved tensile toughness and triggered chemical deconstructability with minimal impacts on Young's moduli, tensile strengths, and glass transition temperatures. These properties result from a transferinker-driven topological transition in network structure from the densely cross-linked long, heterogeneous primary strands of traditional photopolymer networks to more uniform, star-like networks with few dangling ends; the latter structure more effectively bear stress yet is also more easily depercolated via solvolysis. Thus, transferinkers represent a simple and effective strategy for improving the mechanical properties of photopolymer thermosets and providing a mechanism for their triggered deconstructability.

5.
Artículo en Inglés | MEDLINE | ID: mdl-39271152

RESUMEN

BACKGROUND: Loneliness is a biopsychosocial stressor linked to poor health outcomes including dementia. Few studies have focused on this association among men and even fewer have examined racial disparities in loneliness and cognitive functioning among this group. The purpose of this study was to examine racial differences in the association between loneliness and cognitive functioning among men in the 2016 wave of the Health and Retirement Study (HRS). METHODS: This cross-sectional study included Black and White men who completed the core questionnaire and the Leave Behind Questionnaire (n=2227). Any cognitive impairment was the primary outcome and was measured by a dichotomous variable derived from a modified version of the Telephone Interview for Cognitive Status. Loneliness was the primary independent variable and was derived from the 3-item UCLA Loneliness Scale. Modified Poisson regression models with robust standard errors were estimated to generate prevalence ratios and corresponding 95% confidence intervals. RESULTS: Black men comprised 18.4% of the study sample; however, the proportion of this group with scores indicating cognitive impairment (35.9%) doubled the corresponding percentage of white men (17.6%). Findings from race-stratified modified Poisson regression models indicated that loneliness was associated with a higher prevalence of any cognitive impairment for White men (PR=1.24, CI:1.05-1.47), but not for Black men (PR=0.92, CI:0.73-1.16). CONCLUSIONS: Our results underscore the complexity of race when investigating the association between loneliness and cognitive impairment among older men. Additional studies are needed to further examine how loneliness may have racially distinct implications for cognitive outcomes among the population.

6.
Dev Neurorehabil ; : 1-7, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39235762

RESUMEN

INTRODUCTION: To date, there are no caregiver-reported screening measures of oral behaviors related to feeding. The goal of this study was to develop such a measure. METHOD: Caregivers of 803 children referred to a feeding clinic and 188 comparison children reported their children's frequency of nine oral behaviors. These data were used to develop an Oral Behavior Screener (OBS). Both the psychometrics of the OBS and the relations between the OBS and child demographics were examined. RESULTS: As expected, the clinical sample demonstrated more deficits in oral behaviors than the comparison sample. We also found special needs status and age were linked to the OBS summary score. DISCUSSION: The OBS is a brief screener that can be used by clinicians to examine the need for further assessment, possible targets for intervention, oral behaviors often associated with feeding problems.

7.
Biotechnol Bioeng ; 2024 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-39275897

RESUMEN

Harnessing DNA as a high-density storage medium for information storage and molecular recording of signals has been of increasing interest in the biotechnology field. Recently, progress in enzymatic DNA synthesis, DNA digital data storage, and DNA-based molecular recording has been made by leveraging the activity of the template-independent DNA polymerase, terminal deoxynucleotidyl transferase (TdT). TdT adds deoxyribonucleotides to the 3' end of single-stranded DNA, generating random sequences of single-stranded DNA. TdT can use several divalent cations for its enzymatic activity and exhibits shifts in deoxyribonucleotide incorporation frequencies in response to changes in its reaction environment. However, there is limited understanding of sequence-structure-function relationships regarding these properties, which in turn limits our ability to modulate TdT to further advance TdT-based tools. Most TdT literature to-date explores the activity of murine, bovine or human TdTs; studies probing TdT sequence and structure largely focus on strictly conserved residues that are functionally critical to TdT activity. Here, we explore non-conserved TdT sequence space by surveying the natural diversity of TdT. We characterize a diverse set of TdT homologs from different organisms and identify several TdT residues/regions that confer differences in TdT behavior between homologs. The observations in this study can design rules for targeted TdT libraries, in tandem with a screening assay, to modulate TdT properties. Moreover, the data can be useful in guiding further studies of potential residues of interest. Overall, we characterize TdTs that have not been previously studied in the literature, and we provide new insights into TdT sequence-function relationships.

8.
BMC Neurol ; 24(1): 271, 2024 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-39097695

RESUMEN

BACKGROUND: Among ambulatory people with incomplete spinal cord injury (iSCI), balance deficits are a primary factor limiting participation in walking activities. There is broad recognition that effective interventions are needed to enhance walking balance following iSCI. Interventions that amplify self-generated movements (e.g., error augmentation) can accelerate motor learning by intensifying sensorimotor feedback and facilitating exploration of motor control strategies. These features may be beneficial for retraining walking balance after iSCI. We have developed a cable-driven robot that creates a movement amplification environment during treadmill walking. The robot applies a continuous, laterally-directed, force to the pelvis that is proportional in magnitude to real-time lateral velocity. Our purpose is to investigate the effects of locomotor training in this movement amplification environment on walking balance. We hypothesize that for ambulatory people with iSCI, locomotor training in a movement amplification environment will be more effective for improving walking balance and participation in walking activities than locomotor training in a natural environment (no applied external forces). METHODS: We are conducting a two-arm parallel-assignment intervention. We will enroll 36 ambulatory participants with chronic iSCI. Participants will be randomized into either a control or experimental group. Each group will receive 20 locomotor training sessions. Training will be performed in either a traditional treadmill environment (control) or in a movement amplification environment (experimental). We will assess changes using measures that span the International Classification of Functioning, Disability and Health (ICF) framework including 1) clinical outcome measures of gait, balance, and quality of life, 2) biomechanical assessments of walking balance, and 3) participation in walking activities quantified by number of steps taken per day. DISCUSSION: Training walking balance in people with iSCI by amplifying the individual's own movement during walking is a radical departure from current practice and may result in new strategies for addressing balance impairments. Knowledge gained from this study will expand our understanding of how people with iSCI improve walking balance and how an intervention targeting walking balance affects participation in walking activities. Successful outcomes could motivate development of clinically feasible tools to replicate the movement amplification environment within clinical settings. TRIAL REGISTRATION: NCT04340063.


Asunto(s)
Marcha , Traumatismos de la Médula Espinal , Traumatismos de la Médula Espinal/rehabilitación , Traumatismos de la Médula Espinal/fisiopatología , Humanos , Marcha/fisiología , Adulto , Terapia por Ejercicio/métodos , Equilibrio Postural/fisiología , Caminata/fisiología , Masculino , Femenino , Robótica/métodos , Método Simple Ciego , Persona de Mediana Edad , Locomoción/fisiología
9.
Int J Mol Sci ; 25(16)2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39201471

RESUMEN

This study asked whether the P2X7 receptor was necessary and sufficient to trigger astrocyte polarization into neuroinflammatory activation states. Intravitreal injection of agonist BzATP increased gene expression of pan-astrocyte activation markers Gfap, Steap4, and Vim and A1-type astrocyte activation markers C3, Serping1, and H2T23, but also the Cd14 and Ptx3 genes usually associated with the A2-type astrocyte activation state and Tnfa, IL1a, and C1qa, assumed to be upstream of astrocyte activation in microglia. Correlation analysis of gene expression suggested the P2X7 receptor induced a mixed A1/A2-astrocyte activation state, although A1-state genes like C3 increased the most. A similar pattern of mixed glial activation genes occurred one day after intraocular pressure (IOP) was elevated in wild-type mice, but not in P2X7-/- mice, suggesting the P2X7 receptor is necessary for the glial activation that accompanies IOP elevation. In summary, this study suggests stimulation of the P2X7R is necessary and sufficient to trigger the astrocyte activation in the retina following IOP elevation, with a rise in markers for pan-, A1-, and A2-type astrocyte activation. The P2X7 receptor is expressed on microglia, optic nerve head astrocytes, and retinal ganglion cells (RGCs) in the retina, and can be stimulated by the mechanosensitive release of ATP that accompanies IOP elevation. Whether the P2X7 receptor connects this mechanosensitive ATP release to microglial and astrocyte polarization in glaucoma remains to be determined.


Asunto(s)
Adenosina Trifosfato , Astrocitos , Receptores Purinérgicos P2X7 , Receptores Purinérgicos P2X7/metabolismo , Receptores Purinérgicos P2X7/genética , Animales , Astrocitos/metabolismo , Ratones , Adenosina Trifosfato/metabolismo , Adenosina Trifosfato/análogos & derivados , Ratones Noqueados , Ratones Endogámicos C57BL , Presión Intraocular , Biomarcadores , Masculino , Retina/metabolismo , Microglía/metabolismo
10.
Ethn Dis ; 34(3): 137-144, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39211820

RESUMEN

Objectives: We investigated the associations of lifetime and everyday discrimination with cognitive function. Methods: Data were from the Chicago Community Adult Health Study (n=2952, mean age=43 years [SD=17]). We fitted multivariable linear regression models to quantify the discrimination-cognition associations. Results: Major lifetime (ß1 vs 0 episodes of discrimination = 0.56; 95% CI, 0.15-0.96; ß2+ vs 0 episodes of discrimination = 0.64, 95% CI, 0.31-0.97) and everyday (ß=0.10, 95% CI, 0.06-0.14) discrimination were positively associated with cognition, and these associations did not differ by race/ethnicity. Among older adults, major lifetime discrimination, but not everyday discrimination, was positively associated with cognition (ß2+ vs 0 episodes of discrimination =1.79; 95% CI, 0.79-2.79). Discussion: Measurement and selection bias may partially explain the counterintuitive study findings. We call for longitudinal research to further investigate the discrimination-cognition relationship.


Asunto(s)
Cognición , Humanos , Femenino , Masculino , Persona de Mediana Edad , Chicago , Anciano , Adulto
11.
Nucleic Acids Res ; 52(16): 9978-9995, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39149911

RESUMEN

Monoubiquitination of histones H2B-K120 (H2BK120ub) and H2A-K119 (H2AK119ub) play opposing roles in regulating transcription and chromatin compaction. H2BK120ub is a hallmark of actively transcribed euchromatin, while H2AK119ub is highly enriched in transcriptionally repressed heterochromatin. Whereas H2BK120ub is known to stimulate the binding or activity of various chromatin-modifying enzymes, this post-translational modification (PTM) also interferes with the binding of several proteins to the nucleosome H2A/H2B acidic patch via an unknown mechanism. Here, we report cryoEM structures of an H2BK120ub nucleosome showing that ubiquitin adopts discrete positions that occlude the acidic patch. Molecular dynamics simulations show that ubiquitin remains stably positioned over this nucleosome region. By contrast, our cryoEM structures of H2AK119ub nucleosomes show ubiquitin adopting discrete positions that minimally occlude the acidic patch. Consistent with these observations, H2BK120ub, but not H2AK119ub, abrogates nucleosome interactions with acidic patch-binding proteins RCC1 and LANA, and single-domain antibodies specific to this region. Our results suggest a mechanism by which H2BK120ub serves as a gatekeeper to the acidic patch and point to distinct roles for histone H2AK119 and H2BK120 ubiquitination in regulating protein binding to nucleosomes.


Asunto(s)
Microscopía por Crioelectrón , Histonas , Simulación de Dinámica Molecular , Nucleosomas , Ubiquitina , Ubiquitinación , Nucleosomas/metabolismo , Nucleosomas/ultraestructura , Nucleosomas/química , Histonas/metabolismo , Histonas/química , Ubiquitina/metabolismo , Ubiquitina/química , Ubiquitina/genética , Humanos , Unión Proteica , Procesamiento Proteico-Postraduccional
12.
Artículo en Inglés | MEDLINE | ID: mdl-39115540

RESUMEN

BACKGROUND: Intraoperative fluoroscopy is increasingly common in orthopaedics, although recent guidelines have reduced the maximum recommended exposure to 20 mSv annually. A systematic review of the literature was conducted to comprehensively assess current adherence to exposure guidelines, identify practice settings at increased risk for exposure, and determine the best practices and personal protective equipment for ocular radiation risk mitigation. QUESTIONS/PURPOSES: In this systematic review we asked: (1) Is the annual amount of eye irradiation received by orthopaedic surgeons below the recommended limit of 20 mSv? (2) What is the effectiveness of leaded glasses in reducing the eye's exposure to radiation? (3) Which imaging setups and operative techniques reduce ocular irradiation? METHODS: PubMed, Medline, EBSCOhost, and Google Scholar were queried on September 28, 2023, to identify studies assessing intraoperative ocular radiation exposure among orthopaedic surgeons. Studies that measured radiation in or around the eye (such as the bridge of the nose or eyebrows) during orthopaedic procedures were included. Exclusion criteria were duplicate studies, studies that only estimated eye radiation based on the radiation dose recorded at parts of the body distant from the eyes, nonoriginal research, case reports, and articles without full-text English versions available. A total of 393 unique articles were retrieved, and after title, abstract, and full-text screening, 23 dosimetry studies were included, comprising 12 prospective observational studies, 7 phantom models, 1 cadaver model, 2 observational studies, and 1 randomized control trial. Risk of bias was determined via the Methodological Index for Nonrandomized Studies (MINORS) tool. Study quality was generally good to excellent, with noncomparative studies having a mean MINORS score of 14 ± 0 of 16 and comparative studies achieving a mean score of 19 ± 1 of 24, with higher scores representing better study quality. Due to extensive heterogeneity in study design, a meta-analysis was not conducted, with the results rather presented as a narrative summary of key findings. RESULTS: The vast majority of surgeons conducting a variety of orthopaedic and traumatologic procedures were not exposed to a hazardous level of eye irradiation annually, but surgeons who perform a high volume of fluoroscopy-intensive procedures may exceed guidelines. Leaded eyeglasses reduced eye radiation by about 90%, with sport wrap-around glasses offering better shielding than alternatives, although leaded glasses overall were largely underutilized. Positioning mini C-arms in the standard vertical configuration was shown to provide up to a 13-fold decrease in radiation exposure compared with inverted configuration, while standing perpendicular to the fluoroscope further reduced eye irradiation. CONCLUSION: We found that orthopaedic surgeons who perform a high volume of fluoroscopy-intensive procedures may be at risk of exceeding recommendations on annual radiation exposure, although exposure can be mitigated through various simple strategies. In particular, this analysis found that the use of sport wrap-around leaded glasses, positioning of mini-C arms in the standard vertical configuration, and standing perpendicular to the fluoroscope provide the most effective means of limiting ocular radiation exposure. As ophthalmic radiation exposure presents a potentially important occupational health hazard to orthopaedic surgeons, further investigations of radiation exposure specific to high-volume, fluoroscopy-intensive orthopaedic practices and long-term ophthalmic outcomes will help determine the extent of the potential harm posed by frequent exposure to intraoperative radiation over the span of a career. LEVEL OF EVIDENCE: Level III, therapeutic study.

13.
PLoS One ; 19(8): e0308064, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39141608

RESUMEN

The purpose of this study was to determine: (1) whether physically active virtual reality (VR) games exert an acute hypoaglesic effect on the thigh and bicep compared to a non-active VR game and an exercise only condition matched for exercise intensity in healthy individuals, and (2) whether movement variables during gameplay are associated with the hypoalgesic effect of the games. Twenty young adults completed five separate study sessions, with each session devoted to playing one head-mounted display VR game or stationary cycling for 15 minutes. The games included Holopoint at level 2 and level 3, Hot Squat, and Relax Walk. Pressure pain thresholds at the thigh and bicep were measured pre and post VR gameplay and cycling. Participants wore a heart rate monitor and accelerometers on the wrist and thigh during play to measure the intensity and quantity of movement. Repeated measures ANOVAs revealed that pressure pain thresholds on the bicep increased from pre to posttest for each condition. The results also revealed that pressure pain thresholds on the thigh increased only for the conditions eliciting the greatest cardiovascular response, which included Holopoint at level 3, Hot Squat, and cycling. Bivariate correlations indicated that moderate to vigorous physical activity of the thigh was associated with pain reduction at the thigh during Holopoint. These results revealed that active VR games and exercise exerted a more widespread hypoalgesic effect compared to the non-active VR game, which was likely driven in part by the intensity and quantity of movement during gameplay.


Asunto(s)
Umbral del Dolor , Juegos de Video , Realidad Virtual , Humanos , Masculino , Femenino , Adulto Joven , Adulto , Umbral del Dolor/fisiología , Frecuencia Cardíaca/fisiología , Ejercicio Físico/fisiología
14.
Transplantation ; 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39160653

RESUMEN

BACKGROUND: The pulmonary assist system (PAS) is a wearable respiratory support system that is currently under development for patients with chronic lung disease as a bridge to lung transplantation or as destination therapy. This study evaluates the long-term performance and biocompatibility of the PAS in a 5-d awake, ovine model. METHODS: The PAS was attached to normal sheep in venovenous configuration. Components of the PAS included a 0.9 m2 surface area oxygenator and a lightweight, battery-powered axial flow pump. The system was also tested using the Abbott PediMag as the control pump. Each sheep was supported on the PAS for 5 d with 2 L/min blood flow and 4 L/min sweep gas. Activated clotting times of 200-240 s were maintained using intravenous heparin. Pump performance, oxygen transfer, oxygenator resistance, and hematologic parameters were measured throughout the support. RESULTS: The PAS, either using the axial flow pump or PediMag (n = 4 each), was well tolerated by the sheep without signs of device-related organ damage or hemolysis. All the studies achieved the full, 5-d study duration. The oxygenator resistance remained consistent without significant clot formation in all experiments with an average resistance of 2.55 ±â€…0.10 mm Hg/(L/min). The system achieved an average oxygen transfer rate of 116.4 ±â€…5.5 mL/min, with an average Hb concentration of 9.2 ±â€…0.6 g/dL. White blood cell, platelet, and hematocrit levels also remained stable and within normal limits throughout the study period. CONCLUSIONS: The PAS provided 5 d of uncomplicated ambulatory respiratory support with minimal clot formation, stable gas exchange, blood flow resistance, and hematologic parameters.

15.
Sci Rep ; 14(1): 18276, 2024 08 06.
Artículo en Inglés | MEDLINE | ID: mdl-39107468

RESUMEN

Tracking trajectories of body size in children provides insight into chronic disease risk. One measure of pediatric body size is body mass index (BMI), a function of height and weight. Errors in measuring height or weight may lead to incorrect assessment of BMI. Yet childhood measures of height and weight extracted from electronic medical records often include values which seem biologically implausible in the context of a growth trajectory. Removing biologically implausible values reduces noise in the data, and thus increases the ease of modeling associations between exposures and childhood BMI trajectories, or between childhood BMI trajectories and subsequent health conditions. We developed open-source algorithms (available on github) for detecting and removing biologically implausible values in pediatric trajectories of height and weight. A Monte Carlo simulation experiment compared the sensitivity, specificity and speed of our algorithms to three published algorithms. The comparator algorithms were selected because they used trajectory information, had open-source code, and had published verification studies. Simulation inputs were derived from longitudinal epidemiological cohorts. Our algorithms had higher specificity, with similar sensitivity and speed, when compared to the three published algorithms. The results suggest that our algorithms should be adopted for cleaning longitudinal pediatric growth data.


Asunto(s)
Algoritmos , Índice de Masa Corporal , Humanos , Niño , Estudios Longitudinales , Estatura , Femenino , Registros Electrónicos de Salud , Masculino , Peso Corporal , Preescolar , Método de Montecarlo , Adolescente , Lactante
16.
Chest ; 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38964673

RESUMEN

BACKGROUND: When comparing outcomes after sepsis, it is essential to account for patient case mix to make fair comparisons. We developed a model to assess risk-adjusted 30-day mortality in the Michigan Hospital Medicine Safety sepsis initiative (HMS-Sepsis). RESEARCH QUESTION: Can HMS-Sepsis registry data adequately predict risk of 30-day mortality? Do performance assessments using adjusted vs unadjusted data differ? STUDY DESIGN AND METHODS: Retrospective cohort of community-onset sepsis hospitalizations in the HMS-Sepsis registry (April 2022-September 2023), with split-derivation (70%) and validation (30%) cohorts. We fit a risk-adjustment model (HMS-Sepsis mortality model) incorporating acute physiologic, demographic, and baseline health data and assessed model performance using concordance (C) statistics, Brier's scores, and comparisons of predicted vs observed mortality by deciles of risk. We compared hospital performance (first quintile, middle quintiles, fifth quintile) using observed vs adjusted mortality to understand the extent to which risk adjustment impacted hospital performance assessment. RESULTS: Among 17,514 hospitalizations from 66 hospitals during the study period, 12,260 hospitalizations (70%) were used for model derivation and 5,254 hospitalizations (30%) were used for model validation. Thirty-day mortality for the total cohort was 19.4%. The final model included 13 physiologic variables, two physiologic interactions, and 16 demographic and chronic health variables. The most significant variables were age, metastatic solid tumor, temperature, altered mental status, and platelet count. The model C statistic was 0.82 for the derivation cohort, 0.81 for the validation cohort, and ≥ 0.78 for all subgroups assessed. Overall calibration error was 0.0%, and mean calibration error across deciles of risk was 1.5%. Standardized mortality ratios yielded different assessments than observed mortality for 33.9% of hospitals. INTERPRETATION: The HMS-Sepsis mortality model showed strong discrimination and adequate calibration and reclassified one-third of hospitals to a different performance category from unadjusted mortality. Based on its strong performance, the HMS-Sepsis mortality model can aid in fair hospital benchmarking, assessment of temporal changes, and observational causal inference analysis.

17.
Ethn Health ; 29(7): 774-792, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39003724

RESUMEN

Despite the association of neighborhood quality with poorer adult health, limited research has explored the association between neighborhood disadvantage, e.g. Area Deprivation Index (ADI), and older Black adults' health, prospectively. This observational study examined the association between ADI and changes in longitudinal physical health within older Black adults. The analytic sample (n = 317) included data from waves 1 & 2 of the Baltimore Study of Black Aging: Patterns of Cognitive Aging (BSBA-PCA). Study variables included the Area Deprivation Index (ADI), objective (e.g. average heart rate) and subjective (e.g. activities of daily living) measures of physical health. Multiple linear regression models were conducted controlling for sociodemographic and social support characteristics. Participants living in more disadvantaged neighborhoods, based on national and state ADIs, were more likely to have a decreasing heart rate even after adjusting for covariates. Likewise, participants reporting increasing levels of ADL difficulty were living in a neighborhood with greater disadvantage based on national and state ADI rankings. Significant social support received and ADI (national and state) interactions were observed for average heart rate. The findings suggest that research on the effect of neighborhood quality and social support can enhance our understanding of its impact on older Black adults' health prospectively.


Asunto(s)
Negro o Afroamericano , Apoyo Social , Humanos , Baltimore/epidemiología , Masculino , Femenino , Negro o Afroamericano/psicología , Negro o Afroamericano/estadística & datos numéricos , Anciano , Persona de Mediana Edad , Estado de Salud , Actividades Cotidianas , Estudios Longitudinales , Características del Vecindario , Características de la Residencia/estadística & datos numéricos , Frecuencia Cardíaca/fisiología , Envejecimiento/psicología , Envejecimiento/etnología , Estudios Prospectivos , Factores Socioeconómicos , Anciano de 80 o más Años
18.
ACS Synth Biol ; 13(8): 2492-2504, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39083642

RESUMEN

Enzymatic DNA writing technologies based on the template-independent DNA polymerase terminal deoxynucleotidyl transferase (TdT) have the potential to advance DNA information storage. TdT is unique in its ability to synthesize single-stranded DNA de novo but has limitations, including catalytic inhibition by ribonucleotide presence and slower incorporation rates compared to replicative polymerases. We anticipate that protein engineering can improve, modulate, and tailor the enzyme's properties, but there is limited information on TdT sequence-structure-function relationships to facilitate rational approaches. Therefore, we developed an easily modifiable screening assay that can measure the TdT activity in high-throughput to evaluate large TdT mutant libraries. We demonstrated the assay's capabilities by engineering TdT mutants that exhibit both improved catalytic efficiency and improved activity in the presence of an inhibitor. We screened for and identified TdT variants with greater catalytic efficiency in both selectively incorporating deoxyribonucleotides and in the presence of deoxyribonucleotide/ribonucleotide mixes. Using this information from the screening assay, we rationally engineered other TdT homologues with the same properties. The emulsion-based assay we developed is, to the best of our knowledge, the first high-throughput screening assay that can measure TdT activity quantitatively and without the need for protein purification.


Asunto(s)
ADN Nucleotidilexotransferasa , ADN Polimerasa Dirigida por ADN , Ingeniería de Proteínas , Ingeniería de Proteínas/métodos , ADN Polimerasa Dirigida por ADN/metabolismo , ADN Polimerasa Dirigida por ADN/genética , ADN Polimerasa Dirigida por ADN/química , ADN Nucleotidilexotransferasa/metabolismo , ADN Nucleotidilexotransferasa/química , ADN Nucleotidilexotransferasa/genética , Ensayos Analíticos de Alto Rendimiento/métodos , ADN de Cadena Simple/genética , ADN de Cadena Simple/metabolismo , Desoxirribonucleótidos/metabolismo , Mutación
19.
J Neurophysiol ; 132(3): 781-790, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39081214

RESUMEN

During visuomotor learning, improvements in motor performance accompany changes in how people use vision. However, the dependencies between altered visual reliance and improvements in motor skill is unclear. The present studies used an online sequence learning task to quantify how changing the availability of visual information affected motor skill learning (study 1) and how changing motor skill affected visual reliance (study 2). Participants used their keyboard to respond to targets falling vertically down a game screen. In study 1 (n = 49), the availability of visual information was altered by manipulating where the targets were visible on the screen. Three experimental groups practiced the task during full or limited vision conditions (when the targets were only visible in specific areas). We hypothesized that limiting visual information would reduce motor learning (i.e., the rate of improvement during training trial blocks). Instead, although participants performed worse during limited vision trials (P < 0.001), there was no difference in learning rate (P = 0.87). In study 2 (n = 119), all participants practiced the task with full vision and their visual reliance (i.e., their performance change between full and limited vision conditions) was quantified before and after training. We hypothesized that with motor learning, visual reliance on future targets would increase, whereas visual reliance on the current targets would decrease. The results of study 2 partially support our hypotheses with visual reliance decreasing for all visual areas (P < 0.001). Together, the results suggest changing motor skill alters how people use vision, but changing visual availability does not affect motor learning.NEW & NOTEWORTHY Previous research has established how people use visual information changes with motor learning. However, the dependencies of these two processes on each other are unclear. We find that limiting the availability of visual information degrades motor performance but not motor learning. We also find that motor learning reduces the impact of limiting the availability of visual information on motor performance. Together, these results suggest that how people use visual information depends on their motor skill.


Asunto(s)
Aprendizaje , Destreza Motora , Percepción Visual , Humanos , Masculino , Femenino , Aprendizaje/fisiología , Destreza Motora/fisiología , Adulto , Adulto Joven , Percepción Visual/fisiología , Desempeño Psicomotor/fisiología , Visión Ocular/fisiología
20.
Transl Anim Sci ; 8: txae098, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39005630

RESUMEN

The National Beef Quality Audit - 2022 serves as a benchmark of the current fed steer and heifer population of the U.S. beef industry and allows comparison to previous audits as a method of monitoring industry progress. In-plant cooler assessments and collections of beef carcass data took place from July 2021 to November 2022. During in-plant evaluations, 10% of 1-d production was surveyed for quality and yield indicating characteristics of fed beef carcasses (n = 9,746 beef carcasses). Distributions of sex classes among sampled carcasses were steer (65.0%) and heifer (35.0%), whereas distributions of breed type were native (87.7%), dairy (11.3%), and Bos indicus (0.9%). Mean values were observed for USDA Yield Grades (YG; 3.3), USDA Quality Grade (QG; Choice16), marbling score (Small98), ribeye area (91.0 cm2), adjusted fat thickness (1.49 cm), hot carcass weight (401.9 kg), and KPH (2.5%). Mean overall maturity was A66, with a mean lean maturity of A56 and mean skeletal maturity of A72. There were 28.1% of carcasses identified for use in a USDA-certified beef G-Schedule Program. Defects, such as dark cutting and blood splash, were observed at 1.8% and 0.5%, respectively. Distributions of USDA YG were YG 1 (8.2%), YG 2 (30.7%), YG 3 (40.2%), YG 4 (16.6%), and YG 5 (4.3%). USDA QGs were observed at 7.5% Prime, 69.2% Choice, 16.4% Select, and 6.8% other. The results of this study provide an updated look at the current grading trends of beef carcasses in the United States to drive progress in the fed beef industry.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA