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1.
Ann Biomed Eng ; 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39028399

RESUMO

PURPOSE: Measuring head kinematics data is important to understand and develop methods and standards to mitigate head injuries in contact sports. Instrumented mouthguards (iMGs) have been developed to address coupling issues with previous sensors. Although validated with anthropomorphic test devices (ATDs), there is limited post-mortem human subjects (PMHS) data which provides more accurate soft tissue responses. This study evaluated two iMGs (Prevent Biometrics (PRE) and Diversified Technical Systems (DTS) in response to direct jaw impacts. METHODS: Three unembalmed male cadaver heads were properly fitted with two different boil-and-bite iMGs and impacted with hook (4 m/s) and uppercut (3 m/s) punches. A reference sensor (REF) was rigidly attached to the base of the skull, impact kinematics were transformed to the head center of gravity and linear and angular kinematic data were compared to the iMGs including Peak Linear Acceleration, Peak Angular Acceleration, Peak Angular Velocity, Head Injury Criterion (HIC), HIC duration, and Brain Injury Criterion. RESULTS: Compared to the REF sensor, the PRE iMG underpredicted most of the kinematic data with slopes of the validation regression line between 0.72 and 1.04 and the DTS overpredicted all the kinematic data with slopes of the regression line between 1.4 and 8.7. CONCLUSION: While the PRE iMG was closer to the REF sensor compared to the DTS iMG, the results did not support the previous findings reported with use of ATDs. Hence, our study highlights the benefits of using PMHS for validating the accuracy of iMGs since they closely mimic the human body compared to any ATD's mandible.

2.
J Neurosci ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39009438

RESUMO

Neuroticism/Negative Emotionality (N/NE)-the tendency to experience anxiety, fear, and other negative emotions-is a fundamental dimension of temperament with profound consequences for health, wealth, and wellbeing. Elevated N/NE is associated with a panoply of adverse outcomes, from reduced socioeconomic attainment to psychiatric illness. Animal research suggests that N/NE reflects heightened reactivity to uncertain threat in the bed nucleus of the stria terminalis (BST) and central nucleus of the amygdala (Ce), but the relevance of these discoveries to humans has remained unclear. Here we used a novel combination of psychometric, psychophysiological, and neuroimaging approaches to rigorously test this hypothesis in an ethnoracially diverse, sex-balanced sample of 220 emerging adults selectively recruited to encompass a broad spectrum of N/NE. Cross-validated robust-regression analyses demonstrated that N/NE is preferentially associated with heightened BST activation during the uncertain anticipation of a genuinely distressing threat (aversive multimodal stimulation), whereas N/NE was unrelated to BST activation during certain-threat anticipation, Ce activation during either type of threat anticipation, or BST/Ce reactivity to threat-related faces. It is often assumed that different threat paradigms are interchangeable assays of individual differences in brain function, yet this has rarely been tested. Our results revealed negligible associations between BST/Ce reactivity to the anticipation of threat and the presentation of threat-related faces, indicating that the two tasks are non-fungible. These observations provide a framework for conceptualizing emotional traits and disorders; for guiding the design and interpretation of biobank and other neuroimaging studies of psychiatric risk, disease, and treatment; and for informing mechanistic research.Significance statement Neuroticism/Negative Emotionality (N/NE) is a core dimension of mammalian temperament. Elevated levels of N/NE confer risk for a panoply of adversities-from reduced wealth and divorce to depression and death-yet the underlying neurobiology remains unclear. Here we show that N/NE is associated with heightened activation in the bed nucleus of the stria terminalis (BST) during the uncertain anticipation of a genuinely distressing threat. In contrast, N/NE was unrelated to BST reactivity during the certain anticipation of threat or the acute presentation of 'threat-related' faces, two popular probes of the emotional brain. These findings refine our understanding of what has been termed the single most important psychological risk factor in public health, with implications for on-going biobank and therapeutics research.

3.
bioRxiv ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-39026814

RESUMO

Temporal dynamics play a central role in models of emotion: "fear" is widely conceptualized as a phasic response to certain-and-imminent danger, whereas "anxiety" is a sustained response to uncertain-or-distal harm. Yet the underlying human neurobiology remains contentious. Leveraging an ethnoracially diverse sample, translationally relevant paradigm, and theory-driven modeling approach, we demonstrate that certain and uncertain threat recruit a shared threat-anticipation circuit. This circuit exhibits persistently elevated activation when anticipating uncertain threat encounters and a transient burst of activation in the moments before certain encounters. For many scientists and clinicians, feelings are the defining feature of human fear and anxiety. Here we used an independently validated brain signature to covertly decode the momentary dynamics of anticipatory distress for the first time. Results mirrored the dynamics of neural activation. These observations provide fresh insights into the neurobiology of threat-elicited emotions and set the stage for more ambitious clinical and mechanistic research.

4.
Anat Sci Educ ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38954745

RESUMO

Reduced hours of instruction are reported within the gross anatomy education literature. Anatomy instruction continues to be challenged with motivating and inspiring learners to value the contribution of gross anatomy knowledge to their career development alongside increased organizational demands for efficiency and effectiveness. To address these demands, this retrospective study sought to understand how the relative timing and amount of gross anatomy instruction were related to examination performance. Undergraduate and graduate students between 2018 and 2022 were assigned to three cohorts determined by enrollment in prosection-based anatomy only (n = 334), concurrent enrollment in prosection- and dissection-based anatomy in the same semester (n = 67), or consecutive enrollment in the courses one year apart (n = 43). Concurrent students had higher prosection-based anatomy examination scores than prosection-only and consecutive students. Consecutively, enrolled students outperformed concurrently enrolled students on the first two dissection examinations but showed no performance differences on the third and fourth dissection examinations. While the results on the timing and presentation of anatomical instruction were inconclusive, the results do support increased instructional time using both prosection and dissection modalities concurrently to improve performance on identification-based gross anatomy examinations.

5.
bioRxiv ; 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38853920

RESUMO

Social anxiety-which typically emerges in adolescence-lies on a continuum and, when extreme, can be devastating. Socially anxious individuals are prone to heightened fear, anxiety, and the avoidance of contexts associated with potential social scrutiny. Yet most neuroimaging research has focused on acute social threat. Much less attention has been devoted to understanding the neural systems recruited during the uncertain anticipation of potential encounters with social threat. Here we used a novel fMRI paradigm to probe the neural circuitry engaged during the anticipation and acute presentation of threatening faces and voices in a racially diverse sample of 66 adolescents selectively recruited to encompass a range of social anxiety and enriched for clinically significant levels of distress and impairment. Results demonstrated that adolescents with more severe social anxiety symptoms experience heightened distress when anticipating encounters with social threat, and reduced discrimination of uncertain social threat and safety in the bed nucleus of the stria terminalis (BST), a key division of the central extended amygdala (EAc). Although the EAc-including the BST and central nucleus of the amygdala-was robustly engaged by the acute presentation of threatening faces and voices, the degree of EAc engagement was unrelated to the severity of social anxiety. Together, these observations provide a neurobiologically grounded framework for conceptualizing adolescent social anxiety and set the stage for the kinds of prospective-longitudinal and mechanistic research that will be necessary to determine causation and, ultimately, to develop improved interventions for this often-debilitating illness.

6.
Front Psychol ; 15: 1339230, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38903468

RESUMO

Introduction: Childcare center closures during COVID-19 impacted education for approximately 40 million children nationwide. Unfortunately, COVID-19 restrictions significantly limited the extent that outside personnel could provide in-person support to educators, resulting in the need for innovative approaches to meet childcare centers' needs. A virtual robotic telepresence approach was applied to early childhood consultation models to promote child resilience while mitigating COVID-19 risks. The goal of this study was to examine how training influenced consultants' and childcare staff uptake of the virtual robotic telepresence consultation approach and their acceptance of this technology. Methods: Ten early childhood consultants received multimedia/simulation training and weekly communities of practice related to virtual telepresence robotic consultation. Telepresence robotic consultation equipment was deployed to 16 childcare centers in a diverse multilingual metropolitan area as a part of a larger randomized controlled trial. Consultants trained childcare staff (14 center directors and 58 teachers) on how to receive virtual telepresence robotic consultation. Demographic information and measures of technology acceptability and uptake were collected from childcare staff and consultants. A mixed methods approach was used including multilevel modeling and focus groups to examine consultation uptake, acceptability, barriers, and facilitators of virtual telepresence robotic consultation implementation. Results: Consultants and childcare staff generally perceived the virtual telepresence consultation approach to be useful and easy to use. Consultant perceptions of the acceptability of technology did not change over time. Childcare staff, center, and consultant factors impacted the uptake of the virtual robotic telepresence consultation approach and childcare staff acceptance of the technology. Focus groups revealed that consultants believed that additional hands-on training with childcare staff would have benefited implementation and expressed a desire for a hybrid approach for consultation. Discussion: Perceptions of telepresence robotic consultation acceptability are discussed, including future recommendations for training.

7.
Nat Commun ; 15(1): 4601, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38834558

RESUMO

Precise neurostimulation can revolutionize therapies for neurological disorders. Electrode-based stimulation devices face challenges in achieving precise and consistent targeting due to the immune response and the limited penetration of electrical fields. Ultrasound can aid in energy propagation, but transcranial ultrasound stimulation in the deep brain has limited spatial resolution caused by bone and tissue scattering. Here, we report an implantable piezoelectric ultrasound stimulator (ImPULS) that generates an ultrasonic focal pressure of 100 kPa to modulate the activity of neurons. ImPULS is a fully-encapsulated, flexible piezoelectric micromachined ultrasound transducer that incorporates a biocompatible piezoceramic, potassium sodium niobate [(K,Na)NbO3]. The absence of electrochemically active elements poses a new strategy for achieving long-term stability. We demonstrated that ImPULS can i) excite neurons in a mouse hippocampal slice ex vivo, ii) activate cells in the hippocampus of an anesthetized mouse to induce expression of activity-dependent gene c-Fos, and iii) stimulate dopaminergic neurons in the substantia nigra pars compacta to elicit time-locked modulation of nigrostriatal dopamine release. This work introduces a non-genetic ultrasound platform for spatially-localized neural stimulation and exploration of basic functions in the deep brain.


Assuntos
Estimulação Encefálica Profunda , Hipocampo , Ondas Ultrassônicas , Animais , Estimulação Encefálica Profunda/instrumentação , Estimulação Encefálica Profunda/métodos , Camundongos , Camundongos Endogâmicos C57BL , Neurônios Dopaminérgicos , Masculino , Dopamina/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Substância Negra , Neurônios/fisiologia , Transdutores
8.
Ann Biomed Eng ; 2024 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-38910203

RESUMO

Instrumented mouthguard systems (iMGs) are commonly used to study rigid body head kinematics across a variety of athletic environments. Previous work has found good fidelity for iMGs rigidly fixed to anthropomorphic test device (ATD) headforms when compared to reference systems, but few validation studies have focused on iMG performance in human cadaver heads. Here, we examine the performance of two boil-and-bite style iMGs in helmeted cadaver heads. Three unembalmed human cadaver heads were fitted with two instrumented boil-and-bite mouthguards [Prevent Biometrics and Diversified Technical Systems (DTS)] per manufacturer instructions. Reference sensors were rigidly fixed to each specimen. Specimens were fitted with a Riddell SpeedFlex American football helmet and impacted with a rigid impactor at three velocities and locations. All impact kinematics were compared at the head center of gravity. The Prevent iMG performed comparably to the reference system up to ~ 60 g in linear acceleration, but overall had poor correlation (CCC = 0.39). Prevent iMG angular velocity and BrIC generally well correlated with the reference, while underestimating HIC and overestimating HIC duration. The DTS iMG consistently overestimated the reference across all measures, with linear acceleration error ranging from 10 to 66%, and angular acceleration errors greater than 300%. Neither iMG demonstrated consistent agreement with the reference system. While iMG validation efforts have utilized ATD testing, this study highlights the need for cadaver testing and validation of devices intended for use in-vivo, particularly when considering realistic (non-idealized) sensor-skull coupling, when accounting for interactions with the mandible and when subject-specific anatomy may affect device performance.

9.
Cureus ; 16(4): e57972, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38738083

RESUMO

INTRODUCTION:  The transition from pediatric to adult health care is a vulnerable time period for adolescents and young adults (AYA). Guidance on how to effectively implement transition support for AYA with recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) is lacking. METHODS:  To address this gap, we formed a consortium of pancreatic centers that would work in coordination to test interventions to improve the transition for AYA with RAP and CP. We then performed a baseline assessment of consortium resources and patient transition readiness and developed an educational toolkit for AYA with RAP and CP.  Results: Our consortium consists of three National Pancreatic Centers of Excellence, each with a multidisciplinary team to work with AYA with RAP and CP. While our patients ages 18 to 23 were generally seen at the pediatric centers, the baseline assessment of transition readiness suggests that our patients may have higher transition readiness scores than other populations. The educational toolkit contains both pancreas-specific and general guidance to support AYA with RAP and CP during their transition, including guidance on nutrition, pain management, and finding an adult gastroenterologist.  Conclusions: We have formed a consortium to test interventions to improve the transition to adult health care for AYA with RAP and CP. We have completed a baseline assessment and developed our first intervention: an educational tool kit. Future work planned includes tests of the tool kit and efforts to improve rates of transfer to an adult provider for YA with RAP and CP.

10.
Nat Commun ; 15(1): 3636, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38710699

RESUMO

Polypharmacology drugs-compounds that inhibit multiple proteins-have many applications but are difficult to design. To address this challenge we have developed POLYGON, an approach to polypharmacology based on generative reinforcement learning. POLYGON embeds chemical space and iteratively samples it to generate new molecular structures; these are rewarded by the predicted ability to inhibit each of two protein targets and by drug-likeness and ease-of-synthesis. In binding data for >100,000 compounds, POLYGON correctly recognizes polypharmacology interactions with 82.5% accuracy. We subsequently generate de-novo compounds targeting ten pairs of proteins with documented co-dependency. Docking analysis indicates that top structures bind their two targets with low free energies and similar 3D orientations to canonical single-protein inhibitors. We synthesize 32 compounds targeting MEK1 and mTOR, with most yielding >50% reduction in each protein activity and in cell viability when dosed at 1-10 µM. These results support the potential of generative modeling for polypharmacology.


Assuntos
Simulação de Acoplamento Molecular , Humanos , Serina-Treonina Quinases TOR/metabolismo , Polifarmacologia , MAP Quinase Quinase 1/antagonistas & inibidores , MAP Quinase Quinase 1/metabolismo , MAP Quinase Quinase 1/química , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Ligação Proteica , Descoberta de Drogas/métodos , Desenho de Fármacos , Sobrevivência Celular/efeitos dos fármacos
11.
Ear Nose Throat J ; : 1455613241251980, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38708589

RESUMO

Objectives: Substernal goiters often require surgery, yet their location presents challenges. Most can be removed via transcervical approach, but extent and relationship to mediastinal structures can merit consideration of sternotomy and assistance of colleagues. Despite widespread use in sinus surgery and previous literature reports, microdebrider use to facilitate transcervical removal of substernal goiters has not been broadly adopted. Our objective was to report our experience with use of the soft tissue shaver to facilitate substernal goiter deliver through a cervical incision in a community-based thyroidectomy practice. Methods: We reviewed thyroidectomy cases performed by a general otolaryngologist (D.M.Y.) in a community setting from January 2017 through December 2019. Four patients required microdebrider use for intracapsular debulking of substernal goiter to allow for transcervical removal. We discuss pre- and perioperative considerations, present computed tomography (CT) and operative images, review surgical technique, and report estimated blood loss (EBL), surgical time (T), complications, and length of stay. Results: Average EBL was 237.5 ml (range 100-500 ml). Average T was 137 minutes (range 121-170 minutes). No patients required sternotomy. One patient developed postoperative hematoma requiring evacuation and cautery of a bleeding site. No other complications were encountered, all patients were discharged after overnight observation. Conclusions: The microdebrider can be safely utilized by general otolaryngologists to facilitate transcervical removal of substernal goiters. Adoption of this familiar tool for a different surgical application can reduce the need for sternotomy, assistance of colleagues, or referral to a tertiary care center, with associated decrease in risk, morbidity, surgical time, length of stay, and cost, and improved patient convenience and satisfaction.

12.
Adv Mater ; : e2404553, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38770681

RESUMO

1D charge transport offers great insight into strongly correlated physics, such as Luttinger liquids, electronic instabilities, and superconductivity. Although 1D charge transport is observed in nanomaterials and quantum wires, examples in bulk crystalline solids remain elusive. In this work, it is demonstrated that spin-orbit coupling (SOC) can act as a mechanism to induce quasi-1D charge transport in the Ln3MPn5 (Ln = lanthanide; M = transition metal; Pn = Pnictide) family. From three example compounds, La3ZrSb5, La3ZrBi5, and Sm3ZrBi5, density functional theory calculations with SOC included show a quasi-1D Fermi surface in the bismuthide compounds, but an anisotropic 3D Fermi surface in the antimonide structure. By performing anisotropic charge transport measurements on La3ZrSb5, La3ZrBi5, and Sm3ZrBi5, it is demonstrated that SOC starkly affects their anisotropic resistivity ratios (ARR) at low temperatures, with an ARR of ≈4 in the antimonide compared to ≈9.5 and ≈22 (≈32 after magnetic ordering) in La3ZrBi5 and Sm3ZrBi5, respectively. This report demonstrates the utility of spin-orbit coupling to induce quasi-low-dimensional Fermi surfaces in anisotropic crystal structures, and provides a template for examining other systems.

13.
ACS Catal ; 14(8): 5978-5986, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38660614

RESUMO

Reaction products in heterogeneous catalysis can be detected either on the catalyst surface or in the gas phase after desorption. However, if atoms are dissolved in the catalyst bulk, then reaction channels can become hidden. This is the case if the dissolution rate of the deposits is faster than their formation rate. This might lead to the underestimation or even overlooking of reaction channels such as, e.g., carbon deposition during hydrocarbon oxidation reactions, which is problematic as carbon can have a significant influence on the catalytic activity. Here, we demonstrate how such hidden deposition channels can be uncovered by carefully measuring the product formation rates in the local gas phase just above the catalyst surface with time-resolved ambient pressure X-ray photoelectron spectroscopy. As a case study, we investigate methane oxidation on a polycrystalline Pd catalyst in an oxygen-lean environment at a few millibar pressure. By ramping the temperature between 350 and 525 °C, we follow the time evolution of the different reaction pathways. Only in the oxygen mass-transfer limit do we observe CO production, while our data suggests that carbon deposition also happens outside this limit.

14.
J Clin Med ; 13(8)2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38673572

RESUMO

Background: On 18 June 2022, Moderna and Pfizer-BioNTech COVID-19 vaccines were authorized under an Emergency Use Authorization by the United States Food and Drug Administration to prevent severe coronavirus disease in children six months to four years of age. Despite approval of the COVID-19 vaccinations for young children, there remain ongoing challenges reaching widespread coverage due to parental decision-making. Parental decision-making plays a pivotal, yet understudied, role governing vaccine adoption among this priority demographic. Methods: This cross-sectional analysis examined COVID-19 vaccine intentions for 320 predominately Hispanic parents of two to five-year-olds attending Miami-Dade County childcare programs in Florida USA, several months following the June 2022 emergency authorization. Parent's self-reported survey data encompassed vaccine choices and rationales, social determinants of health, and parent immigrant status. Data analyses illustrate the associations between parent decision-making and these variables. Regression modeling and tests of independence identified predicting factors for parental vaccine decision-making. Results: Only 25% of parents intended to vaccinate their young child, while 34% resisted and 41% felt unsure, despite 70% personal vaccination rates. Household income under $25,000, identifying as a migrant, or testing COVID-19-positive significantly predicted unsure decision-making. The majority of hesitant groups expressed concerns around side effects (20%), safety (2.9%), and sufficiency of vaccine knowledge (3.3%). Conclusions: In this sample, the predominance of parents were unsure and resistant rather than accepting of having their child vaccinated despite emergency approval of the pediatric vaccine. Associations and predictive factors are examined.

15.
Curr Opin Cardiol ; 39(4): 315-322, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38661130

RESUMO

PURPOSE OF REVIEW: While pediatric myocarditis incidence has increased since the coronavirus disease 2019 (COVID-19) pandemic, there remain questions regarding diagnosis, risk stratification, and optimal therapy. This review highlights recent publications and continued unanswered questions related to myocarditis in children. RECENT FINDINGS: Emergence from the COVID-19 era has allowed more accurate description of the incidence and prognosis of myocarditis adjacent to COVID-19 infection and vaccine administration as well that of multi-system inflammatory disease in children (MIS-C). As cardiac magnetic resonance technology has shown increased availability and evidence in pediatric myocarditis, it is important to understand conclusions from adult imaging studies and define the use of this imaging biomarker in children. Precision medicine has begun to allow real-time molecular evaluations to help diagnose and risk-stratify cardiovascular diseases, with emerging evidence of these modalities in myocarditis. SUMMARY: Recent information regarding COVID-19 associated myocarditis, cardiac magnetic resonance, and molecular biomarkers may help clinicians caring for children with myocarditis and identify needs for future investigations.


Assuntos
COVID-19 , Miocardite , Humanos , Miocardite/diagnóstico , COVID-19/epidemiologia , COVID-19/complicações , COVID-19/diagnóstico , Criança , SARS-CoV-2 , Biomarcadores , Imageamento por Ressonância Magnética/métodos , Prognóstico , Síndrome de Resposta Inflamatória Sistêmica
16.
Res Sq ; 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38585755

RESUMO

During maturation oocytes undergo a recently discovered mitochondrial proteome remodeling event in flies1, frogs1, and humans2. This oocyte mitochondrial remodeling, which includes substantial changes in electron transport chain (ETC) subunit abundance1,2, is regulated by maternal insulin signaling1. Why oocytes undergo mitochondrial remodeling is unknown, with some speculating that it might be an evolutionarily conserved mechanism to protect oocytes from genotoxic damage by reactive oxygen species (ROS)2. In Caenorhabditis elegans, we previously found that maternal exposure to osmotic stress drives a 50-fold increase in offspring survival in response to future osmotic stress3. Like mitochondrial remodeling, we found that this intergenerational adaptation is also regulated by insulin signaling to oocytes3. Here, we used proteomics and genetic manipulations to show that insulin signaling to oocytes regulates offspring's ability to adapt to future stress via a mechanism that depends on ETC composition in maternal oocytes. Specifically, we found that maternally expressed mutant alleles of nduf-7 (complex I subunit) or isp-1 (complex III subunit) altered offspring's response to osmotic stress at hatching independently of offspring genotype. Furthermore, we found that expressing wild-type isp-1 in germ cells (oocytes) was sufficient to restore offspring's normal response to osmotic stress. Chemical mutagenesis screens revealed that maternal ETC composition regulates offspring's response to stress by altering AMP kinase function in offspring which in turn regulates both ATP and glycerol metabolism in response to continued osmotic stress. To our knowledge, these data are the first to show that proper oocyte ETC composition is required to link a mother's environment to adaptive changes in offspring metabolism. The data also raise the possibility that the reason diverse animals exhibit insulin regulated remodeling of oocyte mitochondria is to tailor offspring metabolism to best match the environment of their mother.

17.
Clin Transl Med ; 14(4): e1650, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38649772

RESUMO

BACKGROUND: Although many molecules have been investigated as biomarkers for spinal cord injury (SCI) or ischemic stroke, none of them are specifically induced in central nervous system (CNS) neurons following injuries with low baseline expression. However, neuronal injury constitutes a major pathology associated with SCI or stroke and strongly correlates with neurological outcomes. Biomarkers characterized by low baseline expression and specific induction in neurons post-injury are likely to better correlate with injury severity and recovery, demonstrating higher sensitivity and specificity for CNS injuries compared to non-neuronal markers or pan-neuronal markers with constitutive expressions. METHODS: In animal studies, young adult wildtype and global Atf3 knockout mice underwent unilateral cervical 5 (C5) SCI or permanent distal middle cerebral artery occlusion (pMCAO). Gene expression was assessed using RNA-sequencing and qRT-PCR, while protein expression was detected through immunostaining. Serum ATF3 levels in animal models and clinical human samples were measured using commercially available enzyme-linked immune-sorbent assay (ELISA) kits. RESULTS: Activating transcription factor 3 (ATF3), a molecular marker for injured dorsal root ganglion sensory neurons in the peripheral nervous system, was not expressed in spinal cord or cortex of naïve mice but was induced specifically in neurons of the spinal cord or cortex within 1 day after SCI or ischemic stroke, respectively. Additionally, ATF3 protein levels in mouse blood significantly increased 1 day after SCI or ischemic stroke. Importantly, ATF3 protein levels in human serum were elevated in clinical patients within 24 hours after SCI or ischemic stroke. Moreover, Atf3 knockout mice, compared to the wildtype mice, exhibited worse neurological outcomes and larger damage regions after SCI or ischemic stroke, indicating that ATF3 has a neuroprotective function. CONCLUSIONS: ATF3 is an easily measurable, neuron-specific biomarker for clinical SCI and ischemic stroke, with neuroprotective properties. HIGHLIGHTS: ATF3 was induced specifically in neurons of the spinal cord or cortex within 1 day after SCI or ischemic stroke, respectively. Serum ATF3 protein levels are elevated in clinical patients within 24 hours after SCI or ischemic stroke. ATF3 exhibits neuroprotective properties, as evidenced by the worse neurological outcomes and larger damage regions observed in Atf3 knockout mice compared to wildtype mice following SCI or ischemic stroke.


Assuntos
Fator 3 Ativador da Transcrição , Biomarcadores , AVC Isquêmico , Neurônios , Traumatismos da Medula Espinal , Animais , Feminino , Humanos , Masculino , Camundongos , Fator 3 Ativador da Transcrição/metabolismo , Fator 3 Ativador da Transcrição/genética , Biomarcadores/metabolismo , Biomarcadores/sangue , Modelos Animais de Doenças , AVC Isquêmico/metabolismo , AVC Isquêmico/genética , AVC Isquêmico/sangue , Camundongos Knockout , Neurônios/metabolismo , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/complicações
18.
Radiol Artif Intell ; 6(3): e230227, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38477659

RESUMO

The Radiological Society of North America (RSNA) has held artificial intelligence competitions to tackle real-world medical imaging problems at least annually since 2017. This article examines the challenges and processes involved in organizing these competitions, with a specific emphasis on the creation and curation of high-quality datasets. The collection of diverse and representative medical imaging data involves dealing with issues of patient privacy and data security. Furthermore, ensuring quality and consistency in data, which includes expert labeling and accounting for various patient and imaging characteristics, necessitates substantial planning and resources. Overcoming these obstacles requires meticulous project management and adherence to strict timelines. The article also highlights the potential of crowdsourced annotation to progress medical imaging research. Through the RSNA competitions, an effective global engagement has been realized, resulting in innovative solutions to complex medical imaging problems, thus potentially transforming health care by enhancing diagnostic accuracy and patient outcomes. Keywords: Use of AI in Education, Artificial Intelligence © RSNA, 2024.


Assuntos
Inteligência Artificial , Radiologia , Humanos , Diagnóstico por Imagem/métodos , Sociedades Médicas , América do Norte
19.
Opt Express ; 32(4): 6168-6177, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38439326

RESUMO

In situ tunable photonic filters and memories are important for emerging quantum and classical optics technologies. However, most photonic devices have fixed resonances and bandwidths determined at the time of fabrication. Here we present an in situ tunable optical resonator on thin-film lithium niobate. By leveraging the linear electro-optic effect, we demonstrate widely tunable control over resonator frequency and bandwidth on two different devices. We observe up to ∼50 × tuning in the bandwidth over ∼50 V with linear frequency control of ∼230 MHz/V. We also develop a closed-form model predicting the tuning behavior of the device. This paves the way for rapid phase and amplitude control over light transmitted through our device.

20.
Mil Med ; 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38518206

RESUMO

INTRODUCTION: There have been nearly 1,600 new diagnoses of Human Immunodeficiency Virus (HIV) across the US Armed Forces between 2017 and 2022. While treatment has improved overall survival, self-perception of acquiring HIV may not align with actual risk of acquiring HIV, thus slowing diagnosis and treatment. We aim to evaluate self-perceived risk (SPR) versus calculated risk (CR) of HIV infection in US Air Force (USAF) members with incident HIV diagnosis. METHODS: All USAF members with new HIV diagnosis evaluated at a specialty care military medical center between January 2015 and March 2020 with case report forms were included (n = 142). SPR was compared to CR using the Denver HIV Risk Score (DHRS). The study was approved by the Army Public Health Center's Public Health Review Board (#14-311) and the Walter Reed Army Institute of Research Human Subjects Protection Branch (#1861E). RESULTS: Patients were predominantly male (98%), with a median age of 26 (IQR 22-30) years, and the majority (85%) reported same-sex partners. Most patients reported a low SPR (n = 78; 55%). A higher proportion of low SPR patients were married or partnered than high SPR patients (29% versus 14%; P = 0.04). Both groups had median DHRS scores in the highest risk category with similar results by reason for HIV screening. CONCLUSION: The majority of USAF members with incident HIV infection reported a low SPR despite risk factors and CRs identical to high SPR patients. In order to inform HIV prevention strategies in the military, further efforts are needed to educate the military population and providers about HIV risk perception.

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