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BACKGROUND: Malnutrition is associated with increased morbidity, mortality, and healthcare costs. Early detection is important for timely intervention. This paper assesses the ability of a machine learning screening tool (MUST-Plus) implemented in registered dietitian (RD) workflow to identify malnourished patients early in the hospital stay and to improve the diagnosis and documentation rate of malnutrition. METHODS: This retrospective cohort study was conducted in a large, urban health system in New York City comprising six hospitals serving a diverse patient population. The study included all patients aged ≥ 18 years, who were not admitted for COVID-19 and had a length of stay of ≤ 30 days. RESULTS: Of the 7736 hospitalisations that met the inclusion criteria, 1947 (25.2%) were identified as being malnourished by MUST-Plus-assisted RD evaluations. The lag between admission and diagnosis improved with MUST-Plus implementation. The usability of the tool output by RDs exceeded 90%, showing good acceptance by users. When compared pre-/post-implementation, the rate of both diagnoses and documentation of malnutrition showed improvement. CONCLUSION: MUST-Plus, a machine learning-based screening tool, shows great promise as a malnutrition screening tool for hospitalised patients when used in conjunction with adequate RD staffing and training about the tool. It performed well across multiple measures and settings. Other health systems can use their electronic health record data to develop, test and implement similar machine learning-based processes to improve malnutrition screening and facilitate timely intervention.
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Aprendizaje Automático , Desnutrición , Tamizaje Masivo , Evaluación Nutricional , Humanos , Estudios Retrospectivos , Desnutrición/diagnóstico , Persona de Mediana Edad , Masculino , Femenino , Ciudad de Nueva York , Anciano , Medición de Riesgo/métodos , Tamizaje Masivo/métodos , Adulto , Hospitalización , Anciano de 80 o más AñosRESUMEN
The human body represents a collection of interacting systems that range in scale from nanometers to meters. Investigations from a systems perspective focus on how the parts work together to enact changes across spatial scales, and further our understanding of how systems function and fail. Here, we highlight systems approaches presented at the 2022 Summer Biomechanics, Bio-engineering, and Biotransport Conference in the areas of solid mechanics; fluid mechanics; tissue and cellular engineering; biotransport; and design, dynamics, and rehabilitation; and biomechanics education. Systems approaches are yielding new insights into human biology by leveraging state-of-the-art tools, which could ultimately lead to more informed design of therapies and medical devices for preventing and treating disease as well as rehabilitating patients using strategies that are uniquely optimized for each patient. Educational approaches can also be designed to foster a foundation of systems-level thinking.
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Bioingeniería , Análisis de Sistemas , Humanos , Fenómenos Biomecánicos , BiofisicaRESUMEN
Generative artificial intelligence (AI) tools such as ChatGPT, Bard, and Claude have recently become a concern in the delivery of engineering education. For courses focused on computer coding, such tools are capable for creating working computer code across a range of computer languages and computing platforms. In a course for mechanical engineers focused on C++ coding for the Arduino microcontroller and coding engineering problems in Matlab, a new approach to assessment of programing homework assignments was developed. This assessment moved the focus of assigned points from the correctness of the code to the effort and understanding of the code demonstrated by the student during in-person grading. Students who participated fully in in-person grading did significantly better on a midterm exam. Relative to a previous semester, where grading was focused on correct code, students had a slightly higher average midterm exam score. This approach appears to be effective in supporting computational learning in the face of evolving tools that could be used to circumvent learning. Future work should examine how to also encourage responsible use of generative AI in computational learning.
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Inteligencia Artificial , Programas Informáticos , Humanos , Aprendizaje , Estudiantes , IngenieríaRESUMEN
Background: High nerve density in tumors and metastasis via nerves (perineural invasion-PNI) have been reported extensively in solid tumors throughout the body including pancreatic, head and neck, gastric, prostate, breast, and colorectal cancers. Ablation of tumor nerves results in improved disease outcomes, suggesting that blocking nerve-tumor communication could be a novel treatment strategy. However, the molecular mechanisms underlying this remain poorly understood. Thus, the aim here was to identify molecular pathways underlying nerve-tumor crosstalk and to determine common molecular features between PNI-associated cancers. Results: Analysis of head and neck (HNSCC), pancreatic, and gastric (STAD) cancer Gene Expression Omnibus datasets was used to identify differentially expressed genes (DEGs). This revealed extracellular matrix components as highly dysregulated. To enrich for pathways associated with PNI, genes previously correlated with PNI in STAD and in 2 HNSCC studies where tumor samples were segregated by PNI status were analyzed. Neurodevelopmental genes were found to be enriched with PNI. In datasets where tumor samples were not segregated by PNI, neurodevelopmental pathways accounted for 12%-16% of the DEGs. Further dysregulation of axon guidance genes was common to all cancers analyzed. By examining paralog genes, a clear pattern emerged where at least one family member from several axon guidance pathways was affected in all cancers examined. Overall 17 different axon guidance gene families were disrupted, including the ephrin-Eph, semaphorin-neuropilin/plexin, and slit-robo pathways. These findings were validated using The Cancer Genome Atlas and cross-referenced to other cancers with a high incidence of PNI including colon, cholangiocarcinoma, prostate, and breast cancers. Survival analysis revealed that the expression levels of neurodevelopmental gene families impacted disease survival. Conclusion: These data highlight the importance of the tumor as a source of signals for neural tropism and neural plasticity as a common feature of cancer. The analysis supports the hypothesis that dysregulation of neurodevelopmental programs is a common feature associated with PNI. Furthermore, the data suggested that different cancers may have evolved to employ alternative genetic strategies to disrupt the same pathways. Overall, these findings provide potential druggable targets for novel therapies of cancer management and provide multi-cancer molecular biomarkers.
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BACKGROUND: Machine learning (ML)-based clinical decision support systems (CDSS) are popular in clinical practice settings but are often criticized for being limited in usability, interpretability, and effectiveness. Evaluating the implementation of ML-based CDSS is critical to ensure CDSS is acceptable and useful to clinicians and helps them deliver high-quality health care. Malnutrition is a common and underdiagnosed condition among hospital patients, which can have serious adverse impacts. Early identification and treatment of malnutrition are important. OBJECTIVE: This study aims to evaluate the implementation of an ML tool, Malnutrition Universal Screening Tool (MUST)-Plus, that predicts hospital patients at high risk for malnutrition and identify best implementation practices applicable to this and other ML-based CDSS. METHODS: We conducted a qualitative postimplementation evaluation using in-depth interviews with registered dietitians (RDs) who use MUST-Plus output in their everyday work. After coding the data, we mapped emergent themes onto select domains of the nonadoption, abandonment, scale-up, spread, and sustainability (NASSS) framework. RESULTS: We interviewed 17 of the 24 RDs approached (71%), representing 37% of those who use MUST-Plus output. Several themes emerged: (1) enhancements to the tool were made to improve accuracy and usability; (2) MUST-Plus helped identify patients that would not otherwise be seen; perceived usefulness was highest in the original site; (3) perceived accuracy varied by respondent and site; (4) RDs valued autonomy in prioritizing patients; (5) depth of tool understanding varied by hospital and level; (6) MUST-Plus was integrated into workflows and electronic health records; and (7) RDs expressed a desire to eventually have 1 automated screener. CONCLUSIONS: Our findings suggest that continuous involvement of stakeholders at new sites given staff turnover is vital to ensure buy-in. Qualitative research can help identify the potential bias of ML tools and should be widely used to ensure health equity. Ongoing collaboration among CDSS developers, data scientists, and clinical providers may help refine CDSS for optimal use and improve the acceptability of CDSS in the clinical context.
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BACKGROUND: "Laparoscopist's thumb," or thenar paresthesia, can result from prolonged or excessive grip force during laparoscopy, as can more general syndromes, such as carpal tunnel syndrome. This is particularly relevant in gynecology, where laparoscopic procedures are standard. Although this method of injury is well known, there is a paucity of data to guide surgeons in selecting more efficient, ergonomic instruments. OBJECTIVE: This study compared the ratio of applied tissue force and required surgeon input in a sample of common ratcheting laparoscopic graspers in a small-handed surgeon, to provide potential metrics applicable to surgical ergonomics and surgeon instrument choice. STUDY DESIGN: Laparoscopic graspers with varied ratcheting mechanisms and tip shapes were evaluated. Brands included Snowden-Pencer, Covidien, Aesculap, and Ethicon. A Kocher was used as an open instrument comparison. Flexiforce A401 thin-film force sensors were used to measure applied forces. Data were collected and calibrated using an Arduino Uno microcontroller board with Arduino and MATLAB software. Single-handed, complete closure of each device's ratcheting mechanism was performed 3 times. The maximum required input force in Newtons was recorded and averaged. The average output force was measured with a bare sensor and the same sensor between 2 different thicknesses of LifeLike BioTissue. RESULTS: The most ergonomic ratcheting grasper for a small-handed surgeon was identified by the output ratio: the highest output force relative to the required surgeon input (the most force for the least amount of effort). The Kocher required an average input force of 33.66 N, with its highest output ratio of 3.46 (112 N output). The Covidien Endo Grasp was the most ergonomic, with an output ratio of 0.96 on the bare force sensor (31.4 N output). The Snowden-Pencer Wavy grasper was the least ergonomic, with an output ratio of 0.06 when applied to the bare force sensor (5.9 N output). All graspers except for the Endo Grasp had improving output ratios as tissue thickness and subsequent grasper contact area increased. Input force above that provided by the ratcheting mechanisms did not increase output force in a clinically relevant amount for any of the instruments evaluated. CONCLUSION: Laparoscopic graspers vary widely in their ability to provide reliable tissue force without requiring excessive input by the surgeon, and a point of diminishing returns often exists with increased surgeon input over designed ratcheting mechanisms. Output force and output ratio are potential quantitative measures of the efficiency of laparoscopic instruments. Providing users with this type of data could assist in optimizing instrument ergonomics.
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Laparoscopía , Quirófanos , Humanos , Diseño de Equipo , Laparoscopía/métodos , Ergonomía , Programas InformáticosRESUMEN
Per- and polyfluoroalkyl substances (PFAS) are a group of manufactured chemicals that are resistant to degradation and thus persistent in the environment. The presence, uptake, and accumulation of PFAS is dependent upon the physiochemical properties of the PFAS and matrix, as well as the environmental conditions since the time of release. The objective of this study was to measure the extent of PFAS contamination in surface water and sediment from nine vulnerable aquatic systems throughout Florida. PFAS were detected at all sampling locations with sediment exhibiting greater PFAS concentrations when compared to surface water. At most locations, elevated concentrations of PFAS were identified around areas of increased human activity, such as airports, military bases, and wastewater effluents. The results from the present study highlight the ubiquitous presence of PFAS in vital Florida waterways and filled an important gap in understanding the distribution of PFAS in dynamic, yet vulnerable, aquatic environments.
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Fluorocarburos , Contaminantes Químicos del Agua , Humanos , Florida , Fluorocarburos/análisis , Contaminantes Químicos del Agua/análisis , Agua , Aguas ResidualesRESUMEN
Per- and polyfluoroalkyl substances (PFAS) are a class of manufactured chemicals that have been extensively utilized worldwide. We hypothesize that the presence, uptake, and accumulation of PFAS in aquatic vegetation (AV) is dependent upon several factors, such as the physiochemical properties of PFAS and proximity to potential sources. In this study, AV was collected from eight locations in Florida to investigate the PFAS presence, accumulation, and spatiotemporal distribution. PFAS were detected in AV at all sampling locations, with a range from 0.18 to 55 ng/g sum (∑)PFAS. Individual PFAS and their concentrations varied by sampling location, time, and AV species. A total of 12 PFAS were identified, with the greatest concentrations measured in macroalgae. The average bioconcentration factor (BCF) among all samples was 1225, indicating high PFAS accumulation in AV from surface water. The highest concentrations, across all AV types, were recorded in the Indian River Lagoon (IRL), a location with a history of elevated PFAS burdens. The present study represents the first investigation of PFAS in naturally existing estuarine AV, filling an important gap on PFAS partitioning within the environment, as well as providing insights into exposure pathways for aquatic herbivores. Examining the presence, fate, and transport of these persistent chemicals in Florida's waterways is critical for understanding their effect on environmental, wildlife, and human health.
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Fluorocarburos , Contaminantes Químicos del Agua , Humanos , Fluorocarburos/análisis , Contaminantes Químicos del Agua/análisis , Agua , Ríos , FloridaRESUMEN
Chronic nipple pain can be challenging to a multidisciplinary care team. We report a case of a patient who experienced years of ineffective treatment before presenting to the pain management clinic. Upon presentation, the patient was trialed on neuropathic agents, topical pain medications, acupuncture, calcium channel blockers, intercostal nerve blocks, pulsed radiofrequency, and a spinal cord stimulator trial. We report the treatment options and what was ultimately effective to improve pain scores and functionality. Presenting this treatment approach will educate the reader about options for multimodal therapy to avoid delayed treatment for other patients in the future.
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Analgesia , Dolor Crónico , Dolor Intratable , Humanos , Manejo del Dolor , Pezones , Dolor Crónico/tratamiento farmacológico , Dolor Intratable/terapiaRESUMEN
Women display a wide range of subjective (self-reported), physiological (genital response), and emotional responses to sexual stimuli. Sexual responses are often assessed using quantitative methodologies; qualitative data can corroborate quantitative data and reveal novel information and avenues for discovery for understanding variations in patterns of sexual response. The current study examined women's (n = 148) responses to various sexual and non-sexual stimuli through open-ended, free response thought journals immediately after watching various neutral (nature themed) and sexually explicit video clips (e.g., solitary masturbation, intercourse). A qualitative content analysis of 842 responses was conducted by five independent coders to determine participants' thoughts immediately after viewing stimuli. Prominent themes included: (1) stimulus appraisals; (2) emotional expressions; and (3) self-reflections and disclosures, which further included participants' sexual-self-disclosures; (4) various degrees of sexual arousal (or lack thereof); and (5) sexual and non-sexual desires. Additional analyses include frequencies and comparisons of specific themes between stimulus types. Findings contribute to understanding cognitive and emotional components of sexual response.
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Nivel de Alerta , Conducta Sexual , Humanos , Femenino , Nivel de Alerta/fisiología , Conducta Sexual/psicología , Excitación Sexual , Emociones , AutoinformeRESUMEN
Tropical cyclones drive coastal ecosystem dynamics, and their frequency, intensity, and spatial distribution are predicted to shift with climate change. Patterns of resistance and resilience were synthesized for 4138 ecosystem time series from n = 26 storms occurring between 1985 and 2018 in the Northern Hemisphere to predict how coastal ecosystems will respond to future disturbance regimes. Data were grouped by ecosystems (fresh water, salt water, terrestrial, and wetland) and response categories (biogeochemistry, hydrography, mobile biota, sedentary fauna, and vascular plants). We observed a repeated pattern of trade-offs between resistance and resilience across analyses. These patterns are likely the outcomes of evolutionary adaptation, they conform to disturbance theories, and they indicate that consistent rules may govern ecosystem susceptibility to tropical cyclones.
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BACKGROUND: Alternative splicing provides a broad strategy to amplify the genome. Yet how alternative splicing influences neurodevelopment or indeed which variants are translated at developmental choice points remains poorly explored. Here we focused on a gene important for neurodevelopment, the Lim homeodomain transcription factor, Lhx9. Lhx9 has two noncanonical splice variants, Lhx9a and Lhx9b which compared with the canonical variant Lhx9c have a truncated homeodomain and an alternative C-terminal sequence, suggesting that, if translated, these variants could differently impact on cellular function. RESULTS: We created a unique antibody tool designed to selectively detect noncanonical Lhx9 variants (Lhx9ab) and used this to examine the protein expression dynamics in embryos. Lhx9ab variants were translated and dynamically expressed similarly between mouse and chicken at key developmental choice points in the spinal cord, limbs and urogenital ridge. Within the spinal cord, enrichment of Lhx9c vs Lhx9ab expression was observed during key migration and axonal projection choice points. CONCLUSIONS: These data support the notion that the expression dynamics between canonical and noncanonical Lhx9 variants could play an important role in spinal neuron maturation. More broadly, determining the temporal dynamics of alternative protein variants is a key entry point to understand how splicing influences developmental processes.
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Proteínas con Homeodominio LIM , Factores de Transcripción , Animales , Pollos , Regulación del Desarrollo de la Expresión Génica , Proteínas con Homeodominio LIM/genética , Proteínas con Homeodominio LIM/metabolismo , Ratones , Mutación , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Vertebrados/genéticaRESUMEN
BACKGROUND: The past two decades have witnessed a surge in the use of cervical spine joint procedures including joint injections, nerve blocks and radiofrequency ablation to treat chronic neck pain, yet many aspects of the procedures remain controversial. METHODS: In August 2020, the American Society of Regional Anesthesia and Pain Medicine and the American Academy of Pain Medicine approved and charged the Cervical Joint Working Group to develop neck pain guidelines. Eighteen stakeholder societies were identified, and formal request-for-participation and member nomination letters were sent to those organizations. Participating entities selected panel members and an ad hoc steering committee selected preliminary questions, which were then revised by the full committee. Each question was assigned to a module composed of 4-5 members, who worked with the Subcommittee Lead and the Committee Chairs on preliminary versions, which were sent to the full committee after revisions. We used a modified Delphi method whereby the questions were sent to the committee en bloc and comments were returned in a non-blinded fashion to the Chairs, who incorporated the comments and sent out revised versions until consensus was reached. Before commencing, it was agreed that a recommendation would be noted with >50% agreement among committee members, but a consensus recommendation would require ≥75% agreement. RESULTS: Twenty questions were selected, with 100% consensus achieved in committee on 17 topics. Among participating organizations, 14 of 15 that voted approved or supported the guidelines en bloc, with 14 questions being approved with no dissensions or abstentions. Specific questions addressed included the value of clinical presentation and imaging in selecting patients for procedures, whether conservative treatment should be used before injections, whether imaging is necessary for blocks, diagnostic and prognostic value of medial branch blocks and intra-articular joint injections, the effects of sedation and injectate volume on validity, whether facet blocks have therapeutic value, what the ideal cut-off value is for designating a block as positive, how many blocks should be performed before radiofrequency ablation, the orientation of electrodes, whether larger lesions translate into higher success rates, whether stimulation should be used before radiofrequency ablation, how best to mitigate complication risks, if different standards should be applied to clinical practice and trials, and the indications for repeating radiofrequency ablation. CONCLUSIONS: Cervical medial branch radiofrequency ablation may provide benefit to well-selected individuals, with medial branch blocks being more predictive than intra-articular injections. More stringent selection criteria are likely to improve denervation outcomes, but at the expense of false-negatives (ie, lower overall success rate). Clinical trials should be tailored based on objectives, and selection criteria for some may be more stringent than what is ideal in clinical practice.
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Dolor de Cuello , Articulación Cigapofisaria , Artralgia , Vértebras Cervicales/diagnóstico por imagen , Vértebras Cervicales/cirugía , Humanos , Inyecciones Intraarticulares , Articulación Cigapofisaria/diagnóstico por imagen , Articulación Cigapofisaria/cirugíaRESUMEN
Acute type I aortic dissection is a life-threatening emergency with potentially devastating complications, including end-organ malperfusion. Early detection of malperfusion with intraoperative imaging allows for efficient transition to appropriate interventions. We present a case of a 65-year-old male with acute type I aortic dissection who underwent emergent surgical repair of the aortic root and hemiarch followed by acutely worsening distal malperfusion. The use of intraoperative transesophageal echocardiography played a critical role in visualizing diversion of flow to the false lumen, prompting urgent vascular surgery consultation and life-saving thoracic endovascular aortic repair.
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Aneurisma de la Aorta Torácica , Disección Aórtica , Enfermedad Aguda , Anciano , Disección Aórtica/diagnóstico , Disección Aórtica/diagnóstico por imagen , Aneurisma de la Aorta Torácica/diagnóstico , Aneurisma de la Aorta Torácica/diagnóstico por imagen , Ecocardiografía Transesofágica , Humanos , Masculino , Resultado del Tratamiento , Procedimientos Quirúrgicos VascularesRESUMEN
BACKGROUND: The past two decades have witnessed a surge in the use of cervical spine joint procedures including joint injections, nerve blocks and radiofrequency ablation to treat chronic neck pain, yet many aspects of the procedures remain controversial. METHODS: In August 2020, the American Society of Regional Anesthesia and Pain Medicine and the American Academy of Pain Medicine approved and charged the Cervical Joint Working Group to develop neck pain guidelines. Eighteen stakeholder societies were identified, and formal request-for-participation and member nomination letters were sent to those organizations. Participating entities selected panel members and an ad hoc steering committee selected preliminary questions, which were then revised by the full committee. Each question was assigned to a module composed of 4-5 members, who worked with the Subcommittee Lead and the Committee Chairs on preliminary versions, which were sent to the full committee after revisions. We used a modified Delphi method whereby the questions were sent to the committee en bloc and comments were returned in a non-blinded fashion to the Chairs, who incorporated the comments and sent out revised versions until consensus was reached. Before commencing, it was agreed that a recommendation would be noted with >50% agreement among committee members, but a consensus recommendation would require ≥75% agreement. RESULTS: Twenty questions were selected, with 100% consensus achieved in committee on 17 topics. Among participating organizations, 14 of 15 that voted approved or supported the guidelines en bloc, with 14 questions being approved with no dissensions or abstentions. Specific questions addressed included the value of clinical presentation and imaging in selecting patients for procedures, whether conservative treatment should be used before injections, whether imaging is necessary for blocks, diagnostic and prognostic value of medial branch blocks and intra-articular joint injections, the effects of sedation and injectate volume on validity, whether facet blocks have therapeutic value, what the ideal cut-off value is for designating a block as positive, how many blocks should be performed before radiofrequency ablation, the orientation of electrodes, whether larger lesions translate into higher success rates, whether stimulation should be used before radiofrequency ablation, how best to mitigate complication risks, if different standards should be applied to clinical practice and trials, and the indications for repeating radiofrequency ablation. CONCLUSIONS: Cervical medial branch radiofrequency ablation may provide benefit to well-selected individuals, with medial branch blocks being more predictive than intra-articular injections. More stringent selection criteria are likely to improve denervation outcomes, but at the expense of false-negatives (ie, lower overall success rate). Clinical trials should be tailored based on objectives, and selection criteria for some may be more stringent than what is ideal in clinical practice.
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Dolor Crónico , Articulación Cigapofisaria , Artralgia , Vértebras Cervicales , Dolor Crónico/terapia , Humanos , Inyecciones IntraarticularesRESUMEN
Nerve agents (NAs) induce a severe cholinergic crisis that can lead to status epilepticus (SE). Current guidelines for treatment of NA-induced SE only include prehospital benzodiazepines, which may not fully resolve this life-threatening condition. This study examined the efficacy of general clinical protocols for treatment of SE in the specific context of NA poisoning in adult male rats. Treatment with both intramuscular and intravenous benzodiazepines was entirely insufficient to control SE. Second line intervention with valproate (VPA) initially terminated SE in 35% of rats, but seizures always returned. Phenobarbital (PHB) was more effective, with SE terminating in 56% of rats and 19% of rats remaining seizure-free for at least 24 h. The majority of rats demonstrated refractory SE (RSE) and required treatment with a continuous third-line anesthetic. Both ketamine (KET) and propofol (PRO) led to high levels of mortality, and nearly all rats on these therapies had breakthrough seizure activity, demonstrating super-refractory SE (SRSE). For the small subset of rats in which SE was fully resolved, significant improvements over controls were observed in recovery metrics, behavioral assays, and brain pathology. Together these data suggest that NA-induced SE is particularly severe, but aggressive treatment in the intensive care setting can lead to positive functional outcomes for casualties.
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Mediastinal masses can be challenging to the surgical team and anesthetic considerations vary according to the location, pathology, surgical approach, and patient comorbidities. We report the case of a 21 cm symptomatic intrathoracic teratoma in a postpartum patient with a history of poliomyelitis. Significant challenges were presented for anesthetic induction, potential extracorporeal membrane oxygenation, and the use of neuraxial pain techniques and neuromuscular blockade. This case report demonstrates techniques to safely manage a patient with a large symptomatic mediastinal mass and potential neuromuscular disease.
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Sensory information relayed to the brain is dependent on complex, yet precise spatial organization of neurons. This anatomical complexity is generated during development from a surprisingly small number of neural stem cell domains. This raises the question of how neurons derived from a common precursor domain respond uniquely to their environment to elaborate correct spatial organization and connectivity. We addressed this question by exploiting genetically labeled mouse embryonic dorsal interneuron 1 (dI1) neurons that are derived from a common precursor domain and give rise to spinal projection neurons with distinct organization of cell bodies with axons projecting either commissurally (dI1c) or ipsilaterally (dI1i). In this study, we examined how the guidance receptor, Robo2, which is a canonical Robo receptor, influenced dI1 guidance during embryonic development. Robo2 was enriched in embryonic dI1i neurons, and loss of Robo2 resulted in misguidance of dI1i axons, whereas dI1c axons remained unperturbed within the mantle zone and ventral commissure. Further, Robo2 profoundly influenced dI1 cell body migration, a feature that was partly dependent on Slit2 signaling. These data suggest that dI1 neurons are dependent on Robo2 for their organization. This work integrated with the field support of a model whereby canonical Robo2 vs. non-canonical Robo3 receptor expression facilitates projection neurons derived from a common precursor domain to read out the tissue environment uniquely giving rise to correct anatomical organization.
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DNA is a powerful tool for programming the three-dimensional organization of nanomaterials, where the specificity of nucleotide base-pairing can enable precise, complex, and dynamically addressable structures like colloidal crystals. However, because these DNA-programmed materials are often only stable in solution, their organization can be easily disrupted by changes to its local environment. Methods to stabilize these materials have been developed, but often come at the expense of altering or permanently fixing the materials' structures, removing many of the benefits of using DNA interactions to program assembly. Thus, these methods limit the application of DNA-assembled structures as dynamic and programmable material components. Here, a method is presented to resolve these drawbacks for DNA-grafted nanoparticles, also known as Programmable Atom Equivalents (PAEs), by embedding assembled lattices within a hydrogel matrix. The preformed lattices are exposed to polymerizable residues that electrostatically bind to the charged backbone of the DNA ligands and form a continuous, permeating gel network that stabilizes the colloidal crystals upon introduction of a radical initiator. After embedding PAEs in a hydrogel, deformation of the macroscopic matrix results in concomitant deformation of the PAE lattices, allowing superlattice structural changes to be induced by chemical methods (such as changing solute concentration to alter swelling pressure) or by application of mechanical strain. Changes to the structure of the PAE lattices are reversible and repeatable over multiple cycles and can be either isotropic (such as by swelling) or anisotropic (such as by mechanical deformation). This method of embedding nanoparticle crystals inside of a flexible and environmentally responsive hydrogel is therefore a useful tool in extending the utility of PAEs and other micro- and nanostructures assembled with DNA.
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ADN/química , Hidrogeles/química , Polielectrolitos/química , Cristalización , Etilaminas/química , Oro/química , Nanopartículas del Metal/química , Ácidos Polimetacrílicos/química , Electricidad EstáticaRESUMEN
OBJECTIVE: Malnutrition among hospital patients, a frequent, yet under-diagnosed problem is associated with adverse impact on patient outcome and health care costs. Development of highly accurate malnutrition screening tools is, therefore, essential for its timely detection, for providing nutritional care, and for addressing the concerns related to the suboptimal predictive value of the conventional screening tools, such as the Malnutrition Universal Screening Tool (MUST). We aimed to develop a machine learning (ML) based classifier (MUST-Plus) for more accurate prediction of malnutrition. METHOD: A retrospective cohort with inpatient data consisting of anthropometric, lab biochemistry, clinical data, and demographics from adult (≥ 18 years) admissions at a large tertiary health care system between January 2017 and July 2018 was used. The registered dietitian (RD) nutritional assessments were used as the gold standard outcome label. The cohort was randomly split (70:30) into training and test sets. A random forest model was trained using 10-fold cross-validation on training set, and its predictive performance on test set was compared to MUST. RESULTS: In all, 13.3% of admissions were associated with malnutrition in the test cohort. MUST-Plus provided 73.07% (95% confidence interval [CI]: 69.61%-76.33%) sensitivity, 76.89% (95% CI: 75.64%-78.11%) specificity, and 83.5% (95% CI: 82.0%-85.0%) area under the receiver operating curve (AUC). Compared to classic MUST, MUST-Plus demonstrated 30% higher sensitivity, 6% higher specificity, and 17% increased AUC. CONCLUSIONS: ML-based MUST-Plus provided superior performance in identifying malnutrition compared to the classic MUST. The tool can be used for improving the operational efficiency of RDs by timely referrals of high-risk patients.