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BACKGROUND: Micronutrient deficiencies associated with malnutrition in patients with inflammatory bowel disease (IBD) can lead to complications including anemia, coagulopathy, poor wound healing, and colorectal cancer. This study aimed to investigate micronutrient deficiencies (copper, vitamins A, B9, E, and K) in IBD patients and highlight associated symptoms to aid in the recognition of micronutrient deficiencies. METHODS: A retrospective electronic chart review was performed on adults diagnosed with Crohn's disease or ulcerative colitis hospitalized at a tertiary care center for IBD flare between January 2013 and June 2017. Patients with serum or whole blood micronutrient levels were included. Pregnant and incarcerated patients were excluded. RESULTS: A total of 611 IBD patients (440 Crohn's disease, 171 ulcerative colitis) met the inclusion criteria. Micronutrients were assessed in a subset of IBD patients (copper: 12.3%, A: 10.1%, B9â :â 95.9%, E: 10.3%, and K: 4.6%). Overall, 10.1% of patients had micronutrient deficiencies. The proportion of patients with copper, A, B9, E, and K deficiencies were 25.4, 53.3, 1.9, 23.7, and 29.4% for Crohn's disease and 50, 52.9, 1.2, 43.8, and 18.2% for ulcerative colitis, respectively. The most common symptoms or historical features associated with micronutrient deficiency were anemia (copper, B9), muscle weakness (copper, E) thrombocytopenia, fatigue (copper, B9), diarrhea (B9), dry skin, hyperkeratosis, pruritus, significant weight loss, elevated C-reactive protein (A), bleeding, and osteoporosis (K). CONCLUSION: Micronutrient deficiencies are common in IBD patients, yet they are not routinely assessed. Copper, vitamins A, E, and K deficiencies are particularly underrecognized. Associated historical features should raise suspicion and prompt assessment and treatment.
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Monitoring of pesticide concentration distribution across farm fields is crucial to ensure precise and efficient application while preventing overuse or untreated areas. Inspired by nature's wettability patterns, we developed a biomimetic fern leaf pesticide collection patch using laser-induced graphene (LIG) alongside an external electrochemical LIG biosensor. This "collect-and-sense" system allows for rapid pesticide spray monitoring in the farm field. The LIG is synthesized and patterned on polyimide through a high-throughput gantry-based CO2 laser process, making it amenable to scalable manufacturing. The resulting LIG-based leaf exhibits a remarkable water collection capacity, harvesting spray mist/fog at a rate approximately 11 times greater than a natural ostrich fern leaf when the collection is normalized to surface area. The developed three-electrode LIG pesticide biosensor, featuring a working electrode functionalized with electrodeposited platinum nanoparticles (PtNPs) and the enzyme glycine oxidase, displayed a linear range of 10-260 µM, a detection limit of 1.15 µM, and a sensitivity of 5.64 nA µM-1 for the widely used herbicide glyphosate. Also, a portable potentiostat with a user-friendly interface was developed for remote operation, achieving an accuracy of up to 97%, when compared to a standard commercial benchtop potentiostat. The LIG "collect-and-sense" system can consistently collect and monitor glyphosate spray after 24-48 hours of spraying, a time that corresponds to the restricted-entry interval required to enter most farm fields after pesticide spraying. Hence, this innovative "collect-and-sense" system not only advances precision agriculture by enabling monitoring and mapping of pesticide distribution but also holds the potential to significantly reduce environmental impact, enhance crop management practices, and contribute to the sustainable and efficient use of agrochemicals in modern agriculture.
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Técnicas Biosensibles , Helechos , Grafito , Rayos Láser , Plaguicidas , Hojas de la Planta , Platino (Metal) , Grafito/química , Técnicas Biosensibles/métodos , Técnicas Biosensibles/instrumentación , Hojas de la Planta/química , Plaguicidas/análisis , Plaguicidas/química , Helechos/química , Platino (Metal)/química , Glicina/química , Glicina/análogos & derivados , Glifosato , Nanopartículas del Metal/química , Biomimética/métodos , Materiales Biomiméticos/químicaRESUMEN
BACKGROUND: Sexual differentiation of the brain occurs in all major vertebrate lineages but is not well understood at a molecular and cellular level. Unlike most vertebrates, sex-changing fishes have the remarkable ability to change reproductive sex during adulthood in response to social stimuli, offering a unique opportunity to understand mechanisms by which the nervous system can initiate and coordinate sexual differentiation. METHODS: This study explores sexual differentiation of the forebrain using single nucleus RNA-sequencing in the anemonefish Amphiprion ocellaris, producing the first cellular atlas of a sex-changing brain. RESULTS: We uncover extensive sex differences in cell type-specific gene expression, relative proportions of cells, baseline neuronal excitation, and predicted inter-neuronal communication. Additionally, we identify the cholecystokinin, galanin, and estrogen systems as central molecular axes of sexual differentiation. Supported by these findings, we propose a model of sexual differentiation in the conserved vertebrate social decision-making network spanning multiple subtypes of neurons and glia, including neuronal subpopulations within the preoptic area that are positioned to regulate gonadal differentiation. CONCLUSIONS: This work deepens our understanding of sexual differentiation in the vertebrate brain and defines a rich suite of molecular and cellular pathways that differentiate during adult sex change in anemonefish.
This study provides key insights into brain sex differences in sex-changing anemonefish (Amphiprion ocellaris), a species that changes sex in adulthood in response to the social environment. Using single nucleus RNA-sequencing, the study provides the first brain cellular atlas showing sex differences in two crucial reproductive areas: the preoptic area and telencephalon. The research identifies notable sex-differences in cell-type proportions and gene expression, particularly in radial glia and glutamatergic neurons that co-express the neuropeptide cholecystokinin. It also highlights differences in preoptic area neurons likely involved in gonadal regulation. This work deepens our understanding of sexual differentiation of the brain in vertebrates, especially those capable of adult sex change, and illuminates key molecular and cellular beginning and endpoints of the process.
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Prosencéfalo , Caracteres Sexuales , Diferenciación Sexual , Animales , Prosencéfalo/fisiología , Prosencéfalo/metabolismo , Masculino , Femenino , Diferenciación Sexual/fisiología , Neuronas/fisiología , Neuronas/metabolismo , Peces/fisiología , Perciformes/fisiología , Galanina/metabolismo , Galanina/genética , Colecistoquinina/metabolismoRESUMEN
Digital twins are a relatively new form of digital modeling that has been gaining popularity in recent years. This is in large part due to their ability to update in real time to their physical counterparts and connect across multiple devices. As a result, much interest has been directed towards using digital twins in the healthcare industry. Recent advancements in smart wearable technologies have allowed for the utilization of human digital twins in healthcare. Human digital twins can be generated using biometric data from the patient gathered from wearables. These data can then be used to enhance patient care through a variety of means, such as simulated clinical trials, disease prediction, and monitoring treatment progression remotely. This revolutionary method of patient care is still in its infancy, and as such, there is limited research on using wearables to generate human digital twins for healthcare applications. This paper reviews the literature pertaining to human digital twins, including methods, applications, and challenges. The paper also presents a conceptual method for creating human body digital twins using wearable sensors.
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The telencephalon has undergone remarkable diversification and expansion throughout vertebrate evolution, exhibiting striking variations in structural and functional complexity. Nevertheless, fundamental features are shared across vertebrate taxa, such as the presence of distinct regions including the pallium, subpallium, and olfactory structures. Teleost fishes have a uniquely "everted" telencephalon, which has confounded comparisons of their brain regions to other vertebrates. Here we combine spatial transcriptomics and single nucleus RNA-sequencing to generate a spatially-resolved transcriptional atlas of the Mchenga conophorus cichlid fish telencephalon. We then compare cell-types and anatomical regions in the cichlid telencephalon with those in amphibians, reptiles, birds, and mammals. We uncover striking transcriptional similarities between cell-types in the fish telencephalon and subpallial, hippocampal, and cortical cell-types in tetrapods, and find support for partial eversion of the teleost telencephalon. Ultimately, our work lends new insights into the organization and evolution of conserved cell-types and regions in the vertebrate forebrain.
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Cíclidos , Prosencéfalo , Telencéfalo , Animales , Telencéfalo/citología , Prosencéfalo/citología , Cíclidos/genética , Transcriptoma , Vertebrados/genética , Evolución BiológicaRESUMEN
The distribution of allelic effects on traits, along with their gene-by-gene and gene-by-environment interactions, contributes to the phenotypes available for selection and the trajectories of adaptive variants. Nonetheless, uncertainty persists regarding the effect sizes underlying adaptations and the importance of genetic interactions. Herein, we aimed to investigate the genetic architecture and the epistatic and environmental interactions involving loci that contribute to multiple adaptive traits using two new panels of Drosophila melanogaster recombinant inbred lines (RILs). To better fit our data, we re-implemented functions from R/qtl (Broman et al. 2003) using additive genetic models. We found 14 quantitative trait loci (QTL) underlying melanism, wing size, song pattern, and ethanol resistance. By combining our mapping results with population genetic statistics, we identified potential new genes related to these traits. None of the detected QTLs showed clear evidence of epistasis, and our power analysis indicated that we should have seen at least one significant interaction if sign epistasis or strong positive epistasis played a pervasive role in trait evolution. In contrast, we did find roles for gene-by-environment interactions involving pigmentation traits. Overall, our data suggest that the genetic architecture of adaptive traits often involves alleles of detectable effect, that strong epistasis does not always play a role in adaptation, and that environmental interactions can modulate the effect size of adaptive alleles.
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Sexual differentiation of the brain occurs in all major vertebrate lineages but is not well understood at a molecular and cellular level. Unlike most vertebrates, sex-changing fishes have the remarkable ability to change reproductive sex during adulthood in response to social stimuli, offering a unique opportunity to understand mechanisms by which the nervous system can initiate and coordinate sexual differentiation. This study explores sexual differentiation of the forebrain using single nucleus RNA-sequencing in the anemonefish Amphiprion ocellaris, producing the first cellular atlas of a sex-changing brain. We uncover extensive sex differences in cell type-specific gene expression, relative proportions of cells, baseline neuronal excitation, and predicted inter-neuronal communication. Additionally, we identify the cholecystokinin, galanin, and estrogen systems as central molecular axes of sexual differentiation. Supported by these findings, we propose a model of neurosexual differentiation in the conserved vertebrate social decision-making network spanning multiple subtypes of neurons and glia, including neuronal subpopulations within the preoptic area that are positioned to regulate gonadal differentiation. This work deepens our understanding of sexual differentiation in the vertebrate brain and defines a rich suite of molecular and cellular pathways that differentiate during adult sex change in anemonefish.
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Oxytocin (OXT) is a highly conserved neuropeptide that modulates social cognition, and variation in its receptor gene (Oxtr) is associated with divergent social phenotypes. The cellular mechanisms connecting Oxtr genotype to social phenotype remain obscure. We exploit an association between Oxtr polymorphisms and striatal-specific OXTR density in prairie voles to investigate how OXTR signaling influences the brain transcriptome. We discover widespread, OXTR signaling-dependent transcriptomic changes. Interestingly, OXTR signaling robustly modulates gene expression of C-type lectin-like receptors (CTLRs) in the natural killer gene complex, a genomic region associated with immune function. CTLRs are positioned to control microglial synaptic pruning; a process important for shaping neural circuits. Similar relationships between OXTR RNA and CTLR gene expression were found in human striatum. These data suggest a potential molecular mechanism by which variation in OXTR signaling due to genetic background and/or life-long social experiences, including nurturing/neglect, may affect circuit connectivity and social behavior.
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Neurobiological consequences of traumatic brain injury (TBI) result from a complex interplay of secondary injury responses and sequela that mediates chronic disability. Endothelial cells are important regulators of the cerebrovascular response to TBI. Our work demonstrates that genetic deletion of endothelial cell (EC)-specific EPH receptor A4 (EphA4) using conditional EphA4f/f/Tie2-Cre and EphA4f/f/VE-Cadherin-CreERT2 knockout (KO) mice promotes blood-brain barrier (BBB) integrity and tissue protection, which correlates with improved motor function and cerebral blood flow recovery following controlled cortical impact (CCI) injury. scRNAseq of capillary-derived KO ECs showed increased differential gene expression of BBB-related junctional and actin cytoskeletal regulators, namely, A-kinase anchor protein 12, Akap12, whose presence at Tie2 clustering domains is enhanced in KO microvessels. Transcript and protein analysis of CCI-injured whole cortical tissue or cortical-derived ECs suggests that EphA4 limits the expression of Cldn5, Akt, and Akap12 and promotes Ang2. Blocking Tie2 using sTie2-Fc attenuated protection and reversed Akap12 mRNA and protein levels cortical-derived ECs. Direct stimulation of Tie2 using Vasculotide, angiopoietin-1 memetic peptide, phenocopied the neuroprotection. Finally, we report a noteworthy rise in soluble Ang2 in the sera of individuals with acute TBI, highlighting its promising role as a vascular biomarker for early detection of BBB disruption. These findings describe a contribution of the axon guidance molecule, EphA4, in mediating TBI microvascular dysfunction through negative regulation of Tie2/Akap12 signaling.
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Barrera Hematoencefálica , Lesiones Traumáticas del Encéfalo , Receptor EphA4 , Animales , Ratones , Proteínas de Anclaje a la Quinasa A/genética , Proteínas de Anclaje a la Quinasa A/metabolismo , Barrera Hematoencefálica/metabolismo , Lesiones Traumáticas del Encéfalo/genética , Lesiones Traumáticas del Encéfalo/metabolismo , Proteínas de Ciclo Celular/metabolismo , Células Endoteliales/metabolismo , Ratones Noqueados , Receptor TIE-2/genética , Receptor TIE-2/metabolismo , Receptor EphA4/genética , Receptor EphA4/metabolismoRESUMEN
Social behaviors are diverse in nature, but it is unclear how conserved genes, brain regions, and cell populations generate this diversity. Here we investigate bower-building, a recently-evolved social behavior in cichlid fishes. We use single nucleus RNA-sequencing in 38 individuals to show signatures of recent behavior in specific neuronal populations, and building-associated rebalancing of neuronal proportions in the putative homolog of the hippocampal formation. Using comparative genomics across 27 species, we trace bower-associated genome evolution to a subpopulation of glia lining the dorsal telencephalon. We show evidence that building-associated neural activity and a departure from quiescence in this glial subpopulation together regulate hippocampal-like neuronal rebalancing. Our work links behavior-associated genomic variation to specific brain cell types and their functions, and suggests a social behavior has evolved through changes in glia.
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Cíclidos , Animales , Cíclidos/genética , Conducta Social , Genoma , Genómica , Secuencia de BasesRESUMEN
Wearable biosensors promise real-time measurements of chemicals in human sweat, with the potential for dramatic improvements in medical diagnostics and athletic performance through continuous metabolite and electrolyte monitoring. However, sweat sensing is still in its infancy, and questions remain about whether sweat can be used for medical purposes. Wearable sensors are focused on proof-of-concept designs that are not scalable for multisubject trials, which could elucidate the utility of sweat sensing for health monitoring. Moreover, many wearable sensors do not include the microfluidics necessary to protect and channel consistent and clean sweat volumes to the sensor surface or are not designed to be disposable to prevent sensor biofouling and inaccuracies due to repeated use. Hence, there is a need to produce low-cost and single-use wearable sensors with integrated microfluidics to ensure reliable sweat sensing. Herein, we demonstrate the convergence of laser-induced graphene (LIG) based sensors with soft tape polymeric microfluidics to quantify both sweat metabolites (glucose and lactate) and electrolytes (sodium) for potential hydration and fatigue monitoring. Distinct LIG-electrodes were functionalized with glucose oxidase and lactate oxidase for selective sensing of glucose and lactate across physiological ranges found in sweat with sensitivities of 26.2 and 2.47 × 10-3 µA mM-1 cm-2, detection limits of 8 and 220 µM, and linear response ranges of 0-1 mM and 0-32 mM, respectively. LIG-electrodes functionalized with a sodium-ion-selective membrane displayed Nernstian sensitivity of 58.8 mV decade-1 and a linear response over the physiological range in sweat (10-100 mM). The sensors were tested in a simulated sweating skin microfluidic system and on-body during cycling tests in a multisubject trial. Results demonstrate the utility of LIG integrated with microfluidics for real-time, continuous measurements of biological analytes in sweat and help pave the way for the development of personalized wearable diagnostic tools.
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Técnicas Biosensibles , Grafito , Dispositivos Electrónicos Vestibles , Humanos , Sudor , Sudoración , Microfluídica , Técnicas Biosensibles/métodos , Sodio , Ácido Láctico , Polímeros , GlucosaRESUMEN
Human activities and climate change threaten coldwater organisms in freshwater ecosystems by causing rivers and streams to warm, increasing the intensity and frequency of warm temperature events, and reducing thermal heterogeneity. Cold-water refuges are discrete patches of relatively cool water that are used by coldwater organisms for thermal relief and short-term survival. Globally, cohesive management approaches are needed that consider interlinked physical, biological, and social factors of cold-water refuges. We review current understanding of cold-water refuges, identify gaps between science and management, and evaluate policies aimed at protecting thermally sensitive species. Existing policies include designating cold-water habitats, restricting fishing during warm periods, and implementing threshold temperature standards or guidelines. However, these policies are rare and uncoordinated across spatial scales and often do not consider input from Indigenous peoples. We propose that cold-water refuges be managed as distinct operational landscape units, which provide a social and ecological context that is relevant at the watershed scale. These operational landscape units provide the foundation for an integrated framework that links science and management by (1) mapping and characterizing cold-water refuges to prioritize management and conservation actions, (2) leveraging existing and new policies, (3) improving coordination across jurisdictions, and (4) implementing adaptive management practices across scales. Our findings show that while there are many opportunities for scientific advancement, the current state of the sciences is sufficient to inform policy and management. Our proposed framework provides a path forward for managing and protecting cold-water refuges using existing and new policies to protect coldwater organisms in the face of global change.
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Ecosistema , Ríos , Humanos , Agua Dulce , Frío , Cambio Climático , AguaRESUMEN
The telencephalon has undergone remarkable diversification and expansion throughout vertebrate evolution, exhibiting striking differences in structural and functional complexity. Nevertheless, fundamental features are shared across vertebrate taxa, such as the presence of distinct regions including the pallium, subpallium, and olfactory structures. Teleost fishes have a uniquely 'everted' telencephalon, which has made it challenging to compare brain regions in fish to those in other vertebrates. Here we combine spatial transcriptomics and single-nucleus RNA-sequencing to generate a spatially-resolved transcriptional atlas of the cichlid fish telencephalon. We then compare cell-types and anatomical regions in the cichlid telencephalon with those in amphibians, reptiles, birds, and mammals. We uncover striking transcriptional similarities between cell populations in the fish telencephalon and subpallial, hippocampal, and cortical cell populations in tetrapods. Ultimately, our work lends new insights into the organization and evolution of conserved cell-types and regions in the vertebrate forebrain.
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Adenosine triphosphate-binding cassette (ABC) transporters, such as multidrug resistance protein 1 (MRP1), protect against cellular toxicity by exporting xenobiotic compounds across the plasma membrane. However, constitutive MRP1 function hinders drug delivery across the blood-brain barrier, and MRP1 overexpression in certain cancers leads to acquired multidrug resistance and chemotherapy failure. Small-molecule inhibitors have the potential to block substrate transport, but few show specificity for MRP1. Here we identify a macrocyclic peptide, named CPI1, which inhibits MRP1 with nanomolar potency but shows minimal inhibition of a related multidrug transporter P-glycoprotein. A cryoelectron microscopy (cryo-EM) structure at 3.27 Å resolution shows that CPI1 binds MRP1 at the same location as the physiological substrate leukotriene C4 (LTC4). Residues that interact with both ligands contain large, flexible sidechains that can form a variety of interactions, revealing how MRP1 recognizes multiple structurally unrelated molecules. CPI1 binding prevents the conformational changes necessary for adenosine triphosphate (ATP) hydrolysis and substrate transport, suggesting it may have potential as a therapeutic candidate.
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Miembro 1 de la Subfamilia B de Casetes de Unión a ATP , Proteínas Asociadas a Resistencia a Múltiples Medicamentos , Adenosina Trifosfato/metabolismo , Subfamilia B de Transportador de Casetes de Unión a ATP/metabolismo , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/química , Transportadoras de Casetes de Unión a ATP/metabolismo , Transporte Biológico , Microscopía por Crioelectrón , Leucotrieno C4/metabolismo , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Péptidos/metabolismo , Péptidos Cíclicos/farmacologíaRESUMEN
Post-transcriptional RNA modifications have been recognized as key regulators of neuronal differentiation and synapse development in the mammalian brain. While distinct sets of 5-methylcytosine (m5C) modified mRNAs have been detected in neuronal cells and brain tissues, no study has been performed to characterize methylated mRNA profiles in the developing brain. Here, together with regular RNA-seq, we performed transcriptome-wide bisulfite sequencing to compare RNA cytosine methylation patterns in neural stem cells (NSCs), cortical neuronal cultures, and brain tissues at three postnatal stages. Among 501 m5C sites identified, approximately 6% are consistently methylated across all five conditions. Compared to m5C sites identified in NSCs, 96% of them were hypermethylated in neurons and enriched for genes involved in positive transcriptional regulation and axon extension. In addition, brains at the early postnatal stage demonstrated substantial changes in both RNA cytosine methylation and gene expression of RNA cytosine methylation readers, writers, and erasers. Furthermore, differentially methylated transcripts were significantly enriched for genes regulating synaptic plasticity. Altogether, this study provides a brain epitranscriptomic dataset as a new resource and lays the foundation for further investigations into the role of RNA cytosine methylation during brain development.
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Metilación de ADN , ARN , Animales , ARN/metabolismo , ARN Mensajero/metabolismo , Citosina/metabolismo , Encéfalo/metabolismo , Transcriptoma , Mamíferos/genéticaRESUMEN
BACKGROUND: Nontraumatic pedicle fracture is uncommon, with sparsely described cases of conservative management versus surgical treatment by open fusion or percutaneous fixation. METHODS: We report the case of a 60-year-old woman with nontraumatic L4 and L5 pedicle fracture who developed additional pedicle fractures at L3 while undergoing conservative management in a brace. The patient underwent percutaneous pediculosynthesis with screw fixation without fusion at L3-5 bilaterally. RESULTS: The treatment led to fracture healing with good radiographic result and resolution of her symptoms. CONCLUSIONS: A trial of conservative management is typically warranted in most cases of nontraumatic pedicle fracture, but there is risk of refractory or progressive symptoms and subsequent fracture. Minimally invasive fixation is a viable surgical option that can be used in multilevel fractures.
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Fracturas por Estrés , Tornillos Pediculares , Fracturas de la Columna Vertebral , Fusión Vertebral , Humanos , Femenino , Persona de Mediana Edad , Fracturas de la Columna Vertebral/diagnóstico por imagen , Fracturas de la Columna Vertebral/cirugía , Vértebras Lumbares/cirugía , Fijación Interna de Fracturas , Resultado del TratamientoRESUMEN
Aerosol jet printing is a noncontact, digital, additive manufacturing technique compatible with a wide variety of functional materials. Although promising, development of new materials and devices using this technique remains hindered by limited rational ink formulation, with most recent studies focused on device demonstration rather than foundational process science. In the present work, a systematic approach to formulating a polymer-stabilized graphene ink is reported, which considers the effect of solvent composition on dispersion, rheology, wetting, drying, and phase separation characteristics that drive process outcomes. It was found that a four-component solvent mixture composed of isobutyl acetate, diglyme, dihydrolevoglucosenone, and glycerol supported efficient ink atomization and controlled in-line drying to reduce overspray and wetting instabilities while maintaining high resolution and electrical conductivity, thus overcoming a trade-off in deposition rate and resolution common to aerosol jet printing. Biochemical sensors were printed for amperometric detection of the pesticide parathion, exhibiting a detection limit of 732 nM and a sensitivity of 34 nA µM-1, demonstrating the viability of this graphene ink for fabricating functional electronic devices.
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Glycerol-3-phosphate acyltransferase (GPAT)1 is a mitochondrial outer membrane protein that catalyzes the first step of de novo glycerolipid biosynthesis. Hepatic expression of GPAT1 is linked to liver fat accumulation and the severity of nonalcoholic fatty liver diseases. Here we present the cryo-EM structures of human GPAT1 in substrate analog-bound and product-bound states. The structures reveal an N-terminal acyltransferase domain that harbors important catalytic motifs and a tightly associated C-terminal domain that is critical for proper protein folding. Unexpectedly, GPAT1 has no transmembrane regions as previously proposed but instead associates with the membrane via an amphipathic surface patch and an N-terminal loop-helix region that contains a mitochondrial-targeting signal. Combined structural, computational and functional studies uncover a hydrophobic pathway within GPAT1 for lipid trafficking. The results presented herein lay a framework for rational inhibitor development for GPAT1.
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Hígado , Membranas Mitocondriales , Humanos , Hígado/metabolismo , Membranas Mitocondriales/metabolismo , Glicerol-3-Fosfato O-Aciltransferasa/química , Glicerol-3-Fosfato O-Aciltransferasa/metabolismo , Secuencia de AminoácidosRESUMEN
STUDY DESIGN: Retrospective case control. OBJECTIVES: The purpose of the current study is to determine risk factors associated with chronic opioid use after spine surgery. METHODS: In our single institution retrospective study, 1,299 patients undergoing elective spine surgery at a tertiary academic medical center between January 2010 and August 2017 were enrolled into a prospectively collected registry. Patients were dichotomized based on renewal of, or active opioid prescription at 3-mo and 12-mo postoperatively. The primary outcome measures were risk factors for opioid renewal 3-months and 12-months postoperatively. These primarily included demographic characteristics, operative variables, and in-hospital opioid consumption via morphine milligram equivalence (MME). At the 3-month and 12-month periods, we analyzed the aforementioned covariates with multivariate followed by bivariate regression analyses. RESULTS: Multivariate and bivariate analyses revealed that script renewal at 3 months was associated with black race (P = 0.001), preoperative narcotic (P < 0.001) or anxiety/depression medication use (P = 0.002), and intraoperative long lumbar (P < 0.001) or thoracic spine surgery (P < 0.001). Lower patient income was also a risk factor for script renewal (P = 0.01). Script renewal at 12 months was associated with younger age (P = 0.006), preoperative narcotics use (P = 0.001), and ≥4 levels of lumbar fusion (P < 0.001). Renewals at 3-mo and 12-mo had no association with MME given during the hospital stay or with the usage of PCA (P > 0.05). CONCLUSION: The current study describes multiple patient-level factors associated with chronic opioid use. Notably, no metric of perioperative opioid utilization was directly associated with chronic opioid use after multivariate analysis.
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STUDY DESIGN: Cross-Sectional Study. OBJECTIVES: Socioeconomic status (SES) is a fundamental root of health disparities, however, its effect on surgical outcomes is often difficult to capture in clinical research, especially in spine surgery. Here, we present a large single-center study assessing whether SES is associated with cause-specific surgical outcomes. METHODS: Patients undergoing spine surgery between 2015 and 2019 were assigned income in accordance with the national distribution and divided into quartiles based on the ZIP code-level median household income. We performed univariate, chi-square, and Analysis of Variance (ANOVA) analysis assessing the independent association of SES, quantified by household income, to operative outcomes, and multiple metrics of opioid consumption. RESULTS: 1199 patients were enrolled, and 1138 patients were included in the analysis. Low household income was associated with the greatest rates of 3-month opioid script renewal (OR:1.65, 95% CI:1.14-2.40). In addition, low-income was associated with higher rates of perioperative opioid consumption compared to higher income including increased mean total morphine milligram equivalent (MME) 252.25 (SD 901.32) vs 131.57 (SD 197.46) (P < .046), and inpatient IV patient-controlled analgesia (PCA) MME 121.11 (SD 142.14) vs 87.60 (SD 86.33) (P < .023). In addition, household income was independently associated with length of stay (LOS), and emergency room (ER) revisits with low-income patients demonstrating significantly longer postop LOS and increasing postoperative ER visits. CONCLUSIONS: Considering the comparable surgical management provided by the single institution, the associated differences in postoperative outcomes as defined by increased morbidities and opioid consumption can potentially be attributed to health disparities caused by SES.