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1.
Prehosp Emerg Care ; : 1-9, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39235330

RESUMO

OBJECTIVES: Data suggest patients suffering acute coronary occlusion myocardial infarction (OMI) benefit from prompt primary percutaneous intervention (PPCI). Many emergency medical services (EMS) activate catheterization labs to reduce time to PPCI, but suffer a high burden of inappropriate activations. Artificial intelligence (AI) algorithms show promise to improve electrocardiogram (ECG) interpretation. The primary objective was to evaluate the potential of AI to reduce false positive activations without missing OMI. METHODS: Electrocardiograms were categorized by (1) STEMI criteria, (2) ECG integrated device software and (3) a proprietary AI algorithm (Queen of Hearts (QOH), Powerful Medical). If multiple ECGs were obtained and any one tracing was positive for a given method, that diagnostic method was considered positive. The primary outcome was OMI defined as an angiographic culprit lesion with either TIMI 0-2 flow; or TIMI 3 flow with either peak high sensitivity troponin-I > 5000 ng/L or new wall motion abnormality. The primary analysis was per-patient proportion of false positives. RESULTS: A total of 140 patients were screened and 117 met criteria. Of these, 48 met the primary outcome criteria of OMI. There were 80 positives by STEMI criteria, 88 by device algorithm, and 77 by AI software. All approaches reduced false positives, 27% for STEMI, 22% for device software, and 34% for AI (p < 0.01 for all). The reduction in false positives did not significantly differ between STEMI criteria and AI software (p = 0.19) but STEMI criteria missed 6 (5%) OMIs, while AI missed none (p = 0.01). CONCLUSIONS: In this single-center retrospective study, an AI-driven algorithm reduced false positive diagnoses of OMI compared to EMS clinician gestalt. Compared to AI (which missed no OMI), STEMI criteria also reduced false positives but missed 6 true OMI. External validation of these findings in prospective cohorts is indicated.

2.
Commun Biol ; 7(1): 1124, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39266695

RESUMO

Thermophily is a trait scattered across the fungal tree of life, with its highest prevalence within three fungal families (Chaetomiaceae, Thermoascaceae, and Trichocomaceae), as well as some members of the phylum Mucoromycota. We examined 37 thermophilic and thermotolerant species and 42 mesophilic species for this study and identified thermophily as the ancestral state of all three prominent families of thermophilic fungi. Thermophilic fungal genomes were found to encode various thermostable enzymes, including carbohydrate-active enzymes such as endoxylanases, which are useful for many industrial applications. At the same time, the overall gene counts, especially in gene families responsible for microbial defense such as secondary metabolism, are reduced in thermophiles compared to mesophiles. We also found a reduction in the core genome size of thermophiles in both the Chaetomiaceae family and the Eurotiomycetes class. The Gene Ontology terms lost in thermophilic fungi include primary metabolism, transporters, UV response, and O-methyltransferases. Comparative genomics analysis also revealed higher GC content in the third base of codons (GC3) and a lower effective number of codons in fungal thermophiles than in both thermotolerant and mesophilic fungi. Furthermore, using the Support Vector Machine classifier, we identified several Pfam domains capable of discriminating between genomes of thermophiles and mesophiles with 94% accuracy. Using AlphaFold2 to predict protein structures of endoxylanases (GH10), we built a similarity network based on the structures. We found that the number of disulfide bonds appears important for protein structure, and the network clusters based on protein structures correlate with the optimal activity temperature. Thus, comparative genomics offers new insights into the biology, adaptation, and evolutionary history of thermophilic fungi while providing a parts list for bioengineering applications.


Assuntos
Evolução Molecular , Genoma Fúngico , Genômica/métodos , Filogenia , Fungos/genética , Fungos/classificação , Adaptação Fisiológica/genética , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo
3.
mSphere ; 9(9): e0030924, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39189783

RESUMO

Mucoromycota fungi and their Mollicutes-related endobacteria (MRE) are an ideal system for studying bacterial-fungal interactions and evolution due to the long-term and intimate nature of their interactions. However, methods for detecting MRE face specific challenges due to the poor representation of MRE in sequencing databases coupled with the high sequence divergence of their genomes, making traditional similarity searches unreliable. This has precluded estimations on the diversity of MRE associated with Mucoromycota. To determine the prevalence of previously undetected MRE in fungal genome sequences, we scanned 389 Mucoromycota genome assemblies available from the National Center for Biotechnology Information for the presence of MRE sequences using publicly available tools to map contigs from fungal assemblies to publicly available MRE genomes. We demonstrate a higher diversity of MRE genomes than previously described in Mucoromycota and a lack of cophylogeny between MRE and the majority of their fungal hosts. This supports the late invasion hypothesis regarding MRE acquisition across most of the examined fungal families. In contrast with other Mucoromycota lineages, MRE from the Gigasporaceae displayed some degree of cophylogeny with their hosts, which may indicate that horizontal transmission is restricted between members of this family or that transmission is strictly vertical. These results underscore the need for a refined process to capture sequencing data from potential fungal endosymbionts to discern their evolution and transmission. Screens of fungal genomes for MRE can help improve the quality of fungal genome assemblies while identifying new MRE lineages to further test hypotheses on their origin and evolution.IMPORTANCEMollicutes-related endobacteria (MRE) are obligate intracellular bacteria found within Mucoromycota fungi. Despite their frequent detection, MRE roles in host functioning are still unknown. Comparative genomic investigations can improve our understanding of the impact of MRE on their fungal hosts by identifying similarities and differences in MRE genome evolution. However, MRE genomes have only been assembled from a small fraction of Mucoromycota hosts. Here, we demonstrate that MRE can be present yet undetected in publicly available Mucoromycota genome assemblies. We use these newfound sequences to assess the broader diversity of MRE and their phylogenetic relationships with respect to their hosts. We demonstrate that publicly available tools can be used to extract novel MRE sequences from assembled fungal genomes leading to insights on MRE evolution. This work contributes to a greater understanding of the fungal microbiome, which is crucial to improving knowledge on the dynamics and impacts of fungi in microbial ecosystems.


Assuntos
Genoma Bacteriano , Genoma Fúngico , Filogenia , Tenericutes/genética , Tenericutes/classificação , Fungos/genética , Fungos/classificação
4.
Front Microbiol ; 15: 1380199, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39171270

RESUMO

Diverse and complex microbiomes are found in virtually every environment on Earth. Bacteria and fungi often co-dominate environmental microbiomes, and there is growing recognition that bacterial-fungal interactions (BFI) have significant impacts on the functioning of their associated microbiomes, environments, and hosts. Investigating BFI in vitro remains a challenge, particularly when attempting to examine interactions at multiple scales of system complexity. Fabricated devices can provide control over both biotic composition and abiotic factors within an experiment to enable the characterization of diverse BFI phenotypes such as modulation of growth rate, production of biomolecules, and alterations to physical movements. Engineered devices ranging from microfluidic chips to simulated rhizosphere systems have been and will continue to be invaluable to BFI research, and it is anticipated that such devices will continue to be developed for diverse applications in the field. This will allow researchers to address specific questions regarding the nature of BFI and how they impact larger microbiome and environmental processes such as biogeochemical cycles, plant productivity, and overall ecosystem resilience. Devices that are currently used for experimental investigations of bacteria, fungi, and BFI are discussed herein along with some of the associated challenges and several recommendations for future device design and applications.

5.
J Imaging ; 10(6)2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38921608

RESUMO

Hyperspectral images include information from a wide range of spectral bands deemed valuable for computer vision applications in various domains such as agriculture, surveillance, and reconnaissance. Anomaly detection in hyperspectral images has proven to be a crucial component of change and abnormality identification, enabling improved decision-making across various applications. These abnormalities/anomalies can be detected using background estimation techniques that do not require the prior knowledge of outliers. However, each hyperspectral anomaly detection (HS-AD) algorithm models the background differently. These different assumptions may fail to consider all the background constraints in various scenarios. We have developed a new approach called Greedy Ensemble Anomaly Detection (GE-AD) to address this shortcoming. It includes a greedy search algorithm to systematically determine the suitable base models from HS-AD algorithms and hyperspectral unmixing for the first stage of a stacking ensemble and employs a supervised classifier in the second stage of a stacking ensemble. It helps researchers with limited knowledge of the suitability of the HS-AD algorithms for the application scenarios to select the best methods automatically. Our evaluation shows that the proposed method achieves a higher average F1-macro score with statistical significance compared to the other individual methods used in the ensemble. This is validated on multiple datasets, including the Airport-Beach-Urban (ABU) dataset, the San Diego dataset, the Salinas dataset, the Hydice Urban dataset, and the Arizona dataset. The evaluation using the airport scenes from the ABU dataset shows that GE-AD achieves a 14.97% higher average F1-macro score than our previous method (HUE-AD), at least 17.19% higher than the individual methods used in the ensemble, and at least 28.53% higher than the other state-of-the-art ensemble anomaly detection algorithms. As using the combination of greedy algorithm and stacking ensemble to automatically select suitable base models and associated weights have not been widely explored in hyperspectral anomaly detection, we believe that our work will expand the knowledge in this research area and contribute to the wider application of this approach.

6.
ISME Commun ; 4(1): ycae057, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38812718

RESUMO

Microbial communities are diverse biological systems that include taxa from across multiple kingdoms of life. Notably, interactions between bacteria and fungi play a significant role in determining community structure. However, these statistical associations across kingdoms are more difficult to infer than intra-kingdom associations due to the nature of the data involved using standard network inference techniques. We quantify the challenges of cross-kingdom network inference from both theoretical and practical points of view using synthetic and real-world microbiome data. We detail the theoretical issue presented by combining compositional data sets drawn from the same environment, e.g. 16S and ITS sequencing of a single set of samples, and we survey common network inference techniques for their ability to handle this error. We then test these techniques for the accuracy and usefulness of their intra- and inter-kingdom associations by inferring networks from a set of simulated samples for which a ground-truth set of associations is known. We show that while the two methods mitigate the error of cross-kingdom inference, there is little difference between techniques for key practical applications including identification of strong correlations and identification of possible keystone taxa (i.e. hub nodes in the network). Furthermore, we identify a signature of the error caused by transkingdom network inference and demonstrate that it appears in networks constructed using real-world environmental microbiome data.

7.
Prehosp Emerg Care ; : 1-6, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38808969

RESUMO

OBJECTIVE: Agitation is a common prehospital problem and frequently presents without a clear etiology. Given the dynamic environment of the prehospital setting, there has historically been a varied approach to treating agitation with a heavy reliance on parenteral medications. Newer best practice guidelines recommend the incorporation of oral medications to treat patients experiencing agitation. Therefore, we evaluated the use of oral risperidone in a single system after a change in protocol occurred. METHODS: This was conducted as a retrospective chart review of an urban/suburban Emergency Medical Services system over the period of 8 months. The first day this medication was implemented throughout the service was included. Charts were included for selection if they included risperidone oral dissolving tablet (ODT) as a charted medication. The primary outcome was administration of additional medications to treat agitation. Exploratory outcome measures included acceptance of medication, documented injury to paramedics, documented injuries to patients, scene times, and adverse events that could possibly be linked to the medication. RESULTS: A total of 552 records were screened for inclusion. Risperidone was offered to 530 patients and accepted by 512 (96.6%). Of these 512 patients, the median age of included patients was 39 years old (IQR 29-52 years old) with a range of 18-89 years old. Rescue or additional medications for agitation were required in 9 (1.8%) cases. There were a total of 4 (0.8%) potential complications following administration of risperidone. There were no reported assaults with subsequent injuries to prehospital personnel or injuries sustained by patients reported in this study. CONCLUSIONS: Risperidone ODT was found to be a safe and effective medication to treat mild agitation in a large urban and suburban EMS system. The need for additional medications to treat agitation was rare, and there were no documented injuries to either patients or paramedics.

8.
Prehosp Emerg Care ; : 1-5, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38781490

RESUMO

Sodium nitrite overdose leads to profound methemoglobinemia and may quickly progress to death. It is an increasingly common method of suicide and is often fatal. Methylene blue is an effective but time-sensitive antidote that has the potential to save lives when administered early. In this case report, we describe a fatal sodium nitrite overdose and the subsequent creation of a prehospital protocol for our large urban Emergency Medical Services system.

9.
Int J Biol Sci ; 20(4): 1218-1237, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38385082

RESUMO

MCJ (Methylation-Controlled J protein), an endogenous repressor of the mitochondrial respiratory chain, is upregulated in multiple liver diseases but little is known about how it is regulated. S-adenosylmethionine (SAMe), the biological methyl donor, is frequently depleted in chronic liver diseases. Here, we show that SAMe negatively regulates MCJ in the liver. While deficiency in methionine adenosyltransferase alpha 1 (MATα1), enzyme that catalyzes SAMe biosynthesis, leads to hepatic MCJ upregulation, MAT1A overexpression and SAMe treatment reduced MCJ expression. We found that MCJ is methylated at lysine residues and that it interacts with MATα1 in liver mitochondria, likely to facilitate its methylation. Lastly, we observed that MCJ is upregulated in alcohol-associated liver disease, a condition characterized by reduced MAT1A expression and SAMe levels along with mitochondrial injury. MCJ silencing protected against alcohol-induced mitochondrial dysfunction and lipid accumulation. Our study demonstrates a new role of MATα1 and SAMe in reducing hepatic MCJ expression.


Assuntos
Hepatopatias Alcoólicas , S-Adenosilmetionina , Humanos , S-Adenosilmetionina/metabolismo , Transporte de Elétrons , Fígado/metabolismo , Mitocôndrias/metabolismo , Hepatopatias Alcoólicas/metabolismo
10.
Ann Emerg Med ; 83(2): 91-99, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37725022

RESUMO

STUDY OBJECTIVE: To determine what patient characteristics were associated with the application of physical restraints in our emergency department (ED). METHODS: This was a retrospective analysis of encounters in the ED of an urban, Level I academic trauma center. We included ED encounters of adult patients (aged ≥18 years) during a 5-year period starting in 2017. We evaluated the independent association of restraint application during an encounter using a generalized estimating equation model. RESULTS: There were 464,031 ED encounters during the time period from 162,244 unique patients, including 34,798 (7.5%) with restraint application, comprising 18,166 unique patients. Several variables were associated with an increased likelihood of restraint use during an encounter. The variable with the highest odds ratio was intoxication with drugs or alcohol (adjusted odds ratio [aOR] 8.29; 95% confidence interval (CI) 7.94 to 8.65). American Indian race was associated with increased odds of restraint application (aOR 1.42; 95% CI 1.31 to 1.54) compared to the reference value of White race. Black race (aOR 0.58; 95% CI 0.55 to 0.61) and Hispanic ethnicity (aOR 0.42; 95% CI 0.37 to 0.48) were associated with lower odds of restraint application. CONCLUSIONS: Drug and alcohol intoxication were most closely associated with restraint. Encounters in which the patient was American Indian had higher odds of restraint, but this study does not replicate prior findings regarding other racial disparities in restraint.


Assuntos
Etnicidade , Grupos Raciais , Restrição Física , Adulto , Humanos , Serviço Hospitalar de Emergência , Estudos Retrospectivos , Indígena Americano ou Nativo do Alasca
11.
Prehosp Emerg Care ; 28(2): 215-220, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37171895

RESUMO

OBJECTIVE: Prehospital clinicians need a practical means of providing adequate preoxygenation prior to intubation. A bag-valve-mask (BVM) can be used for preoxygenation in perfect conditions but is likely to fail in emergency settings. For this reason, many airway experts have moved away from using BVM for preoxygenation and instead suggest using a nonrebreather (NRB) mask with flush rate oxygen.Literature on preoxygenation has suggested that a NRB mask delivering flush rate oxygen (on a 15 L/min O2 regulator, maximum flow, ∼50 L/min) is noninferior to BVM at 15 L/min held with a tight seal. However, in the prehospital setting, where emergency airway management success varies, preoxygenation techniques have not been deeply explored. Our study seeks to determine whether preoxygenation can be optimally performed with NRB at flush rate oxygen. METHODS: We performed a crossover trial using healthy volunteers. Subjects underwent 3-min trials of preoxygenation with NRB mask at 25 L/min oxygen delivered from a portable tank, NRB at flush rate oxygen from a portable tank, NRB with flush rate oxygen from an onboard ambulance tank, and BVM with flush rate oxygen from an onboard ambulance tank. The primary outcome was the fraction of expired oxygen (FeO2). We compared the FeO2 of the BVM-flush to other study groups, using a noninferiority margin of 10%. RESULTS: We enrolled 30 subjects. Mean FeO2 values for NRB-25, NRB-flush ambulance, NRB-flush portable, and BVM-flush were 63% (95% confidence interval [CI] 58-68%), 74% (95%, CI 70-78%), 78% (95%, CI 74-83%), and 80% (95%, CI 75-84%), respectively. FeO2 values for NRB-flush on both portable tank and ambulance oxygen were noninferior to BVM-flush on the ambulance oxygen system (FeO2 differences of 1%, 95% CI -3% to 6%; and 6%, 95% CI 1-10%). FeO2 for the NRB-25 group was inferior to BVM-flush (FeO2 difference 16%, 95% CI 12-21%). CONCLUSIONS: Among healthy volunteers, flush rate preoxygenation using NRB masks is noninferior to BVM using either a portable oxygen tank or ambulance oxygen. This is significant because preoxygenation using NRB masks with flush rate oxygen presents a simpler alternative to the use of BVMs. Preoxygenation using NRB masks at 25 L/min from a portable tank is inferior to BVM at flush rate.


Assuntos
Serviços Médicos de Emergência , Máscaras , Humanos , Manuseio das Vias Aéreas/métodos , Oxigênio , Respiração Artificial/métodos , Estudos Cross-Over
12.
Front Fungal Biol ; 4: 1285531, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38155707

RESUMO

Members of the fungal genus Morchella are widely known for their important ecological roles and significant economic value. In this study, we used amplicon and genome sequencing to characterize bacterial communities associated with sexual fruiting bodies from wild specimens, as well as vegetative mycelium and sclerotia obtained from Morchella isolates grown in vitro. These investigations included diverse representatives from both Elata and Esculenta Morchella clades. Unique bacterial community compositions were observed across the various structures examined, both within and across individual Morchella isolates or specimens. However, specific bacterial taxa were frequently detected in association with certain structures, providing support for an associated core bacterial community. Bacteria from the genus Pseudomonas and Ralstonia constituted the core bacterial associates of Morchella mycelia and sclerotia, while other genera (e.g., Pedobacter spp., Deviosa spp., and Bradyrhizobium spp.) constituted the core bacterial community of fruiting bodies. Furthermore, the importance of Pseudomonas as a key member of the bacteriome was supported by the isolation of several Pseudomonas strains from mycelia during in vitro cultivation. Four of the six mycelial-derived Pseudomonas isolates shared 16S rDNA sequence identity with amplicon sequences recovered directly from the examined fungal structures. Distinct interaction phenotypes (antagonistic or neutral) were observed in confrontation assays between these bacteria and various Morchella isolates. Genome sequences obtained from these Pseudomonas isolates revealed intriguing differences in gene content and annotated functions, specifically with respect to toxin-antitoxin systems, cell adhesion, chitinases, and insecticidal toxins. These genetic differences correlated with the interaction phenotypes. This study provides evidence that Pseudomonas spp. are frequently associated with Morchella and these associations may greatly impact fungal physiology.

14.
Commun Biol ; 6(1): 948, 2023 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-37723238

RESUMO

Diverse members of early-diverging Mucoromycota, including mycorrhizal taxa and soil-associated Mortierellaceae, are known to harbor Mollicutes-related endobacteria (MRE). It has been hypothesized that MRE were acquired by a common ancestor and transmitted vertically. Alternatively, MRE endosymbionts could have invaded after the divergence of Mucoromycota lineages and subsequently spread to new hosts horizontally. To better understand the evolutionary history of MRE symbionts, we generated and analyzed four complete MRE genomes from two Mortierellaceae genera: Linnemannia (MRE-L) and Benniella (MRE-B). These genomes include the smallest known of fungal endosymbionts and showed signals of a tight relationship with hosts including a reduced functional capacity and genes transferred from fungal hosts to MRE. Phylogenetic reconstruction including nine MRE from mycorrhizal fungi revealed that MRE-B genomes are more closely related to MRE from Glomeromycotina than MRE-L from the same host family. We posit that reductions in genome size, GC content, pseudogene content, and repeat content in MRE-L may reflect a longer-term relationship with their fungal hosts. These data indicate Linnemannia and Benniella MRE were likely acquired independently after their fungal hosts diverged from a common ancestor. This work expands upon foundational knowledge on minimal genomes and provides insights into the evolution of bacterial endosymbionts.


Assuntos
Micorrizas , Tenericutes , Filogenia , Genômica , Micorrizas/genética , Tamanho do Genoma
15.
Microbiome ; 11(1): 192, 2023 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-37626434

RESUMO

As microbiome research has progressed, it has become clear that most, if not all, eukaryotic organisms are hosts to microbiomes composed of prokaryotes, other eukaryotes, and viruses. Fungi have only recently been considered holobionts with their own microbiomes, as filamentous fungi have been found to harbor bacteria (including cyanobacteria), mycoviruses, other fungi, and whole algal cells within their hyphae. Constituents of this complex endohyphal microbiome have been interrogated using multi-omic approaches. However, a lack of tools, techniques, and standardization for integrative multi-omics for small-scale microbiomes (e.g., intracellular microbiomes) has limited progress towards investigating and understanding the total diversity of the endohyphal microbiome and its functional impacts on fungal hosts. Understanding microbiome impacts on fungal hosts will advance explorations of how "microbiomes within microbiomes" affect broader microbial community dynamics and ecological functions. Progress to date as well as ongoing challenges of performing integrative multi-omics on the endohyphal microbiome is discussed herein. Addressing the challenges associated with the sample extraction, sample preparation, multi-omic data generation, and multi-omic data analysis and integration will help advance current knowledge of the endohyphal microbiome and provide a road map for shrinking microbiome investigations to smaller scales. Video Abstract.


Assuntos
Microbiota , Multiômica , Análise de Dados , Eucariotos , Microbiota/genética , Células Procarióticas
16.
Fungal Biol ; 127(5): 1005-1009, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37142360

RESUMO

Research on bacterial-fungal interactions (BFIs) has revealed that fungi and bacteria frequently interact with one another within diverse ecosystems and microbiomes. Assessing the current state of knowledge within the field of BFI research, particularly with respect to what interactions between bacteria and fungi have been previously described, is very challenging and time consuming. This is largely due to a lack of any centralized resource, with reports of BFIs being spread across publications in numerous journals using non-standardized text to describe the relationships. To address this issue, we have developed the BFI Research Portal, a publicly accessible database of previously reported interactions between bacterial and fungal taxa to serve as a centralized resource for the field. Users can query bacterial or fungal taxa to see what members from the other kingdom have been observed as interaction partners. Search results are accompanied by interactive and intuitive visual outputs, and the database is a dynamic resource that will be updated as new BFIs are reported.


Assuntos
Fungos , Microbiota , Bactérias
17.
iScience ; 26(2): 105987, 2023 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-36756374

RESUMO

Methionine adenosyltransferase 1a (MAT1A) is responsible for hepatic S-adenosyl-L-methionine (SAMe) biosynthesis. Mat1a -/- mice have hepatic SAMe depletion, develop nonalcoholic steatohepatitis (NASH) which is reversed with SAMe administration. We examined temporal alterations in the proteome/phosphoproteome in pre-disease and NASH Mat1a -/- mice, effects of SAMe administration, and compared to human nonalcoholic fatty liver disease (NAFLD). Mitochondrial and peroxisomal lipid metabolism proteins were altered in pre-disease mice and persisted in NASH Mat1a -/- mice, which exhibited more progressive alterations in cytoplasmic ribosomes, ER, and nuclear proteins. A common mechanism found in both pre-disease and NASH livers was a hyperphosphorylation signature consistent with casein kinase 2α (CK2α) and AKT1 activation, which was normalized by SAMe administration. This was mimicked in human NAFLD with a metabolomic signature (M-subtype) resembling Mat1a -/- mice. In conclusion, we have identified a common proteome/phosphoproteome signature between Mat1a -/- mice and human NAFLD M-subtype that may have pathophysiological and therapeutic implications.

18.
Resuscitation ; 186: 109726, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36764570

RESUMO

AIM: Tracheal intubation is associated with interruption in cardiopulmonary resuscitation (CPR). Current knowledge of tracheal intubation during active CPR focuses on the out-of-hospital environment. We aim to describe characteristics of tracheal intubation during active CPR in the emergency department (ED) and determine whether first attempt success was associated with CPR being continued vs paused. MEASUREMENTS: We reviewed overhead video from adult ED patients receiving chest compressions at the start of the orotracheal intubation attempt. We recorded procedural detail including method of CPR, whether CPR was continued vs paused, and first attempt intubation success (primary outcome). We performed logistic regression to determine whether continuing CPR was associated with first attempt success. RESULTS: We reviewed 169 instances of tracheal intubation, including 143 patients with continued CPR and 26 patients with paused CPR. Those with paused CPR were more likely to be receiving manual rather than mechanical chest compressions. Video laryngoscopy and bougie use were common. First attempt success was higher in the continued CPR group (87%, 95% CI 81% to 92%) than the interrupted CPR group (65%, 95% CI 44% to 83%, difference 22% [95% CI 3% to 41%]). The multivariable model demonstrated an adjusted odds ratio of 0.67 (95% CI 0.17 to 2.60) for first attempt intubation success when CPR was interrupted vs continued. CONCLUSIONS: It was common to continue CPR during tracheal intubation, with success comparable to that achieved in patients without cardiac arrest. It is reasonable to attempt tracheal intubation without interrupting CPR, pausing only if necessary.


Assuntos
Reanimação Cardiopulmonar , Parada Cardíaca , Parada Cardíaca Extra-Hospitalar , Adulto , Humanos , Reanimação Cardiopulmonar/métodos , Parada Cardíaca/terapia , Serviço Hospitalar de Emergência , Intubação Intratraqueal/métodos , Tórax , Parada Cardíaca Extra-Hospitalar/terapia
19.
Ann Emerg Med ; 81(6): 667-676, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36841658

RESUMO

STUDY OBJECTIVE: Bougie use during emergency tracheal intubation has not been well studied in children. METHODS: This was a 10-year observational study of pediatric intubations (<18 years of age) in the emergency department (ED) of an academic institution. Bougie training and use are standard in our ED, including for emergency medicine residents. Study data were collected by a combination of charts and video reviews. We compare first-attempt intubation success and procedural complications between pediatric patients with and without bougie use during tracheal intubation in the ED. In addition, we evaluate the independent association of bougie use with first-attempt intubation success using multivariable logistic regression. RESULTS: We collected data on intubation success and bougie use for 195 pediatric patients over more than 10 years. On the first tracheal intubation attempt, a pediatric bougie was used in 126 patients (65%). Median patient age was 5 years (interquartile range 1.7 to 9) in the bougie group and 1.7 years (interquartile range 0.2 to 5) in the no bougie group. Intubation was successful on the first attempt in 72% of intubations with a bougie versus 78% without a bougie (absolute difference -6%, 95% confidence interval [CI] -19 to 6%); the adjusted odds of first-attempt success with a bougie were 0.54 (95% CI 0.24 to 1.19). A procedural complication occurred for 38% of patients in the bougie group versus 51% in the no bougie group (-13%, 95% CI -27% to 2%). Two neonates, one in each group, experienced a potential injury to the airway or lower respiratory tract. CONCLUSION: In an academic ED where the bougie is commonly used, bougie use in children was not associated with procedural success or complications. Our study suggests that a randomized clinical trial is needed to determine the effect of bougie use during emergency pediatric intubation.


Assuntos
Estado Terminal , Intubação Intratraqueal , Recém-Nascido , Humanos , Criança , Lactente , Pré-Escolar , Estado Terminal/terapia , Intubação Intratraqueal/efeitos adversos , Sistema de Registros , Serviço Hospitalar de Emergência , Modelos Logísticos , Laringoscopia
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