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1.
BMC Genomics ; 23(1): 353, 2022 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-35525948

RESUMO

BACKGROUND: The cotton leafworm, Spodoptera littoralis, is a highly polyphagous pest of many cultivated plants and crops in Africa and Europe. The genome of this pest will help us to further understand the molecular mechanisms of polyphagy. RESULTS: Herein, the high-quality genome of S. littoralis was obtained by Pacific Bioscience (PacBio) sequencing. The assembled genome size of S. littoralis is 436.55 Mb with a scaffold N50 of 6.09 Mb, consisting of 17,207 annotated protein-coding genes. Phylogenetic analysis shows that S. littoralis and its sibling species S. litura diverged about 5.44 million years ago. Expanded gene families were mainly involved in metabolic detoxification and tolerance to toxic xenobiotics based on GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis. Comparative genomics analysis showed that gene families involved in detoxification and chemosensation were significantly expanded in S. littoralis, representing genetic characteristics related to polyphagy and an extensive host range. CONCLUSIONS: We assembled and annotated the reference genome of S. littoralis, and revealed that this pest has the genetic features of strong detoxification capacity, consistent with it being a significant risk to a wide range of host crops. These data resources will provide support for risk assessment and early warning monitoring of major polyphagous agricultural pests.


Assuntos
Genoma , Genômica , Animais , Gossypium/genética , Larva/genética , Filogenia , Spodoptera/genética
2.
FASEB J ; 36 Suppl 12022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35554639

RESUMO

Osteoporosis is a chronic bone disease characterized by decreased bone mass and increased risk of developing fractures, predominantly observed in the elderly. Osteoporosis affects approximately 10 million people in the US, and the number is expected to increase exponentially as the elderly population continues to grow. The pathophysiological cause of the disease is a decrease in the activity of the bone-forming cells (osteoblasts) that alters bone remodeling in favor of bone resorption, leading to a decrease in bone mass. Recent studies identified the G protein-coupled receptor (GPCR) for insulin-like 3 peptide (INSL3), relaxin family peptide receptor 2 (RXFP2), as an attractive target for the treatment of osteoporosis. The goal of this study is to develop small molecule agonists of RXFP2, expressed in osteoblast cells, to promote bone growth and counteract the deleterious effects of osteoporosis. Currently, the most effective available treatment for osteoporosis is an expensive hormone therapy that requires daily injections. We aim to create drugs that are stable and can be delivered orally. Several low molecular weight compounds were identified as agonists of the RXFP2 receptor using a high-throughput screen of the NCATS small molecule library. The screening assay measured cAMP response in RXFP2-transfected HEK293T cells. An extensive structure-activity relationship campaign resulted in highly potent and efficient full RXFP2 agonists. The selectivity and specificity of the compounds for human and mouse RXFP2 was shown using orthogonal cAMP assays, counter-screening against the related relaxin receptor RXFP1, and a GPCRome screen using the PRESTO-Tango assay. The drug candidates were further tested in primary human osteoblasts to demonstrate that they promote mineralization by measuring hydroxyapatite deposition in the cell matrix. We showed that the compounds had low cytotoxicity in various cell types. Using a series of RXFP2/RXFP1 chimeric receptors, we established that the compounds are allosteric agonists of the RXFP2 receptor and identified the GPCR transmembrane domains as the specific region for compound interaction. The RXFP2 agonist with the highest activity in vitro was selected for pharmacokinetics (PK) profiling in mice, showing optimal oral bioavailability and bone exposure. An efficacy study using 2-month-old WT female mice treated orally with 10 mg/kg of compound 3 times a week for 8 weeks showed a significant increase of the vertebral trabecular number and thickness by micro-CT analysis compared to vehicle treated controls. We expect that the further characterization of these compounds may lead to the development of a new class of cost-effective drugs for the treatment of osteoporosis and other diseases associated with bone loss.

3.
Geroscience ; 2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35381951

RESUMO

Elevated serum urate (hyperuricemia) promotes crystalline monosodium urate tissue deposits and gout, with associated inflammation and increased mortality. To identify modifiers of uric acid pathologies, we performed a fly Genome-Wide Association Study (GWAS) on purine metabolites using the Drosophila Genetic Reference Panel strains. We tested the candidate genes using the Drosophila melanogaster model of hyperuricemia and uric acid crystallization ("concretion formation") in the kidney-like Malpighian tubule. Medusa (mda) activity increased urate levels and inflammatory response programming. Conversely, whole-body mda knockdown decreased purine synthesis precursor phosphoribosyl pyrophosphate, uric acid, and guanosine levels; limited formation of aggregated uric acid concretions; and was sufficient to rescue lifespan reduction in the fly hyperuricemia and gout model. Levels of mda homolog FAM214A were elevated in inflammatory M1- and reduced in anti-inflammatory M2-differentiated mouse bone marrow macrophages, and influenced intracellular uric acid levels in human HepG2 transformed hepatocytes. In conclusion, mda/FAM214A acts in a conserved manner to regulate purine metabolism, promotes disease driven by hyperuricemia and associated tissue inflammation, and provides a potential novel target for uric acid-driven pathologies.

5.
Hum Mol Genet ; 2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-35419606

RESUMO

Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by reduced expression of the survival motor neuron (SMN) protein. Current disease-modifying therapies increase SMN levels and dramatically improve survival and motor function of SMA patients. Nevertheless, current treatments are not cures and autopsy data suggest that SMN induction is variable. Our group and others have shown that combinatorial approaches that target different modalities can improve outcomes in rodent models of SMA. Here we explore if slowing SMN protein degradation and correcting SMN splicing defects could synergistically increase SMN production and improve the SMA phenotype in model mice. We show that co-administering ML372, which inhibits SMN ubiquitination, with an SMN modifying antisense oligonucleotide (ASO) increases SMN production in SMA cells and model mice. In addition, we observed improved spinal cord, neuromuscular junction, and muscle pathology when ML372 and the ASO were administered in combination. Importantly, the combinatorial approach resulted in increased motor function and extended survival of SMA mice. Our results demonstrate that a combination of treatment modalities synergistically increases SMN levels and improves pathophysiology of SMA model mice over individual treatment.

6.
Nat Metab ; 4(2): 159-160, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35177853
7.
Planta ; 255(2): 36, 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35015152

RESUMO

MAIN CONCLUSION: Decreased PG constrains PSI activity due to inhibition of transcript and polypeptide abundance of light-harvesting and reaction center polypeptides generating a reversible, yellow phenotype during cold acclimation of pgp1. Cold acclimation of the Arabidopsis pgp1 mutant at 5 °C resulted in a pale-yellow phenotype with abnormal chloroplast ultrastructure compared to its green phenotype upon growth at 20 °C despite a normal cold-acclimation response at the transcript level. In contrast, wild type maintained its normal green phenotype and chloroplast ultrastructure irrespective of growth temperature. In contrast to cold acclimation of WT, growth of pgp1 at 5 °C limited the accumulation of Lhcbs and Lhcas assessed by immunoblotting. However, a novel 43 kD polypeptide of Lhcb1 as well as a 29 kD polypeptide of Lhcb3 accumulated in the soluble fraction which was absent in the thylakoid membrane fraction of cold-acclimated pgp1 which was not observed in WT. Cold acclimation of pgp1 destabilized the Chl-protein complexes associated with PSI and predisposed energy distribution in favor of PSII rather than PSI compared to the WT. Functionally, in vivo PSI versus PSII photochemistry was inhibited in cold-acclimated pgp1 to a greater extent than in WT relative to controls. Greening of the pale-yellow pgp1 was induced when cold-acclimated pgp1 was shifted from 5 to 20 °C which resulted in a marked decrease in excitation pressure to a level comparable to WT. Concomitantly, Lhcbs and Lhcas accumulated with a simultaneous decrease in the novel 43 and 29kD polypeptides. We conclude that the reduced levels of phosphatidyldiacylglycerol in the pgp1 limit the capacity of the mutant to maintain the structure and function of its photosynthetic apparatus during cold acclimation. Thus, maintenance of normal thylakoid phosphatidyldiacylglycerol levels is essential to stabilize the photosynthetic apparatus during cold acclimation.


Assuntos
Arabidopsis , Fotossíntese , Aclimatação , Arabidopsis/genética , Arabidopsis/metabolismo , Clorofila , Temperatura Baixa , Complexos de Proteínas Captadores de Luz , Peptídeos , Fotoquímica , Complexo de Proteína do Fotossistema I/metabolismo , Complexo de Proteína do Fotossistema II/metabolismo
8.
J Allergy Clin Immunol ; 149(3): 1010-1017.e10, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34425177

RESUMO

BACKGROUND: Acute increases of ≥20% + 2 ng/mL (20 + 2 rule) over basal serum tryptase (BST) is the recommended threshold supporting a clinical diagnosis of anaphylaxis. Prospective studies have demonstrated high sensitivity for this algorithm after parenteral exposure, but specificity has not been evaluated. OBJECTIVE: We sought to define a serum tryptase change that distinguishes baseline variability from anaphylaxis on the basis of intraindividual variation in BST. METHODS: Ninety-three total subjects with atopy (n = 62) or hereditary α-tryptasemia (HαT) (n = 31) and ≥2 BST measurements were identified. Sequential BST variability measurements were modeled and threshold ratios that optimized sensitivity and/or specificity determined. Models were tested in 22 individuals with physician-diagnosed anaphylaxis and validated in independent cohorts of individuals with HαT (n = 33), indolent systemic mastocytosis (ISM) (n = 52), and ISM + HαT (n = 12). Mature tryptase levels were measured in HαT (n = 19) and ISM (n = 20). An online application was developed for clinical use. RESULTS: As a result of BST variability, 9.7% (9/93) of primary cohort patients, and 18% (6/33) of HαT, 30% (16/53) of ISM, and 25% (3/12) of ISM + HαT patients from validation cohorts met the 20 + 2 rule despite absent immediate hypersensitivity symptoms; mature tryptase was noncontributory among individuals with HαT or ISM at baseline. A ratio of acute tryptase/BST exceeding 1.685 provided the optimized diagnostic rule for jointly maximizing sensitivity and specificity. Statistically significant improvement in specificity relative to the 20 + 2 rule was observed among individuals with elevated BST caused by HαT and ISM. CONCLUSIONS: Using an acute tryptase/BST ratio of 1.685 improves specificity of measured changes among individuals with HαT and ISM while maintaining high sensitivity for confirmation of anaphylaxis.


Assuntos
Anafilaxia , Mastocitose Sistêmica , Mastocitose , Anafilaxia/diagnóstico , Humanos , Mastócitos , Estudos Prospectivos , Triptases
9.
Geroscience ; 44(1): 19-24, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34370162

RESUMO

Neuronal aging is associated with numerous diseases resulting in memory impairment and functional decline. A common hallmark of these disorders is the accumulation of intracellular and extracellular protein aggregates. The retromer complex plays a central role in sorting proteins by marking them for reuse rather than degradation. Retromer dysfunction has been shown to induce protein aggregates and neurodegeneration, suggesting that it may be important for age-related neuronal decline and disease progression. Despite this, little is known about how aging influences retromer stability and the proteins with which it interacts. Detailed insights into age-dependent changes in retromer structure and function could provide valuable information towards treating and preventing many age-related neurodegenerative disorders. Here, we visit age-related pathways which interact with retromer function that ought to be further explored to determine its role in age-related neurodegeneration.


Assuntos
Doenças Neurodegenerativas , Humanos , Neurônios/metabolismo , Transporte Proteico/fisiologia
10.
Biochim Biophys Acta Gen Subj ; 1866(1): 130017, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34624450

RESUMO

BACKGROUND: Autophagy, a highly conserved homeostatic mechanism, is essential for cell survival. The decline of autophagy function has been implicated in various diseases as well as aging. Although mitochondria play a key role in the autophagy process, whether mitochondrial-derived peptides are involved in this process has not been explored. METHODS: We developed a high through put screening method to identify potential autophagy inducers among mitochondrial-derived peptides. We used three different cell lines, mice, c.elegans, and a human cohort to validate the observation. RESULTS: Humanin, a mitochondrial-derived peptide, increases autophagy and maintains autophagy flux in several cell types. Humanin administration increases the expression of autophagy-related genes and lowers accumulation of harmful misfolded proteins in mice skeletal muscle, suggesting that humanin-induced autophagy potentially contributes to the improved skeletal function. Moreover, autophagy is a critical role in humanin-induced lifespan extension in C. elegans. CONCLUSIONS: Humanin is an autophagy inducer. GENERAL SIGNIFICANCE: This paper presents a significant, novel discovery regarding the role of the mitochondrial derived peptide humanin in autophagy regulation and as a possible therapeutic target for autophagy in various age-related diseases.


Assuntos
Autofagia/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Músculo Esquelético/metabolismo , Envelhecimento , Animais , Caenorhabditis elegans/metabolismo , Linhagem Celular , Sobrevivência Celular , Células HEK293 , Homeostase , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Longevidade , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Músculo Esquelético/fisiologia , Peptídeos/metabolismo
11.
Pest Manag Sci ; 78(4): 1529-1537, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34965003

RESUMO

BACKGROUND: The general principle of using microbes from one species to manage a different pest species has a clear precedent in the large-scale release of mosquitoes carrying a Wolbachia bacterium derived from Drosophila flies. New technologies will facilitate the discovery of microbes that can be used in a similar way. Previously, we found three novel partiti-like viruses in the African armyworm (Spodoptera exempta). To investigate further the utility and consistency of host shift of insect viruses as a potential pest management tool, we tested the interaction between the partiti-like viruses and another novel host, the Egyptian cotton leafworm (Spodoptera littoralis). RESULT: We found that all three partiti-like viruses appeared to be harmful to the novel host S. littoralis, by causing increased larval and pupal mortality. No effect was observed on host fecundity, and partiti-like virus infection did not impact host susceptibility when challenged with another pathogen, the baculovirus SpliNPV. Transcriptome analysis of partiti-like virus-infected and noninfected S. littoralis indicated that the viruses could impact host gene-expression profiles of S. littoralis, but they impact different pathways to the two other Spodoptera species through effects on pathways related to immunity (Jak-STAT/Toll and Imd) and reproduction (insulin signaling/insect hormones). CONCLUSION: Taken together with the previous findings in the novel host S. frugiperda, these results indicate a parasitic relationship between the partiti-like viruses and novel insect hosts, suggesting a possible use and novel pest management strategy through the artificial host shift of novel viruses. © 2021 Society of Chemical Industry.


Assuntos
Baculoviridae , Animais , Egito , Larva , Pupa , Spodoptera
12.
Sci Rep ; 11(1): 20757, 2021 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-34675253

RESUMO

Understanding the population structure and movements of the invasive fall armyworm (FAW, Spodoptera frugiperda) is important as it can help mitigate crop damage, and highlight areas at risk of outbreaks or evolving insecticide resistance. Determining population structure in invasive FAW has been a challenge due to genetic mutations affecting the markers traditionally used for strain and haplotype identification; mitochondrial cytochrome oxidase I (COIB) and the Z-chromosome-linked Triosephosphate isomerase (Tpi). Here, we compare the results from COIB and Tpi markers with highly variable repeat regions (microsatellites) to improve our understanding of FAW population structure in Africa. There was very limited genetic diversity using the COIB marker, whereas using the TpiI4 marker there was greater diversity that showed very little evidence of genetic structuring between FAW populations across Africa. There was greater genetic diversity identified using microsatellites, and this revealed a largely panmictic population of FAW alongside some evidence of genetic structuring between countries. It is hypothesised here that FAW are using long-distance flight and prevailing winds to frequently move throughout Africa leading to population mixing. These approaches combined provide important evidence that genetic mixing between invasive FAW populations may be more common than previously reported.


Assuntos
Espécies Introduzidas , Repetições de Microssatélites , Spodoptera/genética , África , Animais , Haplótipos , Resistência a Inseticidas , Masculino , Mutação
13.
Mol Cell ; 81(18): 3675-3676, 2021 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-34547232

RESUMO

We highlight Martinez-Miguel et al. (2021), which demonstrates that an amino acid substitution in RPS23 found in thermophilic archaea contributes to increased translation fidelity, lifespan, and stress response but slows development and reproduction in other organisms.


Assuntos
Longevidade , Reprodução , Longevidade/genética
14.
Cell Metab ; 33(11): 2142-2173, 2021 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-34555343

RESUMO

Dietary restriction (DR) has long been viewed as the most robust nongenetic means to extend lifespan and healthspan. Many aging-associated mechanisms are nutrient responsive, but despite the ubiquitous functions of these pathways, the benefits of DR often vary among individuals and even among tissues within an individual, challenging the aging research field. Furthermore, it is often assumed that lifespan interventions like DR will also extend healthspan, which is thus often ignored in aging studies. In this review, we provide an overview of DR as an intervention and discuss the mechanisms by which it affects lifespan and various healthspan measures. We also review studies that demonstrate exceptions to the standing paradigm of DR being beneficial, thus raising new questions that future studies must address. We detail critical factors for the proposed field of precision nutrigeroscience, which would utilize individualized treatments and predict outcomes using biomarkers based on genotype, sex, tissue, and age.


Assuntos
Restrição Calórica , Longevidade , Envelhecimento , Humanos , Longevidade/genética
17.
Glob Chang Biol ; 27(19): 4498-4515, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34236759

RESUMO

Species are frequently responding to contemporary climate change by shifting to higher elevations and poleward to track suitable climate space. However, depending on local conditions and species' sensitivity, the nature of these shifts can be highly variable and difficult to predict. Here, we examine how the American pika (Ochotona princeps), a philopatric, montane lagomorph, responds to climatic gradients at three spatial scales. Using mixed-effects modeling in an information-theoretic approach, we evaluated a priori model suites regarding predictors of site occupancy, relative abundance, and elevational-range retraction across 760 talus patches, nested within 64 watersheds across the Northern Rocky Mountains of North America, during 2017-2020. The top environmental predictors differed across these response metrics. Warmer temperatures in summer and winter were associated with lower occupancy, lower relative abundances, and greater elevational retraction across watersheds. Occupancy was also strongly influenced by habitat patch size, but only when combined with climate metrics such as actual evapotranspiration. Using a second analytical approach, acute heat stress and summer precipitation best explained retraction residuals (i.e., the relative extent of retraction given the original elevational range of occupancy). Despite the study domain occurring near the species' geographic-range center, where populations might have higher abundances and be at lower risk of climate-related stress, 33.9% of patches showed evidence of recent extirpations. Pika-extirpated sites averaged 1.44℃ warmer in summer than did occupied sites. Additionally, the minimum elevation of pika occupancy has retracted upslope in 69% of watersheds (mean: 281 m). Our results emphasize the nuance associated with evaluating species' range dynamics in response to climate gradients, variability, and temperature exceedances, especially in regions where species occupy gradients of conditions that may constitute multiple range edges. Furthermore, this study highlights the importance of evaluating diverse drivers across response metrics to improve the predictive accuracy of widely used, correlative models.


Assuntos
Mudança Climática , Lagomorpha , Animais , Ecossistema , Estações do Ano , Temperatura
18.
Elife ; 102021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34263726

RESUMO

Bacillus thuringiensis (Bt) crops have been widely planted and the effects of Bt-crops on populations of the target and non-target insect pests have been well studied. However, the effects of Bt-crops exposure on microorganisms that interact with crop pests have not previously been quantified. Here, we use laboratory and field data to show that infection of Helicoverpa armigera with a densovirus (HaDV2) is associated with its enhanced growth and tolerance to Bt-cotton. Moreover, field monitoring showed a much higher incidence of cotton bollworm infection with HaDV2 in regions cultivated with Bt-cotton than in regions without it, with the rate of densovirus infection increasing with increasing use of Bt-cotton. RNA-seq suggested tolerance to both baculovirus and Cry1Ac were enhanced via the immune-related pathways. These findings suggest that exposure to Bt-crops has selected for beneficial interactions between the target pest and a mutualistic microorganism that enhances its performance on Bt-crops under field conditions.


Assuntos
Bacillus thuringiensis , Densovirus , Gossypium , Inseticidas , Animais , Toxinas de Bacillus thuringiensis , Baculoviridae , China , Endotoxinas , Proteínas Hemolisinas , Insetos , Resistência a Inseticidas , Mariposas , Plantas Geneticamente Modificadas , Simbiose
19.
Front Physiol ; 12: 650769, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34305630

RESUMO

Diseases, such as diabetes and hypertension, often lead to chronic kidney failure. The peptide hormone relaxin has been shown to have therapeutic effects in various organs. In the present study, we tested the hypothesis that ML290, a small molecule agonist of the human relaxin receptor (RXFP1), is able to target the kidney to remodel the extracellular matrix and reduce apoptosis induced by unilateral ureteral obstruction (UUO). UUO was performed on the left kidney of humanized RXFP1 mice, where the right kidneys served as contralateral controls. Mice were randomly allocated to receive either vehicle or ML290 (30 mg/kg) via daily intraperitoneal injection, and kidneys were collected for apoptosis, RNA, and protein analyses. UUO significantly increased expression of pro-apoptotic markers in both vehicle- and ML290-treated mice when compared to their contralateral control kidneys. Specifically, Bax expression and Erk1/2 activity were upregulated, accompanied by an increase of TUNEL-positive cells in the UUO kidneys. Additionally, UUO induced marked increase in myofibroblast differentiation and aberrant remodeling on the extracellular matrix. ML290 suppressed these processes by promoting a reduction of pro-apoptotic, fibroblastic, and inflammatory markers in the UUO kidneys. Finally, the potent effects of ML290 to remodel the extracellular matrix were demonstrated by its ability to reduce collagen gene expression in the UUO kidneys. Our data indicate that daily administration of ML290 has renal protective effects in the UUO mouse model, specifically through its anti-apoptotic and extracellular matrix remodeling properties.

20.
J Trauma Acute Care Surg ; 91(4): 621-626, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34225345

RESUMO

BACKGROUND: Injury Severity Score (ISS) is a widely used metric for trauma research and center verification; however, it does not account for age-related physiologic parameters. We hypothesized that a novel age-based injury severity metric would better predict mortality. METHODS: Adult patients (≥18 years) sustaining blunt trauma (BT) or penetrating trauma (PT) were abstracted from the 2010 to 2016 National Trauma Data Bank. Admission vitals, Glasgow Coma Scale, ISS, mechanism, and outcomes were analyzed. Patients with incomplete/non-physiologic vital signs were excluded. For each age: (1) a cut point analysis was used to determine the ISS with the highest specificity and sensitivity for predicting mortality and (2) a linear discriminant analysis was performed using ISS, ISS greater than 16, Trauma and Injury Severity Score, and Revised Trauma Scale to compare each scoring system's mortality prediction. A novel injury severity metric, the trauma component score (TCS), was developed for each age using significant (p < 0.05) variables selected from Abbreviated Injury Scale scores, Glasgow Coma Scale, vital signs, and gender. Receiver operator curves were developed and the areas under the curve were compared between the TCS and other systems. RESULTS: There 777,794 patients studied (BT, 91.1%; PT, 8.9%). Blunt trauma patients were older (53.6 ± 21.3 years vs. 34.4 ± 13.8 years), had higher ISS scores (11.1 ± 8.5 vs. 8.5 ± 8.9), and lower mortality (2.9% vs. 3.4%) than PT patients (p < 0.05). When assessing the entire PT and BT cohort the optimal ISS cut point was 16. The optimal ISS was between 20 and 25 for BT younger than 70 years. For those older than 70 years, the optimal BT ISS steadily declined as age increased PT's cut point was 16 or less for all ages assessed. When the injury metrics were compared by area under the curve, our novel TCS more accurately predicted mortality across all ages in both BT and PT (p < 0.001). CONCLUSION: Injury Severity Score is a poor mortality predictor in older patients and those sustaining penetrating trauma. The age-based TCS is a superior metric for mortality prediction across all ages. LEVEL OF EVIDENCE: Clinical outcomes, Level IV.


Assuntos
Escala de Coma de Glasgow , Escala de Gravidade do Ferimento , Ferimentos não Penetrantes/mortalidade , Ferimentos Penetrantes/mortalidade , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros/estatística & dados numéricos , Estudos Retrospectivos , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Fatores Sexuais , Centros de Traumatologia/estatística & dados numéricos , Ferimentos não Penetrantes/diagnóstico , Ferimentos não Penetrantes/terapia , Ferimentos Penetrantes/diagnóstico , Ferimentos Penetrantes/terapia , Adulto Jovem
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