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BACKGROUND: Tripartite motif (TRIM46) is a relatively novel protein that belongs to tripartite motif family. TRIM46 organizes parallel microtubule arrays on the axons, which are important for neuronal polarity and axonal function. TRIM46 is highly expressed in the brain, but its biological function in adults has not yet been determined. RESULTS: Trim46 knockout (KO) rat line was established using CRISPR/cas9. Trim46 KO rats had smaller hippocampus sizes, fewer neuronal dendritic arbors and dendritic spines, and shorter and more distant axon initial segment. Furthermore, the protein interaction between endogenous TRIM46 and FK506 binding protein 5 (FKBP5) in brain tissues was determined; Trim46 KO increased hippocampal FKBP5 protein levels and decreased hippocampal protein kinase B (Akt) phosphorylation, gamma-aminobutyric acid type A receptor subunit alpha1 (GABRA1) and glutamate ionotropic receptor NMDA type subunit 1 (NMDAR1) protein levels. Trim46 KO rats exhibited hypoactive behavioral changes such as reduced spontaneous activity, social interaction, sucrose preference, impaired prepulse inhibition (PPI), and short-term reference memory. CONCLUSIONS: These results demonstrate the significant impact of Trim46 KO on brain structure and behavioral function. This study revealed a novel potential association of TRIM46 with dendritic development and neuropsychiatric behavior, providing new insights into the role of TRIM46 in the brain.
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Hipocampo , Animais , Ratos , Hipocampo/metabolismo , Neurônios/metabolismo , Comportamento Animal/fisiologia , Masculino , Ratos Sprague-Dawley , Técnicas de Inativação de Genes , Proteínas com Motivo Tripartido/metabolismo , Proteínas com Motivo Tripartido/genética , Dendritos/metabolismoRESUMO
We are studying the mechanisms of H-reflex operant conditioning, a simple form of learning. Modelling studies in the literature and our previous data suggested that changes in the axon initial segment (AIS) might contribute. To explore this, we used blinded quantitative histological and immunohistochemical methods to study in adult rats the impact of H-reflex conditioning on the AIS of the spinal motoneuron that produces the reflex. Successful, but not unsuccessful, H-reflex up-conditioning was associated with greater AIS length and distance from soma; greater length correlated with greater H-reflex increase. Modelling studies in the literature suggest that these increases may increase motoneuron excitability, supporting the hypothesis that they may contribute to H-reflex increase. Up-conditioning did not affect AIS ankyrin G (AnkG) immunoreactivity (IR), p-p38 protein kinase IR, or GABAergic terminals. Successful, but not unsuccessful, H-reflex down-conditioning was associated with more GABAergic terminals on the AIS, weaker AnkG-IR, and stronger p-p38-IR. More GABAergic terminals and weaker AnkG-IR correlated with greater H-reflex decrease. These changes might potentially contribute to the positive shift in motoneuron firing threshold underlying H-reflex decrease; they are consistent with modelling suggesting that sodium channel change may be responsible. H-reflex down-conditioning did not affect AIS dimensions. This evidence that AIS plasticity is associated with and might contribute to H-reflex conditioning adds to evidence that motor learning involves both spinal and brain plasticity, and both neuronal and synaptic plasticity. AIS properties of spinal motoneurons are likely to reflect the combined influence of all the motor skills that share these motoneurons. KEY POINTS: Neuronal action potentials normally begin in the axon initial segment (AIS). AIS plasticity affects neuronal excitability in development and disease. Whether it does so in learning is unknown. Operant conditioning of a spinal reflex, a simple learning model, changes the rat spinal motoneuron AIS. Successful, but not unsuccessful, H-reflex up-conditioning is associated with greater AIS length and distance from soma. Successful, but not unsuccessful, down-conditioning is associated with more AIS GABAergic terminals, less ankyrin G, and more p-p38 protein kinase. The associations between AIS plasticity and successful H-reflex conditioning are consistent with those between AIS plasticity and functional changes in development and disease, and with those predicted by modelling studies in the literature. Motor learning changes neurons and synapses in spinal cord and brain. Because spinal motoneurons are the final common pathway for behaviour, their AIS properties probably reflect the combined impact of all the behaviours that use these motoneurons.
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Segmento Inicial do Axônio , Reflexo H , Neurônios Motores , Ratos Sprague-Dawley , Animais , Neurônios Motores/fisiologia , Ratos , Masculino , Reflexo H/fisiologia , Segmento Inicial do Axônio/fisiologia , Aprendizagem/fisiologia , Medula Espinal/fisiologia , Medula Espinal/citologia , Axônios/fisiologia , Plasticidade Neuronal/fisiologia , Condicionamento Operante/fisiologia , Anquirinas/metabolismoRESUMO
OBJECTIVE: Hysterectomy has been the historical gold standard final step in the treatment algorithm of adenocarcinoma in situ (AIS) recommended by most North American colposcopy guidelines. AIS disproportionately affects young childbearing age women, therefore a fertility sparing treatment option is desirable. Our study examines the impact of conservative treatment of AIS with conization followed by serial surveillance. METHODS: A retrospective chart review was completed of patients treated for AIS from 2006 to 2020. Charts were identified by pathologic diagnosis of AIS on cervical and uterine specimens. Charts were excluded if AIS was not treated with conization, if AIS was not confirmed on initial conization specimen, or if invasive disease was found at initial conization. RESULTS: 121 patient charts were analyzed. Median age of patients at first conization and hysterectomy was 34.8 and 40.9, respectively. First conization was by Cold Knife Cone in 58% of patients, and by Loop Electrosurgical Excisional Procedure in 42% of patients. Median follow-up period in our study was 609 days. 5% of patients had recurrence, with only one patient who recurred as cancer. One case of recurrence had a positive initial conization margin. Median time to recurrence was 700 days. 47% of patients underwent eventual hysterectomy. Residual AIS was found in 23% of hysterectomy specimens. Adenocarcinoma was diagnosed on hysterectomy specimen in four patients. CONCLUSION: Our study demonstrates the oncologic safety of treating AIS with conization and serial surveillance. Routine hysterectomy completed as a part of the AIS treatment algorithm, as in current clinical guidelines, is unnecessary.
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Adenocarcinoma in Situ , Conização , Histerectomia , Neoplasias do Colo do Útero , Humanos , Feminino , Conização/métodos , Neoplasias do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/patologia , Estudos Retrospectivos , Adulto , Adenocarcinoma in Situ/cirurgia , Adenocarcinoma in Situ/patologia , Histerectomia/métodos , Histerectomia/estatística & dados numéricos , Seguimentos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/epidemiologia , Preservação da Fertilidade/métodos , Adulto JovemRESUMO
OBJECTIVES: The longer-term impact of introducing human papillomavirus (HPV) testing into routine cervical cancer screening on precancer and cancer rates by histologic type has not been well described. Calendar trends in diagnoses were examined using data from Kaiser Permanente Northern California, which introduced triennial HPV and cytology co-testing in 2003 for women aged ≥30 years. METHODS: We examined trends in cervical precancer (cervical intraepithelial neoplasia grade 3 [CIN3] and adenocarcinoma in situ [AIS]) and cancer (squamous cell carcinoma [SCC] and adenocarcinoma [ADC]) diagnoses per 1000 screened during 2003-2018. We examined ratios of squamous vs. glandular diagnoses (SCC:ADC and CIN3:AIS). RESULTS: CIN3 and AIS diagnoses increased approximately 2% and 3% annually, respectively (ptrend < 0.001 for both). While SCC diagnoses decreased by 5% per annually (ptrend < 0.001), ADC diagnoses did not change. These patterns were generally observed within each age group (30-39, 40-49, and 50-64 years). ADC diagnoses per 1000 screened did not change even among those who underwent co-testing starting in 2003-2006. SCC:ADC decreased from approximately 2.5:1 in 2003-2006 to 1.3:1 in 2015-2018 while the CIN3:AIS remained relatively constant, â¼10:1. CONCLUSIONS: Since its introduction at KPNC, co-testing increased the detection of CIN3 over time, which likely caused a subsequent reduction of SCC. However, there has been no observed decrease in ADC. One possible explanation for lack of effectiveness against ADC is the underdiagnosis of AIS. Novel strategies to identify and treat women at high risk of ADC need to be developed and clinically validated.
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Detecção Precoce de Câncer , Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/virologia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/patologia , California/epidemiologia , Adulto , Pessoa de Meia-Idade , Displasia do Colo do Útero/diagnóstico , Displasia do Colo do Útero/epidemiologia , Displasia do Colo do Útero/virologia , Displasia do Colo do Útero/patologia , Detecção Precoce de Câncer/métodos , Detecção Precoce de Câncer/estatística & dados numéricos , Detecção Precoce de Câncer/tendências , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Adenocarcinoma in Situ/patologia , Adenocarcinoma in Situ/diagnóstico , Adenocarcinoma in Situ/epidemiologia , Adenocarcinoma in Situ/virologia , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/epidemiologia , Lesões Pré-Cancerosas/virologia , Lesões Pré-Cancerosas/patologia , Idoso , Esfregaço Vaginal/tendências , Esfregaço Vaginal/métodos , Adenocarcinoma/diagnóstico , Adenocarcinoma/epidemiologia , Adenocarcinoma/patologia , Adenocarcinoma/virologia , Papillomavirus Humano , CitologiaRESUMO
INTRODUCTION: Transportation databases have limited data regarding injury severity of pedestrian versus automobile patients. To identify opportunities to reduce injury severity, transportation and trauma databases were integrated to examine the differences in pedestrian injury severity at street crossings that were signalized crossings (SCs) versus nonsignalized crossings (NSCs). It was hypothesized that trauma database integration would enhance safety analysis and pedestrians struck at NSC would have greater injury severity. METHODS: Single-center retrospective review of all pedestrian versus automobile patients treated at a level 1 trauma center from 2014 to 2018 was performed. Patients were matched to the transportation database by name, gender, and crash date. Google Earth Pro satellite imagery was used to identify SC versus NSC. Injury severity of pedestrians struck at SC was compared to NSC. RESULTS: A total of 512 patients were matched (median age = 41 y [Q1 = 26, Q3 = 55], 74% male). Pedestrians struck at SC (n = 206) had a lower injury severity score (ISS) (median = 9 [4, 14] versus 17 [9, 26], P < 0.001), hospital length of stay (median = 3 [0, 7] versus 6 [1, 15] days, P < 0.001), and mortality (21 [10%] versus 52 [17%], P = 0.04), as compared to those struck at NSC (n = 306). The transportation database had a sensitivity of 63.4% (55.8%-70.4%) and specificity of 63.4% (57.7%-68.9%) for classifying severe injuries (ISS >15). CONCLUSIONS: Pedestrians struck at SC were correlated with a lower ISS and mortality compared to those at NSC. Linkage with the trauma database could increase the transportation database's accuracy of injury severity assessment for nonfatal injuries. Database integration can be used for evidence-based action plans to reduce pedestrian morbidity, such as increasing the number of SC.
Assuntos
Pedestres , Ferimentos e Lesões , Humanos , Masculino , Adulto , Feminino , Acidentes de Trânsito/prevenção & controle , Meios de Transporte , Centros de Traumatologia , Bases de Dados Factuais , Ferimentos e Lesões/diagnóstico , Ferimentos e Lesões/epidemiologiaRESUMO
BACKGROUND: Pediatric arterial ischemic stroke (AIS) is a rare disorder, associated with severe morbidity. In adults, elevated lipoprotein(a) (Lp(a)), a cholesterol-like particle, is associated with ischemic stroke. However, data on Lp(a) and pediatric AIS are scarce. Therefore, we evaluated the association between Lp(a) levels and pediatric AIS. METHODS: We included children who suffered an AIS (≤18 years) and were treated in a tertiary center in Amsterdam, the Netherlands. Two groups of children with AIS were identified: (i) neonates and (ii) children older than 29 days. A case-control study was performed, with the latter group as cases and children without AIS as control group. Cases and controls were matched for age of Lp(a) testing and sex. Multivariable logistic regression models were used. RESULTS: Thirteen neonates and 23 children were included. Mean (SD) age of AIS was 0.6 (2.0) days and 9.2 (6.3) years, respectively. Children with AIS were matched to 62 controls. Lp(a) levels of greater than 50 mg/dL were more prevalent in children with AIS compared to controls (21.7% vs. 3.2%, p = .02). A significant association was found between Lp(a) and AIS (odds ratio [OR] adjusted for age at Lp(a) testing, body mass index [BMI], measurement assay: 1.36 per 10 mg/dL increase of Lp(a), 95% confidence interval [CI]: 1.02-1.82, p = .041). CONCLUSIONS: In this study, Lp(a) levels were positively associated with the risk of AIS in children, suggesting that high Lp(a) might be an independent risk factor for AIS. This underlines the importance of Lp(a) measurement in children with AIS.
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AVC Isquêmico , Lipoproteína(a) , Humanos , Lipoproteína(a)/sangue , Estudos de Casos e Controles , Masculino , Feminino , AVC Isquêmico/sangue , AVC Isquêmico/etiologia , Criança , Recém-Nascido , Pré-Escolar , Lactente , Adolescente , Fatores de Risco , Seguimentos , PrognósticoRESUMO
Seabirds interact with fishing vessels to consume fishing discards and baits, sometimes resulting in incidental capture (bycatch) and the death of the bird, which has clear conservation implications. To understand seabird-fishery interactions at large spatiotemporal scales, researchers are increasing their use of simultaneous seabird and fishing vessel tracking. However, vessel tracking data can contain gaps due to technical problems, illicit manipulation, or lack of adoption of tracking monitoring systems. These gaps might lead to underestimating the fishing effort and bycatch rates and jeopardize the effectiveness of marine conservation. We deployed bird-borne radar detector tags capable of recording radar signals from vessels. We placed tags on 88 shearwaters (Calonectris diomedea, Calonectris borealis, and Calonectris edwardsii) that forage in the northwestern Mediterranean Sea and the Canary Current Large Marine Ecosystem. We modeled vessel radar detections registered by the tags in relation to gridded automatic identification system (AIS) vessel tracking data to examine the spatiotemporal dynamics of seabird-vessel interactions and identify unreported fishing activity areas. Our models showed a moderate fit (area under the curve >0.7) to vessel tracking data, indicating a strong association of shearwaters to fishing vessels in major fishing grounds. Although in high-marine-traffic regions, radar detections were also driven by nonfishing vessels. The tags registered the presence of potential unregulated and unreported fishing vessels in West African waters, where merchant shipping is unusual but fishing activity is intense. Overall, bird-borne radar detectors showed areas and periods when the association of seabirds with legal and illegal fishing vessels was high. Bird-borne radar detectors could improve the focus of conservation efforts.
Uso de radares en aves para analizar las interacciones de las pardelas con las pesquerías legales e ilegales Resumen Las aves marinas interactúan con los barcos pesqueros para consumir los cebos y lo que descartan, lo que a veces resulta en la captura accesoria y la muerte del ave, por lo que esto tiene implicaciones claras para la conservación. Los investigadores cada vez usan más el rastreo simultáneo de las aves marinas y los barcos pesqueros para comprender las interacciones aves marinas pesquerías a gran escala espaciotemporal. Sin embargo, los datos del rastreo de barcos pueden incluir vacíos por problemas técnicos, manipulación ilícita o porque no adoptan sistemas para monitorear el rastreo. Estos vacíos pueden llevar a subestimar el esfuerzo de pesca y las tasas de captura accesoria y a comprometer la efectividad de la conservación marina. Desplegamos marcas detectoras de radar encima de aves capaces de registrar las señales de radar de los barcos. Colocamos estas marcas en 88 pardelas (Calonectris diomedea, C. borealis, y C. edwardsii) que forrajean en el noroeste del Mar Mediterráneo y el Gran Ecosistema Marino de Canarias. Modelamos las detecciones del radar de los barcos registradas por las marcas en relación con los datos reticulados de rastreo de barcos del sistema de identificación automático (AIS) para analizar las dinámicas espaciotemporales de las interacciones aves marinasbarcos e identificar áreas con actividad pesquera no reportada. Nuestros modelos mostraron un ajuste moderado (área bajo la curva > 0.7) a los datos de rastreo de barcos, lo que indica una fuerte asociación entre las pardelas y los barcos en los principales sitios de pesca, aunque en las regiones con alto tránsito de barcos las detecciones por radar también fueron causadas por barcos no pesqueros. Las marcas registraron la presencia del potencial de barcos pesqueros sin regular y sin reportar en aguas del oeste de África, en donde los buques mercantes son poco comunes pero la actividad pesquera es intensa. En general, los detectores por radar en las aves mostraron áreas y periodos en donde la asociación entre las aves marinas y los barcos pesqueros legales e ilegales es alta. Estos detectores por radar podrían mejorar el enfoque de los esfuerzos de conservación.
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Aves , Conservação dos Recursos Naturais , Pesqueiros , Radar , Animais , Aves/fisiologia , Conservação dos Recursos Naturais/métodos , Mar Mediterrâneo , Navios , EspanhaRESUMO
PURPOSE: We investigated the role of lnc_AABR07044470.1 on the occurrence and development of acute ischemic stroke (AIS) and neuronal injury by targeting the miR-214-3p/PERM1 axis to find a novel clinical drug target and prediction and treatment of AIS. METHODS: The mouse AIS animal model was used in vivo experiments and hypoxia/reoxygenation cell model in vitro was established. Firstly, infarction volume and pathological changes of mouse hippocampal neurons were detected using HE staining. Secondly, rat primary neuron apoptosis was detected by flow cytometry assay. The numbers of neuron, microglia and astrocytes were detected using immunofluorescence (IF). Furthermore, binding detection was performed by bioinformatics database and double luciferase reporter assay. Lnc_AABR07044470.1 localization was performed using fluorescence in situ hybridization (FISH).Lnc_AABR07044470.1, miR-214-3pand PERM1mRNA expression was performed using RT-qPCR. NLRP3, ASC, Caspase-1 and PERM1 protein expression was performed using Western blotting. IL-1ß was detected by ELISA assay. RESULTS: Mouse four-vessel occlusion could easily establish the animal model, and AIS animal model had an obvious time-dependence. HE staining showed that, compared with the sham group, infarction volume and pathological changes of mouse hippocampal neurons were deteriorated in the model group. Furthermore, compared with the sham group, neurons were significantly reduced, while microglia and astrocytes were significantly activated. Moreover, the bioinformatics prediction and detection of double luciferase reporter confirmed the binding site of lnc_AABR07044470.1 to miR-214-3p and miR-214-3p to Perm1. lnc_AABR07044470.1 and PERM1 expression was significantly down-regulated and miR-214-3pexpression was significantly up-regulated in AIS animal model in vivo. At the same time, the expression of inflammasome NLRP3, ASC, Caspase-1 and pro-inflammatory factor IL-1ß was significantly up-regulated in vivo and in vitro. The over-expression of lnc_AABR07044470.1 and miR-214-3p inhibitor could inhibit the neuron apoptosis and the expression of inflammasome NLRP3, ASC, Caspase-1 and pro-inflammatory factor IL-1ß and up-regulate the expression of PERM1 in vitro. Finally, over-expression of lnc_AABR07044470.1 and miR-214-3p inhibitor transfected cell model was significant in relieving the AIS and neuronal injury. CONCLUSION: Lnc_AABR07044470.1 promotes inflammatory response to neuronal injury via miR-214-3p/PERM1 axis in AIS.
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AVC Isquêmico , MicroRNAs , RNA Longo não Codificante , Ratos , Camundongos , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , AVC Isquêmico/genética , AVC Isquêmico/metabolismo , Hibridização in Situ Fluorescente , Apoptose , Caspase 1/genética , Caspase 1/metabolismo , Neurônios/metabolismo , Infarto/metabolismo , Infarto/patologia , Luciferases/genética , Proteínas Musculares/genéticaRESUMO
OBJECTIVE: Patients with chronic pain often have sleep disturbances, and many patients receive sleep medications in addition to analgesics. Although there have been scattered reports of negative pain-sleep interactions, only a few reports have investigated the efficacy of sleep medication interventions in patients with chronic pain for improving sleep disturbances and reducing pain. We retrospectively examined whether lemborexant, an orexin receptor antagonist, is effective in improving sleep disturbances and reducing pain in patients with chronic pain. This study was approved by the Ethics Committee of our hospital. METHODS: The subjects were 26 patients with chronic pain undergoing treatment at our pain clinic between July 2021 and March 2022, who had been diagnosed with insomnia, with an Athens Insomnia Scale (AIS) score of ≥6 and had been started on lemborexant. The AIS score and pain score (Numeric Rating Scale [NRS]) before and after 2 and 4 weeks of starting lemborexant were investigated. RESULTS: Patients who were already taking other sleep medications, such as benzodiazepines were switched to 5 mg of lemborexant after all the other sleep medications were discontinued. Those who had not yet used sleeping pills were started on 5 mg of lemborexant. During the study course, the dose of lemborexant was adjusted at the discretion of the attending physician, based on improvement of insomnia symptoms and secondary symptoms, such as daytime sleepiness and lightheadedness. The study finally included 21 patients, excluding 5 who could not continue taking lemborexant due to side effects, such as lightheadedness. The AIS scores significantly improved, decreasing from baseline (mean ± standard deviation: 12.5 ± 4.9) to 2 weeks (7.8 ± 3.1) and 4 weeks (5.3 ± 2.9) after the start of lemborexant. No significant difference was observed in the degree of improvement in sleep disturbance between patients with or without previous sleep medications, and there was also no statistically significant improvement in the NRS score before (6.1 ± 2.7) and after 2 weeks (5.5 ± 2.3) and 4 weeks (5.9 ± 2.2) from treatment initiation.
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Dor Crônica , Piridinas , Pirimidinas , Distúrbios do Início e da Manutenção do Sono , Humanos , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Dor Crônica/tratamento farmacológico , Tontura , Estudos Retrospectivos , SonoRESUMO
Eukaryotic elongation factor 1 alpha 2 (eEF1A2) encodes an isoform of the alpha subunit of the elongation factor 1 complex and is responsible for the enzymatic delivery of aminoacyl tRNA to the ribosome. Our proteomic analysis has identified eEF1A2 as one of the proteins expressed during malignant progression from adenocarcinoma in situ (AIS) to early invasive lung adenocarcinoma. The expression level of eEF1A2 in 175 lung adenocarcinomas was examined by immunohistochemical staining in relation to patient prognosis and clinicopathological factors. Quantitative PCR analysis and fluorescence in situ hybridization (FISH) were performed to evaluate the amplification of the eEF1A2 gene. Relatively high expression of eEF1A2 was observed in invasive adenocarcinoma (39/144 cases) relative to minimally invasive adenocarcinoma (1/10 cases) or AIS (0/21 cases). Among invasive adenocarcinomas, solid-type adenocarcinoma (15/32 cases, 47%) showed higher expression than other histological subtypes (23/92, 25%). Patients with eEF1A2-positive tumors had a significantly poorer prognosis than those with eEF1A2-negative tumors. Of the five tumors that were eEF1A2-positive, two cases showed amplified genomic eEF1A2 DNA, which was confirmed by both qPCR and FISH. These findings indicate that eEF1A2 overexpression occurs in the course of malignant transformation of lung adenocarcinomas and is partly due to eEF1A2 gene amplification.
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Adenocarcinoma de Pulmão , Adenocarcinoma , Biomarcadores Tumorais , Neoplasias Pulmonares , Fator 1 de Elongação de Peptídeos , Humanos , Fator 1 de Elongação de Peptídeos/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Prognóstico , Masculino , Feminino , Adenocarcinoma/patologia , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Pessoa de Meia-Idade , Idoso , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/metabolismo , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Hibridização in Situ Fluorescente , Adulto , Idoso de 80 Anos ou mais , Imuno-HistoquímicaRESUMO
Soluble CD163 (sCD163) is a biomarker of macrophage activation, not previously investigated in the circulation of traumatized patients. A biobank of 398 adult trauma patients was analyzed. Patients with an Injury Severity Score (ISS) >8 served as trauma patients (n = 195) and those with ISS ≤8 as trauma controls (n = 203). Serum samples obtained upon admission, 15h and 72h after were analyzed for sCD163 using an in-house ELISA. Multiple linear regression was used to analyze the association between admission levels of sCD163 with, 1: overall trauma severity (ISS), and 2: severity of injury to specified organs using Abbreviated Injury Score (AIS) and Glasgow Coma Scale (GCS). The association between the peak level of sCD163 with 1-year all-cause mortality was analyzed by logistic regression analysis. Median admission levels of sCD163 were higher in trauma patients than trauma controls [2.32 (IQR 1.73 to 2.86) vs. 1.92 (IQR 1.41 to 2.51) mg/L, p < 0.01]. Worsening GCS score was associated with a 10.3% (95% CI: 17.0 to 3.1, p < 0.01) increase in sCD163. Increasing Head-AIS score was associated with a 5.1% (95% CI: -0.5 to 11.0, p = 0.07) increase in sCD163. The remaining AIS scores and ISS were not consistently associated with sCD163 admission levels. Each mg/L increase in sCD163 peak level had an odds ratio 1.34 (95%CI: 0.98 to 1.83), p = 0.06) after adjustment for age, sex, and GCS. Circulating sCD163 is increased in traumatized patients and associated with worsening GCS. Our findings suggest an association between circulating sCD163 levels with 1-year all-cause mortality.
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PURPOSE: Spinal fusion is the standard treatment for severe forms of adolescent idiopathic scoliosis (AIS). However, with the lowest instrumented vertebra that is usually located at L3 or L4, patients are prone to develop adjacent segment degeneration in the long term. Vertebral body tethering (VBT) as motion preserving technique has become an alternative for select patients with AIS. Several studies have presented the outcome after thoracic VBT but no study has analyzed the outcome after VBT for Lenke type 6 curves. METHODS: This is a retrospective single center data analysis of patients who have had bilateral VBT for Lenke type 6 curves and a minimum follow up of 24 months. Radiographic analysis was performed on several time points. Suspected tether breakages were additionally analyzed with respect to location and time at occurrence. RESULTS: 25 patients were included. Immediate thoracic curve correction was 55.4% and 71.7% for TL/L curves. Loss of correction was higher for TL/L curves and resulted in a correction rate of 48.3% for thoracic curves and 48.9% for TL/L curves at 24 months post-operatively. 22 patients were suspected to have at least one segment with a tether breakage. Three patients required a re-VBT but no patient received posterior spinal fusion. CONCLUSION: Bilateral VBT for Lenke type 6 curves is feasible and shows a significant curve correction for thoracic and TL/L curves at a minimum of 24 months post-operatively. Tether breakage rate and loss of correction remain an unfavorable observation that needs to be improved in the future.
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Escoliose , Fusão Vertebral , Vértebras Torácicas , Humanos , Escoliose/cirurgia , Escoliose/diagnóstico por imagem , Adolescente , Feminino , Estudos Retrospectivos , Masculino , Fusão Vertebral/métodos , Vértebras Torácicas/cirurgia , Vértebras Torácicas/diagnóstico por imagem , Resultado do Tratamento , Corpo Vertebral/cirurgia , Corpo Vertebral/diagnóstico por imagem , Criança , Vértebras Lombares/cirurgia , Vértebras Lombares/diagnóstico por imagemRESUMO
PURPOSE: Vertebral Body Tethering (VBT) has been shown to have a less predictable outcome compared to spinal fusion in patients with adolescent idiopathic scoliosis (AIS). Tether breakage is a common mechanical event that sometimes leads to loss of correction. No data has been published that evaluates the outcome of re-tethering in patients who underwent revision surgery for failed VBT, which was the purpose of this study. METHODS: This is an analysis of a prospectively collected single center database of 290 patients who have had VBT. Patients for this study were included if they have had re-tethering after failed VBT and a minimum follow up of 24 months after index surgery as well as a minimum follow up of 12 months after revision surgery. Revision surgeries included tether exchange, tether reinforcement and/or mono- and bisegmental lateral fusion. Main outcome of interest was curve magnitude at latest follow up. RESULTS: 11 patients were identified who received VBT for 16 curves of which 13 curves have had failed index surgery. Mean follow up from index surgery was 40 months, time between index and revision surgery was 22 months and latest follow up after revision surgery 19 months. Re-tethering resulted in an additional correction of 42% for thoracic and 63% for thoracolumbar curves. These results remained clinically stable with only minor loss of correction at final follow up. No patient underwent or was indicated for spinal fusion. CONCLUSION: Re-tethering is feasible and able to achieve additional correction and a sustainable result.
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Reoperação , Escoliose , Fusão Vertebral , Humanos , Escoliose/cirurgia , Escoliose/diagnóstico por imagem , Adolescente , Feminino , Masculino , Reoperação/estatística & dados numéricos , Reoperação/métodos , Seguimentos , Fusão Vertebral/métodos , Resultado do Tratamento , Corpo Vertebral/cirurgia , Corpo Vertebral/diagnóstico por imagem , Radiografia , CriançaRESUMO
INTRODUCTION: Vertebral body tethering (VBT) has become an alternative option for select patients with idiopathic scoliosis. However, studies have shown a high number of tether breakages, specifically after thoracolumbar (TL) VBT, that can have a negative impact on the outcome, when the breakage occurs within the first year after surgery. In order to overcome this problem, we have started to apply an apical fusion (AF) in combination with TL VBT for select patients. This study aims to analyze the outcome after AF plus VBT. METHODS: This is a retrospective single surgeon's data analysis. All patients were included who have had TL VBT after January 2022 and a follow-up of 12 months. Patients were grouped based on whether they only had VBT or VBT + AF. RESULTS: Twenty-five patients were analyzed (15 VBT, 10 VBT + AF). Both groups showed a significant curve correction for thoracic and TL curves. Minor loss of correction was observed in both groups. A significant difference was seen regarding early tether breakages, which were found in 60% of VBT patients and 10% of VBT + AF patients. CONCLUSION: The preliminary data shows a significant reduction of early tether breakages when TL VBT is applied in combination with AF.
Assuntos
Vértebras Lombares , Escoliose , Fusão Vertebral , Vértebras Torácicas , Humanos , Escoliose/cirurgia , Escoliose/diagnóstico por imagem , Fusão Vertebral/métodos , Feminino , Vértebras Torácicas/cirurgia , Vértebras Torácicas/diagnóstico por imagem , Adolescente , Masculino , Vértebras Lombares/cirurgia , Vértebras Lombares/diagnóstico por imagem , Estudos Retrospectivos , Resultado do Tratamento , Corpo Vertebral/cirurgia , Corpo Vertebral/diagnóstico por imagem , CriançaRESUMO
PURPOSE: To understand how the axial plane deformity contributes to progression of the three-dimensional spinal deformity of Adolescent Idiopathic Scoliosis (AIS), with a main thoracic curve type, using a series of sequential magnetic resonance images (MRI). METHODS: Twenty-seven AIS patients (at scan 1: mean 12.4 years (± 1.5), mean Cobb angle 29.1°(± 8.8°)) had 3 MRI scans (T4-L1) performed at intervals of mean 0.7 years (± 0.4). The outer profile of the superior and inferior endplates were traced on a reformatted axial image using ImageJ (NIH). Endplate AVR, and intravertebral rotation (IVR), defined as the difference between superior and inferior endplate AVR, was calculated for each vertebral level. RESULTS: For all patients and scans, the mean AVR was greatest at the curve apex, with AVR diminishing in a caudal and cephalic direction from the apex. At scan 3 the mean apical AVR was 15.1°(± 4.6°) with a mean change in apical AVR between MRI 1 and 3 of 2.7°(± 2.9°). The increase in standing height between MRI 1 and 3 was mean 7.4 cm (± 4.6). Linear regression showed a positive correlation between apical AVR and Cobb angle (R2 = 0.57, P < 0.001), and a positive correlation between apical AVR and rib hump (R2 = 0.54, p < 0.001). The mean change in IVR was greater 3 vertebral levels cephalic and caudal to the apex (1.4°(± 4.1°) and 1.2°(± 2.0°), respectively), compared to the apex (0.4°(± 3.1°)). CONCLUSIONS: AVR increased, during curve progression, most markedly at the curve apex. The greatest IVR was observed at the periapical levels, with the apex by contrast having only a modest degree of rotation, suggesting the periapical vertebral levels of the scoliosis deformity may be a significant driver in the progression of AIS.
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Escoliose , Humanos , Adolescente , Escoliose/diagnóstico por imagem , Estatura , Modelos Lineares , Imageamento por Ressonância Magnética , RotaçãoRESUMO
PURPOSE: The PDDD is a ratchet-based, unidirectional expandable rod to treat adolescent idiopathic scoliosis (AIS), primarily by correcting scoliotic deformity without full spinal fusion. We hypothesized that the device will be fully tolerated by the host and, if aseptic screw loosening occurs, it will be unrelated to wear particle formation. METHODS: This study comprised tissue samples from seven patients from a prospective study (NCT04296903) to assess the PDDD's safety and benefits, reoperated due to complications. Host response was assessed from histological slides (four levels/implant) in accordance with GLP and ISO10993-6:2016. The elementary chemical composition of wear particles present in tissue sections was quantified by energy dispersive X-ray spectroscopy (EDX). RESULTS: Host reaction was minor, characterized by low levels of diverse inflammatory cells, mild fibrosis, occasional small necrotic foci, neovascularization, hemorrhage, and, rarely, small bone fragments. Twenty-four of 28 tissue sections displayed varying degrees of wear particles (black discoloration), and most sections (17) were scored as 1 (< 25% of the sample). The discoloration observed corresponded to black-appearing, fine granular pigment. EDX analysis confirmed particles were composed of titanium, aluminum, and vanadium. Twenty-six of 28 samples were scored zero for necrosis and 2/28 were scored 1. Eleven samples were scored zero for fibrosis, 12 as 1, and five as 2. No aseptic screw loosening occurred. CONCLUSION: The PDDD induced minimal host reaction with little or no degeneration, inflammation or fibrosis. No changes present could be expected to promote device failure. The PDDD implant for treating AIS is well-tolerated and locally safe.
Assuntos
Escoliose , Humanos , Escoliose/cirurgia , Adolescente , Feminino , Masculino , Estudos Prospectivos , CriançaRESUMO
PURPOSE: To present a novel set of Left-Right Trunk Asymmetry (LRTA) indices and use them to assess the postoperative appearance of the trunk in Adolescent Idiopathic Scoliosis (AIS) patients. METHODS: We hypothesize that LRTA measurements provide complementary information to existing trunk asymmetry indices when documenting the outcome of scoliosis surgery. Forty-nine AIS patients with thoracic curves who underwent posterior spinal fusion were included. All had surface topography scans taken preoperatively and at least 6 months postoperatively. We documented spinal curvature using Radiographic Cobb angles, scoliometer readings and coronal balance. To evaluate Global Trunk Asymmetry (GTA), we used the standard measures of Back Surface Rotation (BSR) and Trunk Lateral Shift (TLS). To measure LRTA, we identified asymmetry areas as regions of significant deviation between the left and right sides of the 3D back surface. New parameters called Deformation Rate (DR) and Maximum Asymmetry (MA) were measured in different regions based on the asymmetry areas. We compared the GTA and LRTA changes with those in spinal curvature before and after surgery. RESULTS: The GTA indices, mainly TLS, showed improvement for more than 75% of patients. There was significant improvement of LRTA in the shoulder blades and waist regions (95% and 80% of patients respectively). CONCLUSION: We report positive outcomes for LRTA in the majority of patients, specifically in the shoulder blades and waist, even when no reduction of BSR is observed. The proposed indices can evaluate local trunk asymmetries and the degree to which they are improved or worsened after scoliosis surgery.
Assuntos
Escoliose , Fusão Vertebral , Adolescente , Humanos , Escoliose/diagnóstico por imagem , Escoliose/cirurgia , Rotação , Período Pós-Operatório , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/cirurgiaRESUMO
The identification of maritime targets plays a critical role in ensuring maritime safety and safeguarding against potential threats. While satellite remote-sensing imagery serves as the primary data source for monitoring maritime targets, it only provides positional and morphological characteristics without detailed identity information, presenting limitations as a sole data source. To address this issue, this paper proposes a method for enhancing maritime target identification and positioning accuracy through the fusion of Automatic Identification System (AIS) data and satellite remote-sensing imagery. The AIS utilizes radio communication to acquire multidimensional feature information describing targets, serving as an auxiliary data source to complement the limitations of image data and achieve maritime target identification. Additionally, the positional information provided by the AIS can serve as maritime control points to correct positioning errors and enhance accuracy. By utilizing data from the Jilin-1 Spectral-01 satellite imagery with a resolution of 5 m and AIS data, the feasibility of the proposed method is validated through experiments. Following preprocessing, maritime target fusion is achieved using a point-set matching algorithm based on positional features and a fuzzy comprehensive decision method incorporating attribute features. Subsequently, the successful fusion of target points is utilized for positioning error correction. Experimental results demonstrate a significant improvement in maritime target positioning accuracy compared to raw data, with over a 70% reduction in root mean square error and positioning errors controlled within 4 pixels, providing relatively accurate target positions that essentially meet practical requirements.
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Satellite-derived Sea Surface Temperature (SST) and sea-surface Chlorophyll a concentration (Chl-a), along with Automatic Identification System (AIS) data of fishing vessels, were used in the examination of the correlation between fishing operations and oceanographic factors within the northern Indian Ocean from March 2020 to February 2023. Frequency analysis and the empirical cumulative distribution function (ECDF) were used to calculate the optimum ranges of two oceanographic factors for fishing operations. The results revealed a substantial influence of the northeast and southwest monsoons significantly impacting fishing operations in the northern Indian Ocean, with extensive and active operations during the period from October to March and a notable reduction from April to September. Spatially, fishing vessels were mainly concentrated between 20° N and 6° S, extending from west of 90° E to the eastern coast of Africa. Observable seasonal variations in the distribution of fishing vessels were observed in the central and southeastern Arabian Sea, along with its adjacent high sea of the Indian Ocean. Concerning the marine environment, it was observed that during the northeast monsoon, the suitable SST contributed to high CPUEs in fishing operation areas. Fishing vessels were widely distributed in the areas with both mid-range and low-range Chl-a concentrations, with a small part distributed in high-concentration areas. Moreover, the monthly numbers of fishing vessels showed seasonal fluctuations between March 2020 and February 2023, displaying a periodic pattern with an overall increasing trend. The total number of fishing vessels decreased due to the impact of the COVID-19 pandemic in 2020, but this was followed by a gradual recovery in the subsequent two years. For fishing operations in the northern Indian Ocean, the optimum ranges for SST and Chl-a concentration were 27.96 to 29.47 °C and 0.03 to 1.81 mg/m3, respectively. The preliminary findings of this study revealed the spatial-temporal distribution characteristics of fishing vessels in the northern Indian Ocean and the suitable ranges of SST and Chl-a concentration for fishing operations. These results can serve as theoretical references for the production and resource management of off-shore fishing operations in the northern Indian Ocean.
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OBJECTIVE: This study aimed to validate the iScore, ASTRAL score, DRAGON score, and THRIVE score for assessing large vessel occlusion-acute ischemic stroke (AIS-LVO) and establish a predictive model for AIS-LVO patients that has better performance to guide clinical practice. METHODS: We retrospectively included 439 patients with AIS-LVO and collected baseline data from all of them. External validation of the iScore, ASTRAL score, DRAGON score, and THRIVE score was performed. All variables were compared between groups via univariate analysis, and the results are expressed as ORs and 95â¯% CIs. Independent variables with P < 0.25 were included in the multivariate logistic analysis, and statistically significant differences (P < 0.05) were identified as risk factors for prognosis in AIS-LVO patients. Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were used to evaluate the predictive value of our model. RESULTS: Our external validation resulted in an iScore under the curve (AUC) of 0.8475, an ASTRAL AUC of 0.8324, a DRAGON AUC of 0.8196, and a THRIVE AUC of 0.8039. In our research, multivariate Cox regression revealed 8 independent predictors. We used a nomogram to visualize the results of the data analysis. The AUC for the training cohort was 0.8855 (95â¯% CI, 0.8487-0.9222), and that in the validation cohort was 0.8992 (95â¯% CI, 0.8496-0. 9488). CONCLUSIONS: In this study, we verified that the above scores have excellent efficacy in predicting the prognosis of AIS-LVO patients. The nomogram we developed was able to predict the prognosis of AIS-LVO more accurately and may contribute to personalized clinical decision-making and treatment for future clinical work.