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A super-resolution deep learning reconstruction (SR-DLR) algorithm trained using data acquired on the ultrahigh spatial resolution computed tomography (UHRCT) has the potential to provide better image quality of coronary arteries on the whole-heart, single-rotation cardiac coverage on a 320-detector row CT scanner. However, the advantages of SR-DLR at coronary computed tomography angiography (CCTA) have not been fully investigated. The present study aimed to compare the image quality of the coronary arteries and in-stent lumen between SR-DLR and model-based iterative reconstruction (MBIR). We prospectively enrolled 70 patients (median age, 69 years; interquartile range [IQR], 59-75 years; 50 men) who underwent CCTA using a 320-detector row CT scanner between January and August 2022. The image noise in the ascending aorta, left atrium, and septal wall of the ventricle was measured, and the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) in the proximal coronary arteries were calculated. Of the twenty stents, stent strut thickness and luminal diameter were quantitatively evaluated. The image noise on SR-DLR was significantly lower than that on MBIR (median 22.1 HU; IQR, 19.3-24.9 HU vs. 27.4 HU; IQR, 24.2-31.2 HU, p < 0.01), whereas the SNR (median 16.3; IQR, 11.8-21.8 vs. 13.7; IQR, 9.9-18.4, p = 0.01) and CNR (median 24.4; IQR, 15.5-30.2 vs. 19.2; IQR, 14.1-23.2, p < 0.01) on SR-DLR were significantly higher than that on MBIR. Stent struts were significantly thinner (median, 0.68 mm; IQR, 0.61-0.78 mm vs. 0.81 mm; IQR, 0.72-0.96 mm, p < 0.01) and in-stent lumens were significantly larger (median, 1.84 mm; IQR, 1.65-2.26 mm vs. 1.52 mm; IQR, 1.28-2.25 mm, p < 0.01) on SR-DLR than on MBIR. Although further large-scale studies using invasive coronary angiography as the reference standard, comparative studies with UHRCT, and studies in more challenging population for CCTA are needed, this study's initial experience with SR-DLR would improve the utility of CCTA in daily clinical practice due to the better image quality of the coronary arteries and in-stent lumen at CCTA compared with conventional MBIR.
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Angiografía por Tomografía Computarizada , Aprendizaje Profundo , Masculino , Humanos , Anciano , Angiografía por Tomografía Computarizada/métodos , Vasos Coronarios/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Angiografía Coronaria/métodos , Stents , Atrios Cardíacos , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Algoritmos , Dosis de RadiaciónRESUMEN
The best cardiac phases in retrospective ECG-gated CT for detecting an intimal tear (IT) in aortic dissection (AD) and an ulcer-like projection (ULP) in an intramural hematoma (IMH) have not been established. This study aimed to compare the detection accuracy of diastolic-phase and systolic-phase ECG-gated CT for IT in AD and ULP in IMH, with subsequent surgical or angiographical confirmation as the reference standard.In total, 81 patients (67.6 ± 11.8 years; 41 men) who underwent emergency ECG-gated CT and subsequent open surgery or thoracic endovascular aortic repair for AD (n = 52) or IMH (n = 29) were included. The accuracies of detecting IT and ULP were compared among only diastolic-phase, only systolic-phase, and both diastolic-phase and systolic-phase methods of retrospective ECG-gated CT; surgical or angiographical findings were used as the reference standard. The detection accuracy for IT and ULP using only diastolic-phase, only systolic-phase, and both diastolic-phase and systolic-phase methods of ECG-gated CT was 93% [95% CI: 87-97], 94% [95% CI: 88-97], and 95% [95% CI: 90-97], respectively. There were no significant differences in detection accuracy among the 3 acquisition methods (P = 0.55). Similarly, there were no significant differences in the accuracy of detecting IT in AD (P = 0.55) and ULP in IMH (P > 0.99) among only diastolic-phase, only systolic-phase, and both diastolic- and systolic-phase ECG-gated CT.Retrospective ECG-gated CT for detecting IT in AD and ULP in IMH yields highly accurate findings. There were no significant differences seen among only diastolic-phase, only systolic-phase, and both diastolic-phase and systolic-phase ECG-gated CT.
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Sindrome Aortico Agudo , Enfermedades de la Aorta , Disección Aórtica , Masculino , Humanos , Enfermedades de la Aorta/diagnóstico por imagen , Enfermedades de la Aorta/cirugía , Estudios Retrospectivos , Disección Aórtica/diagnóstico por imagen , Disección Aórtica/cirugía , Tomografía Computarizada por Rayos X/métodos , Electrocardiografía , Hematoma/cirugíaRESUMEN
Interactions between different animal species are a critical determinant of each species' evolution and range expansion. Chemical, visual, and mechanical interactions have been abundantly reported, but the importance of electric interactions is not well understood. Here, we report the discovery that the nematode Caenorhabditis elegans transfers across electric fields to achieve phoretic attachment to insects. First, we found that dauer larvae of C. elegans nictating on a substrate in a Petri dish moved directly to the lid through the air due to the electrostatic force from the lid. To more systematically investigate the transfer behavior, we constructed an assay system with well-controlled electric fields: the worms flew up regardless of whether a positive or negative electric field was applied, suggesting that an induced charge within the worm is related to this transfer. The mean take-off speed is 0.86 m/s, and the worm flies up under an electric field exceeding 200 kV/m. This worm transfer occurs even when the worms form a nictation column composed of up to 100 worms; we term this behavior "multiworm transfer." These observations led us to conclude that C. elegans can transfer and attach to the bumblebee Bombus terrestris, which was charged by rubbing with flower pollen in the lab. The charge on the bumblebee was measured with a coulomb-meter to be 806 pC, which was within the range of bumblebee charges and of the same order of flying insect charges observed in nature, suggesting that electrical interactions occur among different species.
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Caenorhabditis elegans , Insectos , Animales , Larva , Conducta Animal , ElectricidadRESUMEN
Nutritional requirements for maintaining metabolic health may vary with each life stage, such as young, middle, and old age. To investigate the appropriate ratio of nutrients, particularly proteins, for maintaining metabolic health while approaching old age, young (6-month-old) and middle-aged (16-month-old) mice were fed isocaloric diets with varying protein percentages (5%, 15%, 25%, 35%, and 45% by calorie ratio) for two months. The low-protein diet developed mild fatty liver, with middle-aged mice showing more lipids than young mice, whereas the moderate-protein diet suppressed lipid contents and lowered the levels of blood glucose and lipids. Self-organizing map (SOM) analysis revealed that plasma amino acid profiles differed depending on age and difference in protein diet and were associated with hepatic triglyceride and cholesterol levels. Results indicate that the moderate protein intake percentages (25% and 35%) are required for maintaining metabolic health in middle-aged mice, which is similar to that in young mice.
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Dieta , Hígado , Ratones , Animales , Hígado/metabolismo , Ingestión de Energía , Triglicéridos , Glucemia/metabolismoRESUMEN
PURPOSE: Dark band (DB) artifact in head and neck computed tomography (CT) is caused by beam hardening (BH), and decreased CT values in the X-ray target become a problem. Therefore, we investigated whether it is possible to reduce DB artifact in the head and neck with a compensation filter. METHODS: We made 2 types of filters with alcohol and water. We set each of these filters in front of the chest phantom's clavicle and evaluated DB artifact. The evaluation method measured CT values in the DB artifact area and background (BG) area by changing each compensation filter thickness and the distance between the chest phantom's surface and each compensation filter. In addition, we measured average standard deviation (SD) in the BG area by the presence of each compensation filter. RESULTS: CT values in the DB artifact area were approximate to those in the BG area by setting the thickness of each compensation filter to more than 30 mm. Furthermore, these CT values were decreased by separating the distance between the chest phantom's surface and each compensation filter. Average SD in the BG area showed no significant difference between no filter and each compensation filter. CONCLUSION: It was possible to reduce DB artifact by a compensation filter for DB.
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Artefactos , Tomografía Computarizada por Rayos X , Tomografía Computarizada por Rayos X/métodos , Cuello/diagnóstico por imagen , Cabeza/diagnóstico por imagen , Fantasmas de Imagen , AlgoritmosRESUMEN
Bicuspid aortic valve (BAV) patients with aortic stenosis (AS) are known to develop dilatation of the ascending aorta at a younger age, but the morphology of the aorta in these patients is yet to be investigated. Thus, in this study, we aim to evaluate the aortic morphology of BAV patients with severe AS using thin-slice electrocardiogram (ECG) -gated computed tomography (CT) and identify the possible contributing effect of age.In this retrospective study, 122 BAV and 154 tricuspid aortic valve (TAV) patients who received aortic valve replacement for severe AS were assessed by thin-slice ECG-gated CT and three-dimensional reconstruction. The morphology of the ascending aorta was also evaluated among BAV patients aged < 70 (n = 72) and ≥ 70 (n = 50) years old. As per our findings, BAV patients with severe AS had significantly greater diameter (P < 0.01), elongation (P < 0.01), and tortuosity (P = 0.03) of the ascending aorta; minimum aortic arch angle (P < 0.01); and significantly lower calcified plaque (P < 0.01) compared with those of TAV patients even after adjusting for background. Multiple regression analysis showed that standardized partial regression coefficients (ß) of dilatation (0.5) and elongation (0.35) were higher among other measurements of aortic morphology for BAV patients. BAV patients with severe AS aged ≥ 70 years had significantly greater diameter (42.0 [37.2-46.1] mm versus 40.4 [35.2-44.2] mm, P = 0.049) and elongation (133.8 [123.5-147.3] mm versus 127.0 [111.0-140.0] mm, P = 0.01) of the ascending aorta than those aged < 70 years.BAV patients with severe AS were determined to have greater dilatation and elongation of the ascending aorta. Moreover, BAV patients older than 70 years had greater diameter and elongation of the ascending aorta.
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Estenosis de la Válvula Aórtica , Enfermedad de la Válvula Aórtica Bicúspide , Anciano , Aorta/cirugía , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/diagnóstico , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Electrocardiografía , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Tomografía Computarizada por Rayos XRESUMEN
Many studies have shown the beneficial effects of calorie restriction (CR) on rodents' aging; however, the molecular mechanism explaining these beneficial effects is still not fully understood. Previously, we conducted transcriptomic analysis on rat liver with short-term and mild-to-moderate CR to elucidate its early response to such diet. Here, we expanded transcriptome analysis to muscle, adipose tissue, intestine, and brain and compared the gene expression profiles of these multiple organs and of our previous dataset. Several altered gene expressions were found, some of which known to be related to CR. Notably, the commonly regulated genes by CR include nicotinamide phosphoribosyltransferase and heat shock protein 90, which are involved in declining the aging process and thus potential therapeutic targets for aging-related diseases. The data obtained here provide information on early response markers and key mediators of the CR-induced delay in aging as well as on age-associated pathological changes in mammals.
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Restricción Calórica , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Especificidad de Órganos/genética , Animales , Regulación hacia Abajo/genética , Masculino , Metaanálisis como Asunto , Ratas Wistar , Regulación hacia Arriba/genéticaRESUMEN
PURPOSE: To develop and validate a CT diagnostic algorithm for bicuspid aortic valve (BAV) classification. MATERIALS AND METHODS: This retrospective study included 212 consecutive patients with severe aortic stenosis who underwent CT followed by aortic valve replacement (mean age, 71 years [range, 27-93 years]; 125 women; 37% with a BAV) from 2012 to 2017. BAV diagnosis and BAV category were determined by using the CT diagnostic algorithm developed and were compared with those attained through surgical diagnosis. Reproducibility and agreement were assessed using the Cohen kappa (κ) coefficient. The value of adding CT to age, aortic diameter index, and transthoracic echocardiography (TTE) was evaluated by using the area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), and decision-curve analysis. RESULTS: Intra- and interobserver reproducibility were good or excellent for all CT diagnoses (κ ≥ 0.6 for all). Agreement between CT and surgical diagnoses was excellent (κ = 0.90) for BAV detection and good (κ = 0.69) for BAV categorization. Sixteen percent (five of 31) of patients with functional BAV diagnosed by using CT received a diagnosis of congenital BAV at surgery. The addition of CT to age, aortic diameter, and TTE showed a higher AUC (with CT, 0.97 [95% CI: 0.91, 0.99] vs without CT, 0.91 [95% CI: 0.85, 0.95]; P = .003) and NRI (1.79 [95% CI: 1.65, 1.92], P < .001) and a higher net benefit among all BAV probabilities. CONCLUSION: CT diagnosis was consistent with surgical diagnosis and had an additive value over traditional diagnostic methods; however, there was a risk of overlooking congenital BAV in patients with functional BAV diagnosed by using CT.Supplemental material is available for this article.© RSNA, 2021.
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A fungal metabolite, diatretol, has shown to be a promising antimalarial agent. Diatretol displayed potent in vitro antiparasitic activity against the Plasmodium falciparum K1 strain, with an IC50 value of 378 ng ml-1, as well as in vivo efficacy in a Plasmodium berghei-infected mice model, with ca. 50% inhibition at 30 mg/kg (p.o.).
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Antimaláricos/farmacología , Malaria/tratamiento farmacológico , Animales , Antimaláricos/química , Dicetopiperazinas/química , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Eritrocitos/parasitología , Humanos , Malaria/parasitología , Ratones Endogámicos ICR , Parasitemia/tratamiento farmacológico , Parasitemia/parasitología , Plasmodium berghei/parasitología , Plasmodium falciparum/efectos de los fármacosRESUMEN
Break-induced replication (BIR) is a specialized homologous-recombination pathway for DNA double-strand break (DSB) repair, which often induces genome instability. In this study, we establish EGFP-based recombination reporters to systematically study BIR in mammalian cells and demonstrate an important role of human PIF1 helicase in promoting BIR. We show that at endonuclease cleavage sites, PIF1-dependent BIR is used for homology-initiated recombination requiring long track DNA synthesis, but not short track gene conversion (STGC). We also show that structure formation-prone AT-rich DNA sequences derived from common fragile sites (CFS-ATs) induce BIR upon replication stress and oncogenic stress, and PCNA-dependent loading of PIF1 onto collapsed/broken forks is critical for BIR activation. At broken replication forks, even STGC-mediated repair of double-ended DSBs depends on POLD3 and PIF1, revealing an unexpected mechanism of BIR activation upon replication stress that differs from the conventional BIR activation model requiring DSB end sensing at endonuclease-generated breaks. Furthermore, loss of PIF1 is synthetically lethal with loss of FANCM, which is involved in protecting CFS-ATs. The breast cancer-associated PIF1 mutant L319P is defective in BIR, suggesting a direct link of BIR to oncogenic processes.
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ADN Helicasas/metabolismo , Replicación del ADN , Reparación del ADN por Recombinación , Roturas del ADN de Doble Cadena , ADN Helicasas/genética , ADN Polimerasa III/metabolismo , Células HCT116 , Humanos , Mutación , Antígeno Nuclear de Célula en Proliferación/metabolismoRESUMEN
Calorie restriction (CR) by 30-40% decreases morbidity of age-related diseases and prolongs the lifespan of various laboratory animal species. Taurine (2-aminoethanesulfonic acid) is an important nutrient for lipid metabolism as it conjugates bile acids. Here, we investigated how taurine supplementation induces effects similar to the CR beneficial effects. Sprague Dawley rats were fed a diet containing different taurine concentrations (0, 0.5, 1.0, 3.0, 5.0%) to analyze the effects on growth, blood, and hepatic parameters. Rats fed a 5% taurine-supplemented diet showed a significant decrease in visceral fat weight, compared with control rats. Moreover, there were significant decreases in the serum total cholesterol, hepatic cholesterol and triglyceride concentrations in the taurine-supplemented groups compared with the control group in a dose-dependent manner. These results were associated with decreased mRNA expression of fatty acid synthase, and increased mRNA expression of carnitine palmitoyltransferase 1α. C57BL/6 mice were fed a 5.0% taurine-supplemented diet, and their response to 3-nitropropionic acid-induced oxidative stress was analyzed. The rate of weight loss due to oxidative stress decreased and the survival rate significantly increased in the taurine-supplemented groups compared with the control group. Finally, cells were treated with 100 µM taurine and their resistance to UV-induced oxidative stress was analyzed. We found that the p53-Chk1 pathway was less activated in taurine-treated cells compared with control cells. Furthermore, damage to cells evaluated by oxidative stress indicators revealed a reduction in oxidative damage with taurine treatment. These findings suggest that taurine partially acts as a CR mimetic.
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Suplementos Dietéticos , Metabolismo de los Lípidos , Estrés Oxidativo , Taurina/administración & dosificación , Animales , Colesterol/sangre , Colesterol/metabolismo , Dieta , Grasa Intraabdominal/efectos de los fármacos , Metabolismo de los Lípidos/genética , Hígado/metabolismo , Masculino , Potencial de la Membrana Mitocondrial , Ratones Endogámicos C57BL , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Triglicéridos/metabolismoRESUMEN
AIM: Caloric restriction (CR), which limits the caloric intake to 60-70% of ad libitum (AL) amounts in various experimental animals, delays aging and extends the lifespan. We previously showed that neuropeptide Y (NPY), an appetite-stimulating peptide, is essential for the anti-oxidative and life-extending effects of CR. Here, we investigated whether a Japanese traditional herbal medicine, rikkunshito (RKT), which induces NPY activation, has CR-like life-extending effects. METHODS: First, we evaluated the life-extending activity of RKT by examining the effect of long-term RKT administration on wild-type and NPY knockout mice. Furthermore, we tested whether RKT enhances CR-mediated beneficial effects under AL conditions with a normal diet and under mild CR conditions with a high-fat diet. We then used 3-nitropropionic acid or doxorubicin to induce oxidative stress, and analyzed the differences in survival rate, weight loss, gene expression and cellular oxidative damage among groups. RESULTS: RKT administration did not extend the lifespan of wild-type or NPY knockout mice. In the oxidative stress models, RKT treatment upregulated anti-oxidative gene expression in the liver. Furthermore, RKT administration reduced the oxidative damage in the liver compared to the CR conditions alone. However, on induction of oxidative stress by 3-nitropropionic acid or doxorubicin, RKT administration did not affect the survival rate. CONCLUSIONS: These results show that RKT administration only partially mimics the effects of CR at the cellular level, but not at the organismal level to increase the lifespan of mice. Geriatr Gerontol Int 2019; â¢â¢: â¢â¢-â¢â¢.
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Medicamentos Herbarios Chinos/administración & dosificación , Longevidad/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Animales , Restricción Calórica , Suplementos Dietéticos , Femenino , Ghrelina/metabolismo , Masculino , Ratones , Ratones NoqueadosRESUMEN
The structure-specific endonuclease ERCC1/XPF plays an important role in nucleotide excision repair and interstrand cross-link repair. In this study, we identified new functions of ERCC1/XPF in DNA double-strand break (DSB) repair. We found that the conserved function of ERCC1/XPF to remove non-homologous sequences at DSBs is a rate-limiting step for homologous recombination in mammalian cells, and more importantly, we uncovered an indispensable role of ERCC1/XPF in repair of DSBs containing DNA secondary structures, including the structure-prone AT-rich DNA sequences derived from common fragile sites and G-quadruplexes (G4s). We also demonstrated a synthetic lethal interaction of XPF with DNA translocase FANCM that is involved in removing DNA secondary structures. Furthermore, inactivation of XPF sensitizes FANCM-deficient cells to G4-interacting compounds. These results suggest an important function of ERCC1/XPF in protecting DNA secondary structures and provide a rationale for targeted treatment of FANCM-deficient tumors through inhibition of XPF.
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DNA polymerase θ (POLQ) plays an important role in alternative nonhomologous end joining or microhomology-mediated end joining (alt-NHEJ/MMEJ). Here, we show that POLQ is not only required for MMEJ to repair DNA double-strand breaks (DSBs) generated by endonucleases such as I-SceI or Cas9, but is also needed for repair of DSBs derived from DNA nicks generated by Cas9 nickase. Consistently, we found that POLQ deficiency leads to sensitivity to topoisomerase inhibitors that cause DNA single-strand break (SSB) accumulation at replication forks and to ATR inhibitors that induce replication fork collapse. These studies support the function of POLQ in coping with replication stress and repairing DSBs upon fork collapse. POLQ overexpression is present in many cancer types and is associated with poor prognosis, including breast cancer regardless of BRCA1 status. We provide proof-of-concept evidence to support a novel cancer treatment strategy that combines POLQ inhibition with administration of topoisomerase or ATR inhibitors, which induces replication stress and fork collapse. Given the prevalence of POLQ overexpression in tumors, such strategy may have a significant impact on developing targeted cancer treatment.
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Roturas del ADN de Doble Cadena , Reparación del ADN , Replicación del ADN , ADN Polimerasa Dirigida por ADN/metabolismo , Camptotecina/farmacología , Células Cultivadas , Roturas del ADN de Doble Cadena/efectos de los fármacos , Replicación del ADN/efectos de los fármacos , ADN Polimerasa Dirigida por ADN/deficiencia , ADN Polimerasa Dirigida por ADN/genética , Relación Dosis-Respuesta a Droga , Humanos , Isoxazoles/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Pirazinas/farmacología , Relación Estructura-Actividad , Inhibidores de Topoisomerasa/farmacología , ADN Polimerasa thetaRESUMEN
BACKGROUND: Radical esophagectomy remains the primary treatment option for resectable esophageal cancer. However, it sometimes induces postoperative complications due to its invasive nature. Recently, the impact of loss of muscle mass on postoperative complications and survival among cancer patients has been highlighted. This study aimed to identify the impact of low hand grip strength (HGS) on postoperative complications after esophagectomy. METHODS: A total of 188 patients (male: 166, female: 22) who underwent radical esophagectomy with gastric tube reconstruction between 2008 and 2014 were included. The correlation between HGS and age was analyzed using Pearson's correlation coefficient. Due to the small patient numbers, only male patients were stratified into two groups according to age (<70 years: non-elderly group, ≥70 years: elderly group). Receiver operating characteristic curve analysis was performed for each group using postoperative complication occurrence as the endpoint to determine an optimal HGS cutoff value. RESULTS: Postoperative complications occurred in 60.9% of the elderly group and 47.4% of the non-elderly group. When the cutoff values were set at 30.5 and 37 kg for the elderly and non-elderly group, respectively, low HGS was an independent predictive factor of postoperative complications on multivariate analysis only in the elderly group (p = 0.008). In the elderly group, the incidence of postoperative pneumonia was 39.5% among patients with low HGS vs. 3.8% among patients with high HGS. CONCLUSION: Preoperative HGS is an independent predictive factor of postoperative complications, especially postoperative pneumonia, for elderly male patients with esophageal cancer treated with radical esophagectomy.
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Neoplasias Esofágicas/cirugía , Esofagectomía/efectos adversos , Fuerza de la Mano , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Envejecimiento/fisiología , Neoplasias Esofágicas/fisiopatología , Femenino , Volumen Espiratorio Forzado/fisiología , Fuerza de la Mano/fisiología , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/fisiopatología , Cuidados Preoperatorios/métodos , Pronóstico , Curva ROC , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Proteasome inhibitors (PI), mainly targeting the ß5 subunit of the 20S proteasome, are widely used in the treatment of multiple myeloma (MM). However, PI resistance remains an unresolved problem in the therapy of relapsed and refractory MM. To develop a new PI that targets other proteasome subunits, we examined the anti-MM activity of a novel syringolin analog, syringolog-1, which inhibits the activity of both the ß5 and ß2 subunits. Syringolog-1 exhibited marked cytotoxicity against various MM cell lines and anti-tumor activity towards bortezomib (Btz)-resistant MM cells through the dual inhibition of chymotrypsin-like (ß5 subunit) and trypsin-like (ß2 subunit) activities. MM cells, including Btz-resistant cells, showed elevated CHOP and NOXA expression after syringolog-1 treatment, indicating the induction of excessive endoplasmic reticulum stress during syringolog-1 treatment. Similar activities of syringolog-1 were also observed in freshly prepared MM cells derived from patients. To clarify the anti-tumor mechanism of dual inhibition of both the ß5 and ß2 subunits of the proteasome, PSMB5 and PSMB7 were co-inhibited in MM cells. This resulted in increased apoptosis of MM cells accompanied by accumulation of ubiquitinated proteins compared to inhibition of either PSMB7 or PSMB5 alone, indicating an enhanced effect by double inhibition of ß2 and ß5 activities. In conclusion, this syringolin analog, a dual inhibitor of proteasome ß2 and ß5 activities, exhibited potent anti-tumor effects on MM cells and may be useful for overcoming Btz-resistance in the treatment of MM.
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OBJECTIVES: Preoperative identification of the artery of Adamkiewicz can help prevent postoperative spinal cord injury in patients undergoing thoracic and thoraco-abdominal aortic aneurysm repair. Although several studies have shown the feasibility of evaluating the artery of Adamkiewicz using multidetector row computed tomography (MDCT), no detailed investigations regarding the collateral circulation to the artery of Adamkiewicz have been performed. The purpose of this study was to investigate the collateral circulation to the artery of Adamkiewicz using MDCT in patients with thoracic and thoraco-abdominal aortic aneurysms. METHODS: Our institutional review board approved this study. Sixty-four patients with descending thoracic and thoraco-abdominal aortic aneurysms associated with the occlusion of the segmental artery from which the artery of Adamkiewicz originated were scanned using 64- or 320-detector row computed tomography. Two independent observers evaluated the MDCT images based on the degree of visualization of the artery of Adamkiewicz and its collateral circulation using a 4-point scale. RESULTS: The average visualization score was 2.8 ± 0.6. In 53 of the 64 (83%) patients, image quality was judged to be diagnostic. MDCT demonstrated 75 collateral pathways to the artery of Adamkiewicz in these 53 patients. Sixty-four of the 75 (85%) pathways were collaterals around the spinal column, and the remaining 11 (15%) pathways were collateral arteries in the thoracic wall. CONCLUSIONS: MDCT revealed the collateral pathways to the artery of Adamkiewicz around the spinal column and in the thoracic wall in 83% of our patients with thoracic and thoraco-abdominal aortic aneurysms.
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Aneurisma de la Aorta Torácica/cirugía , Circulación Colateral , Angiografía por Tomografía Computarizada/métodos , Médula Espinal/irrigación sanguínea , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Imagenología Tridimensional/métodos , Masculino , Persona de Mediana Edad , Tomografía Computarizada Multidetector/métodos , Variaciones Dependientes del Observador , Complicaciones Posoperatorias/prevención & control , Cuidados Preoperatorios/métodos , Estudios Retrospectivos , Médula Espinal/diagnóstico por imagen , Traumatismos de la Médula Espinal/prevención & controlRESUMEN
PURPOSE: Preoperative identification of the artery of Adamkiewicz can help prevent postoperative spinal cord injury following thoracic and thoracoabdominal aortic repair. Several studies have demonstrated the feasibility of evaluating the artery of Adamkiewicz using multi-detector row computed tomography (CT), but precise visualization remains a challenge. The present study was conducted to evaluate the usefulness of ultra-high-resolution CT for visualizing the artery of Adamkiewicz with a slice thickness of 0.25 versus 0.5 mm in patients with aortic aneurysms. METHODS: Our institutional review board approved this study. Twenty-four patients with thoracic and thoracoabdominal aneurysms were scanned with beam collimation of 0.25 mm × 128. Images were reconstructed with slice thicknesses of 0.25 and 0.5 mm. The signal-to-noise ratio (SNR) of the aorta and contrast-to-noise ratio (CNR) between the anterior spinal artery and spinal cord were measured. Two independent observers evaluated visualization of the artery of Adamkiewicz and its continuity between the anterior spinal artery and the aorta using a four-point scale. RESULTS: No significant differences in the SNR of the aorta or CNR of the anterior spinal artery were observed between 0.25- and 0.5-mm slices. The average visualization score was significantly higher for 0.25-mm slices (3.58 ± 0.78) than for 0.5-mm slices (3.13 ± 0.99) (p = 0.01). The percentage of patients with nondiagnostic image quality was significantly lower for 0.25-mm slices (8.3%) than for 0.5-mm slices (33.3%) (p = 0.03). CONCLUSION: In patients with aortic aneurysms, ultra-high-resolution CT with 0.25-mm slices significantly improves visualization of the artery of Adamkiewicz compared to 0.5-mm slices.
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Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Torácica/diagnóstico por imagen , Angiografía por Tomografía Computarizada/métodos , Columna Vertebral/irrigación sanguínea , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Interpretación de Imagen Radiográfica Asistida por Computador , Estudios Retrospectivos , Relación Señal-RuidoRESUMEN
In the course of screening for new anti-influenza virus antibiotics, we isolated herquline A from a culture broth of the fungus, Penicillium herquei FKI-7215. Herquline A inhibited replication of influenza virus A/PR/8/34 strain in a dose-dependent manner without exhibiting cytotoxicity against several human cell lines. It did not inhibit the viral neuraminidase.