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BACKGROUND: Eating disorders (ED) are serious psychiatric disorders, taking a life every 52 minutes, with high relapse. There are currently no support or effective intervention therapeutics for individuals with an ED in their everyday life. The aim of this study is to build idiographic machine learning (ML) models to evaluate the performance of physiological recordings to detect individual ED behaviors in naturalistic settings. METHODS: From an ongoing study (Final N = 120), we piloted the ability for ML to detect an individual's ED behavioral episodes (e.g. purging) from physiological data in six individuals diagnosed with an ED, all of whom endorsed purging. Participants wore an ambulatory monitor for 30 days and tapped a button to denote ED behavioral episodes. We built idiographic (N = 1) logistic regression classifiers (LRC) ML trained models to identify onset of episodes (~600 windows) v. baseline (~571 windows) physiology (Heart Rate, Electrodermal Activity, and Temperature). RESULTS: Using physiological data, ML LRC accurately classified on average 91% of cases, with 92% specificity and 90% sensitivity. CONCLUSIONS: This evidence suggests the ability to build idiographic ML models that detect ED behaviors from physiological indices within everyday life with a high level of accuracy. The novel use of ML with wearable sensors to detect physiological patterns of ED behavior pre-onset can lead to just-in-time clinical interventions to disrupt problematic behaviors and promote ED recovery.
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Transtornos da Alimentação e da Ingestão de Alimentos , Dispositivos Eletrônicos Vestíveis , Humanos , Transtornos da Alimentação e da Ingestão de Alimentos/diagnóstico , Transtornos da Alimentação e da Ingestão de Alimentos/terapia , Comportamento Alimentar/psicologia , Estudos LongitudinaisRESUMO
PURPOSE: To improve radiopacity of radiolucent absorbable poly-p-dioxanone (PPDO) inferior vena cava filters (IVCFs) and demostrate their effectiveness in clot-trapping ability. MATERIALS AND METHODS: Tungsten nanoparticles (WNPs) were incorporated along with polyhydroxybutyrate (PHB), polycaprolactone (PCL), and polyvinylpyrrolidone (PVP) polymers to increase the surface adsorption of WNPs. The physicochemical and in vitro and in vivo imaging properties of PPDO IVCFs with WNPs with single-polymer PHB (W-P) were compared with those of WNPs with polymer blends consisting of PHB, PCL, and PVP (W-PB). RESULTS: In vitro analyses using PPDO sutures showed enhanced radiopacity with either W-P or W-PB coating, without compromising the inherent physicomechanical properties of the PPDO sutures. W-P- and W-PB-coated IVCFs were deployed successfully into the inferior vena cava of pig models with monitoring by fluoroscopy. At the time of deployment, W-PB-coated IVCFs showed a 2-fold increase in radiopacity compared to W-P-coated IVCFs. Longitudinal monitoring of in vivo IVCFs over a 12-week period showed a drastic decrease in radiopacity at Week 3 for both filters. CONCLUSIONS: The results highlight the utility of nanoparticles (NPs) and polymers for enhancing radiopacity of medical devices. Different methods of incorporating NPs and polymers can still be explored to improve the effectiveness, safety, and quality of absorbable IVCFs.
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Nanopartículas , Filtros de Veia Cava , Suínos , Animais , Tungstênio , Polímeros , Veia Cava Inferior/diagnóstico por imagem , Veia Cava Inferior/cirurgia , Remoção de DispositivoRESUMO
BACKGROUND: Candida represents a prevalent fungal infection, notable for its substantial implications on morbidity and mortality rates. In the landscape of prospective treatments, quinoxaline derivatives emerge as a category of compact compounds exhibiting notable potential in addressing infections. These derivatives showcase promising antimicrobial efficacy coupled with favorable pharmacokinetic and safety characteristics. AIMS: The central aim of this investigation was to examine the antifungal characteristics of 2-Chloro-3-hydrazinylquinoxaline against diverse strains of Candida and Aspergillus in vitro. Additionally, we endeavored to assess the in vivo efficacy of 2-Chloro-3-hydrazinylquinoxaline using a murine model for oral candidiasis induced by C. albicans cells ATCC 10231. RESULTS: 2-Chloro-3-hydrazinylquinoxaline demonstrated noteworthy effectiveness when tested against various reference strains of Candida species. It exhibited heightened efficacy, particularly against Candida krusei isolates. However, its performance against Candida albicans, Candida tropicalis, Candida glabrata, Candida parapsilosis, and Candida auris isolates exhibited variability. Notably, 2-Chloro-3-hydrazinylquinoxaline manifests variable efficacy against Aspergillus fumigatus, Aspergillus niger, Aspergillus terreus and Aspergillus flavus and no effect against Aspergillus brasiliensis. In a murine model, 2-Chloro-3-hydrazinylquinoxaline exhibited significant efficacy in combating the C. albicans cells ATCC 10231 strain, underscoring its potential as a viable treatment option. CONCLUSION: 2-Chloro-3-hydrazinylquinoxaline has demonstrated substantial potential in effectively addressing various Candida and Aspergillus species, showcasing dual attributes of antifungal and anti-inflammatory properties. However, to attain a more comprehensive understanding of its therapeutic capabilities, further investigations, incorporating additional tests and experiments, are imperative.
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Antifúngicos , Candida , Testes de Sensibilidade Microbiana , Quinoxalinas , Antifúngicos/farmacologia , Antifúngicos/química , Quinoxalinas/farmacologia , Quinoxalinas/química , Animais , Candida/efeitos dos fármacos , Camundongos , Modelos Animais de Doenças , Candidíase/tratamento farmacológico , Candidíase/microbiologia , FemininoRESUMO
[This corrects the article DOI: 10.1371/journal.pone.0303373.].
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The objective of the research is to develop novel materials that are both inexpensive and have a low density, while also being able to endure the transportation of γ-photons with low-to-medium energy levels. The outcome consisted of four epoxy resins that were strengthened with different quantities of heavy metallic waste. The density of the formed composites improved from 1.134 ± 0.022 g/cm3 to 1.560 ± 0.0312 g/cm3 when the waste content was raised from 0 to 40 weight percent. The theoretical investigation was determined using Monte Carlo (MCNP) simulation software, and the results of linear attenuation coefficient were justified experimentally in a low and medium energy range of 15-662 keV. The mass attenuation coefficient results in a low gamma energy range (15-122 keV) varied in between 3.175 and 0.159 cm2/g (for E-MW0 composite) and in between 8.212 and 0.164 cm2/g (for E-MW40 composite). The decrease in mass attenuation coefficient was detected in a medium gamma photon energy range (122-662 keV) with 0.123-0.082 cm2/g (for E-MW0 composite) and 0.121-0.080 cm2/g (for E-MW40 composite). The density of the enhanced composites influenced these parameters. As the metallic waste composition increased, the fabricated composites' half-value thickness decreased. At 15 keV, the half-value thickness decreased from 0.19 to 0.05 cm. At 59 keV, it fell from 2.70 to 1.41 cm. At 122 keV, it fell from 3.90 to 2.72 cm. At 662 keV, it fell from 7.45 to 5.56 cm. This decrease occurred as the heavy metal waste concentration increased from 0 to 40 wt.%. The study indicates that as metallic waste concentrations rise, there is a rise in the effective atomic number and a decline in the buildup factors.
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Resorbable inferior vena cava (IVC) filters require embedded contrast for image-guided placement and integrity monitoring. We calculated correction factors to account for partial volume averaging of thin nanoparticle (NP)-embedded materials, accounting for object and slice thicknesses, background signal, and nanoparticle concentration. We used phantoms containing polycaprolactone disks embedded with bismuth (Bi) or ytterbium (Yb): 0.4- to 1.2-mm-thick disks of 20 mg ml-1NPs (thickness phantom), 0.4-mm-thick disks of 0-20 mg ml-1NPs in 2 mg ml-1iodine (concentration phantom), and 20 mg ml-1NPs in 0.4-mm-thick disks in 0-10 mg ml-1iodine (background phantom). Phantoms were scanned on a dual-source CT with 80, 90, 100, and 150 kVp with tin filtration and reconstructed at 1.0- to 1.5-mm slice thickness with a 0.1-mm interval. Following scanning, disks were processed for inductively coupled plasma optical emission spectrometry (ICP-OES) to determine NP concentration. Mean and maximum CT numbers (HU) of all disks were measured over a 0.5-cm2area for each kVp. HU was converted to concentration using previously measured calibrations. Concentration measurements were corrected for partial volume averaging by subtracting residual slice background and extrapolating disk thickness to both nominal and measured slice sensitivity profiles (SSP, mm). Slice thickness to agreement (STTA, mm) was calculated by replacing the CT-derived concentrations with ICP-OES measurements and solving for thickness. Slice thickness correction factors improved agreement with ICP-OES for all measured data. Yb corrections resulted in lower STTA than Bi corrections in the concentration phantom (1.01 versus 1.31 STTA/SSP, where 1.0 is perfect agreement), phantoms with varying thickness (1.30 versus 1.87 STTA/SSP), and similar ratio in phantoms with varying background iodine concentration (1.34 versus 1.35 STTA/SSP). All measured concentrations correlated strongly with ICP-OES and all corrections for partial volume averaging increased agreement with ICP-OES concentration, demonstrating potential for monitoring the integrity of thin IVC resorbable filters with CT.
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Imagens de Fantasmas , Tomografia Computadorizada por Raios X , Tomografia Computadorizada por Raios X/métodos , Poliésteres/química , Polímeros/química , Meios de Contraste/química , Itérbio/química , Bismuto/química , Humanos , Nanoestruturas/química , Nanopartículas/química , Processamento de Imagem Assistida por Computador/métodosRESUMO
Deep skin wounds represent a serious condition and frequently require split-thickness skin grafts (STSG) to heal. The application of autologous human-skin-cell-suspension (hSCS) requires less donor skin than STSG without compromising the healing capacity. Impaired function and replicative ability of senescent cutaneous cells in the aging skin affects healing with autologous hSCS. Major determinants of senescence are telomere erosion and DNA damage. Human telomerase reverse transcriptase (hTERT) adds telomeric repeats to the DNA and can protect against DNA damage. Herein, hTERT mRNA lipid nanoparticles (LNP) are proposed and evaluated for enhancing cellular engraftment and proliferation of hSCS. Transfection with optimized hTERT mRNA LNP system enables delivery and expression of mRNA in vitro in keratinocytes, fibroblasts, and in hSCS prepared from donors' skin. Telomerase activity in hSCS is significantly increased. hTERT mRNA LNP enhance the generation of a partial-thickness human skin equivalent in the mouse model, increasing hSCS engraftment (Lamin) and proliferation (Ki67), while reducing cellular senescence (p21) and DNA damage (53BP1).
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Telomerase , Animais , Camundongos , Humanos , Telomerase/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Senescência Celular/genética , CicatrizaçãoRESUMO
In the context of arteriovenous fistula (AVF) failure, local delivery enables the release of higher concentrations of drugs that can suppress neointimal hyperplasia (NIH) while reducing systemic adverse effects. However, the radiolucency of polymeric delivery systems hinders long-term in vivo surveillance of safety and efficacy. We hypothesize that using a radiopaque perivascular wrap to deliver anti-NIH drugs could enhance AVF maturation. Through electrospinning, we fabricated multifunctional perivascular polycaprolactone (PCL) wraps loaded with bismuth nanoparticles (BiNPs) for enhanced radiologic visibility and drugs that can attenuate NIHârosuvastatin (Rosu) and rapamycin (Rapa). The following groups were tested on the AVFs of a total of 24 Sprague-Dawley rats with induced chronic kidney disease: control (i.e., without wrap), PCL-Bi (i.e., wrap with BiNPs), PCL-Bi-Rosu, and PCL-Bi-Rapa. We found that BiNPs significantly improved the wraps' radiopacity without affecting biocompatibility. The drug release profiles of Rosu (hydrophilic drug) and Rapa (hydrophobic drug) differed significantly. Rosu demonstrated a burst release followed by gradual tapering over 8 weeks, while Rapa demonstrated a gradual release similar to that of the hydrophobic BiNPs. In vivo investigations revealed that both drug-loaded wraps can reduce vascular stenosis on ultrasonography and histomorphometry, as well as reduce [18F]Fluorodeoxyglucose uptake on positron emission tomography. Immunohistochemical studies revealed that PCL-Bi-Rosu primarily attenuated endothelial dysfunction and hypoxia in the neointimal layer, while PCL-Bi-Rapa modulated hypoxia, inflammation, and cellular proliferation across the whole outflow vein. In summary, the controlled delivery of drugs with different properties and mechanisms of action against NIH through a multifunctional, radiopaque perivascular wrap can improve imaging and histologic parameters of AVF maturation.
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Bismuto , Ratos Sprague-Dawley , Rosuvastatina Cálcica , Sirolimo , Animais , Ratos , Sirolimo/química , Sirolimo/farmacologia , Rosuvastatina Cálcica/química , Rosuvastatina Cálcica/farmacologia , Rosuvastatina Cálcica/farmacocinética , Bismuto/química , Bismuto/farmacologia , Poliésteres/química , Masculino , Fístula Arteriovenosa/patologia , Nanopartículas Metálicas/química , Neointima/patologia , Nanopartículas/química , Humanos , Liberação Controlada de FármacosRESUMO
Cobalt-doped titania nanocomposites were fabricated to be utilized for radiation shielding aims. The chemical composition of the composites was measured using the energy-dispersive X-ray spectrometer. Moreover, the structure of the composites was evaluated using the X-ray diffractometer, and the morphology of the fabricated composites was presented using the scanning electron microscope. Furthermore, the γ-ray shielding properties were estimated using the Monte Carlo simulation between 0.059 and 2.506 MeV. The linear attenuation coefficient of the fabricated composites decreased by factors of 93% for all samples by raising the incident γ-energy between 0.059 and 2.506 MeV. Moreover, the partial replacement of the Ti4+ by Co3+ slightly enhanced the linear attenuation coefficient from 0.607 to 0.630 cm-1 when the Co3+ increased from 0 to 3.7 wt%. The improvement in the linear attenuation coefficient causes an enhancement in other radiation shielding properties.
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OBJECTIVE: Granulomatosis with polyangiitis is an unusual multisystemic inflammatory disease, with vasculitis of small- and medium-sized vessels, with a predilection for upper lower airways and kidneys. The etiology remains unknown although it may originate from different stimuli, in genetically susceptible patients. MATERIALS AND METHODS: A detailed database search was performed. The variables were demographics, localization, histopathological findings, antineutrophil cytoplasmic autoantibody, cytoplasmic (c-ANCA) tests, treatment, and follow-up. RESULTS: Fifty-two cases were identified; the mean age was 49.6 years, with a range from 6 to 87 years. It was most frequently seen in females (57.7%). The most common race was white (59.6%). The most frequent location was in the maxillary gingiva (28.8%), followed by both the upper and lower gingiva (19.2%). The most common clinical presentation was "strawberry gingivitis" (61.5%). The main symptom was pain, in 50%. Regarding the c-ANCA test, it was positive in 71.2% of cases. The most common therapy was prednisone and cyclophosphamide, utilized in 51.9%. The average follow-up was 23.6 months, and 88.5% of patients were still alive at follow-up. CONCLUSION: The diagnosis initially was difficult to establish, an early diagnosis and treatment are mandatory. If untreated the disease can be associated with morbidity and mortality. For the oral clinician, this disease needs to be addressed in the differential diagnosis of oral lesions.
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Granulomatose com Poliangiite , Feminino , Humanos , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Granulomatose com Poliangiite/diagnóstico , Granulomatose com Poliangiite/terapia , Granulomatose com Poliangiite/complicações , Anticorpos Anticitoplasma de Neutrófilos/uso terapêutico , Ciclofosfamida/uso terapêuticoRESUMO
The use of absorbable inferior vena cava filters (IVCFs) constructed with poly-p-dioxanone (PPDO) eliminates risks and complications associated with the use of retrievable metallic filters. Radiopacity of radiolucent PPDO IVCFs can be improved with the incorporation of nanoparticles (NPs) made of high-atomic number materials such as gold and bismuth. In this study, we focused on incorporating tungsten NPs (WNPs), along with polyhydroxybutyrate (PHB), polycaprolactone (PCL), and polyvinylpyrrolidone (PVP) polymers to increase the surface adsorption of the WNPs. We compared the imaging properties of WNPs with single-polymer PHB (W-P) and WNPs with polymer blends consisting of PHB, PCL, and PVP (W-PB). Our in vitro analyses using PPDO sutures showed enhanced radiopacity with either W-P or W-PB coating, without compromising the inherent physico-mechanical properties of the PPDO sutures. We observed a more sustained release of WNPs from W-PB-coated sutures than W-P-coated sutures. We successfully deployed W-P- and W-PB-coated IVCFs into the inferior vena cava of pig models, with monitoring by fluoroscopy. At the time of deployment, W-PB-coated IVCFs showed a 2-fold increase in radiopacity compared to W-P-coated IVCFs. Longitudinal monitoring of in vivo IVCFs over a 12-week period showed a drastic decrease in radiopacity at week 3 for both filters. Results of this study highlight the utility of NPs and polymers for enhancing radiopacity of medical devices; however, different methods of incorporating NPs and polymers can still be explored to improve the efficacy, safety, and quality of absorbable IVCFs.
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The present work novelty pointed to fabricate new clay bricks doped with heavy minerals to be used in the building materials as a candidate for radiation shielding. The bricks were manufactured as (y)Iron mineral+ (1-y)clay, where y = 0, 0.1, 0.2 and 0.3 fractional weight. The prepared bricks' chemical composition and density were introduced to the MCNP-5 code to assess the prepared bricks' protection capacity. The simulated linear attenuation coefficient (LAC) was confirmed by comparing the simulated results with those calculated by the Phy-X/PSD program. We found that the simulated and calculated LAC were close together. The diff (%) between the MCNP-5 and Phy-X/PSD is in the range ±2% for all the fabricated bricks. The maximum LAC values occurred at 0.015 MeV, varied between 21.540 and 39.553 cm-1 for bricks N0 and N30. The lowest LAC achieved at 15 MeV varied between 0.068 and 0.090 cm-1. Bricks without heavy mineral addition have the lowest LAC values at all energies, ranging from 21.540 cm-1 to 0.068 cm-1, while bricks with 30 wt% heavy minerals have the highest LAC. The half-value layer (HVL) values decreased gradually with increasing the mineral ratio in the fabricated bricks. The thinner brick HVL achieved for the sample N 30 with 30 wt % heavy mineral, growing from 0.017 to 7.675 cm. The effective atomic number (Zeff) was reported, and we found that the minimum Zeff values equal to 14.006, 14.865, 15.705, and 16.394 for bricks N 0, N 10, N 20, N 30, respectively.
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Argila , Raios gama , Minerais/química , Proteção Radiológica/instrumentação , Método de Monte CarloRESUMO
Current anti-angiogenic therapy for cancer is based mainly on inhibition of the vascular endothelial growth factor pathway. However, due to the transient and only modest benefit from such therapy, additional approaches are needed. Deregulation of microRNAs (miRNAs) has been demonstrated to be involved in tumor angiogenesis and offers opportunities for a new therapeutic approach. However, effective miRNA-delivery systems are needed for such approaches to be successful. In this study, miRNA profiling of patient data sets, along with in vitro and in vivo experiments, revealed that miR-204-5p could promote angiogenesis in ovarian tumors through THBS1. By binding with scavenger receptor class B type 1 (SCARB1), reconstituted high-density lipoprotein-nanoparticles (rHDL-NPs) were effective in delivering miR-204-5p inhibitor (miR-204-5p-inh) to tumor sites to suppress tumor growth. These results offer a new understanding of miR-204-5p in regulating tumor angiogenesis.
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Inibidores da Angiogênese/uso terapêutico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/genética , MicroRNAs , Neovascularização Patológica/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Inibidores da Angiogênese/farmacologia , Animais , Carcinoma Epitelial do Ovário/irrigação sanguínea , Carcinoma Epitelial do Ovário/patologia , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HEK293 , Humanos , Camundongos , Camundongos Nus , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Terapia de Alvo Molecular/métodos , Neovascularização Patológica/tratamento farmacológico , Neoplasias Ovarianas/irrigação sanguínea , Neoplasias Ovarianas/patologia , RNA Interferente Pequeno/farmacologia , RNA Interferente Pequeno/uso terapêutico , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Systematic approaches for accurate repurposing of targeted therapies are needed. We developed and aimed to biologically validate our therapy predicting tool (TPT) for the repurposing of targeted therapies for specific tumor types by testing the role of Bromodomain and Extra-Terminal motif inhibitors (BETi) in inhibiting BRD4 function and downregulating Notch3 signaling in ovarian cancer.Utilizing established ovarian cancer preclinical models, we carried out in vitro and in vivo studies with clinically relevant BETis to determine their therapeutic effect and impact on Notch3 signaling.Treatment with BETis or siRNA-mediated BRD4 knockdown resulted in decreased cell viability, reduced cell proliferation, and increased cell apoptosis in vitro. In vivo studies with orthotopic mouse models demonstrated that treatment with BETi decreased tumor growth. In addition, knockdown of BRD4 with doxycycline-inducible shRNA increased survival up to 50% (P < 0.001). Treatment with either BETis or BRD4 siRNA decreased Notch3 expression both in vitro and in vivo BRD4 inhibition also decreased the expression of NOTCH3 targets, including HES1 Chromatin immunoprecipitation revealed that BRD4 was present at the NOTCH3 promoter.Our findings provide biological validation for the TPT by demonstrating that BETis can be an effective therapeutic agent for ovarian cancer by downregulating Notch3 expression.The TPT could rapidly identify candidate drugs for ovarian or other cancers along with novel companion biomarkers.
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Acetamidas/administração & dosagem , Azepinas/administração & dosagem , Proteínas Nucleares/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Receptor Notch3/metabolismo , Fatores de Transcrição/metabolismo , Acetamidas/farmacologia , Animais , Azepinas/farmacologia , Proteínas de Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Proteínas Nucleares/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Fatores de Transcrição/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Hyperthermia has been investigated as a potential treatment for cancer. However, specificity in hyperthermia application remains a significant challenge. Magnetic fluid hyperthermia (MFH) may be an alternative to surpass such a challenge, but implications of MFH at the cellular level are not well understood. Therefore, the present work focused on the examination of gene expression after MFH treatment and using such information to identify target genes that when inhibited could produce an enhanced therapeutic outcome after MFH. Genomic analyzes were performed using ovarian cancer cells exposed to MFH for 30 minutes at 43°C, which revealed that heat shock protein (HSP) genes, including HSPA6, were upregulated. HSPA6 encodes the Hsp70, and its expression was confirmed by PCR in HeyA8 and A2780cp20 ovarian cancer cells. Two strategies were investigated to inhibit Hsp70-related genes, siRNA and Hsp70 protein function inhibition by 2-phenylethyenesulfonamide (PES). Both strategies resulted in decreased cell viability following exposure to MFH. Combination index was calculated for PES treatment reporting a synergistic effect. In vivo efficacy experiments with HSPA6 siRNA and MFH were performed using the A2780cp20 and HeyA8 ovarian cancer mouse models. A significantly reduction in tumor growth rate was observed with combination therapy. PES and MFH efficacy were also evaluated in the HeyA8 intraperitoneal tumor model, and resulted in robust antitumor effects. This work demonstrated that HSP70 inhibition combination with MFH generate a synergistic effect and could be a promising target to enhance MFH therapeutic outcomes in ovarian cancer. Mol Cancer Ther; 16(5); 966-76. ©2017 AACR.
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Proteínas de Choque Térmico HSP70/genética , Hipertermia Induzida , Neoplasias Ovarianas/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Terapia Combinada , Feminino , Proteínas de Choque Térmico HSP70/antagonistas & inibidores , Humanos , Fenômenos Magnéticos , Camundongos , Neoplasias Ovarianas/patologia , RNA Interferente Pequeno/genéticaRESUMO
Even though hyperthermia is a promising treatment for cancer, the relationship between specific temperatures and clinical benefits and predictors of sensitivity of cancer to hyperthermia is poorly understood. Ovarian and uterine tumors have diverse hyperthermia sensitivities. Integrative analyses of the specific gene signatures and the differences in response to hyperthermia between hyperthermia-sensitive and -resistant cancer cells identified CTGF as a key regulator of sensitivity. CTGF silencing sensitized resistant cells to hyperthermia. CTGF small interfering RNA (siRNA) treatment also sensitized resistant cancers to localized hyperthermia induced by copper sulfide nanoparticles and near-infrared laser in orthotopic ovarian cancer models. CTGF silencing aggravated energy stress induced by hyperthermia and enhanced apoptosis of hyperthermia-resistant cancers.
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Fator de Crescimento do Tecido Conjuntivo/metabolismo , Hipertermia Induzida , Neoplasias Ovarianas/metabolismo , Neoplasias Uterinas/metabolismo , Animais , Linhagem Celular Tumoral , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Genes Neoplásicos , Humanos , Camundongos , Modelos Biológicos , Neoplasias Ovarianas/genética , Proteômica , Neoplasias Uterinas/genéticaRESUMO
This study was done on 65 workers working in power station I (Shoubra El-Kheima) where they are exposed to natural gas and mazout, 74 workers in power station II (El-Gharb) where there is mazout exposure only and 74 individuals acting as controls. All these individuals were admitted to a questionnaire, examined clinically and they were investigated to assess their respiratory, liver and kidney function tests. This is in addition to a complete blood picture. Air pollution inside these stations was assessed. The study aimed at determining the pollutants inside and outside the stations and to investigate the health hazards of the workers exposed to these pollutants. It aimed also to see if it is important and urgent to replace the mazout by natural gas as a fuel in these power stations. The results showed that by-products of mazout have bad effect on the environment. When mazout is used alone as a fuel, it has an adverse effect on the respiratory system and the liver. There is a need for a prospective study to assess the causal relationship between mazout by-products and health hazards before taking the decision of replacing mazout by natural gas.
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Poluentes Ocupacionais do Ar , Combustíveis Fósseis , Óleos Combustíveis , Exposição por Inalação , Exposição Ocupacional , Centrais Elétricas , Poluentes Ocupacionais do Ar/análise , Poluentes Ocupacionais do Ar/intoxicação , Análise de Variância , Estudos de Casos e Controles , Doença Hepática Induzida por Substâncias e Drogas , Egito , Monitoramento Ambiental , Combustíveis Fósseis/análise , Combustíveis Fósseis/intoxicação , Óleos Combustíveis/análise , Óleos Combustíveis/intoxicação , Humanos , Exposição por Inalação/efeitos adversos , Exposição por Inalação/análise , Nefropatias/induzido quimicamente , Nefropatias/diagnóstico , Testes de Função Renal , Hepatopatias/diagnóstico , Hepatopatias/metabolismo , Testes de Função Hepática , Pneumopatias/induzido quimicamente , Pneumopatias/diagnóstico , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/análise , Testes de Função Respiratória , Inquéritos e QuestionáriosRESUMO
Objectives: Choosing the best induction technique used on each patient is a process that involves the analysis of the patient's comorbid conditions and their hemodynamic effects, i.e. the effect on heart rate, arterial blood pressure, end-tidal carbon dioxide, oxygen saturation and mean arterial pressure during induction. This study aims to compare two anesthetic protocols commonly used during anesthetic induction: propofol and ketamine vs. propofol and fentanyl in patients undergoing elective surgery. Methods: A cross-sectional study was performed between September, 2013, and January, 2014, including all patients ASA I-II undergoing elective surgery; it was a convenience sample with a ratio of 1:1. Results: A total of 60 patients were included, 30 received propofol and ketamine and 30 patients received propofol and fentanyl, both groups were comparable. The risk of bradycardia at minute 5 was measured on each group; on the group receiving propofol and fentanyl was OR=7.2 (95% CI 1.81-64.4 ) p=0.005, and the risk of tachycardia with propofol and ketamine OR=14.5 (95% CI 1.7 - 122 ) p=0,002. Changes in mean arterial pressure were only significant during the first five minutes for both groups. Conclusion: The combination of fentanyl and propofol is more likely to produce bradycardia and hypotension while propofol and ketamine is more likely to generate hypertension and tachycardia. Larger studies are needed to establish what the best induction protocol.
Objetivo: La técnica anestésica utilizada en cada paciente es diferente según sus enfermedades concomitantes y se escoge con el fin de disminuir posibles efectos hemodinámicos, como alteraciones de la frecuencia cardiaca y la tensión arterial durante la inducción. En el presente estudio se pretendió comparar dos técnicas anestésicas, propofol-ketamina frente a propofol-fentanilo, en pacientes llevados a cirugía electiva. Metodología: Se llevó a cabo un estudio de corte transversal entre septiembre de 2013 y enero de 2014, que incluyó todos los pacientes con ASA I-II. Se hizo un muestreo por conveniencia con una relación de 1:1. Resultados: Se incluyeron 60 pacientes, 30 recibieron propofol-ketamina y 30 recibieron propofol-fentanilo. Las poblaciones eran comparables. El riesgo de bradicardia con propofol-fentanilo al minuto cinco, mostró OR=7.2 (IC95% 1.81-64.4) (p=0,005); el riesgo de taquicardia con propofol-ketamina al minuto cinco, mostró OR=14.5 (IC95% 1.7-122) (p=0,002). Las alteraciones de la tensión arterial media solo fueron significativas durante los cinco primeros minutos para ambos grupos. Discusión: La técnica anestésica con propofol-fentanilo tiene mayor probabilidad de producir bradicardia e hipotensión, mientras que la técnica con propofol-ketamina tiene mayor probabilidad de generar hipertensión y taquicardia. Se requieren estudios más amplios para establecer cuál es la mejor técnica anestésica.