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1.
Neuroreport ; 35(14): 936-946, 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39171853

RESUMO

This study aimed to elucidate the effects of sucrose (SUC) consumption on neurodevelopmental processes through behavioral changes in rodents and determine whether these effects could be because of sweet taste, energy supply, or both. Mice were divided into five groups based on the time of SUC or sucralose (SUR, a noncaloric sweetener) administration: for 6 days from gestation day (GTD) 7, to birth from GTD13 and for 15 days from postnatal day (PND) 21, PND38, and PND56. SUC and SUR administration did not impact body weight. However, food intake in the PND56 group and water intake in the GTD13 and PND56 groups were increased by SUC and SUR administration. Amphetamine (0.5, 1, 2, and 3 mg/kg), a dopamine reuptake inhibitor, administration to assess alterations in the dopaminergic system induced increases in distance traveled after SUC administration in the GTD13 and PND21 groups compared with that in the control (vehicle administration) group. In contrast, the SUR group showed a decrease in the distance traveled in the PND56 group. Although there were no differences in locomotor activity and foraging behavior, SUC preference increased in the SUC group regarding the GTD13 and PND38 groups. The correlations between SUC preference and foraging behavior and between SUC preference and amphetamine response varied in both groups according to the developmental stage. Excessive SUC consumption might affect neural function at different developmental stages, as it could affect brain function through complex mechanisms involving sweet taste and energy supply and influence the dopaminergic system.


Assuntos
Sacarose , Animais , Sacarose/administração & dosagem , Sacarose/análogos & derivados , Feminino , Camundongos , Gravidez , Masculino , Anfetamina/farmacologia , Comportamento Animal/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Ingestão de Alimentos/fisiologia , Atividade Motora/efeitos dos fármacos , Edulcorantes/administração & dosagem , Peso Corporal/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal , Ingestão de Líquidos/efeitos dos fármacos
2.
Artigo em Inglês | MEDLINE | ID: mdl-39037931

RESUMO

OBJECTIVES: Unraveling the mechanisms underlying treatment response for targeted therapeutics in systemic lupus erythematosus (SLE) patients is challenging due to the limited understanding of diverse responses of circulating immune cells, particularly B cells. We investigated B lymphocyte dynamics during anti-BAFF treatment, utilizing longitudinal single-cell transcriptome data. METHODS: We conducted single-cell RNA sequencing on PBMCs in four Korean SLE patients before and after belimumab treatment at the following time points: 2 weeks, 1, 3, 6, and 12 months. RESULTS: Analyzing over 73 000 PBMCs, we identified 8 distinct subsets of B cells and plasmablasts and analyzed dynamic changes within these cell subsets: initial declines in naive and transitional B cells followed by an increase at three months, contrasted by an initial increase and subsequent decrease in memory B cells by the third month. Meanwhile, plasmablasts exhibited a consistent decline throughout treatment. B cell activation pathways, specifically in naive and memory B cells, were downregulated during the third and sixth months. These findings were validated at the protein level throughout the first four weeks of treatment using flow cytometry. Comparative analysis with bulk transcriptome data from 22 Japanese SLE patients showed increased NR4A1 expression six months post-belimumab treatment, indicating its role in restricting self-reactive B cells, thereby contributing to the biological responses of anti-BAFF treatment. CONCLUSION: The observed B cell dynamics provided insights into the immunological mechanisms underlying the therapeutic effects of anti-BAFF in SLE patients. Furthermore, it underscores the need for research in predicting drug responses based on immune profiling.

3.
ACS Appl Mater Interfaces ; 15(29): 34462-34474, 2023 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-37438323

RESUMO

Natural phenolic compounds have antioxidant properties owing to their free radical-scavenging capability. The combined effect of a mixture of phenolic compounds has been studied; however, the detailed investigation for finding a correlation between single phenolic molecules and antioxidant activity has not been explored. Herein, we revealed that the number of phenolic hydroxyl groups in phenolics played a central role in their antioxidant capacity. Based on the finding, tannic acid showed the most effective antioxidant potential, e.g., 76% in tannic acid versus 22% in vitamin C as a standard antioxidant component. Because cancer progression is closely related to oxidative processes at the cellular level, we further applied the surface treatment of tannic acid drug-delivery nanocarriers. Tannic acid-loaded nanocarriers reduced reactive oxygen species of cancer cells as much as 41% of vehicle treatment and remodeled cytoskeletal network. By a gelatin degradation study, TA-loaded nanocarrier-treated cells induced 44.6% reduction of degraded area than vehicle-treated cells, implying a potential of blocking invasiveness of cancer cells.


Assuntos
Antioxidantes , Neoplasias , Antioxidantes/farmacologia , Fenóis/farmacologia , Oxirredução , Taninos/farmacologia , Espécies Reativas de Oxigênio
4.
Nutr Res Pract ; 17(3): 408-420, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37266125

RESUMO

BACKGROUND/OBJECTIVES: Hizikia fusiformis (HF) is a class of brown seaweeds whose active ingredients exert central nervous system protective effects, such as neuroprotection; however, the underlying mechanisms remain unknown. Given that dopamine (DA) and serotonin (5HT) are two major neurotransmitters involved in various psychiatric disorders and neuronal growth in early neurodevelopmental processes, we investigated whether HF extract could modulate the molecular expression associated with DA and 5HT transmission as well as the structural formation of neurons. MATERIALS/METHODS: In vitro cell cultures were prepared from cerebral cortical neurons obtained from CD-1 mice on embryonic day 14. Cultured cells were treated with 0.1, 1.0, or 10.0 µg/mL of HT extract for 24 h, followed by fluorescence immunostaining for DA and 5HT-related receptors and transporters and some neuronal structural formation-associated molecules. RESULTS: HF extract dose-dependently upregulated the expression levels of selective DA and 5HT receptors, and downregulated the levels of DA and 5HT transporters. Moreover, HF extract increased the neurofilament light chain expression. CONCLUSION: These results suggest that HF may modulate DA and 5HT transmission, thereby affecting neurodevelopment.

5.
Front Public Health ; 10: 871354, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35719622

RESUMO

Most coronavirus disease 2019 (COVID-19) models use a combination of agent-based and equation-based models with only a few incorporating environmental factors in their prediction models. Many studies have shown that human and environmental factors play huge roles in disease transmission and spread, but few have combined the use of both factors, especially for SARS-CoV-2. In this study, both man-made policies (Stringency Index) and environment variables (Niño SST Index) were combined to predict the number of COVID-19 cases in South Korea. The performance indicators showed satisfactory results in modeling COVID-19 cases using the Non-linear Autoregressive Exogenous Model (NARX) as the modeling method, and Stringency Index (SI) and Niño Sea Surface Temperature (SST) as model variables. In this study, we showed that the accuracy of SARS-CoV-2 transmission forecasts may be further improved by incorporating both the Niño SST and SI variables and combining these variables with NARX may outperform other models. Future forecasting work by modelers should consider including climate or environmental variables (i.e., Niño SST) to enhance the prediction of transmission and spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).


Assuntos
COVID-19 , COVID-19/epidemiologia , Clima , Previsões , Humanos , SARS-CoV-2 , Temperatura
6.
PLoS One ; 17(6): e0268023, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35675344

RESUMO

Understanding the underlying and unpredictable dynamics of the COVID-19 pandemic is important. We supplemented the findings of Jones and Strigul (2020) and described the chaotic behavior of COVID-19 using state space plots which depicted the changes in asymptotic behavior and trajectory brought about by the increase or decrease in the number of cases which resulted from the easing or tightening of restrictions and other non-pharmaceutical interventions instituted by governments as represented by the country's stringency index (SI). We used COVID-19 country-wide case count data and analyzed it using convergent cross-mapping (CCM) and found that the SI influence on COVID-19 case counts is high in almost all the countries considered. When we utilized finer granular geographical data ('barangay' or village level COVID-19 case counts in the Philippines), the effects of SI were reduced as the population density increased. The authors believe that the knowledge of the chaotic behavior of COVID-19 and the effects of population density as applied to finer granular geographical data has the potential to generate more accurate COVID-19 non-linear prediction models. This could be used at the local government level to guide strategic and highly targeted COVID-19 policies which are favorable to public health systems but with limited impact to the economy.


Assuntos
COVID-19 , COVID-19/epidemiologia , Governo , Humanos , Pandemias , Filipinas , Densidade Demográfica
7.
Sci Total Environ ; 825: 154015, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35189238

RESUMO

The increasing amount of plastic waste has raised concerns about microplastics (MPs) in aquatic environments. MPs can be fragmented into nanoplastics that can pass through water treatment processes and into tap water; potentially threatening human health because of their high adsorption capacity for hazardous organic materials and their intrinsic toxicity. This case study investigates the identification, fate, and removal efficiency of MPs in Korean drinking water treatment plants. Two sites on the Nakdong River, two lake reservoirs (raw water sources), and four corresponding drinking water treatment plants were targeted to trace the amounts, types, and sizes of MPs throughout the treatment process. Monthly quantitative and qualitative analyses were conducted by chemical image mapping using micro-Fourier-transform infrared spectroscopy. MPs larger than 20 µm were detected, and their sizes and types were quantified using siMPle software. Overall, the number of MPs in the river sites (January to April and October to November) exceeded those in the reservoirs, but only slight differences in the number of MPs between rivers and lake reservoirs were detected from June to October. The annual average number of MPs in River A, B and Lack C and D was not distinctively different (2.65, 2.48, 2.46 and 1.87 particles/L, respectively). The majority of MPs found in raw waters were polyethylene (PE)/polypropylene (PP) (> 60%) and polyethylene terephthalate (PET)/poly(methyl methacrylate) (PMMA) (20%), in addition to polyamide (<10%) in the river and polystyrene (<10%) in the lake reservoirs. Approximately 70-80% of the MPs were removed by pre-ozonation/sedimentation; 81-88% of PE/PP was removed by this process. PET/PMMA was removed by filtration. Correlation of MPs with water quality parameters showed that the Mn concentration was moderately correlated with the MP abundance in rivers and lake reservoirs, excluding the lake with the lowest Mn concentration, while the total organic carbon was negatively correlated with the MP abundance in both rivers (A and B) and lake reservoir C.


Assuntos
Água Potável , Poluentes Químicos da Água , Purificação da Água , Água Potável/análise , Monitoramento Ambiental , Humanos , Microplásticos , Plásticos/análise , Polietileno/análise , Polimetil Metacrilato/análise , Polipropilenos/análise , Poluentes Químicos da Água/análise
8.
ACS Biomater Sci Eng ; 8(2): 847-858, 2022 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-35073046

RESUMO

Titanium (Ti) is the most commonly used biomaterial for dental implants. When inserting Ti implants into jawbones, the main issue is the lack of strong bonding between the Ti implant and the host bone (osseointegration). Inspired by the outstanding adhesion performance of natural phenolic compounds on metal substrates and promoting effect for cell adhesion, we coated a natural plant extract, Dipterocarpus tuberculatus (MED), on Ti implants. We tested three groups of Ti plates and screw-shaped fixtures: nontreated Ti as commercially produced, ozone-treated Ti as commonly used surface modification for dental implants, and MED-coated Ti. Interestingly, the MED coating on the Ti plate preserved the surface wetting property for 20 days, whereas the hydrophilic wetting of ozone-treated Ti was readily transformed to hydrophobic within a day. Computerized tomography and histopathological analysis revealed that MED coating enhanced new bone tissue formation and regeneration. The gene expression level of integrin as a bone cell adhesion receptor and its downstream key regulators was significantly increased than that of ozone-treated Ti. Therefore, we suggest considering MED-mediated cell signaling pathways in screening natural products for cell adhesion and osseointegration, and MED as a suitable coating agent for improving Ti implantation.


Assuntos
Osseointegração , Titânio , Extratos Vegetais/farmacologia , Próteses e Implantes , Propriedades de Superfície , Titânio/química , Titânio/farmacologia
9.
ChemistryOpen ; 10(8): 852-859, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34437767

RESUMO

Marine mussels contain an abundant catechol moiety, 3,4-dihydroxyphenylalanine (DOPA), in their interfacial foot proteins. DOPA contributes to both surface adhesion and bridging between the surface and overhead proteins (surface priming) by taking advantage of the unique redox properties of catechol. Inspired by the mussel surface priming mechanism, herein we synthesized a series of DOPA-mimetic analogs - a bifunctional group molecule, consisting of a catechol group and an acrylic group at the opposite ends. The surface primers with differently substituted (-COOH, -CH3 ) alkyl chains in the middle spacer were synthesized. Time-dependent oxidation and redox potentials of the surface primers were studied in an oxidizing environment to gain a better understanding of the mussel's redox chemistry. The thickness and degree of priming of the surface primers on silicon-based substrates were analyzed by ellipsometry and UV/Vis absorption spectroscopy. The post-reactivity of the acrylic groups of the primed layer was first visualized through a reaction with an acrylic group-reactive dye.

10.
Clin Exp Emerg Med ; 8(2): 120-127, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34237817

RESUMO

OBJECTIVE: Recent studies have suggested that deep-learning models can satisfactorily assist in fracture diagnosis. We aimed to evaluate the performance of two of such models in wrist fracture detection. METHODS: We collected image data of patients who visited with wrist trauma at the emergency department. A dataset extracted from January 2018 to May 2020 was split into training (90%) and test (10%) datasets, and two types of convolutional neural networks (i.e., DenseNet-161 and ResNet-152) were trained to detect wrist fractures. Gradient-weighted class activation mapping was used to highlight the regions of radiograph scans that contributed to the decision of the model. Performance of the convolutional neural network models was evaluated using the area under the receiver operating characteristic curve. RESULTS: For model training, we used 4,551 radiographs from 798 patients and 4,443 radiographs from 1,481 patients with and without fractures, respectively. The remaining 10% (300 radiographs from 100 patients with fractures and 690 radiographs from 230 patients without fractures) was used as a test dataset. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of DenseNet-161 and ResNet-152 in the test dataset were 90.3%, 90.3%, 80.3%, 95.6%, and 90.3% and 88.6%, 88.4%, 76.9%, 94.7%, and 88.5%, respectively. The area under the receiver operating characteristic curves of DenseNet-161 and ResNet-152 for wrist fracture detection were 0.962 and 0.947, respectively. CONCLUSION: We demonstrated that DenseNet-161 and ResNet-152 models could help detect wrist fractures in the emergency room with satisfactory performance.

11.
J Pers Med ; 10(4)2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33172076

RESUMO

Mammography plays an important role in screening breast cancer among females, and artificial intelligence has enabled the automated detection of diseases on medical images. This study aimed to develop a deep learning model detecting breast cancer in digital mammograms of various densities and to evaluate the model performance compared to previous studies. From 1501 subjects who underwent digital mammography between February 2007 and May 2015, craniocaudal and mediolateral view mammograms were included and concatenated for each breast, ultimately producing 3002 merged images. Two convolutional neural networks were trained to detect any malignant lesion on the merged images. The performances were tested using 301 merged images from 284 subjects and compared to a meta-analysis including 12 previous deep learning studies. The mean area under the receiver-operating characteristic curve (AUC) for detecting breast cancer in each merged mammogram was 0.952 ± 0.005 by DenseNet-169 and 0.954 ± 0.020 by EfficientNet-B5, respectively. The performance for malignancy detection decreased as breast density increased (density A, mean AUC = 0.984 vs. density D, mean AUC = 0.902 by DenseNet-169). When patients' age was used as a covariate for malignancy detection, the performance showed little change (mean AUC, 0.953 ± 0.005). The mean sensitivity and specificity of the DenseNet-169 (87 and 88%, respectively) surpassed the mean values (81 and 82%, respectively) obtained in a meta-analysis. Deep learning would work efficiently in screening breast cancer in digital mammograms of various densities, which could be maximized in breasts with lower parenchyma density.

12.
Mol Diagn Ther ; 24(5): 579-592, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32676933

RESUMO

INTRODUCTION: Next-generation sequencing (NGS) panels have recently been introduced to efficiently detect genetic variations in hematologic malignancies. OBJECTIVES: Our aim was to evaluate the performance of the commercialized Oncomine™ myeloid research assay (OMA) for myeloid neoplasms. METHODS: Certified reference materials and clinical research samples were used, including 60 genomic DNA and 56 RNA samples. NGS was performed using OMA, which enables the interrogation of 40 target genes, 29 gene fusions, and five expression target genes with five expression control genes by the Ion S5 XL Sequencer. The analyzed data were compared with clinical data using karyotyping, reverse transcription polymerase chain reaction (PCR), fluorescence in situ hybridization, Sanger sequencing, customized NGS panel, and fragment analysis. RESULTS: All targets of reference materials were detected except three (two ASXL1 and one CEBPA) mutations, which we had not expected OMA to detect. In clinical search samples, OMA satisfactorily identified DNA variants, including 90 single nucleotide variants (SNVs), 48 small insertions and deletions (indels), and eight FLT3 internal tandem duplications (ITDs) (Kappa agreement 0.938). The variant allele frequencies of SNVs and indels measured by OMA correlated well with clinical data, whereas those of FLT3-ITDs were significantly lower than with fragment analysis (P = 0.008). Together, OMA showed strong ability to identify RNA gene fusions (Kappa agreement 0.961), except one RUNX1-MECOM. The MECOM gene was highly expressed in all five samples with MECOM-associated rearrangements, including inv(3), t(3;3), and t(3;21). CONCLUSION: OMA revealed excellent analytical and potential clinical performance and could be a good replacement for conventional molecular tests.


Assuntos
Técnicas de Diagnóstico Molecular , Transtornos Mieloproliferativos/diagnóstico , Biomarcadores Tumorais , Gerenciamento Clínico , Suscetibilidade a Doenças , Predisposição Genética para Doença , Variação Genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mutação INDEL , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Diagnóstico Molecular/normas , Transtornos Mieloproliferativos/etiologia , Polimorfismo de Nucleotídeo Único , Reprodutibilidade dos Testes
13.
Clin Orthop Surg ; 11(4): 427-435, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31788166

RESUMO

BACKGROUND: The purpose of this study was to investigate the incidence of acromial fracture after reverse total shoulder arthroplasty (RTSA) and clinical and radiological outcomes of treatment of the fracture. METHODS: A systematic review was performed to identify studies that reported the results of treatment of acromial fractures after RTSA. A literature search was conducted by two investigators using four databases (PubMed, Embase, Cochrane, and Ovid Medline). RESULTS: Fifteen studies (2,857 shoulders) satisfied our inclusion criteria. The incidence of acromial fracture after RTSA was 4.0% (114 / 2,857). The mean age of the patients at the time of fracture was 72.9 years (range, 51 to 91 years). The mean time from RTSA to diagnosis of acromial fracture was 9.4 months (range, 1 to 94 months). One hundred shoulders (87.7%) were treated conservatively and 14 shoulders (12.3%) were treated surgically. The mean follow-up period after acromial fracture was 33.8 months. The overall union rate was 50.0% (43.8% for conservative treatment and 87.5% for operative treatment). The fracture incidence was significantly different among the medial glenoid and medial humerus prosthesis design (8.4%), the lateral glenoid and medial humerus design (4.0%), and the medial glenoid and lateral humerus design (2.8%). The mean values at final follow-up were as follows: visual analog scale score, 2.2; American Shoulder and Elbow Surgeons score, 59.1; Constant score, 59.7; and Simple Shoulder Test, 5.8. The mean forward flexion, abduction, and external rotation were 102.3°, 92.3°, and 25.8°, respectively. CONCLUSIONS: Acromial fractures after RTSA are a complication neither uncommon nor negligible. In the absence of studies with high-level evidence, there is a controversy on the outcomes after treatment. Further well-designed prospective randomized controlled studies with a long-term follow-up should be performed to ascertain the diagnosis, treatment, and prognosis of acromial fractures after RTSA.


Assuntos
Acrômio/lesões , Artroplastia do Ombro/efeitos adversos , Fraturas Ósseas/etiologia , Complicações Pós-Operatórias/etiologia , Humanos
14.
J Neurosci ; 39(18): 3537-3550, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30819799

RESUMO

The circadian clock organizes the physiology and behavior of organisms to their daily environmental rhythms. The central circadian timekeeping mechanism in eukaryotic cells is the transcriptional-translational feedback loop (TTFL). In the Drosophila TTFL, the transcription factors CLOCK (CLK) and CYCLE (CYC) play crucial roles in activating expression of core clock genes and clock-controlled genes. Many signaling pathways converge on the CLK/CYC complex and regulate its activity to fine-tune the cellular oscillator to environmental time cues. We aimed to identify factors that regulate CLK by performing tandem affinity purification combined with mass spectrometry using Drosophila S2 cells that stably express HA/FLAG-tagged CLK and V5-tagged CYC. We identified SNF4Aγ, a homolog of mammalian AMP-activated protein kinase γ (AMPKγ), as a factor that copurified with HA/FLAG-tagged CLK. The AMPK holoenzyme composed of a catalytic subunit AMPKα and two regulatory subunits, AMPKß and AMPKγ, directly phosphorylated purified CLK in vitro Locomotor behavior analysis in Drosophila revealed that knockdown of each AMPK subunit in pacemaker neurons induced arrhythmicity and long periods. Knockdown of AMPKß reduced CLK levels in pacemaker neurons, and thereby reduced pre-mRNA and protein levels of CLK downstream core clock genes, such as period and vrille Finally, overexpression of CLK reversed the long-period phenotype that resulted from AMPKß knockdown. Thus, we conclude that AMPK, a central regulator of cellular energy metabolism, regulates the Drosophila circadian clock by stabilizing CLK and activating CLK/CYC-dependent transcription.SIGNIFICANCE STATEMENT Regulation of the circadian transcription factors CLK and CYC is fundamental to synchronize the core clock with environmental changes. Here, we show that the AMPKγ subunit of AMPK, a central regulator of cellular metabolism, copurifies with the CLK/CYC complex in Drosophila S2 cells. Furthermore, the AMPK holoenzyme directly phosphorylates CLK in vitro This study demonstrates that AMPK activity regulates the core clock in Drosophila by activating CLK, which enhances circadian transcription. In mammals, AMPK affects the core clock by downregulating circadian repressor proteins. It is intriguing to note that AMPK activity is required for core clock regulation through circadian transcription enhancement, whereas the target of AMPK action is different in Drosophila and mammals (positive vs negative element, respectively).


Assuntos
Proteínas Quinases Ativadas por AMP/genética , Proteínas CLOCK/genética , Ritmo Circadiano/genética , Proteínas de Drosophila/genética , Regulação da Expressão Gênica , Animais , Regulação para Baixo , Drosophila melanogaster , Locomoção/genética , Masculino , Neurônios/metabolismo , Subunidades Proteicas/metabolismo
15.
Clin Shoulder Elb ; 22(2): 106-109, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33330203

RESUMO

Acromial fractures are well-documented complications subsequent to reverse shoulder arthroplasty (RSA), and most appear as stress fractures with no history of single trauma. To date, no study has reported the occurrence of acute displaced acromial fracture due to sudden strong deltoid contraction during heavy work. Displacement of the fracture results in a challenging surgery since it is difficult to obtain adequate fixation in thin and osteoporotic bones. We report a rare case of acute displaced acromial fracture after successful RSA treatment, using a novel technique of open reduction and internal fixation, applying two 4.5 mm cannulated screws and lateral clavicle pre-contoured plate.

16.
Arch Orthop Trauma Surg ; 138(9): 1223-1234, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29774386

RESUMO

INTRODUCTION: It is likely that posterior-wall involvement in association with two-column fractures plays a pivotal role in outcomes because of the potential for hip instability if it is not anatomically reduced and fixed. Uncertainty remains about how this fracture is best treated, especially regarding how posterior-wall involvement may affect functional results. MATERIALS AND METHODS: To better understand the role that posterior-wall involvement may play in determining functional results, we compared data for outcomes for patients with posterior-wall involvement and for those without in a consecutive series of two-column fractures. Between 2000 and 2013, 42 patients who underwent surgical treatment for two-column acetabular fractures were evaluated after a minimum follow-up period of 1 year. Data were prospectively collected and retrospectively evaluated. Of the 42 patients, 25 had only a two-column fracture (group 1) and 17 had a two-column fracture with posterior-wall involvement (group 2). RESULTS: There were no differences between groups in terms of reduction accuracy, radiographic results, clinical results, or complication rates. All hips in patients with internal fixation for the associated posterior-wall fracture had anatomical reduction. At the latest follow-up evaluation, three patients from group 1 (without posterior-wall involvement) and three patients from group 2 (with posterior-wall involvement) had undergone total hip arthroplasty. CONCLUSION: These results suggest that a posterior-wall fracture in a two-column fracture does not compromise functional outcomes when the treatment algorithm discussed here is followed.


Assuntos
Acetábulo/lesões , Fixação Interna de Fraturas/métodos , Fraturas Ósseas/cirurgia , Acetábulo/cirurgia , Adolescente , Adulto , Idoso , Placas Ósseas/efeitos adversos , Parafusos Ósseos/efeitos adversos , Feminino , Fixação Interna de Fraturas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
17.
Exp Mol Med ; 50(2): e448, 2018 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-29472703

RESUMO

The molecular mechanism underlying the initiation of somatic cell reprogramming into induced pluripotent stem cells (iPSCs) has not been well described. Thus, we generated single-cell-derived clones by using a combination of drug-inducible vectors encoding transcription factors (Oct4, Sox2, Klf4 and Myc) and a single-cell expansion strategy. This system achieved a high reprogramming efficiency after metabolic and epigenetic remodeling. Functional analyses of the cloned cells revealed that extracellular signal-regulated kinase (ERK) signaling was downregulated at an early stage of reprogramming and that its inhibition was a driving force for iPSC formation. Among the reprogramming factors, Myc predominantly induced ERK suppression. ERK inhibition upregulated the conversion of somatic cells into iPSCs through concomitant suppression of serum response factor (SRF). Conversely, SRF activation suppressed the reprogramming induced by ERK inhibition and negatively regulated embryonic pluripotency by inducing differentiation via upregulation of immediate early genes, such as c-Jun, c-Fos and EGR1. These data reveal that suppression of the ERK-SRF axis is an initial molecular event that facilitates iPSC formation and may be a useful surrogate marker for cellular reprogramming.


Assuntos
Reprogramação Celular , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Fator de Resposta Sérica/metabolismo , Transdução de Sinais , Animais , Biomarcadores , Linhagem Celular , Transformação Celular Neoplásica , Células Cultivadas , Reprogramação Celular/genética , Fibroblastos/citologia , Fibroblastos/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Genes myc , Imuno-Histoquímica , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Fator 4 Semelhante a Kruppel , Camundongos , Camundongos Transgênicos , Fenótipo , Fosforilação , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
18.
Nucl Med Rev Cent East Eur ; 20(1): 32-38, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28198519

RESUMO

BACKGROUND: Tumor hypoxia induces the expression of several genes via the hypoxia-inducible transcription factor-1 alpha (HIF-1a). It is associated with the prognosis of several cancers. We studied the immunohistochemical expression of HIF-1a in patients with invasive ductal cancer (IDC) of the breast and the possible correlation with the maximum standardized uptake value of the primary tumor (pSUVmax) as well as other biological parameters. Prognostic significance of pSUVmax and expression of HIF-1a for the prediction of progression-free survival (PFS) was also assessed. MATERIAL AND METHODS: Two-hundred seven female patients with IDC who underwent pretreatment fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) were enrolled. The pSUVmax was compared with clinicopathological parameters including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), axillary lymph node (LN) metastasis, stage and HIF-1a expression. The prognostic value of pSUVmax for PFS was assessed using the Kaplan-Meier method. RESULTS: pSUVmax was significantly higher in patients with HIF-1a expression ≥ 2 compared to patients with HIF-1a expression < 2 (5.2 ± 4.5 vs. 3.7 ± 3.1, p = 0.008). pSUVmax was also significantly higher in higher stage (p < 0.000001), ER-negative tumors (p < 0.0001), PR-negative tumors (p = 0.0011) and positive LN metastasis (p = 0.0013). pSUVmax was significantly higher in patients with progression compared to patients who were disease-free (6.8 ± 4.4 vs. 4.1 ± 3.7, p = 0.0005). A receiver-operating characteristic curve demonstrated a pSUVmax of 6.51 to be the optimal cutoff for predicting PFS (sensitivity: 53.6%, specificity: 86.0%). Patients with high pSUVmax (> 6.5) had significantly shorter PFS compared to patients with low pSUVmax (p < 0.0001). CONCLUSIONS: pSUVmax on pretreatment F-18 FDG PET/ CT reflect expression of HIF-1a and can be used as a good surrogate marker for the prediction of progression in patients with IDC. The amount of FDG uptake is determined by the presence of glucose metabolism and hypoxia in breast cancer cell.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/metabolismo , Fluordesoxiglucose F18/farmacocinética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Imagem Molecular/métodos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/estatística & dados numéricos , Prevalência , Compostos Radiofarmacêuticos/farmacocinética , República da Coreia/epidemiologia , Fatores de Risco , Sensibilidade e Especificidade , Taxa de Sobrevida , Hipóxia Tumoral
19.
Knee Surg Relat Res ; 28(1): 55-61, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26955613

RESUMO

PURPOSE: To evaluate the radiological stability according to the number of modular augments after revision of infected total knee arthroplasty (TKA). MATERIALS AND METHODS: Between February 2006 and September 2013, 37 patients (39 knees) followed ≥2 years after revision of infected TKA using modular metal augments for bone defects were reviewed retrospectively. We divided the patients into 3 groups according to the number of augments into group A (≤2 augments, 14 knees), group B (3-4 augments, 18 knees), and group C (5≥ augments, 7 knees) and evaluated the width of radiolucent zones around the implant at the last follow-up. RESULTS: There were 3 Anderson Orthopedic Research Institute type I, 33 type II, and 3 type III bone defects. The mean number of radiolucent zones of group A was 3 and the sum of width averaged 4.4 mm. In group B, the values were 4.8 and 6.2 mm, respectively. In group C, the values were 8.1 and 12.9 mm, respectively. The differences between the three groups were statistically significant. CONCLUSIONS: In revision TKA with modular metal augmentation caused by infected TKA, increased modularity can result in radiological instability.

20.
Clin Orthop Surg ; 7(2): 234-40, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26217471

RESUMO

BACKGROUND: The literature does not provide consistent information on the impact of patients' gender on recovery after rotator cuff repair. The purpose of this study was to determine whether gender affects pain and functional recovery in the early postoperative period after rotator cuff repair. METHODS: Eighty patients (40 men and 40 women) were prospectively enrolled. Pain intensity and functional recovery were evaluated, using visual analog scale (VAS) pain score and range of motion on each of the first 5 postoperative days, at 2 and 6 weeks and at 3, 6, and 12 months after surgery. Perioperative medication-related adverse effects and postoperative complications were also assessed. RESULTS: The mean VAS pain score was significantly higher for women than men at 2 weeks after surgery (p = 0.035). For all other periods, there was no significant difference between men and women in VAS pain scores, although women had higher scores than men. Mean forward flexion in women was significantly lower than men at 6 weeks after surgery (p = 0.033) and the mean degree of external rotation in women was significantly lower than men at 6 weeks (p = 0.007) and at 3 months (p = 0.017) after surgery. There was no significant difference in medication-related adverse effects or postoperative complications. CONCLUSIONS: Women had more pain and slower recovery of shoulder motion than men during the first 3 months after rotator cuff repair. These findings can serve as guidelines for pain management and rehabilitation after surgery and can help explain postoperative recovery patterns to patients with scheduled rotator cuff repair.


Assuntos
Recuperação de Função Fisiológica , Manguito Rotador/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Amplitude de Movimento Articular , Fatores Sexuais , Fatores de Tempo , Resultado do Tratamento
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