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BACKGROUND: The primary treatment for non-metastatic rectal cancer is curative resection. However, sphincter-preserving surgery may lead to complications. This study aims to develop a predictive model for stoma non-closure in rectal cancer patients who underwent curative-intent low anterior resection. METHODS: Consecutive patients diagnosed with non-metastatic rectal cancer between January 2005 and December 2017, who underwent low anterior resection, were retrospectively included in the Chang Gung Memorial Foundation Institutional Review Board. A comprehensive evaluation and analysis of potential risk factors linked to stoma non-closure were performed. RESULTS: Out of 956 patients with temporary stomas, 10.3% (n = 103) experienced non-closure primarily due to cancer recurrence and anastomosis-related issues. Through multivariate analysis, several preoperative risk factors significantly associated with stoma non-closure were identified, including advanced age, anastomotic leakage, positive nodal status, high preoperative CEA levels, lower rectal cancer presence, margin involvement, and an eGFR below 30 mL/min/1.73m2. A risk assessment model achieved an AUC of 0.724, with a cutoff of 2.5, 84.5% sensitivity, and 51.4% specificity. Importantly, the non-closure rate could rise to 16.6% when more than two risk factors were present, starkly contrasting the 3.7% non-closure rate observed in cases with a risk score of 2 or below (p < 0.001). CONCLUSION: Prognostic risk factors associated with the non-closure of a temporary stoma include advanced age, symptomatic anastomotic leakage, nodal status, high CEA levels, margin involvement, and an eGFR below 30 mL/min/1.73m2. Hence, it is crucial for surgeons to evaluate these factors and provide patients with a comprehensive prognosis before undergoing surgical intervention.
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Neoplasias Retais , Estomas Cirúrgicos , Humanos , Neoplasias Retais/cirurgia , Neoplasias Retais/patologia , Estudos Retrospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Estomas Cirúrgicos/efeitos adversos , Idoso , Prognóstico , Fatores de Risco , Seguimentos , Fístula Anastomótica/etiologia , Fístula Anastomótica/epidemiologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/cirurgia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Adulto , Protectomia/métodos , Protectomia/efeitos adversos , Idoso de 80 Anos ou maisRESUMO
OBJECTIVES: Orthodontic mechanical force on the periodontal ligament induces extracellular adenosine triphosphate (ATP) release. However, mechanosensitive molecules have not been confirmed functionally in periodontal ligament cells. In the present study, we examined the roles of mechanosensitive PIEZO channels in the mechanically stimulated release of ATP in human periodontal ligament fibroblasts (HPdLFs). MATERIALS AND METHODS: To examine PIEZO expression in HPdLFs, we performed reverse transcription-quantitative polymerase chain reaction, fluorescent immunostaining, and Ca2+ imaging. ATP concentrations were measured in culture medium after applications of the PIEZO1 agonist Yoda1 and compression force in a newly developed in vitro weight-loaded cell model (IVWLC) using balance weights and a 48-well plate. The mechanosensitive channel inhibitor GsMTx4 and the ATP-releasing route inhibitors clodronic acid, meclofenamic acid, and probenecid were used. To suppress PIEZO1 expression, short interference RNA (siRNA) treatment of the PIEZO1 gene was performed. RESULTS: PIEZO1 mRNA was expressed more abundantly than PIEZO2 mRNA in HPdLFs. HPdLF cell bodies were immunoreactive to anti-PIEZO1 antibody. Yoda1 increased intracellular Ca2+ and extracellular ATP concentrations in a dose-dependent manner. ATP release was inhibited by GsMTx4 and inhibitors of ATP release routes. In the IVWLC, HPdLFs released ATP in response to compression force but not in response to hypoxic stimulation that was simultaneously applied to cells. Mechanically stimulated ATP release was inhibited by GsMTx4, inhibitors of ATP-releasing routes and siRNA treatment of PIEZO1. CONCLUSIONS: PIEZO1 on the cell membranes of HPdLFs is activated by compression force and then induces ATP release via intracellular Ca2+-dependent exocytosis and ATP-permeable channels.
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Cálcio , Ligamento Periodontal , Humanos , Fibroblastos , Trifosfato de Adenosina , RNA Interferente PequenoRESUMO
Mammalian taste bud cells have a limited lifespan and differentiate into type I, II, and III cells from basal cells (type IV cells) (postmitotic precursor cells). However, little is known regarding the cell lineage within taste buds. In this study, we investigated the cell fate of Mash1-positive precursor cells utilizing the Cre-loxP system to explore the differentiation of taste bud cells. We found that Mash1-expressing cells in Ascl1CreERT2::CAG-floxed tdTomato mice differentiated into taste bud cells that expressed aromatic L-amino acid decarboxylase (AADC) and carbonic anhydrase IV (CA4) (type III cell markers), but did not differentiate into most of gustducin (type II cell marker)-positive cells. Additionally, we found that Mash1-expressing cells could differentiate into phospholipase C ß2 (PLCß2)-positive cells, which have a shorter lifespan compared with AADC- and CA4-positive cells. These results suggest that Mash1-positive precursor cells could differentiate into type III cells, but not into most of type II cells, in the taste buds.
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Envelhecimento/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Diferenciação Celular , Fosfolipase C beta/metabolismo , Papilas Gustativas/citologia , Papilas Gustativas/metabolismo , Animais , Biomarcadores/metabolismo , CamundongosAssuntos
Anticoagulantes , Artroplastia de Substituição , Aspirina , Enoxaparina , Tromboembolia Venosa , Humanos , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Aspirina/efeitos adversos , Aspirina/uso terapêutico , Enoxaparina/efeitos adversos , Enoxaparina/uso terapêutico , Complicações Pós-Operatórias/prevenção & controle , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle , Artroplastia de Substituição/efeitos adversosRESUMO
Oral perception of food particles is important in mastication and swallowing. However, the mechanism underlying particle perception remains poorly understood because of the lack of suitable experimental systems. We evaluated microparticle perception in rats utilizing insoluble cellulose particles of varying diameters (20-170 µm). The cellulose additives have polycrystalline morphologies and contain smaller crushed particles. The filtrate containing 20 µm particles at a concentration of 1.6% was passed through 3 µm pore-size filter paper, and numerous small particles equivalent to a 0.25 mM soluble solution were observed. In two-bottle preference tests, rats showed no innate preference or avoidance of particles of any size at concentrations ranging from 0.05-1.6%. Next, conditioned preference learning tests employing 8% glucose and fructose solutions were performed. After being repeatedly presented with glucose and fructose solutions containing particles of different sizes (170 and 20 µm particles or 20 µm filtrate) at a concentration of 1.6%, the rats preferred particles in glucose solution even without glucose presentation. Intriguingly, rats preferred the filtrate following repeated presentations of glucose-containing filtrate and water containing fructose. These results suggest that rats can distinguish microparticles in water. The preference learning test is useful for analyzing particle perception mechanisms in mammals.
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Celulose , Condicionamento Clássico , Ratos , Animais , Celulose/farmacologia , Frutose/farmacologia , Glucose , Água , Preferências Alimentares , MamíferosRESUMO
OBJECTIVES: It is unclear which mechanical properties of foods cause the texture sensation in humans. This study aimed to investigate the relationship between unilateral compression measurements and the sensations of hardness and springiness in gels. METHODS: Three different concentrations of agar and gelatin gels were prepared by the addition of agar (1%, 2%, and 3%) and gelatin (4%, 8%, and 16%) to water or apple juice. In a stress-rupture test, stress-strain curves were obtained by the application of uniaxial compression with a disc plunger at a compression rate of 10 mm/s. The hardness, springiness, and palatability of the gels were evaluated by 12 healthy volunteers using a visual analog scale. RESULTS: The sensation of hardness was positively correlated with the sensation of springiness for the agar and gelatin gels. Palatability decreased as hardness increased for both gels. In terms of mechanical properties, the sensation of hardness was only significantly correlated with the initial elastic modulus, while the sensation of springiness was correlated with the late elastic modulus and other mechanical properties such as fracture strain, time, and stress. CONCLUSIONS: These results suggest that sensations of hardness and springiness are produced in the initial and late stages, respectively, during the food-crushing process using the tongue, palate, and teeth.
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Gelatina , Sensação , Humanos , Dureza , Ágar , GéisRESUMO
Background: Ewing sarcoma (ES) is a common primary bone tumor in children. Our study aimed to compare overall survival (OS) between pediatric and adult bone ES patients, identify independent prognostic factors and develop a nomogram for predicting OS in adult patients with ES of bone. Methods: We retrospectively analyzed data for the 2004-2015 period from the Surveillance, Epidemiology, and End Results (SEER) database. To guarantee well-balanced characteristics between the comparison groups, propensity score matching (PSM) was used. Kaplan-Meier (KM) curves were used to compare OS between pediatric and adult patients with ES of bone. Univariate and multivariate Cox regression analyses were used to screen independent prognostic factors for ES of bone, and a prognostic nomogram was constructed by using the factors identified. The prediction accuracy and clinical benefit were evaluated using receiver operating characteristic (ROC) curves, areas under the curves (AUCs), calibration curves, and decision curve analysis (DCA). Results: Our results showed that adult ES patients had lower OS than younger ES patients. Age, surgery, chemotherapy, and TNM stage were independent risk factors for bone ES in adults and were used to develop a nomogram. AUCs for 3-, 5-, and 10-year OS were 76.4 (67.5, 85.3), 77.3 (68.6, 85.9) and 76.6 (68.6, 84.5), respectively. Calibration curves and DCA results indicated excellent performance for our nomogram. Conclusion: We found that ES pediatric patients have better OS than adult ES patients, and we constructed a practical nomogram to predict the 3-, 5- and 10-year OS of adult patients with ES of bone based on independent prognostic factors (age, surgery, chemotherapy, T stage, N stage and M stage).
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The deposits of human islet amyloid polypeptide (IAPP), also called amylin, in the pancreas have been postulated to be a factor of pancreatic ß-cell dysfunction and is one of the common pathological hallmarks of type II diabetes mellitus (T2DM). Therefore, it is imperative to gain an in-depth understanding of the formation of these aggregates. In this study, we demonstrate a rationally-designed strategy of an environmentally sensitive near-infrared (NIR) molecular rotor utilizing thioflavin T (ThT) as a scaffold for IAPP deposits. We extended the π delocalized system not only to improve the viscosity sensitivity but also to prolong the emission wavelength to the NIR region. A naphthalene moiety was also introduced to adjust the sensitivity of our designed probes to differentiate the binding microenvironment polarity of different targeted proteins. As a result, a novel NIR fluorogenic probe toward IAPP aggregates, namely AmySP-4-Nap-Ene, was first developed. When attached to different protein aggregates, this probe exhibited distinct fluorescence emission profiles. In a comparison with ThT, the fluorescence emission of non-ionic AmySP-4-Nap-Ene exhibits a significant difference between the presence of non-fibrillar and fibrillar IAPP and displays a higher binding affinity toward IAPP fibrils. Further, the AmySP-4-Nap-Ene can be utilized to monitor IAPP accumulating process and image fibrils both in vitro and in living cells.
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Diabetes Mellitus Tipo 2 , Células Secretoras de Insulina , Humanos , Polipeptídeo Amiloide das Ilhotas Pancreáticas/química , Diabetes Mellitus Tipo 2/metabolismo , Corantes Fluorescentes/química , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Amiloide/química , Amiloide/metabolismoRESUMO
Piperic acid derivatives were found to affect the islet amyloid polypeptide (IAPP) aggregation process. Structure-activity relationship studies revealed that PAD-13 was an efficient molecular modulator to accelerate IAPP fibril formation by promoting primary and secondary nucleation and reducing its antimicrobial activity.
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Anti-Infecciosos , Polipeptídeo Amiloide das Ilhotas Pancreáticas , Polipeptídeo Amiloide das Ilhotas Pancreáticas/farmacologia , Polipeptídeo Amiloide das Ilhotas Pancreáticas/química , Amiloide/química , Ácidos Graxos Insaturados , Anti-Infecciosos/farmacologiaRESUMO
Video game streaming has become a popular leisure activity which, depending on content, level of skill, and user interest, reaches a wide array of audiences. Using streaming platforms, client users are able to broadcast their video gameplays and use chat rooms to interact with other viewers and game players in real time. This paper aimed to develop and examine a theoretical explanation concerning the formation of client users' satisfaction with, perceived net benefits of, and continuance intention to use a particular streaming platform. The study employed the updated IS Success Model. An online questionnaire was designed for individuals who were game streaming users of a streaming platform. A total of 632 usable responses were used in the data analysis. The results pointed out that system quality, information quality, service quality, and user motivation all positively and significantly affected user satisfaction. User satisfaction had a positive and significant effect on perceived net benefits and continuance intention to use a streaming platform. Perceived net benefits positively and significantly related to continuance intention to use a particular streaming platform. The moderating effect of emotional involvement between user satisfaction and perceived net benefits was confirmed.
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OBJECTIVE: The aim of this study is to investigate effects of cisplatin preadministration on oral ulcerative mucositis-induced nociception by using an experimental model of rats. DESIGN: After two rounds of cisplatin administration, oral ulcers developed with topical acetic acid treatment in rats. Spontaneous mouth rubbing behavior was observed as spontaneous nociceptive behavior in a plastic cage. Head-withdrawal behavior was observed as mechanical allodynia by using von Frey test in the oral mucosa of conscious rats. Bacterial invasion and inflammatory cell infiltration into oral ulcerative region and systemic leukocyte phagocytic activity were assessed. RESULTS: Following cisplatin preadministration, oral ulcerative mucositis-induced spontaneous nociceptive behavior was not observed in the model. The preadministration enhanced leukocyte phagocytic activity, leading to reduce bacterial invasion and inflammatory cell infiltration in the oral ulcerative region. In contrast, oral ulcerative mucositis-induced mechanical allodynia was induced. The exaggerated mechanical allodynia in the oral ulcerative region was largely inhibited by topical treatment with the antioxidative drug, É-lipoic acid, or the blocker of N-formyl peptide receptor 1, N-t-butoxycarbonyl-methionyl-leucyl-phenylalanine. CONCLUSIONS: These results suggest that cisplatin preadministration suppresses spontaneous nociception in oral ulcerative region, due to antiinflammatory effects by enhancement of leukocyte phagocytic activity, but exaggerates mechanical allodynia due to oxidative stress with N-formyl peptide receptor 1 activation. The suppression of spontaneous nociception is one of the advantages of cisplatin treatment for head and neck cancer patients although the exaggerated allodynia is a serious symptom.
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Mucosite , Úlceras Orais , Estomatite , Ratos , Animais , Cisplatino/efeitos adversos , Nociceptividade , Hiperalgesia/induzido quimicamente , Úlceras Orais/induzido quimicamente , Úlceras Orais/tratamento farmacológico , Receptores de Formil Peptídeo , Mucosite/induzido quimicamente , Estomatite/tratamento farmacológico , Estomatite/induzido quimicamenteRESUMO
OBJECTIVE: Cisplatin, a platinum-based anticancer drug, produces reactive oxygen species (ROS) in many cell types and induces mechanical allodynia in the hands and/or feet (chemotherapy-induced painful neuropathy: CIPN). In this study, we examined the possibility of inducing neuropathy in the oral region using oral keratinocytes and rats. METHODS: Human oral keratinocytes (HOKs) were used to evaluate ROS generation after cisplatin application by a ROS-reactive fluorescent assay. In rats, after cisplatin administrations (two times), the trigeminal ganglion (TG) was investigated by electron microscopy and quantitative RT-PCR. Using our proprietary assay system, oral pain-related behaviors were observed in cisplatin-treated rats. RESULTS: In rats, cisplatin administration reduced food intake and body weight. In electron microscopic analysis, glycogen granules in the TG were depleted following administration, although organelles were intact. In HOK cells, cisplatin significantly increased ROS generation with cell death, similar to glycolysis inhibitors. Cisplatin administration did not show any effects on Trpa1 mRNA levels in the TG. However, the same procedure induced hypersensitivity to mechanical stimulation and the TRPA1 agonist allyl isothiocyanate in the oral mucosa. Mechanical hypersensitivity was inhibited by the antioxidative drug α-lipoic acid and the TRPA1 antagonist HC-030031, similar to that of the hind paw. CONCLUSION: The present findings suggest that cisplatin induces TRPA1-mediated CIPN due to ROS generation in the oral region. This study will provide a better understanding of persistent oral pain in cancer patients.
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Cisplatino , Doenças do Sistema Nervoso Periférico , Animais , Cisplatino/toxicidade , Humanos , Hiperalgesia/induzido quimicamente , Mucosa Bucal , Ratos , Canal de Cátion TRPA1RESUMO
Texture has enormous effects on food preferences. The materials used to study texture discrimination also have tastes that experimental animal can detect; therefore, such studies must be designed to exclude taste differences. In this study, to minimize the effects of material tastes, we utilized high- and low-viscosity forms of carboxymethyl cellulose (CMC-H and CMC-L, respectively) at the same concentrations (0.1-3%) for viscosity discrimination tests in rats. In two-bottle preference tests of water and CMC, rats avoided CMC-H solutions above 1% (63 mPa·s) but did not avoid less viscous CMC-L solutions with equivalent taste magnitudes, suggesting that rats spontaneously avoided high viscosity. To evaluate low-viscosity discrimination, we performed conditioned aversion tests to 0.1% CMC, which initially showed a comparable preference ratio to water in the two-bottle preference tests. Conditioning with 0.1% CMC-L (1.5 mPa·s) did not induce aversion to 0.1% CMC-L or CMC-H. However, rats acquired a conditioned aversion to 0.1% CMC-H (3.6 mPa·s) even after latent inhibition to CMC taste by pre-exposure to 0.1% CMC-L. These results suggest that rats can discriminate considerably low viscosity independent of CMC taste. This novel approach for viscosity discrimination can be used to investigate the mechanisms of texture perception in mammals.
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Carboximetilcelulose Sódica , Roedores , Animais , Ratos , Paladar/fisiologia , Viscosidade , ÁguaRESUMO
Promoting successful aging strategies through well-reasoned caregiving programs is, and should be, one of the main objectives of many government policies and their implementing agencies. Well-being has been considered an important indicator of successful aging. Leisure is a key life domain and a core ingredient for overall well-being. Yet, within well-being research, few studies have made the connection between leisure participation as accepted behavior and subjective well-being in senior citizens. This study proposed to examine the applicability of the Unified Theory of Acceptance and Use of Technology (UTAUT) in explaining senior citizens' decision-making processes in terms of leisure participation behavior and the effect of such behavioral engagement on subjective well-being. The respondents were senior citizens in Taiwan who played gateball and were aged 60 years or older. A total of 595 usable responses were obtained and used to answer the research question. The empirical results indicate that performance expectancy, social influence, and facilitating conditions are positively and significantly related to senior citizens' gateball participation behavior. In addition, gateball participation behavior had a positive and significant effect on respondents' subjective well-being. The results of this study not only extend the application of UTAUT in terms of participation behavior in leisure activities, but also can provide gateball associations and government entities a theoretical model for developing and promoting gateball programs which serve or involve the elderly, as well as helping older adults to pursue satisfactory levels of wellbeing.
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Envelhecimento , Atividades de Lazer , Idoso , Comportamentos Relacionados com a Saúde , Humanos , Políticas , TecnologiaRESUMO
Theoretical explanation concerning the psychological well-being of elderly adults as they participate in a particular leisure activity has been rare. Based on the theory of planned behavior and the technology acceptance model, this study sought to understand the Tai Chi Chuan (TCC) participation influence factors, process, and psychological well-being of Chinese people. A self-developed questionnaire was developed to test the hypotheses of this study. Applying structural equation models, a survey of 769 TCC participations were used to test the theoretical model. The results indicated that perceived usefulness significantly and positively affect respondent attitude, family members' influences significantly and positively affect participants' subjective norm, and resource facilitating conditions significantly and positively affect perceived behavioral control. Perceived behavioral control, attitude, and subjective norm significantly and positively affect TCC participants. The study lends support to the notion that leisure activity participation is vital for elderly adults and their well-being, and it develops a theoretical reference model for better understanding the leisure participation perceptual reasoning processes of elderly adults. Furthermore, the results offer important implications for health policy makers, clinical prevention, and interventions using participation behavior relationships to develop well-constructed leisure programs to attract and inspire participation and, hence, improve the psychological well-being of elderly adults.