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Understanding the role of mechanical force on tissue nutrient transport is essential, as sustained force may affect nutrient levels within the disc and initiate disc degeneration. This study aims to evaluate the time-dependent effects of different compressive force amplitudes as well as tensile force on glucose concentration and cell viability within the disc. Based on the mechano-electrochemical mixture theory, a multiphasic finite element model of the lumbar intervertebral disc was developed. The minimum glucose concentration and minimum cell density in both normal and degenerated discs were predicted for different compressive force amplitudes, tensile force, and corresponding creep time. Under high compressive force, the minimum glucose concentration exhibited an increasing and then decreasing trend with creep time in the normal disc, whereas that of the degenerated disc increased, then decreased, and finally increased again. At steady state, a higher compressive force was accompanied by a lower glucose concentration distribution. In the degenerated disc, the minimum cell density was negatively correlated with creep time, with a greater range of affected tissue under a higher compressive force. For tensile force, the minimum glucose concentration of the degenerated disc raised over time. This study highlighted the importance of creep time, force magnitude, and force type in affecting nutrient concentration and cell viability. Sustained weight-bearing activities could deteriorate the nutrient environment of the degenerated disc, while tensile force might have a nonnegligible role in effectively improving nutrient levels within the degenerated disc.
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Sobrevivência Celular , Força Compressiva , Análise de Elementos Finitos , Glucose , Disco Intervertebral , Resistência à Tração , Glucose/metabolismo , Disco Intervertebral/metabolismo , Disco Intervertebral/citologia , Modelos Biológicos , Fenômenos Biomecânicos , Estresse MecânicoRESUMO
ABSTRACT: Male infertility is a global issue caused by poor sperm quality, particularly motility. Enhancement of the sperm quality may improve the fertilization rate in assisted reproductive technology (ART) treatment. Scriptaid, with a novel human sperm motility-stimulating activity, has been investigated as a prospective agent for improving sperm quality and fertilization rate in ART. We evaluated the effects of Scriptaid on asthenozoospermic (AZS) semen, including its impact on motility stimulation and protective effects on cryopreservation and duration of motility, by computer-aided sperm analysis (CASA). Sperm quality improvement by Scriptaid was characterized by increased hyaluronan-binding activity, tyrosine phosphorylation, adenosine triphosphate (ATP) concentration, mitochondrial membrane potential, and an ameliorated AZS fertilization rate in clinical intracytoplasmic sperm injection (ICSI) experiments. Furthermore, our identification of active Scriptaid analogs and different metabolites induced by Scriptaid in spermatozoa lays a solid foundation for the future biomechanical exploration of sperm function. In summary, Scriptaid is a potential candidate for the treatment of male infertility in vitro as it improves sperm quality, prolongs sperm viability, and increases the fertilization rate.
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BACKGROUND: Various postoperative staging systems were developed to assess the outcome of differentiated thyroid cancer from initial risk after surgery to dynamic changing prognosis during follow-up. The objective of our retrospective cohort study was to identify risk factors contributing to macroscopic positive surgical margin (R2 resection) and parameters in discriminating the treatment responses and prognosis among R2 patients. METHODS: In total, 242 differentiated thyroid cancer patients with extrathyroidal extension who underwent a thyroidectomy at Kaohsiung Chang Gung Memorial Hospital between January 2013 and July 2018, were included. The patients were grouped according to the presence or absence of gross residual disease (R2). The R2 patients were further classified into two categories according to their treatment response into excellent and nonexcellent groups. The parameters and treatment outcomes were compared between these groups. RESULTS: The mean follow-up time was 45.3 months. Two hundred seven (85.5%) patients had either surgery-free or microscopic margins (R0/R1), while 35 (14.5%) had R2 resection. In the R2 group (n = 35), 15 (42.9%) patients achieved an excellent response, while 20 (57.1%) achieved a nonexcellent response. Statistically significant differences were observed in the extent of neck dissection, TSH-Tg level, post-RAI Tg level, nodal status, and recurrence between the two groups. The Kaplan-Meier curves for 5-year local and distant recurrence-free survival of R0/R1 versus R2 patients were 90.0% versus 66.3%, and 98.4% versus 90.7%, respectively ( p < 0.001). Among the R2 patients, the excellent responders had a higher local recurrence-free survival than nonexcellent responders (93.3% vs. 45.1%, p = 0.008). CONCLUSION: There are significant disparities in recurrence-free survival among R2 patients with different treatment responses. The nodal status of papillary thyroid cancer and thyroglobulin level after thyroidectomy and RAI were factors contributing to difference in their treatment responses.
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Neoplasia Residual , Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/mortalidade , Pessoa de Meia-Idade , Masculino , Estudos Retrospectivos , Feminino , Adulto , Prognóstico , Idoso , Tireoidectomia , Resultado do TratamentoRESUMO
Recent studies have emphasized the importance of dynamic activity in the development of myelopathy. However, current knowledge of how degenerative factors affect the spinal cord during motion is still limited. This study aimed to investigate the effect of various types of preexisting herniated cervical disc and the ligamentum flavum ossification on the spinal cord during cervical flexion and extension. A detailed dynamic fluid-structure interaction finite element model of the cervical spine with the spinal cord was developed and validated. The changes of von Mises stress and maximum principal strain within the spinal cord in the period of normal, hyperflexion, and hyperextension were investigated, considering various types and grades of disc herniation and ossification of the ligamentum flavum. The flexion and extension of the cervical spine with spinal canal encroachment induced high stress and strain inside the spinal cord, and this effect was also amplified by increased canal encroachments and cervical hypermobility. The spinal cord might evade lateral encroachment, leading to a reduction in the maximum stress and principal strain within the spinal cord in local-type herniation. Although the impact was limited in the case of diffuse type, the maximum stress tended to appear in the white matter near the encroachment site while compression from both ventral and dorsal was essential to make maximum stress appear in the grey matter. The existence of canal encroachment can reduce the safe range for spinal cord activities, and hypermobility activities may induce spinal cord injury. Besides, the ligamentum flavum plays an important role in the development of central canal syndrome.Significance. This model will enable researchers to have a better understanding of the influence of cervical degenerative diseases on the spinal cord during extension and flexion.
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Pescoço , Medula Espinal , Análise de Elementos Finitos , Vértebras Cervicais , OsteogêneseRESUMO
Ossification of the ligamentum flavum (OLF) is thought to be an influential etiology of myelopathy, as thickened ligamentum flavum causes the stenosis of the vertebral canal, which could subsequently compress the spinal cord. Unfortunately, there was little information available on the effects of cervical OLF on spinal cord compression, such as the relationship between the progression of cervical OLF and nervous system symptoms during dynamic cervical spine activities. In this research, a finite element model of C1-C7 including the spinal cord featured by dynamic fluid-structure interaction was reconstructed and utilized to analyze how different types of cervical OLF affect principal strain and stress distribution in spinal cord during spinal activities towards six directions. For patients with cervical OLF, cervical extension induces higher stress within the spinal cord among all directions. From the perspective of biomechanics, extension leads to stress concentration in the lateral corticospinal tracts or the posterior of gray matter. Low energy damage to the spinal cord would be caused by the high and fluctuating stresses during cervical movements to the affected side for patients with unilateral OLF at lower grades.
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Ligamento Amarelo , Ossificação Heterotópica , Compressão da Medula Espinal , Doenças da Medula Espinal , Humanos , Osteogênese , Doenças da Medula Espinal/complicações , Compressão da Medula Espinal/etiologia , Ossificação Heterotópica/complicações , Vértebras TorácicasRESUMO
Ossification of the posterior longitudinal ligament (OPLL) has been identified as an important cause of cervical myelopathy. However, the biomechanical mechanism between the OPLL type and the clinical characteristics of myelopathy remains unclear. The aim of this study was to evaluate the effect of different types of OPLL on the dynamic biomechanical response of the spinal cord. A three-dimensional finite element model of the fluid-structure interaction of the cervical spine with spinal cord was established and validated. The spinal cord stress and strain, cervical range of motion (ROM) in different types of OPLL models were predicted during dynamic flexion and extension activity. Different types of OPLL models showed varying degrees of increase in stress and strain under the process of flexion and extension, and there was a surge toward the end of extension. Larger spinal cord stress was observed in segmental OPLL. For continuous and mixed types of OPLL, the adjacent segments of OPLL showed a dramatic increase in ROM, while the ROM of affected segments was limited. As a dynamic factor, flexion and extension of the cervical spine play an amplifying role in OPLL-related myelopathy, while appropriate spine motion is safe and permitted. Segmental OPLL patients are more concerned about the spinal cord injury induced by large stress, and patients with continuous OPLL should be noted to progressive injuries of adjacent level.
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Ossificação do Ligamento Longitudinal Posterior , Doenças da Medula Espinal , Humanos , Ligamentos Longitudinais/fisiologia , Análise de Elementos Finitos , Osteogênese , Doenças da Medula Espinal/etiologia , Ossificação do Ligamento Longitudinal Posterior/complicações , Vértebras CervicaisRESUMO
Objectives. Menstrual hygiene management is one of the main barriers to girls' education attainment in low-and middle-income countries. Poor access to sanitary products and lack of menstrual knowledge affect students' performance at school compared to the opposite sex. Limited evidence is available to provide solutions for schoolgirls. This study examines the effectiveness of menstrual health education programs on well-being and behavioral change among adolescent girls in rural Uganda. Methods. A cluster randomized controlled trial was conducted across 3 schools, including 66 girls aged 13-17 years, in a rural village in Mukono District, Uganda. Schools were randomly allocated to 2 groups: i) health education program intervention and ii) control group (no intervention). Results. After 5 weeks of the Health Education Program, the schoolgirls in experiment groups showed significantly less fear of sharing the menstruation-related concern with parents and pupils [Mean Difference (MD)=0.87, P=0.029) (MD=2.02, P=0.000), and the sense of shameful feelings during menstruation (MD=1.65, P= 0.004); conversely, the fear to go to school during menstruation did not differ between experiment and control groups (MD=-0.04, P=0.94). However, the changes in feeling comfortable having a period at school were significantly different between the experiment and control groups (P=0.001). Conclusions. The study demonstrated promising results of a low-cost intervention for enhancing girls' menstrual health education in a low-income context. Puberty education and reusable pad sewing provision were strongly associated with improving schoolgirls' psychosocial wellbeing related to menstrual management.
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Phosphodiesterase (PDE) inhibitors can improve sperm motility in patients with asthenozoospermia. However, the most commonly reported nonselective PDE inhibitor pentoxifylline and PDE5 inhibitor sildenafil have the disadvantages of requiring a high concentration and destroying sperm integrity. We examined the PDE10A inhibitor PF-2545920 to compare its ability to promote sperm motility with that of pentoxifylline and sildenafil. After seminal plasma was discarded, several semen samples were subjected to four treatments (control, PF-2545920, pentoxifylline, and sildenafil) to evaluate their ability to affect motility, viability, and spontaneous acrosome reactions. Intracellular calcium and adenosine triphosphate (ATP), mitochondrial membrane potential, and penetration through viscous medium were assessed by flow cytometry, luciferase, and hyaluronic acid after treatment with PF-2545920. Statistical analyses were performed using the analysis of variance statistical test. PF-2545920 elevated the percentage of motile spermatozoa compared to the control, pentoxifylline, and sildenafil groups at 10 µmol l -1 ( P < 0.01). It is less toxic to GC-2spd mouse spermatocytes cells and spermatozoa and causes fewer spontaneous acrosomal reactions ( P < 0.05). PF-2545920 also increased mitochondrial membrane potential ( P < 0.001) and altered intracellular calcium ( P < 0.05) in a dose-dependent manner, including increasing sperm hyaluronic acid penetrating ability ( P < 0.05). Therefore, PF-2545920 might be an excellent choice for stimulating the sperm motility.
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OBJECTIVE: The aim of this review was to evaluate the overall diagnostic performance of e-devices for detection of health problems in older adults at home. METHODS: A systematic review was conducted following the PRISMA-DTA guidelines. RESULTS: 31 studies were included with 24 studies included in meta-analysis. The included studies were divided into four categories according to the signals detected: physical activity (PA), vital signs (VS), electrocardiography (ECG) and other. The meta-analysis showed the pooled estimates of sensitivity and specificity were 0.94 and 0.98 respectively in the 'VS' group. The pooled sensitivity and specificity were 0.97 and 0.98 respectively in the 'ECG' group. CONCLUSIONS: All kinds of e-devices perform well in diagnosing the common health problems. While ECG-based health problems detection system is more reliable than VS-based ones. For sole signal detection system has limitation in diagnosing specific health problems, more researches should focus on developing new systems combined of multiple signals.
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Exercício Físico , Humanos , Idoso , Sensibilidade e EspecificidadeRESUMO
Although the success rates of non-surgical treatments for Graves' disease such as antithyroid medication and radioiodine ablation were good, there were still failure of treatments or intolerance for some patients. Traditional thyroid surgery could treat these patients but result in unaesthetic neck scars. Herein, we report the preliminary results of our combination of treatments with the transoral endoscopic thyroidectomy vestibular approach for Graves' disease. A retrospective review of patients who underwent the transoral endoscopic thyroidectomy vestibular approach for the treatment of different sizes of goiters between January 2019 and December 2020 was performed. The demographic and clinical data of patients were collected. All patients were followed up for > 12 months. Each patient's goiter size was determined using four grades-from 0 to 3. In total, 14 female patients receiving the combination treatment with > 1 year of follow-up and a median (range) age of 35 (20-48) years at surgery were included. There were two, three, four, and five patients with grade 0, 1, 2, and 3 goiters, respectively. The median (range) intraoperative blood loss was higher in grade 3 patients (100 [20-850] mL) than in grade 2 patients (20 [10-200] mL) and grade 1 and 0 patients (both < 10 mL) (p = 0.033). All patients had normal-looking necks with a euthyroid or hypothyroid status within 1 year. There were no complications, including re-operation for bleeding, hypoparathyroidism, vocal cord palsy, or infections. The designed combination treatment with the transoral endoscopic thyroidectomy vestibular approach for Graves' disease provides optimal cosmetic results with a high success rate.
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Bócio , Doença de Graves , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Tireoidectomia/efeitos adversos , Tireoidectomia/métodos , Radioisótopos do Iodo , Doença de Graves/cirurgia , Doença de Graves/etiologia , Endoscopia/métodos , Bócio/cirurgia , Estudos RetrospectivosRESUMO
This retrospective study was designed to compare the treatment response of patients with differentiated thyroid cancer (DTC) prepared for radioiodine ablation (RIA) with thyroid hormone withdrawal (THW) or recombinant human thyrotropin (rhTSH) stimulation. Patients with DTC were followed-up retrospectively between 2013 and 2018 in Kaohsiung Chang Gung Memorial Hospital, Taiwan. We compared the excellent response ratios between THW (49.9%) and rhTSH (50.1%) stimulation. Patients were then divided into subgroups, on the basis of age, sex, extrathyroidal extension, lymph node metastasis, and tumor-node-metastasis stage, for analysis. In all, 647 patients were followed-up after RIA. The ratios of THW or rhTSH use in the different subgroups were not statistically significant. In all the patients, the excellent response rate with THW and rhTSH was 80% and 76.5%, respectively, which was not statistically significant. The subgroup analysis, including age, sex, extrathyroidal extension, lymph node metastasis, and tumor-node-metastasis stage (low and high risk), showed similar results. Furthermore, the logistic regression analysis revealed no statistically significant differences among the subgroups. The multivariate analysis showed extrathyroidal extension, lymph node metastasis, and high I131 dose were the prognostic factors affecting the excellent response rate. In conclusion, the THW and rhTSH preparations for RIA were similar in terms of the excellent response rates and subgroup clinical outcomes.
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Adenocarcinoma , Radioisótopos do Iodo , Neoplasias da Glândula Tireoide , Tirotropina Alfa , Humanos , Radioisótopos do Iodo/uso terapêutico , Metástase Linfática , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos , Hormônios Tireóideos/uso terapêutico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/cirurgia , Tireotropina/uso terapêutico , Tirotropina Alfa/uso terapêutico , Resultado do Tratamento , Suspensão de TratamentoRESUMO
Spinal cord injury (SCI), a debilitating medical condition that can cause irreversible loss of neurons and permanent paralysis, currently has no cure. However, regenerative medicine may offer a promising treatment. Given that numerous regenerative strategies aim to deliver cells and materials in the form of tissue-engineered therapies, understanding and characterising the mechanical properties of the spinal cord tissue is very important. In this study, we have systematically characterised the spatiotemporal changes in elastic stiffness (elastic modulus, Pa) and viscosity (drop in peak force, %) of injured rat thoracic spinal cord tissues at distinct time points after crush injury using the indentation technique. Our results demonstrate that in comparison with uninjured spinal cord tissue, the injured tissues exhibited lower stiffness (median 3281 Pa versus 9632 Pa; P < 0.001) but demonstrated elevated viscosity (median 80% versus 57%; P < 0.001) at 3 days postinjury. Between 4 and 6 weeks after SCI, the overall viscoelastic properties of injured tissues returned to baseline values. At 12 weeks after SCI, in comparison with uninjured tissue, the injured spinal cord tissues displayed a significant increase in both elasticity (median 13698 Pa versus 9920 Pa; P < 0.001) and viscosity (median 64% versus 58%; P < 0.001). This work constitutes the first quantitative mapping of spatiotemporal changes in spinal cord tissue elasticity and viscosity in injured rats, providing a mechanical basis of the tissue for future studies on the development of biomaterials for SCI repair. STATEMENT OF SIGNIFICANCE: Spinal cord injury (SCI) is a devastating disease often leading to permanent paralysis. While enormous progress in understanding the molecular pathomechanisms of SCI has been made, the mechanical properties of injured spinal cord tissue have received considerably less attention. This study provides systematic characterization of the biomechanical evolution of rat spinal cord tissue after SCI using a microindentation test method. We find spinal cord tissue behaves significantly softer but more viscous immediately postinjury. As time passes, the lesion site gradually returns to baseline values and then displays pronounced increased viscoelastic properties. As host tissue mechanical properties are a crucial consideration for any biomaterial implanted into central nervous system, our results may have important implications for further studies of SCI repair.
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Traumatismos da Medula Espinal , Ratos , Animais , Traumatismos da Medula Espinal/terapia , Traumatismos da Medula Espinal/patologia , Medula Espinal/patologia , Elasticidade , Fenômenos Mecânicos , Paralisia/patologiaRESUMO
This study aims to establish and validate a poroelastic L4-L5 finite element model to evaluate the effect of different sitting postures and their durations on the mechanical responses of the disc. During the sustained loading conditions, the height loss, fluid loss and von-Mises stress gradually increased, but the intradiscal pressure decreased. The varying rates of aforementioned parameters were more significant at the initial loading stage and less so at the end. The predicted values in the flexed sitting posture were significantly greater than other postures. The extended sitting posture caused an obvious von-Mises stress concentration in the posterior region of the inter-lamellar matrix. From the biomechanical perspective, prolonged sitting may pose a high risk of lumbar disc degeneration, and therefore adjusting the posture properly in the early stage of sitting time may be useful to mitigate that. Additionally, upright sitting is a safer posture, while flexed sitting posture is more harmful.
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Degeneração do Disco Intervertebral , Disco Intervertebral , Humanos , Análise de Elementos Finitos , Vértebras Lombares/fisiologia , Postura Sentada , Fenômenos Biomecânicos/fisiologia , Disco Intervertebral/fisiologia , Postura/fisiologiaRESUMO
Aim: To explore the effectiveness of home-based exercise programs with e-devices (HEPEs) on falls among community-dwelling older adults. Methods: Twelve randomized controlled trials were included in the meta-analysis considering four fall-related outcomes. Results: HEPEs significantly reduced the rate of falls (risk ratio: 0.82; 95% CI: 0.72-0.95; p = 0.006) and improved lower extremity strength (mean difference: -0.94; 95% CI: -1.71 to -0.47; p < 0.001). There was a significant improvement favoring HEPEs on balance if the participants were aged >75 years (mean difference: -0.55; 95% CI: -1.05 to -0.05; p = 0.03), or the intervention duration was at least 16 weeks (mean difference: -0.81; 95% CI: -1.58 to -0.05; p = 0.04). Conclusion: HEPEs demonstrated an overall positive effect on falls among community-dwelling older adults.
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Vida Independente , Equilíbrio Postural , Idoso , Terapia por Exercício , HEPES , HumanosRESUMO
Spinal cord injury (SCI) is a global problem that brings a heavy burden to both patients and society. Recent investigations indicated degenerative disease is taking an increasing part in SCI with the growth of the aging population. However, little insight has been gained about the effect of cervical degenerative disease on the spinal cord during dynamic activities. In this work, a dynamic fluid-structure interaction model was developed and validated to investigate the effect of anterior and posterior encroachment caused by degenerative disease on the spinal cord during normal extension and flexion. Maximum von-Mises stress and maximum principal strain were observed at the end of extension and flexion. The abnormal stress distribution caused by degenerative factors was concentrated in the descending tracts of the spinal cord. Our finding indicates that the excessive motion of the cervical spine could potentially exacerbate spinal cord injury and enlarge injury areas. Stress and strain remained low compared to extension during moderate flexion. This suggests that patients with cervical degenerative disease should avoid frequent or excessive flexion and extension which could result in motor function impairment, whereas moderate flexion is safe. Besides, encroachment caused by degenerative factors that are not significant in static imaging could also cause cord compression during normal activities.
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Medula Cervical , Traumatismos da Medula Espinal , Humanos , Idoso , Análise de Elementos Finitos , Medula Espinal , Vértebras CervicaisRESUMO
Irritable bowel syndrome (IBS) is characterized by visceral hypersensitivity (VH) associated with abnormal serotonin/5-hydroxytryptamine (5-HT) metabolism and neurotrophin-dependent mucosal neurite outgrowth. The underlying mechanisms of VH remain poorly understood. We investigated the role of 5-HT7 receptor in mucosal innervation and intestinal hyperalgesia. A high density of mucosal nerve fibres stained for 5-HT7 was observed in colonoscopic biopsy specimens from IBS patients compared with those from healthy controls. Staining of 5-HT3 and 5-HT4 receptors was observed mainly in colonic epithelia with comparable levels between IBS and controls. Visceromotor responses to colorectal distension were evaluated in two mouse models, one postinfectious with Giardia and subjected to water avoidance stress (GW) and the other postinflammatory with trinitrobenzene sulfonic acid-induced colitis (PT). Increased VH was associated with higher mucosal density of 5-HT7-expressing nerve fibres and elevated neurotrophin and neurotrophin receptor levels in the GW and PT mice. The increased VH was inhibited by intraperitoneal injection of SB-269970 (a selective 5-HT7 antagonist). Peroral multiple doses of CYY1005 (a novel 5-HT7 ligand) decreased VH and reduced mucosal density of 5-HT7-expressing nerve fibres in mouse colon. Human neuroblastoma SH-SY5Y cells incubated with bacteria-free mouse colonic supernatant, 5-HT, nerve growth factor, or brain-derived neurotrophic factor exhibited nerve fibre elongation, which was inhibited by 5-HT7 antagonists. Gene silencing of HTR7 also reduced the nerve fibre length. Activation of 5-HT7 upregulated NGF and BDNF gene expression, while stimulation with neurotrophins increased the levels of tryptophan hydroxylase 2 and 5-HT7 in neurons. A positive-feedback loop was observed between serotonin and neurotrophin pathways via 5-HT7 activation to aggravate fibre elongation, whereby 5-HT3 and 5-HT4 had no roles. In conclusion, 5-HT7-dependent mucosal neurite outgrowth contributed to VH. A novel 5-HT7 antagonist could be used as peroral analgesics for IBS-related pain.
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Síndrome do Intestino Irritável , Neuroblastoma , Animais , Humanos , Mucosa Intestinal , Camundongos , Crescimento Neuronal , SerotoninaRESUMO
Elucidating the structural variations of lignin during the pretreatment is very important for lignin valorization. Herein, poplar wood was pretreated with an integrated process, which was composed of AlCl3-catalyzed hydrothermal pretreatment (HTP, 130-150 °C, 1.0 h) and mild deep-eutectic solvents (DES, 100 °C, 10 min) delignification for recycling lignin fractions. Confocal Raman Microscopy (CRM) was developed to visually monitor the delignification process during the HTP-DES pretreatment. NMR characterizations (2D-HSQC and 31P NMR) and elemental analysis demonstrated that the lignin fractions had undergone the following structural changes, such as dehydration, depolymerization, condensation. Molecular weights (GPC), microstructure (SEM and TEM), and antioxidant activity (DPPH analysis) of the lignins revealed that the DES delignification resulted in homogeneous lignin fragments (1.32 < PDI < 1.58) and facilitated the rapid assemblage of lignin nanoparticles (LNPs) with controllable nanoscale sizes (30-210 nm) and excellent antioxidant activity. These findings will enhance the understanding of structural transformations of the lignin during the integrated process and maximize the lignin valorization in a current biorefinery process.
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Lignina , Populus , Antioxidantes/farmacologia , Biomassa , Solventes Eutéticos Profundos , Hidrólise , Lignina/química , Solventes/químicaRESUMO
Atrial fibrillation (AF) is the most common cardiovascular disease (CVD), and most existing algorithms are usually designed for the diagnosis (i.e., feature classification) or prediction of AF. Artificial intelligence (AI) algorithms integrate the diagnosis of AF electrocardiogram (ECG) and predict the possibility that AF will occur in the future. In this paper, we utilized the MIT-BIH AF Database (AFDB), which is composed of data from normal people and patients with AF and onset characteristics, and the AFPDB database (i.e., PAF Prediction Challenge Database), which consists of data from patients with Paroxysmal AF (PAF; the records contain the ECG preceding an episode of PAF), and subjects who do not have documented AF. We extracted the respective characteristics of the databases and used them in modeling diagnosis and prediction. In the aspect of model construction, we regarded diagnosis and prediction as two classification problems, adopted the traditional support vector machine (SVM) algorithm, and combined them. The improved quantum particle swarm optimization support vector machine (IQPSO-SVM) algorithm was used to speed the training time. During the verification process, the clinical FZU-FPH database created by Fuzhou University and Fujian Provincial Hospital was used for hybrid model testing. The data were obtained from the Holter monitor of the hospital and encrypted. We proposed an algorithm for transforming the PDF ECG waveform images of hospital examination reports into digital data. For the diagnosis model and prediction model trained using the training set of the AFDB and AFPDB databases, the sensitivity, specificity, and accuracy measures were 99.2% and 99.2%, 99.2% and 93.3%, and 91.7% and 92.5% for the test set of the AFDB and AFPDB databases, respectively. Moreover, the sensitivity, specificity, and accuracy were 94.2%, 79.7%, and 87.0%, respectively, when tested using the FZU-FPH database with 138 samples of the ECG composed of two labels. The composite classification and prediction model using a new water-fall ensemble method had a total accuracy of approximately 91% for the test set of the FZU-FPH database with 80 samples with 120 segments of ECG with three labels.
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Fibrilação Atrial , Máquina de Vetores de Suporte , Algoritmos , Inteligência Artificial , Fibrilação Atrial/diagnóstico , Eletrocardiografia , HumanosRESUMO
The monoamine oxidase-B (MAO-B) inhibitors with neuroprotective effects are better for Parkinson's disease (PD) treatment, due to the complicated pathogenesis of PD. To develop new hMAO-B inhibitors with neuroprotection, a novel series of 3,4-dihydrocoumarins was designed as selective and reversible hMAO-B inhibitors to treat PD. Most compounds showed potent and selective inhibition for hMAO-B over hMAO-A with IC50 values ranging from nanomolar to sub-nanomolar. Among them, compound 4d was the most potent hMAO-B inhibitor (IC50 = 0.37 nM) being about 20783-fold more active than iproniazid, and exhibited the highest selectivity for hMAO-B (SI > 270,270). Kinetic studies revealed that compound 4d was a reversible and competitive inhibitor of hMAO-B. Neuroprotective studies indicated that compound 4d could protect PC12 cells from the damage induced by 6-OHDA and rotenone. Besides, compound 4d did not exhibit acute toxicity at a dose up to 2500 mg/kg (po), and could cross the BBB in parallel artificial membrane permeability assay. More importantly, compound 4d was able to significantly prevent the motor deficits in the MPTP-induced PD model. These results indicate that compound 4d is an effective and promising candidate against PD.
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Cumarínicos/química , Desenho de Fármacos , Intoxicação por MPTP/tratamento farmacológico , Inibidores da Monoaminoxidase/farmacologia , Monoaminoxidase/metabolismo , Animais , Indanos/farmacologia , Camundongos , Modelos Moleculares , Estrutura Molecular , Inibidores da Monoaminoxidase/química , Oxidopamina/toxicidade , Células PC12 , Conformação Proteica , Ratos , Rotenona/toxicidade , Relação Estrutura-AtividadeRESUMO
Differentiated thyroid cancer (DTC) survivors are at increased risk of developing double primary malignancy (DPM). The aim of this study was to investigate clinicopathological characteristics and survival in DTC patients diagnosed with DPM. A total of 975 patients with DTC diagnosed between 2013 and 2017, treated, and followed at a medical center in Taiwan were retrospectively reviewed. Data from enrolled patients were analyzed for differences in prognosis dependent on the presence of DPM, and which clinicopathological variables affected their prognosis. Among 975 thyroid cancer patients, 94 (9.6%) were diagnosed with DPMs and 16 (1.6%) patients died of any cause. DPM patients had a greater proportion of males, had a higher mean age, more commonly presented with a thyroid mass incidentally by imaging and cervical lymph node metastases, showed a more advanced thyroid cancer stage, and had a higher proportion of lymph node metastases. Overall survival (OS) was significantly lower in patients diagnosed with DPM. Male gender (hazard ratio [HR] = 4.597), two or more DPMs (HR = 8.071), and shorter time interval between two cancers occurrences (HR = 7.101) were significantly risk factors for DPM-related death. In conclusion, the risk of developing DPM in DTC patients was elevated in older, male patients with an advanced tumor-node-metastasis stage. DPM adversely affected the OS of thyroid cancer patients. Male gender, two or more DPMs, and shorter time interval between occurrences were significant risk factors for OS in DPM patients.