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The core of occupational therapy is to help patients with mental illness recover their social work, give play to their self-worth, obtain financial resources, and improve their self-confidence. Occupational therapy can help patients relieve symptoms and restore social function, reduce disease recurrence, and improve the reemployment rate and the overall health level of patients. In order to deeply excavate the inner connection between the mental health status and physical exercise status of college students, the physical exercise behavior of college students during home isolation is studied. First, the "physical exercise behavior questionnaire" and "symptom self-assessment scale" were used to investigate the physical exercise behavior and mental health status of college students. Second, descriptive statistics, correlation analysis, independent sample t-test, and variance analysis were carried out on the survey results using mathematical statistics methods and big data technology. The survey results show high reliability, and the Cronbach's α coefficients were all greater than 0.9. There was a positive correlation between physical exercise methods and mental health in general, and the difference in the degree of exercise is significantly different from the mental health of students (p < 0.05). With the increase of exercise intensity, the score of "symptom self-assessment scale" first decreased and then increased, and the exercise intensity of medium and high intensity showed the best psychological state. And the correlation dimension of depression was the highest. This indicated that the students who liked family physical exercise were less likely to suffer from depression. In addition, depression was the most relevant dimension with self demand physical exercise, and interpersonal sensitivity was the most relevant dimension with social expansion physical exercise. The conclusion shows that the more active the students participate in family physical exercise, the healthier their mental state is. Occupational therapy has obvious curative effect on depression, which can improve patients' negative symptoms, their living ability, and social function. Meanwhile, analyzing data through big data technology reduces human workload and improves data processing efficiency and accuracy. The scheme proposed here provides some ideas for the application of big data technology in occupational therapy.
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Terapia Ocupacional , Inteligência Artificial , Exercício Físico , Nível de Saúde , Humanos , Reprodutibilidade dos Testes , Estudantes/psicologia , Tecnologia , UniversidadesRESUMO
Titanium alloys are widely used in the aerospace industry. However, due to presence of microtexture, which is characterized by preferred crystallographic orientation clustering of thousands of alpha crystallites, cold dwell fatigue may significantly reduce the part life. To satisfy the practical need for nondestructive microtexture characterization, an inverse ultrasonic methodology is proposed to quantify mean parameters of microtexture regions (MTRs) having ellipsoidal shapes. One limitation of previous model-based ultrasonic inversion methods is required knowledge of elastic constants of the crystallites, which are rarely available for engineering alloys. This study overcomes this constraint by adopting the far field attenuation model, JASA, 137 (5), 2655-2669 (2015), and the backscattering model for ultrasonic wave interaction with microtexture. In the methodology developed, all necessary averaged MTR characteristics are obtained solely from directional ultrasonic measurements (backscattering, attenuation, and velocity) without a prior knowledge of material microstructures or elastic properties of different material phases. The inversion method is illustrated by simulations. To support the inversion methodology, the mean MTR sizes, morphology, and elastic scattering factors are determined from the ultrasonic experiment on a Ti-6242 alloy sample. The inversion results are compared with destructive electron backscatter diffraction (EBSD) analysis from which the MTRs are segmented using a non-contiguous grouping criteria. Good agreement is found.
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This work develops a second-order approximation (SOA) model and a three-dimensional (3D) finite element (FE) model to calculate scattering-induced attenuation for elastic wave propagation in polycrystals with elongated grains of arbitrary crystal symmetry. The SOA model accounts for some degree of multiple scattering, whereas the 3D FE model includes all scattering possibilities. The SOA model incorporates the accurate geometric two-point correlation function obtained from the FE material systems to enable comparative studies between the two models. Also, the analytical Rayleigh and stochastic asymptotes are presented to provide explicit insights into propagation behaviors. Quantitative agreement is found between the FE and analytical models for all evaluated cases. In particular, the FE simulations support the SOA model prediction that grain shape does not exert influence on attenuation in the Rayleigh regime and its effect emerges as frequency increases to the stochastic regime showing anisotropy in attenuation. This attenuation anisotropy intensifies with the increase in frequency, but it exhibits a complicated behavior as frequency transits into the geometric regime. Wavefield fluctuations captured from the FE simulations are provided to help observe these complex scattering behaviors. The proportionality of attenuation to elastic scattering factors is also quantitatively evaluated.
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OBJECTIVES: To explore the association between inflammatory cytokines and intrinsic capacity in older adults. METHOD: Data were retrieved from the Cardiovascular Health, Cognition and Aging Study. A total of 130 participants aged 60-99 years (mean age 73.11±9.02 years) were recruited. Intrinsic capacity was assessed by the five domains recommended by the World Health Organization: locomotion, cognition, vitality, sensory and psychological domains. Circulating interleukin-6, tumor necrosis factor receptor 1 (TNFR1), insulin-like growth factor-1, and vaspin levels were measured. Logistic regression was conducted for factors associated with intrinsic capacity decline. RESULTS: Intrinsic capacity decline was associated with older age, kidney diseases, olfactory disturbances and lower grip strength. Logistic regression showed that circulating TNFR1 was independently associated with intrinsic capacity decline after adjustments for age, sex, education, chronic diseases, grip strength, and physical activity. CONCLUSION: Elevated circulating TNFR1 levels are independently associated with declined intrinsic capacity, suggesting that chronic inflammation may underlie intrinsic capacity decline.
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Envelhecimento/sangue , Citocinas/metabolismo , Avaliação Geriátrica/métodos , Receptores Tipo I de Fatores de Necrose Tumoral/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Autophagy is a highly conservative and multi-component activated energy metabolism and self-renewal mechanism, which plays a crucial regulatory role in maintaining the normal physiological state of cells and is involved in various pathological processes. In recent years, the mechanism study has made great progress in regulating autophagy with effective components of Chinese materia medica(CMM),which are reported to prevent and treat cancers, neurodegenerative diseases, cardiovascular diseases and metabolic and immune-related diseases. This review outlines the molecular regulation mechanisms of cell autophagy with CMM components in controlling the above-mentioned diseases. There are many relevant reports on the regulatory mechanisms of autophagy in tumor and cardiovascular cells with CMM monomers. The main chemical structural types are alkaloids, saponins, polyphenols, flavonoids and terpenes. And m-TOR pathway is the main mechanism relating to the regulatory mechanisms of autophagy with CMM. Therefore, the regulatory mec-hanisms of cell autophagy become a new research targeting strategy of therapies with CMM. This review provides evidences for the effectiveness and scientificity of CMM in regulating autophagy, in the expectation of providing references for the in-depth studies of CMM in the field of autophagy and the development of natural autophagy regulators.
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Medicamentos de Ervas Chinesas , Materia Medica , Saponinas , Povo Asiático , Autofagia , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Medicina Tradicional ChinesaRESUMO
The phase velocity dispersion of longitudinal waves in polycrystals with elongated grains of arbitrary crystallographic symmetry is studied in all frequency ranges by the theoretical second-order approximation (SOA) and numerical three-dimensional finite element (FE) models. The SOA and FE models are found to be in excellent agreement for three studied polycrystals: cubic Al, Inconel, and a triclinic material system. A simple Born approximation for the velocity, not containing the Cauchy integrals, and the explicit analytical quasi-static velocity limit (Rayleigh asymptote) are derived. As confirmed by the FE simulations, the velocity limit provides an accurate velocity estimate in the low-frequency regime where the phase velocity is nearly constant on frequency; however, it exhibits dependence on the propagation angle. As frequency increases, the phase velocity increases towards the stochastic regime and then, with further frequency increase, behaves differently depending on the propagation direction. It remains nearly constant for the wave propagation in the direction of the smaller ellipsoidal grain radius and decreases in the grain elongation direction. In the Rayleigh and stochastic frequency regimes, the directional velocity change shows proportionalities to the two elastic scattering factors even for the polycrystal with the triclinic grain symmetry.
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Three-dimensional finite element (FE) modelling, with representation of materials at grain scale in realistic sample volumes, is capable of accurately describing elastic wave propagation and scattering within polycrystals. A broader and better future use of this FE method requires several important topics to be fully understood, and this work presents studies addressing this aim. The first topic concerns the determination of effective media parameters, namely, scattering induced attenuation and phase velocity, from measured coherent waves. This work evaluates two determination approaches, through-transmission and fitting, and it is found that these approaches are practically equivalent and can thus be used interchangeably. For the second topic of estimating modelling errors and uncertainties, this work performs thorough analytical and numerical studies to estimate those caused by both FE approximations and statistical considerations. It is demonstrated that the errors and uncertainties can be well suppressed by using a proper combination of modelling parameters. For the last topic of incorporating FE model information into theoretical models, this work presents elaborated investigations and shows that to improve agreement between the FE and theoretical models, the symmetry boundary conditions used in FE models need to be considered in the two-point correlation function, which is required by theoretical models.
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Better understanding of elastic wave propagation in polycrystals has interest for applications in seismology and nondestructive material characterization. In this study, a second-order wave propagation (SOA) model that considers forward multiple scattering events is developed for macroscopically isotropic polycrystals with equiaxed grains of arbitrary anisotropy (triclinic). It predicts scattering-induced wave attenuation and dispersion of phase velocity. The SOA model implements the generalized two-point correlation (TPC) function, which relates to the actual numeric TPC of simulated microstructure. The analytical Rayleigh and stochastic asymptotes for both attenuation and phase velocity are derived for triclinic symmetry grains, which elucidate the effects of the elastic scattering factors and the generalized TPC in different frequency regimes. Also, the computationally efficient far field approximation attenuation model is obtained for this case; it shows good agreement with the SOA model in all frequency ranges. To assess the analytical models, a three-dimensional (3D) finite element (FE) model for triclinic polycrystals is developed and implemented on simulated 3D triclinic polycrystalline aggregates. Quantitative agreement is observed between the analytical and the FE simulations for both the attenuation and phase velocity. Also, the quasi-static velocities obtained from the SOA and FE models are in excellent agreement with the static self-consistent velocity.
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BACKGROUND: Because frailty is a major health concern among older patients, identifying frailty-related biomarkers will help in the early detection and prevention of frailty. Thus, we aimed to determine the association between circulating levels of silent mating-type information regulation 2 homolog 1 (SIRT1) and frailty. METHODS: We assessed circulating SIRT1 levels in 16 robust, 74 prefrail, and 40 frail older adults. Frailty was diagnosed based on the Fried phenotype. Circulating cytokine and adipokine (e.g., vaspin, adiponectin, and leptin) levels were assessed. Differences in SIRT1 levels among the three subject groups were compared; correlations of SIRT1 levels with physical function and adipokine and cytokine levels were analyzed. RESULTS: Serum SIRT1 levels were significantly higher among frail older adults than among robust ones. Older adults with slowness or weight loss had high SIRT1 levels. Serum SIRT1 levels negatively correlated with gait speed, even after adjustment for age and sex; age; and insulin, vaspin, and leptin levels; they correlated negatively with phospholipase A2 levels. CONCLUSIONS: High SIRT1 levels were observed in frail elderly patients and were correlated with decreased physical function. Insulin and adipokine levels might be the link between SIRT1 and frailty, whereas inflammation may not be involved in this process.
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Adipocinas/metabolismo , Fragilidade/sangue , Avaliação Geriátrica/métodos , Sirtuína 1/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Sirtuína 1/sangue , Sirtuína 1/metabolismoRESUMO
The elastodynamic behavior of polycrystalline cubic materials is studied through the fundamental propagation properties, the attenuation and wave speed, of a longitudinal wave. Predictions made by different analytical models are compared to both numerical and experimental results. The numerical model is based on a three-dimensional Finite Element (FE) simulation which provides a full-physics solution to the scattering problem. The three main analytical models include the Far-Field Approximation (FFA), the Self-Consistent Approximation (SCA) to the reference medium, and the herein derived Second Order Approximation (SOA). The classic Stanke and Kino model is also included, which by comparison to the SOA, reveals the importance of the distribution of length-scales described in terms of the two-point correlation function in determining scattering behavior. Further comparison with the FE model demonstrates that the FFA provides a simple but satisfactory approximation, whereas the SOA shows all-around excellent agreement. The experimental wave velocity data evaluated against the SOA and SC reveal a better agreement when the Voigt reference is used in second order models. The use of full-physics numerical simulations has enabled the study of wave behavior in these random media which will be important to inform the ongoing development of analytical models and the understanding of observations.
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A single mode approximation for the transverse attenuation coefficient in polycrystals is obtained from the far field approximation model (Rokhlin et al., 2015). The model is applicable in all frequency ranges to polycrystals with ellipsoidal grains of triclinic symmetry and is shown to be in favorable agreement with other second order models. In the frame of this model, the transverse wave attenuation coefficient depends on a single elastic scattering factor only (it solely encompasses dependence on the crystallite elastic moduli and the elastic covariance). Therefore in this approximation the attenuation coefficient can be scaled with this factor (normalized), obtaining the universal (master) curve. The admissibility of scaling is supported by the use of the second order model (the type of Stanke-Kino) for a large number of material systems with different grain anisotropies. Within the second order model, the behavior of the scaled transverse wave attenuation coefficient versus frequency is nearly independent of the material system and is a function of the grain geometrical characteristics only. The scaling of the transverse wave attenuation coefficient is tested on the measurements for Ti alloy samples performed in this work and a large set of experimental data obtained for different material systems available in the literature. The results confirm the scaled coefficient independence of the material and good agreement between the data and the universal attenuation curve.
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Conventional metals become harder with decreasing grain sizes, following the classical Hall-Petch relationship. However, this relationship fails and softening occurs at some grain sizes in the nanometer regime for some alloys. In this study, we discovered that plastic deformation mechanism of extremely fine nanograined metals and their hardness are adjustable through tailoring grain boundary (GB) stability. The electrodeposited nanograined nickel-molybdenum (Ni-Mo) samples become softened for grain sizes below 10 nanometers because of GB-mediated processes. With GB stabilization through relaxation and Mo segregation, ultrahigh hardness is achieved in the nanograined samples with a plastic deformation mechanism dominated by generation of extended partial dislocations. Grain boundary stability provides an alternative dimension, in addition to grain size, for producing novel nanograined metals with extraordinary properties.
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The scattering treated here arises when elastic waves propagate within a heterogeneous medium defined by random spatial fluctuation of its elastic properties. Whereas classical analytical studies are based on lower-order scattering assumptions, numerical methods conversely present no such limitations by inherently incorporating multiple scattering. Until now, studies have typically been limited to two or one dimension, however, owing to computational constraints. This article seizes recent advances to realize a finite-element formulation that solves the three-dimensional elastodynamic scattering problem. The developed methodology enables the fundamental behaviour of scattering in terms of attenuation and dispersion to be studied. In particular, the example of elastic waves propagating within polycrystalline materials is adopted, using Voronoi tessellations to randomly generate representative models. The numerically observed scattering is compared against entirely independent but well-established analytical scattering theory. The quantitative agreement is found to be excellent across previously unvisited scattering regimes; it is believed that this is the first quantitative validation of its kind which provides significant support towards the existence of the transitional scattering regime and facilitates future deployment of numerical methods for these problems.
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A simple approximate model is developed for ultrasonic wave propagation in a random elastic medium. The model includes second order multiple scattering and is applicable in all frequency ranges including geometric. It is based on the far field approximation of the reference medium Green's function and simplifications of the mass operator in addition to those of the first smooth approximation. In this approximation, the dispersion equation for the perturbed wave number is obtained; its solution yields the dispersive ultrasonic velocity and attenuation coefficients. The approximate solution is general and is suitable for nonequiaxed grains with arbitrary elastic symmetry. For equiaxed cubic grains, the solution is compared with the existing second order models and with the Born approximation. The comparison shows that the obtained solution has smaller error than the Born approximation and shows reasonably well the onset of multiple scattering and the applicability limit of the Born approximation at high frequency. The perturbed wave number in the developed model does not depend explicitly on the crystallite elastic properties even for arbitrary crystallographic symmetry; it depends on two nondimensional scattering elastic parameters and the macroscopic ultrasonic velocity (those are dependent on the crystallite moduli). This provides an advantage for potential schemes for inversion from attenuation to material microstructure.
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Evidence has shown that miR-146a is involved in carcinogenesis and a common G/C variant (rs2910164) in the pre-miR-146a gene has been found to be associated with various cancers. We investigated the potential prognostic role of miR-146a polymorphism in prostate cancer after radical prostatectomy. Seventy-two southern Chinese with prostate cancer undergoing radical prostatectomy were included in this study. miR-146a polymorphism was analyzed by PCR-RFLP. Its prognostic role in biochemical recurrence was assessed using Kaplan-Meier analysis and Cox regression model. We did not find a significant association between miR-146a polymorphism and prostrate-specific antigen failure in the Chinese population [HR (95%CI): 0.83 (0.30-2.32) for CC vs GG/GC]. However, high Gleason score (over 8) was associated with increased biochemical recurrence and poorer PSA-free survival. This study was limited by the length of follow-up. Future studies with longer follow-up would allow evaluation of more direct metrics, such as disease-specific survival, metastasis-free survival, and overall survival.
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MicroRNAs/genética , Polimorfismo Genético , Prostatectomia/estatística & dados numéricos , Neoplasias da Próstata/diagnóstico , Idoso , China , Humanos , Masculino , Prognóstico , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/cirurgia , Recidiva , Fatores de RiscoRESUMO
Precipitates (ppts) in new generation aluminum-lithium alloys (AA2099 and AA2199) were characterised using scanning and transmission electron microscopy and atom probe tomography. Results obtained on the following ppts are reported: Guinier-Preston zones, T1 (Al2 CuLi), ß' (Al3 Zr) and δ' (Al3 Li). The focus was placed on their composition and the presence of minor elements. X-ray energy-dispersive spectrometry in the electron microscopes and mass spectrometry in the atom probe microscope showed that T1 ppts were enriched in zinc (Zn) and magnesium up to about 1.9 and 3.5 at.%, respectively. A concentration of 2.5 at.% Zn in the δ' ppts was also measured. Unlike Li and copper, Zn in the T1 ppts could not be detected using electron energy-loss spectroscopy in the transmission electron microscope because of its too low concentration and the small sizes of these ppts. Indeed, Monte Carlo simulations of EEL spectra for the Zn L2,3 edge showed that the signal-to-noise ratio was not high enough and that the detection limit was at least 2.5 at.%, depending on the probe current. Also, the simulation of X-ray spectra confirmed that the detection limit was exceeded for the Zn Kα X-ray line because the signal-to-noise ratio was high enough in that case, which is in agreement with our observations.
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Evidence has shown that miR-146a is involved in carcinogenesis, and a common G/C variant (rs2910164) in the pre-miR-146a gene has been associated with various types of cancer. We summarized the data from 22 published case-control studies on the association between rs2910164 and cancer risk and performed subgroup analyses by ethnicity, gender and smoking status. We found a significant association between the pre-miR-146a polymorphism and cancer risk in Caucasian populations (odds ratio (OR) = 0.93, 95% confidence interval (CI) = 0.88-0.99 for G- vs C-allele), while the significance was borderline in Asian populations (OR = 1.11, 95%CI = 1.00-1.23 for G- vs C-allele). A significantly increased risk of cancer was found in males with GG/GC genotypes (OR = 1.23, 95%CI = 1.10- 1.37), and the significance was more pronounced in smokers (OR = 1.82, 95%CI = 1.32-2.51) than in non-smokers (OR = 1.24, 95%CI = 1.01-1.53). We conclude that there is evidence that the pre-miR-146a polymorphism contributes to cancer susceptibilities and that gender and smoking status affect the probability of cancer in individuals with this polymorphism.
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Predisposição Genética para Doença , MicroRNAs/genética , Neoplasias/etnologia , Neoplasias/genética , Polimorfismo de Nucleotídeo Único/genética , Caracteres Sexuais , Fumar/genética , Estudos de Casos e Controles , Feminino , Frequência do Gene/genética , Humanos , Masculino , Modelos Genéticos , Razão de Chances , Viés de Publicação , Precursores de RNA/genética , Fatores de RiscoRESUMO
Nanometre scale clusters form in Cu-containing reactor pressure vessel (RPV) steels during neutron irradiation. These clusters have a deleterious effect on mechanical properties, which can result in embrittlement and limit the reactor operating life. Thermal ageing of RPV steels can also induce the formation of solute clusters but it is not clear how similar these are to those formed during irradiation. In this work atom probe tomography, combined with detailed structural assessments of the structure of solute clusters, is used to address this issue. A series of thermal ageing heat treatments has been performed on several high- and low-Ni RPV welds to produce 1-4 nm diameter solute clusters. The same materials have also been neutron irradiated. The results show that CuMnNiSi enriched clusters formed during thermal ageing have, on average, higher Cu contents and lower Mn, Ni and Si contents than those found in irradiation-induced clusters. The effect of increasing bulk Ni is to encourage the formation of clusters with significantly higher Ni content, slightly higher Mn and Si contents and significantly lower Cu contents. At very high doses and dose rates MnNiSi enriched clusters can form even in high-Cu welds. Despite differences in the compositions of individual clusters formed during irradiation and during thermal ageing, clusters in both exhibit similar structure. In particular, well developed clusters in both materials have Cu-enriched cores whose peripheries are enriched in Ni, Mn and, in most cases, Si.
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OBJECTIVE: Tacrolimus concentrations are associated with CYP3A5 genotype. The purpose of this study was to evaluate the outcomes and drug concentrations/doses among a posttransplant population with various CYP3A5 genotypes within 12 months. METHODS: Sixty seven kidney recipients receiving immunosuppression with tacrolimus + mycophenolate mofetil + prednisolone were grouped according to their CYP3A5 genotypes (*1/*1; *1/*3; *3/*3). The initial dose of tacrolimus (0.15 mg/kg/d) was adjusted according to achieve a target therapeutic window. All patients underwent a protocol biopsy at 1 month posttransplantation. We assayed serum creatinine and tacrolimus blood trough concentrations to calculate the concentration per dosage during follow-up. We also investigated the incidence of acute rejection episodes and the nephrotoxicity of tacrolimus according to the renal biopsy. RESULTS: There was no significant difference among serum creatinine concentrations. Tracrolimus blood concentrations showed a significant difference at day 7 and 1 month with no significant difference at 3, 6, or 12 months among the three groups. The CYP3A5*3/*3 group showed the largest concentration per dosage (C/D) and CYP3A5*1/*1, the smallest C/D. There was a significant difference among the three groups. The occurrence of an acute rejection episode within 3 months showed a significant difference among the three groups but not from 3 to 12 months after transplantation. Nephrotoxicity was greatest among the CYP3A5*3/*3 group. CONCLUSION: CYP3A5 influenced the blood concentrations of tacrolimus. Our study suggested to choose the initial dosage according to the CYP3A5 genotype to obtain a better outcome and reduce the incidences of acute rejection episodes and nephrotoxicity.
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Citocromo P-450 CYP3A/genética , Transplante de Rim/imunologia , Polimorfismo Genético , Tacrolimo/uso terapêutico , Adolescente , Adulto , Cadáver , Criança , Creatinina/sangue , Quimioterapia Combinada , Feminino , Genótipo , Humanos , Imunossupressores/sangue , Imunossupressores/uso terapêutico , Transplante de Rim/patologia , Túbulos Renais/patologia , Masculino , Pessoa de Meia-Idade , Tacrolimo/sangue , Doadores de Tecidos , Transplante Homólogo , Adulto JovemRESUMO
OBJECTIVE: Our aim was to evaluate the prognostic effect of peripheral blood lymphocyte subgroup CD4+ and CD8+ cells on renal transplant patients with cytomegalovirus (CMV) viremia. MATERIALS AND METHODS: Using 41 renal transplant patients with CMV-PCR(+) in peripheral blood and stable values of serum creatinine (SCr), we evaluated the changes in lymphocyte subgroup CD4+ and CD8+ cells with onset of antiviral therapy with gancyclovir for treatment of pneumonia. We compared patients with or without pneumonia. RESULTS: The lower the peripheral blood lymphocyte subgroup CD4+ and CD8+ cell numbers, the higher the incidence of CMV pneumonia. The numbers of CD4+ and CD8+ cells at 1 month posttransplantation and at the time of CMV-PCR(+) detection were significantly lower than those before transplantation in the CMV pneumonia group (P < .01) and also in the nonpneumonia group. CONCLUSIONS: The decrease in peripheral blood lymphocyte subgroup CD4+ and CD8+ cells after renal transplantation in patients with CMV viremia showed prognostic value for pneumonia. Increased CD4+ and CD8+ cells in peripheral blood combined with preemptive therapy may reduce the incidence of pneumonia among patients with CMV viremia.