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1.
Math Biosci Eng ; 21(4): 5283-5307, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38872536

RESUMO

The novel coronavirus disease (COVID-19) pandemic has profoundly impacted the global economy and human health. The paper mainly proposed an improved susceptible-exposed-infected-recovered (SEIR) epidemic model with media coverage and limited medical resources to investigate the spread of COVID-19. We proved the positivity and boundedness of the solution. The existence and local asymptotically stability of equilibria were studied and a sufficient criterion was established for backward bifurcation. Further, we applied the proposed model to study the trend of COVID-19 in Shanghai, China, from March to April 2022. The results showed sensitivity analysis, bifurcation, and the effects of critical parameters in the COVID-19 model.


Assuntos
COVID-19 , Pandemias , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , China/epidemiologia , Meios de Comunicação de Massa , Simulação por Computador , Algoritmos
2.
Cardiovasc Diabetol ; 23(1): 217, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38915040

RESUMO

BACKGROUND: Diabetic peripheral neuropathy (DPN) is the most prevalent complication of diabetes, and has been demonstrated to be independently associated with cardiovascular events and mortality. This aim of this study was to investigate the subclinical left ventricular (LV) myocardial dysfunction in type 2 diabetes mellitus (T2DM) patients with and without DPN. METHODS: One hundred and thirty T2DM patients without DPN, 61 patients with DPN and 65 age and sex-matched controls who underwent cardiovascular magnetic resonance (CMR) imaging were included, all subjects had no symptoms of heart failure and LV ejection fraction ≥ 50%. LV myocardial non-infarct late gadolinium enhancement (LGE) was determined. LV global strains, including radial, circumferential and longitudinal peak strain (PS) and peak systolic and diastolic strain rates (PSSR and PDSR, respectively), were evaluated using CMR feature tracking and compared among the three groups. Multivariable linear regression analyses were performed to determine the independent factors of reduced LV global myocardial strains in T2DM patients. RESULTS: The prevalence of non-infarct LGE was higher in patients with DPN than those without DPN (37.7% vs. 19.2%, p = 0.008). The LV radial and longitudinal PS (radial: 36.60 ± 7.24% vs. 33.57 ± 7.30% vs. 30.72 ± 8.68%; longitudinal: - 15.03 ± 2.52% vs. - 13.39 ± 2.48% vs. - 11.89 ± 3.02%), as well as longitudinal PDSR [0.89 (0.76, 1.05) 1/s vs. 0.80 (0.71, 0.93) 1/s vs. 0.77 (0.63, 0.87) 1/s] were decreased significantly from controls through T2DM patients without DPN to patients with DPN (all p < 0.001). LV radial and circumferential PDSR, as well as circumferential PS were reduced in both patient groups (all p < 0.05), but were not different between the two groups (all p > 0.05). Radial and longitudinal PSSR were decreased in patients with DPN (p = 0.006 and 0.003, respectively) but preserved in those without DPN (all p > 0.05). Multivariable linear regression analyses adjusting for confounders demonstrated that DPN was independently associated with LV radial and longitudinal PS (ß = - 3.025 and 1.187, p = 0.014 and 0.003, respectively) and PDSR (ß = 0.283 and - 0.086, p = 0.016 and 0.001, respectively), as well as radial PSSR (ß = - 0.266, p = 0.007). CONCLUSIONS: There was more severe subclinical LV dysfunction in T2DM patients complicated with DPN than those without DPN, suggesting further prospective study with more active intervention in this cohort of patients.


Assuntos
Doenças Assintomáticas , Diabetes Mellitus Tipo 2 , Cardiomiopatias Diabéticas , Neuropatias Diabéticas , Imagem Cinética por Ressonância Magnética , Valor Preditivo dos Testes , Disfunção Ventricular Esquerda , Função Ventricular Esquerda , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/etiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Neuropatias Diabéticas/fisiopatologia , Neuropatias Diabéticas/diagnóstico por imagem , Neuropatias Diabéticas/etiologia , Neuropatias Diabéticas/diagnóstico , Neuropatias Diabéticas/epidemiologia , Idoso , Estudos de Casos e Controles , Cardiomiopatias Diabéticas/fisiopatologia , Cardiomiopatias Diabéticas/diagnóstico por imagem , Cardiomiopatias Diabéticas/etiologia , Fatores de Risco , Prevalência , Estudos Transversais , Volume Sistólico , Contração Miocárdica
3.
Aging (Albany NY) ; 16(4): 3856-3879, 2024 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-38372705

RESUMO

Ulcerative colitis (UC) is a serious inflammatory bowel disease (IBD) with high morbidity and mortality worldwide. As the traditional diagnostic techniques have various limitations in the practice and diagnosis of early ulcerative colitis, it is necessary to develop new diagnostic models from molecular biology to supplement the existing methods. In this study, we developed a machine learning-based synthesis to construct an artificial intelligence diagnostic model for ulcerative colitis, and the correctness of the model is verified using an external independent dataset. According to the significantly expressed genes related to the occurrence of UC in the model, an unsupervised quantitative ulcerative colitis related score (UCRScore) based on principal coordinate analysis was established. The UCRScore is not only highly generalizable across UC bulk cohorts at different stages, but also highly generalizable across single-cell datasets, with the same effect in terms of cell numbers, activation pathways and mechanisms. As an important role of screening genes in disease occurrence, based on connectivity map analysis, 5 potential targeting molecular compounds were identified, which can be used as an additional supplement to the therapeutic of UC. Overall, this study provides a potential tool for differential diagnosis and assessment of bio-pathological changes in UC at the macroscopic level, providing an opportunity to optimize the diagnosis and treatment of UC.


Assuntos
Colite Ulcerativa , Doenças Inflamatórias Intestinais , Humanos , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/genética , Inteligência Artificial , Expressão Gênica
4.
Curr Probl Cardiol ; 48(5): 101601, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36681211

RESUMO

We aimed to investigate sex-related differences in left ventricular (LV) deformation in heart failure with reduced ejection fraction (HFrEF) patients with comorbid hypertension (HTN) by cardiac MRI. A total of 281 patients with HFrEF who underwent cardiac MRI were enrolled in this study. Sex-related differences in LV structure, function and strains derived from cardiac cine MRI in the context of HTN were measured and compared. The clinical variables associated with LV strains in HFrEF patients with comorbid HTN and determinants of impaired LV strains were investigated for both sexes. The prevalence of HTN did not differ between the sexes (P > 0.05). Despite having a similar LVEF, hypertensive men displayed decreased LV deformation in all 3 directions compared with hypertensive women (all P < 0.05). Male sex and its interaction with HTN were associated with higher LV mass index, reduced LV GCPS and GLPS compared with hypertensive women (all P < 0.05). Male sex was associated with LV deformation impairment in hypertensive HFrEF patients (all P < 0.05). After adjustment for covariates in HFrEF patients, HTN was found to be an independent determinant of impaired LV GCPS [ß = 0.17; P = 0.022] and GLPS [ß = 0.25; P < 0.001]) in men but not in women (all P > 0.05). Sex had a modifying effect on LV deformation in hypertensive HFrEF patients, with greater adverse effects on LV strains in men than in women. Sex-tailored treatment approaches may be considered in the future for HFrEF patients with comorbid HTN.


Assuntos
Insuficiência Cardíaca , Hipertensão , Disfunção Ventricular Esquerda , Humanos , Masculino , Feminino , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/epidemiologia , Volume Sistólico , Hipertensão/complicações , Hipertensão/epidemiologia , Hipertensão/tratamento farmacológico , Imageamento por Ressonância Magnética , Disfunção Ventricular Esquerda/complicações , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/epidemiologia , Espectroscopia de Ressonância Magnética , Função Ventricular Esquerda
5.
Obesity (Silver Spring) ; 30(12): 2477-2488, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36372681

RESUMO

OBJECTIVE: High BMI is associated with many comorbidities and mortality. This study aimed to elucidate the overall clinical risk of obesity using a genome- and phenome-wide approach. METHODS: This study performed a phenome-wide association study of BMI using a clinical cohort of 736,726 adults. This was followed by genetic association studies using two separate cohorts: one consisting of 65,174 adults in the Electronic Medical Records and Genomics (eMERGE) Network and another with 405,432 participants in the UK Biobank. RESULTS: Class 3 obesity was associated with 433 phenotypes, representing 59.3% of all billing codes in individuals with severe obesity. A genome-wide polygenic risk score for BMI, accounting for 7.5% of variance in BMI, was associated with 296 clinical diseases, including strong associations with type 2 diabetes, sleep apnea, hypertension, and chronic liver disease. In all three cohorts, 199 phenotypes were associated with class 3 obesity and polygenic risk for obesity, including novel associations such as increased risk of renal failure, venous insufficiency, and gastroesophageal reflux. CONCLUSIONS: This combined genomic and phenomic systematic approach demonstrated that obesity has a strong genetic predisposition and is associated with a considerable burden of disease across all disease classes.


Assuntos
Diabetes Mellitus Tipo 2 , Fenômica , Humanos , Registros Eletrônicos de Saúde , Estudo de Associação Genômica Ampla , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Polimorfismo de Nucleotídeo Único , Genômica , Predisposição Genética para Doença , Obesidade/epidemiologia , Obesidade/genética , Fenótipo , Efeitos Psicossociais da Doença
6.
Cardiovasc Diabetol ; 21(1): 69, 2022 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-35524215

RESUMO

BACKGROUND: Heart failure with reduced ejection fraction (HFrEF) is a major health burden worldwide with high morbidity and mortality. Comorbidities of HFrEF complicate treatment and lead to poor prognosis, among which hypertension (HTN) and diabetes mellitus (DM) are common and frequently cooccur. DM was found to have additive effects on cardiac function and structure in hypertensive patients, while its effects on the HFrEF cohort in the context of HTN remain unclear. METHODS: A total of 171 patients with HFrEF were enrolled in our study, consisting of 51 HFrEF controls, 72 hypertensive HFrEF patients (HTN-HFrEF [DM-]) and 48 hypertensive HFrEF patients with comorbid DM (HTN-HFrEF [DM+]). Cardiac MRI-derived left ventricular (LV) strains, including global radial (GRPS), circumferential (GCPS) and longitudinal (GLPS) peak strain, and remodeling parameters were measured and compared among groups. The determinants of impaired LV function and LV remodeling in HFrEF patients were investigated by multivariable linear regression analyses. RESULTS: Despite a similar LV ejection fraction, patients in the HTN-HFrEF (DM+) and HTN-HFrEF (DM-) groups showed a higher LV mass index and LV remodeling index than those in the HFrEF control group (all p < 0.05). Compared with the HTN-HFrEF (DM-) and HFrEF control groups, the HTN-HFrEF (DM+) group exhibited the most severe GLPS impairment (p < 0.001). After adjustment for covariates in HFrEF patients, DM was found to be an independent determinant of impaired LV strains in all three directions (GRPS [ß = - 0.189; p = 0.011], GCPS [ß = 0.217; p = 0.005], GLPS [ß = 0.237; p = 0.002]). HTN was associated with impaired GLPS (ß = 0.185; p = 0.016) only. However, HTN rather than DM was associated with LV remodeling in HFrEF patients in the multivariable regression analysis (p < 0.05). CONCLUSIONS: DM aggravated LV longitudinal dysfunction in hypertensive HFrEF patients without further changes in LV remodeling, indicating that HFrEF patients with comorbid HTN and DM may have a hidden high-risk phenotype of heart failure that requires more advanced and personalized management.


Assuntos
Diabetes Mellitus , Insuficiência Cardíaca , Hipertensão , Disfunção Ventricular Esquerda , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/epidemiologia , Humanos , Hipertensão/complicações , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Imageamento por Ressonância Magnética , Volume Sistólico , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/epidemiologia , Função Ventricular Esquerda , Remodelação Ventricular
7.
ACS Appl Mater Interfaces ; 11(27): 23893-23900, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31188555

RESUMO

Acellular cardiac patches made of various biomaterials have shown to improve heart function after myocardial infarction (MI). Extracellular matrix scaffold derived from a decellularized tissue has unique advantages to serve as an acellular cardiac patch due to its biomimetic nature. In this study, we examined the therapeutic outcomes of using a decellularized porcine myocardium slice (dPMS) as an acellular patch in a rat acute MI model. dPMSs with two different thicknesses (300 and 600 µm) were patched to the infarcted area of the rat myocardium, and their effects on cardiac function and host interactions were assessed. We found that the implanted dPMS firmly attached to host myocardium after implantation and prevented thinning of the left ventricular (LV) wall after an MI. A large number of host cells were identified to infiltrate into the implanted dPMS, and a significant number of vessel structures was observed in the dPMS and infarcted area. We detected a significantly higher density of M2 macrophages in the groups treated with dPMSs as compared to the MI group. Contraction of the LV wall and cardiac functional parameters (left ventricular ejection fraction and fractional shortening) was significantly improved in the treatment groups (300 and 600 µm dPMS) 4 weeks after surgery. Our results proved the therapeutic benefits of using dPMS as an acellular cardiac patch for the treatment of acute myocardial infarction.


Assuntos
Matriz Extracelular , Infarto do Miocárdio , Miocárdio/química , Neovascularização Fisiológica , Animais , Modelos Animais de Doenças , Matriz Extracelular/química , Matriz Extracelular/transplante , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/cirurgia , Ratos , Ratos Sprague-Dawley , Volume Sistólico , Suínos
8.
Huan Jing Ke Xue ; 40(4): 1726-1733, 2019 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-31087913

RESUMO

In order to better understand phthalate esters (PAEs) pollution in Jiaozhou Bay, surface water samples were collected for content analysis in August and November 2015 and January 2016. Fifteen kinds of PAEs were detected by stir bar sorptive extraction and gas chromatography-mass spectrometry. The content, composition, spatial distribution, seasonal variation, and ecological risk assessment of the PAEs in the surface waters were examined and analyzed. The results showed that:① The total concentrations of PAEs in the surface seawater in August and November 2015 and January 2016 were 3.63-21.20 µg·L-1, 2.24-12.60 µg·L-1, and 0.01-4.15 µg·L-1, respectively, and the average concentrations were 11.10 µg·L-1, 5.26 µg·L-1, and 0.80 µg·L-1, respectively. ② Influenced by runoff and ocean currents, the concentration of PAEs in the surface water of Jiaozhou Bay is higher near the shore and lower in the middle, and the total concentration of the east coast is higher than that of the west coast. Compared with surveys of other rivers and oceans, the PAEs content in the surface water of Jiaozhou Bay is moderate, but it is heavily polluted compared with other oceans. ③ Considering the rainfall and other factors, the distribution of PAEs in the three seasons followed the order summer > autumn > winter. The main PAEs detected were DBP, BBP, and DEHP. ④ The results of the ecological risk assessment showed that the risk quotient (RQ) of DBP at each station in Jiaozhou Bay was greater than 1; that is, the ecological risk was relatively large, while the risk of the other PAEs (RQ<1) was small. PAEs have become a potentially threatening organic pollutant in Jiaozhou Bay. Their behavior and the ecological hazards that they present to the environment still require further study.

9.
AMB Express ; 8(1): 182, 2018 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-30415449

RESUMO

Selection of optimal primer pairs in 16S rRNA gene sequencing is a pivotal issue in microorganism diversity analysis. However, limited effort has been put into investigation of specific primer sets for analysis of the bacterial diversity of aging flue-cured tobaccos (AFTs), as well as prediction of the function of the bacterial community. In this study, the performance of four primer pairs in determining bacterial community structure based on 16S rRNA gene sequences in AFTs was assessed, and the functions of genes were predicted using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). Results revealed that the primer set 799F-1193R covering the amplification region V5V6V7 gave a more accurate picture of the bacterial community structure of AFTs, with lower co-amplification levels of chloroplast and mitochondrial genes, and more genera covered than when using the other primers. In addition, functional gene prediction suggested that the microbiome of AFTs was involved in kinds of interested pathways. A high abundance of functional genes involved in nitrogen metabolism was detected in AFTs, reflecting a high level of bacteria involved in degrading harmful nitrogen compounds and generating nitrogenous nutrients for others. Additionally, the functional genes involved in biosynthesis of valuable metabolites and degradation of toxic compounds provided information that the AFTs possess a huge library of microorganisms and genes that could be applied to further studies. All of these findings provide a significance reference for researchers working on the bacterial diversity assessment of tobacco-related samples.

10.
Sci Rep ; 7(1): 7734, 2017 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-28798294

RESUMO

Between July 2014 and November 2015, we compared the curative effects and cost-effectiveness of two kinds of nasal endoscopic surgery for nasolacrimal duct obstruction (NLDO) in a single-centre, two-armed clinical trial with a 1-year follow-up. We included two groups: a recessive spherical headed silicone intubation (RSHSI) group and an endonasal dacryocystorhinostomy (En-DCR) group; both received nasal endoscopy. Patients were recruited from the Otorhinolaryngology and Ophthalmology departments. The main outcome measures were epiphora improvement (classified as cure, effective, or invalid), cost-effectiveness, visual analogue scale (VAS) intraoperative pain score, bleeding volume, operating time, hospitalisation time, total cost, and VAS postoperative epiphora score. No significant group difference was identified in postoperative epiphora VAS scores (P > 0.050) or success rate (P = 0.406). However, average VAS intraoperative pain score, operating time, bleeding volume, hospitalisation time and total cost in the RSHSI group were clearly lower to those in the En-DCR group (P = 0.000). In conclusion, RSHSI under nasal endoscopy can provide similar treatment outcomes to En-DCR. RSHSI has advantages including minimal invasiveness, reduced risk, shorter duration of surgery and hospitalisation, reduced intraoperative discomfort, and lower financial burden, which is more acceptable to patients. Thus, RSHSI may be the preferred option for NLDO.


Assuntos
Dacriocistorinostomia , Endoscopia , Intubação , Obstrução dos Ductos Lacrimais/terapia , Ducto Nasolacrimal/patologia , Ducto Nasolacrimal/cirurgia , Adulto , Análise Custo-Benefício , Dacriocistorinostomia/efeitos adversos , Dacriocistorinostomia/métodos , Endoscopia/efeitos adversos , Endoscopia/métodos , Feminino , Seguimentos , Humanos , Intubação/efeitos adversos , Intubação/métodos , Obstrução dos Ductos Lacrimais/diagnóstico , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Resultado do Tratamento
11.
Environ Monit Assess ; 189(8): 368, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28674757

RESUMO

In this paper, five particulate emission points from a sinter plant in China, including anthracite crusher, raw material blender, sinter strand, screener, and circular cooler, were selected for particle sampling. The particle size distribution, the toxic element content (As, Cd, Co, Cr, Cu, Ni, Pb, Ti, and Zn), and the morphology of the samples were determined by the gravimetric method, the ICP-OES, and the SEM-EDS, respectively. In addition, the gray relational analysis method was used to evaluate the rank of the particulate emission points in the sinter plant. The results show that the emission factor of PMTSP, PM10, and PM2.5 of the whole sintering process is 0.121, 0.075, and 0.039 kg/t-sinter, respectively. Furthermore, the total toxic element emission factor is 5282.49 mg/t-sinter. The sinter strand is the most important emitter and contributes 43.8% of PMTSP, 53.3% of PM10, 56.4% of PM2.5, and 81.1% of total toxic element in the sinter plant. Nevertheless, particles emitted from the post-sintering process are non-negligible and contribute 48.8% of PMTSP, 41.3% of PM10, 38.5% of PM2.5, and 15.5% of total toxic element in the sinter plant.


Assuntos
Poluentes Atmosféricos/análise , Monitoramento Ambiental , Metalurgia , Material Particulado/análise , China , Carvão Mineral/análise , Tamanho da Partícula
12.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 48(2): 295-298, 2017 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-28612546

RESUMO

OBJECTIVES: To synthesize 3'-deoxy-3'-¹8F-fluorotyhymidine)(¹8F-FLT) using CFN-MPS-200 automatic synthesis module, and evaluate its distribution in Wistar rats. METHODS: We used 3-N-Boc-5!d-O-dimethoxytrityl-3!d-O-nosyl-thymidine (Boc-FLT)-percursor as raw material to synthesize ¹8F-FLT without residual solvents. Its radiochemical purity was confirmed with radio-HPLC and thin layer chromatography (TLC). Normal Wistar rats were injected with 18 F-FLT and underwent PET scanning. RESULTS: The entire preparation procedure took about 60 min, which resulted in a radio chemical yield of (24±5)% (after attenuation correction, n =20) and radiochemical purity of over 99%, with 1.11×108 Bq/mL specific activity. The ¹8F-FLT solution was colorless and had a pH value between 7.0-8.0. ¹8F-FLT was mainly concentrated in the kidney, bladder, liver, bone marrow and Liver of normal Wistar rats. CONCLUSION: Automated synthesis of ¹8F-FLT using CFN-MPS-200 is a stable method, with high yield, safety without solvent, and acceptable quality.


Assuntos
Didesoxinucleosídeos/síntese química , Compostos Radiofarmacêuticos/síntese química , Animais , Tomografia por Emissão de Pósitrons , Controle de Qualidade , Ratos , Ratos Wistar
13.
Pharmacol Ther ; 175: 75-90, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28213088

RESUMO

Pharmacogenomics (PGx), a substantial component of "personalized medicine", seeks to understand each individual's genetic composition to optimize drug therapy -- maximizing beneficial drug response, while minimizing adverse drug reactions (ADRs). Drug responses are highly variable because innumerable factors contribute to ultimate phenotypic outcomes. Recent genome-wide PGx studies have provided some insight into genetic basis of variability in drug response. These can be grouped into three categories. [a] Monogenic (Mendelian) traits include early examples mostly of inherited disorders, and some severe (idiosyncratic) ADRs typically influenced by single rare coding variants. [b] Predominantly oligogenic traits represent variation largely influenced by a small number of major pharmacokinetic or pharmacodynamic genes. [c] Complex PGx traits resemble most multifactorial quantitative traits -- influenced by numerous small-effect variants, together with epigenetic effects and environmental factors. Prediction of monogenic drug responses is relatively simple, involving detection of underlying mutations; due to rarity of these events and incomplete penetrance, however, prospective tests based on genotype will have high false-positive rates, plus pharmacoeconomics will require justification. Prediction of predominantly oligogenic traits is slowly improving. Although a substantial fraction of variation can be explained by limited numbers of large-effect genetic variants, uncertainty in successful predictions and overall cost-benefit ratios will make such tests elusive for everyday clinical use. Prediction of complex PGx traits is almost impossible in the foreseeable future. Genome-wide association studies of large cohorts will continue to discover relevant genetic variants; however, these small-effect variants, combined, explain only a small fraction of phenotypic variance -- thus having limited predictive power and clinical utility.


Assuntos
Farmacogenética , Medicina de Precisão , Rotulagem de Medicamentos , Genótipo , Humanos , Resultado do Tratamento
14.
Dis Colon Rectum ; 59(8): 789-99, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27384098

RESUMO

BACKGROUND: The prognosis of rectal cancer is directly related to the stage of the tumor at diagnosis. Accurate preoperative staging is essential for selecting patients to receive optimal treatment. OBJECTIVE: The purpose of this study was to evaluate the diagnostic performance of MRI in tumor staging and circumferential resection margin involvement in rectal cancer. DATA SOURCES: A systematic literature search was performed in MEDLINE, EMBASE, PubMed, Cochrane Database of Systematic Reviews, and Web of Science database. STUDY SELECTION: Original articles from 2000 to 2016 on the diagnostic performance of MRI in the staging of rectal cancer and/or assessment of mesorectal fascia status were eligible. MAIN OUTCOME MEASURES: Pooled diagnostic statistics including sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were calculated for invasion of muscularis propria, perirectal tissue, and adjacent organs and for circumferential resection margin involvement through bivariate random-effects modeling. Summary receiver operating characteristic curves were fitted, and areas under summary receiver operating characteristic curves were counted to evaluate the diagnostic performance of MRI for each outcome. RESULTS: Thirty-five studies were eligible for this meta-analysis. Preoperative MRI revealed the highest sensitivity of 0.97 (95% CI, 0.96-0.98) and specificity of 0.97 (95% CI, 0.96-0.98) for muscularis propria invasion and adjacent organ invasion. Areas under summary receiver operating characteristic curves indicated good diagnostic accuracy for each outcome, with the highest of 0.9515 for the assessment of adjacent organ invasion. Significant heterogeneity existed among studies. There was no notable publication bias for each outcome. LIMITATIONS: This meta-analysis revealed relatively high diagnostic accuracy for preoperative MRI, although significant heterogeneity existed. Therefore, exploration should be focused on standardized interpretation criteria and optimal MRI protocols for future studies. CONCLUSIONS: MRI showed relatively high diagnostic accuracy for preoperative T staging and circumferential resection margin assessment and should be reliable for clinical decision making.


Assuntos
Imageamento por Ressonância Magnética , Margens de Excisão , Cuidados Pré-Operatórios , Neoplasias Retais/patologia , Reto/patologia , Humanos , Modelos Estatísticos , Estadiamento de Neoplasias , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/cirurgia , Reto/diagnóstico por imagem , Reto/cirurgia
15.
BioData Min ; 9: 12, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27042214

RESUMO

Genetic studies of human diseases have identified many variants associated with pathogenesis and severity. However, most studies have used only statistical association to assess putative relationships to disease, and ignored other factors for evaluation. For example, evolution is a factor that has shaped disease risk, changing allele frequencies as human populations migrated into and inhabited new environments. Since many common variants differ among populations in frequency, as does disease prevalence, we hypothesized that patterns of disease and population structure, taken together, will inform association studies. Thus, the population distributions of allelic risk variants should reflect the distributions of their associated diseases. Evolutionary Triangulation (ET) exploits this evolutionary differentiation by comparing population structure among three populations with variable patterns of disease prevalence. By selecting populations based on patterns where two have similar rates of disease that differ substantially from a third, we performed a proof of principle analysis for this method. We examined three disease phenotypes, lactase persistence, melanoma, and Type 2 diabetes mellitus. We show that for lactase persistence, a phenotype with a simple genetic architecture, ET identifies the key gene, lactase. For melanoma, ET identifies several genes associated with this disease and/or phenotypes related to it, such as skin color genes. ET was less obviously successful for Type 2 diabetes mellitus, perhaps because of the small effect sizes in known risk loci and recent environmental changes that have altered disease risk. Alternatively, ET may have revealed new genes involved in conferring disease risk for diabetes that did not meet nominal GWAS significance thresholds. We also compared ET to another method used to filter for phenotype associated genes, population branch statistic (PBS), and show that ET performs better in identifying genes known to associate with diseases appropriately distributed among populations. Our results indicate that ET can filter association results to improve our ability to discover disease loci.

16.
Int J Mol Sci ; 17(3): 358, 2016 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-26978355

RESUMO

Monoclonal antibodies are the dominant agents used in inhibition of biological target molecules for disease therapeutics, but there are concerns of immunogenicity, production, cost and stability. Oligonucleotide aptamers have comparable affinity and specificity to targets with monoclonal antibodies whilst they have minimal immunogenicity, high production, low cost and high stability, thus are promising inhibitors to rival antibodies for disease therapy. In this review, we will compare the detailed advantages and disadvantages of antibodies and aptamers in therapeutic applications and summarize recent progress in aptamer selection and modification approaches. We will present therapeutic oligonucleotide aptamers in preclinical studies for skeletal diseases and further discuss oligonucleotide aptamers in different stages of clinical evaluation for various disease therapies including macular degeneration, cancer, inflammation and coagulation to highlight the bright commercial future and potential challenges of therapeutic oligonucleotide aptamers.


Assuntos
Aptâmeros de Nucleotídeos/biossíntese , Aptâmeros de Nucleotídeos/uso terapêutico , Animais , Anticorpos Monoclonais/biossíntese , Anticorpos Monoclonais/economia , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/uso terapêutico , Aptâmeros de Nucleotídeos/economia , Aptâmeros de Nucleotídeos/imunologia , Ensaios Clínicos como Assunto , Avaliação Pré-Clínica de Medicamentos , Humanos
17.
Dalton Trans ; 44(41): 18207-14, 2015 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-26422065

RESUMO

The development of highly efficient As(iii) adsorbents is critical to largely simplify the arsenic treatment process and lower its cost. For the first time, SnO2 nanospheres were demonstrated to possess a highly efficient As(iii) adsorption capability from water in a near neutral pH environment as predicted by the material criterion we recently developed for the selection of highly efficient arsenic adsorbents. These SnO2 nanospheres were synthesized by a simple and cost-effective hydrolysis process with the assistance of ethyl acetate under ambient conditions, which had a good dispersity, a narrow size distribution, a relatively large specific surface area, and a porous structure. A fast As(iii) adsorption was observed in the kinetics study on these SnO2 nanospheres, and their Langmuir adsorption capacity was determined to be ∼112.7 mg g(-1) at pH ∼7. The As(iii) adsorption mechanism on SnO2 nanospheres was examined by both macroscopic and microscopic techniques, which demonstrated that it followed the inner-sphere complex model. These SnO2 nanospheres demonstrated effective As(iii) adsorption even with exceptionally high concentrations of co-existing ions, and a good regeneration capability by washing with NaOH solution.


Assuntos
Arsênio/isolamento & purificação , Nanosferas/química , Compostos de Estanho/química , Poluentes Químicos da Água/isolamento & purificação , Purificação da Água/métodos , Água/análise , Adsorção , Purificação da Água/economia
18.
PLoS One ; 10(6): e0130987, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26115034

RESUMO

PURPOSE: To evaluate the feasibility and diagnostic accuracy of retrospective electrocardiographically (ECG)-gated dual-source computed tomography (DSCT) for the assessment of double outlet right ventricle (DORV) and associated multiple malformations in pediatric patients. MATERIALS AND METHODS: Forty-seven patients <10 years of age with DORV underwent retrospective ECG-gated DSCT. The location of the ventricular septal defect (VSD), alignment of the two great arteries, and associated malformations were assessed. The feasibility of retrospective ECG-gated DSCT in pediatric patients was assessed, the image quality of DSCT and the agreement of the diagnosis of associated malformations between DSCT and transthoracic echocardiography (TTE) were evaluated, the diagnostic accuracies of DSCT and TTE were referred to surgical results, and the effective doses were calculated. RESULTS: Apart from DORV, 109 associated malformations were confirmed postoperatively. There was excellent agreement (κ = 0.90) for the diagnosis of associated malformations between DSCT and TTE. However, DSCT was superior to TTE in demonstrating paracardiac anomalies (sensitivity, coronary artery anomalies: 100% vs. 80.00%, anomalies of great vessels: 100% vs. 88.57%, separate thoracic and abdominal anomalies: 100% vs. 76.92%, respectively). Combined with TTE, DSCT can achieve excellent diagnostic performance in intracardiac anomalies (sensitivity, 91.30% vs. 100%). The mean image quality score was 3.70 ± 0.46 (κ = 0.76). The estimated mean effective dose was < 1 mSv (0.88 ± 0.34 mSv). CONCLUSIONS: Retrospective ECG-gated DSCT is a better diagnostic tool than TTE for pediatric patients with complex congenital heart disease such as DORV. Combined with TTE, it may reduce or even obviate the use of invasive cardiac catheterization, and thus expose the patients to a much lower radiation dose.


Assuntos
Técnicas de Imagem de Sincronização Cardíaca/métodos , Dupla Via de Saída do Ventrículo Direito/diagnóstico por imagem , Dupla Via de Saída do Ventrículo Direito/diagnóstico , Tomografia Computadorizada por Raios X/métodos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino
19.
J Hazard Mater ; 289: 101-107, 2015 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-25710820

RESUMO

The main objective of this study was to evaluate the toxicity of 4-chlorophenol (4-CP) to aerobic granular sludge in the process of treating ammonia rich wastewater. In the short-term exposure of 4-CP of 5 and 10 mg/L, ammonia nitrogen removal efficiencies in the batch reactors decreased to 87.18±2.81 and 41.16±3.55%, which were remarkably lower than that of control experiment (99.83±0.54%). Correspondingly, the respirometric activities of heterotrophic and autotrophic bacteria of aerobic granular sludge were significantly inhibited in the presence of 4-CP. Moreover, the main components of extracellular polymeric substances (EPS) including polysaccharides and proteins increased from 18.74±0.29 and 22.57±0.34 mg/g SS to 27.79±0.51 and 24.69±0.38 mg/g SS, respectively, indicating that the presence of 4-CP played an important role on the EPS production. Three-dimensional excitation-emission matrix (3D-EEM) fluorescence spectroscopy further showed that the intensities of EPS samples were obviously quenched with the increased of 4-CP concentrations. To be more detailed, synchronous fluorescence spectra indicated that the interaction between EPS and 4-CP was mainly caused by tryptophan residues. The mechanism of fluorescence quenching belongs to static quenching with a formation constant (KA) of 0.07×10(4) L/mol, implying the strong formation of EPS and 4-CP complex. The results could provide reliable and accurate information to determine the potential toxicity of 4-CP on the performance of aerobic granular sludge system.


Assuntos
Clorofenóis/toxicidade , Polímeros/metabolismo , Esgotos/microbiologia , Aerobiose , Amônia/análise , Nitrogênio/análise , Polissacarídeos/análise , Espectrometria de Fluorescência , Triptofano/análise , Eliminação de Resíduos Líquidos
20.
PLoS One ; 9(9): e104312, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25180597

RESUMO

PURPOSE: To determine whether 3.0-T magnetic resonance imaging (MRI) could assess right ventricular (RV) function in patients with hypertrophic cardiomyopathy (HCM), and if this assessment is correlated with the New York Heart Function Assessment (NYHA) classification. MATERIALS AND METHODS: Forty-six patients with HCM and 23 normal individuals were recruited. Left and right ventricular function parameters including end-diastolic and end-systolic volumes (EDV, ESV), stroke volume (SV) and ejection fraction (EF) and dimensions were measured and compared using 3.0-T MRI. RV function parameters between HCM patients and controls were compared using independent sample t tests. A one way ANOVA test with Bonferroni correction was used to determine significant differences among different NYHA groups. Receiver operating characteristic analyses calculated the sensitivity and specificity of RV dysfunction on MRI for the prediction of HCM severity. RESULTS: Statistical analysis revealed significant differences of left ventricular (LV) and RV volumetric values and masses between the HCM patients and controls (all p<0.05). Within the HCM group, the simultaneously decreased maximum RVEDD correlated well with the LVEDD (r = 0.53; p<0.001). The function and dimension parameters among Class I to III were not determined to be significantly different (all p>0.05). However, significant differences between the Class IV and I-III groups (all P<0.0167) indicated that the diastolic and systolic function in both the RV and LV were impaired in Class IV patients. ROC analyses identified the EDV, ESV and EDD of both the LV and RV with a high sensitivity cutoff value to predict the HCM patients with severe heart failure (Class IV) with high sensitivity and specificity. CONCLUSIONS: RV involvements were comparable to those of LV global function impairments in patients with HCM. The presence of RV dysfunction and decreased dimension on the MRI helped to predict the severe symptomatic HCM with high sensitivity and specificity.


Assuntos
Cardiomiopatia Hipertrófica/fisiopatologia , Imageamento por Ressonância Magnética , Função Ventricular Direita , Cardiomiopatia Hipertrófica/patologia , Estudos de Casos e Controles , Diástole/fisiologia , Feminino , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , New York , Variações Dependentes do Observador , Curva ROC
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