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1.
Med Sci Monit ; 29: e940691, 2023 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-37660251

RESUMO

BACKGROUND Controlled attenuation parameter (CAP) is a recent ultrasound-based method for measuring hepatic steatosis, which is common in patients with metabolic syndrome (MetS). The fatty liver index (FLI), an algorithm-based method, is frequently used to evaluate hepatic steatosis. This study assessed how FLI and CAP relate to the earlier MetS stage and their ability to identify it. MATERIAL AND METHODS A total of 170 community-based individuals were studied. Demographic information, body mass index, waist circumference, and blood pressures were collected. CAP was assessed by FibroScan. Fasting glucose, lipid tests, and γ-glutamyl transferase were measured. The CAP and FLI results were categorized into quartiles, with the MetS stages as the main outcomes. The odds ratio (OR) of the outcomes was calculated using logistic regression. The area under the curve in receiver operating characteristic analysis (AUC-ROC) was used to detect the stages of MetS. Sensitivity, specificity, and appropriate cut-offs based on ROC analysis are shown. RESULTS The higher the FLI or CAP category, the lower the proportion of non-MetS and the higher the proportion of moderate MetS. Each single-quartile increase in FLI and CAP was associated with an increased likelihood of being in the higher MetS stages - FLI: adjusted OR 3.1 (2.23-4.32); CAP: adjusted OR 1.96 (1.48-2.59). In the ROC analysis, FLI had a higher AUC-ROC than CAP in separating the stages of MetS, although findings were significant (P<0.001). FLI in detecting the stages of mild-to-severe versus non-MetS performed well (AUC-ROC [95% confidence interval]: 0.79 [0.72-0.87]), with high sensitivity (0.86) but low specificity (0.62). CONCLUSIONS FLI and CAP were positively associated with the MetS stage and its components, suggesting that they could be used as a MetS screening tool in community studies.


Assuntos
Técnicas de Imagem por Elasticidade , Fígado Gorduroso , Síndrome Metabólica , Humanos , gama-Glutamiltransferase , Algoritmos
2.
Gut ; 71(11): 2152-2166, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36002247

RESUMO

The Asia-Pacific region has the largest number of cases of colorectal cancer (CRC) and one of the highest levels of mortality due to this condition in the world. Since the publishing of two consensus recommendations in 2008 and 2015, significant advancements have been made in our knowledge of epidemiology, pathology and the natural history of the adenoma-carcinoma progression. Based on the most updated epidemiological and clinical studies in this region, considering literature from international studies, and adopting the modified Delphi process, the Asia-Pacific Working Group on Colorectal Cancer Screening has updated and revised their recommendations on (1) screening methods and preferred strategies; (2) age for starting and terminating screening for CRC; (3) screening for individuals with a family history of CRC or advanced adenoma; (4) surveillance for those with adenomas; (5) screening and surveillance for sessile serrated lesions and (6) quality assurance of screening programmes. Thirteen countries/regions in the Asia-Pacific region were represented in this exercise. International advisors from North America and Europe were invited to participate.


Assuntos
Adenoma , Pólipos do Colo , Neoplasias Colorretais , Adenoma/diagnóstico , Adenoma/epidemiologia , Adenoma/cirurgia , Ásia/epidemiologia , Colonoscopia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Consenso , Detecção Precoce de Câncer , Humanos
3.
Endoscopy ; 54(3): 290-298, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-33271603

RESUMO

BACKGROUND: The likelihood of advanced or synchronous neoplasms is significantly higher in fecal immunochemical test (FIT)-positive individuals than in the general population. The magnitude of the colonoscopy-related complication rate in FIT-positive individuals remains unknown. This study aimed to elucidate the colonoscopy-related complication rate after a positive FIT result and compare it with the rate when colonoscopy was performed for other purposes. METHODS: Information regarding colonoscopy-related severe complications after a positive FIT result (FIT-colonoscopy) and ordinary colonoscopy during 2010-2014 was collected from the Taiwanese Colorectal Cancer Screening Program Database and National Health Insurance Research Database. Severe complications included significant bleeding, perforation, and cardiopulmonary events ≤ 14 days after colonoscopy. The number of events per 1000 procedures was used to quantify complication rates. Multivariate analysis was conducted to assess the association of various factors with severe complications associated with FIT-colonoscopy compared with ordinary colonoscopy. RESULTS: 319 114 FIT-colonoscopies (214 955 patients) were identified, 51 242 (16.1 %) of which included biopsy and 94 172 (29.5 %) included polypectomy. Overall, 2125 significant bleedings (6.7 ‰) and 277 perforations (0.9 ‰) occurred ≤ 14 days after FIT-colonoscopy. Polypectomy, antiplatelet use, and anticoagulant use were associated with higher risk of complications (adjusted odds ratio [aOR] 4.41, 95 % confidence interval [CI] 4.05-4.81); aOR 1.35, 95 %CI 1.12-1.53; aOR 1.88, 95 %CI 0.61-5.84, respectively). Compared with ordinary colonoscopy, FIT-colonoscopy involved significantly higher risk of significant bleeding (aOR 3.10, 95 %CI 2.90-3.32). CONCLUSIONS: FIT-colonoscopy was associated with a more than two-fold risk of significant bleeding, especially when polypectomy was performed.


Assuntos
Neoplasias Colorretais , Detecção Precoce de Câncer , Biópsia , Colonoscopia/efeitos adversos , Colonoscopia/métodos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Detecção Precoce de Câncer/efeitos adversos , Detecção Precoce de Câncer/métodos , Fezes , Humanos , Programas de Rastreamento/métodos , Sangue Oculto
4.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 53(6): 998-1002, 2022 Nov.
Artigo em Zh | MEDLINE | ID: mdl-36443041

RESUMO

Objective: To explore the relationship between social isolation and health behaviors and ulcer severity in patients with diabetic foot. Methods: A cross-sectional study was conducted with 160 patients suffering from type 2 diabetes mellitus combined with diabetic foot. The patients received treatment at the Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University between September 2020 and December 2021. Patient information was collected, including the scores for Lubben Social Network Scale and the Wagner classification of foot ulcers. Analysis was conducted to study the characteristics of the patients' health behaviors, including whether they received information and education on diabetic foot, whether there were delays in their attempt to access medical service, the frequency of foot examinations, etc. In addition, patient demographic data were collected, including sex, age, education, and employment status. According to their scores for Lubben Social Network Scale, the patients were divided into a social isolation group ( n=60) and a non-social-isolation group ( n=100). The severity of the foot ulcers and the health behaviors of the two groups were compared to identify differences. Results: The findings suggest that, compared with the non-social-isolation group, the social isolation group had a higher proportion of diabetic foot patients with Wagner grade 3-5 diabetic foot ulcers ( P<0.05). Analysis of the health behaviors showed that the social isolation group had a higher proportion of diabetes foot patients who had never undergone examination of their feet and those who had delayed attempts to access medical service for their condition ( P<0.05). There were no significant differences between the two groups in terms of whether the patients had received information and education concerning diabetic foot, causes of foot injury, self-treatment of wounds, smoking, and drinking. Correlational analysis suggested that the scores of Lubben Social Network Scale were negatively correlated with the delayed attempts to access medical service ( r=-0.353, P=0.001), that is, the higher the degree of social isolation, the longer the delay in patients' attempt to access medical service for their diabetic foot. Conclusions: Social isolation is correlated to health behaviors and ulcer severity in patients with diabetic foot. Giving more attention to the problem of social isolation of diabetic foot patients and increasing their ties with the social environment and the members of their social network may have a positive effect on improving the delays in diabetic foot patients' attempt to access medical service, which is particularly important for follow-up treatment.


Assuntos
Diabetes Mellitus Tipo 2 , Pé Diabético , Humanos , Diabetes Mellitus Tipo 2/complicações , Estudos Transversais , Comportamentos Relacionados com a Saúde , Isolamento Social
5.
J Proteome Res ; 20(9): 4248-4257, 2021 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-34406011

RESUMO

Catechol estrogens (CEs) are genotoxic metabolites whose detection is challenging due to their low concentrations and high variability in the blood. By intact protein and free CE measurement of the spiked hemolysate, endogenous CEs were revealed to mainly (>99%) exist as hemoglobin (Hb) adducts in red blood cells. In order to detect endogenous CE-Hb adducts, we developed a two-step method that involved protein precipitation and solid phase extraction to purify Hb from red blood cells, and the method was coupled with proteomics using liquid chromatography-tandem mass spectrometry. Using bottom-up proteomics and standard additions, we identified C93 and C112 of Hb-ß as the main adduction sites of Hb, and this accounted for CE-induced oxidization of adducted peptides by sample preparation. The non-adducted, adducted, and oxidized tryptic peptides that covered the same Hb-ß sequences were targeted by parallel reaction monitoring to determine the adduction level in red blood cells. A quantification limit (S/N < 8) below the endogenous CE-Hb adduction level with relative standard errors that ranged from 5 to 22% was achieved and applied to clinical samples. The human serum albumin (HSA) adduction levels from the same patient were also determined using a previously developed method (Anal. Chem.2019,91, 15922-15931). A positive correlation (R2 = 0.673) between the CE-HSA and CE-Hb adduction level was obtained from all clinical samples, and both levels were significantly (p < 0.005) higher for patients with breast cancer compared to healthy controls. However, double indexes derived from the red blood cell and the serum, respectively, provide higher precision and confidence in predicting cancer risk than the single index. This study reported an efficient sample preparation for proteomics-based Hb adducts and revealed the potential of using multiple blood proteins for developing more reliable and specific markers based on protein adductomics.


Assuntos
Hemoglobinas , Proteômica , Cromatografia Líquida , Estrogênios de Catecol , Humanos , Albumina Sérica Humana
6.
Nature ; 523(7561): 431-436, 2015 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-26176913

RESUMO

Traumatic brain injury (TBI), characterized by acute neurological dysfunction, is one of the best known environmental risk factors for chronic traumatic encephalopathy and Alzheimer's disease, the defining pathologic features of which include tauopathy made of phosphorylated tau protein (P-tau). However, tauopathy has not been detected in the early stages after TBI, and how TBI leads to tauopathy is unknown. Here we find robust cis P-tau pathology after TBI in humans and mice. After TBI in mice and stress in vitro, neurons acutely produce cis P-tau, which disrupts axonal microtubule networks and mitochondrial transport, spreads to other neurons, and leads to apoptosis. This process, which we term 'cistauosis', appears long before other tauopathy. Treating TBI mice with cis antibody blocks cistauosis, prevents tauopathy development and spread, and restores many TBI-related structural and functional sequelae. Thus, cis P-tau is a major early driver of disease after TBI and leads to tauopathy in chronic traumatic encephalopathy and Alzheimer's disease. The cis antibody may be further developed to detect and treat TBI, and prevent progressive neurodegeneration after injury.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/farmacologia , Lesões Encefálicas/patologia , Lesões Encefálicas/prevenção & controle , Tauopatias/prevenção & controle , Proteínas tau/antagonistas & inibidores , Proteínas tau/química , Doença de Alzheimer/complicações , Doença de Alzheimer/prevenção & controle , Animais , Anticorpos Monoclonais/uso terapêutico , Afinidade de Anticorpos , Axônios/metabolismo , Axônios/patologia , Encéfalo/metabolismo , Encéfalo/patologia , Lesões Encefálicas/complicações , Lesões Encefálicas/metabolismo , Modelos Animais de Doenças , Epitopos/química , Epitopos/imunologia , Feminino , Humanos , Masculino , Camundongos , Fosfoproteínas/antagonistas & inibidores , Fosfoproteínas/biossíntese , Fosfoproteínas/imunologia , Fosfoproteínas/toxicidade , Estresse Fisiológico , Tauopatias/complicações , Tauopatias/metabolismo , Tauopatias/patologia , Proteínas tau/biossíntese , Proteínas tau/imunologia , Proteínas tau/toxicidade
7.
Anal Chem ; 91(24): 15922-15931, 2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31794208

RESUMO

Abundant blood proteins adducted by active electrophiles are excellent markers to predict the risk of electrophile-induced toxicity. However, detecting endogenously adducted proteins by bottom-up selective (or parallel) reaction monitoring (SRM/PRM) is challenging because of the high variability in sample preparation and detection as well as low adduction levels. Here, we reported a new approach in developing PRM methods by combining intact protein measurement with standard additions to target optimal conditions for detecting catechol estrogens (CEs)-adducted human serum albumin (HSA). Blood serum was added with multiple amounts of CEs to obtain serum standards. Intact protein measurement revealed two linear ranges of adduction levels (adducted-CE/HSA): 0.34-0.42 (R2 > 0.94) and 0.81-8.54 (R2 > 0.96) against the amount of added CEs, respectively. Six adduction sites were identified by trypsin (K20, C34, K73, K281, H338, K378) or chymotrypsin (K20, C34, K378) digestion. PRM methods targeting all adducted/nonadducted peptide pairs based on chymotrypsin or trypsin digestion were developed, and the data were compared with those obtained by intact protein measurement. Correlation plots indicated that chymotrypsin-PRM leads to poor sensitivity and largely underestimated protein adduction levels. Trypsin-PRM leads to sensitive and highly correlated (R2 > 0.91) protein adduction levels with a detection limit below the endogenous level and relative standard deviation <25%. As a proof of concept, clinical serum samples were examined by trypsin-PRM, and a slightly higher adduction level was observed for the obesity group when compared with the healthy group. This is the first report on determining adduction levels of blood proteins for long-term exposure to CEs. The standard addition approach can be generally applied to protein adductomics with resolvable mass increments by intact protein measurement to accelerate the development of bottom-up methods close to the inherent limit.


Assuntos
Estrogênios de Catecol/química , Espectrometria de Massas/métodos , Peptídeos/análise , Albumina Sérica/química , Cromatografia Líquida de Alta Pressão , Quimotripsina/metabolismo , Estrogênios de Catecol/metabolismo , Humanos , Espectrometria de Massas/normas , Nanotecnologia , Peptídeos/metabolismo , Peptídeos/normas , Padrões de Referência , Albumina Sérica/metabolismo , Tripsina/metabolismo
8.
Mikrochim Acta ; 186(11): 718, 2019 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-31654134

RESUMO

Popcorn nanoparticles (pop-NPs) consisting of a Pd/Cu alloy were synthesized using a seed-mediated growth method. The Cu and Pd atoms were co-deposited on a cubic Pd seed to reduce the energy of fault stacking. The same synthesis method with a reduced volume of the Cu(II) salt leads to Pd/Cu alloy nanoparticles with branches (br-NPs). Large Pd nanocubes (Pd NCs) were prepared via epitaxial deposition and using tetrachloropalladate (PdCl42-) only. The high-resolution TEM analysis results show the pop-NPs and br-NPs to be single crystals with [Formula: see text] and [Formula: see text] planes, respectively. The results of X-ray photoelectron spectroscopy and cyclic voltammetry measurements corroborated that Pd is enriched on both surfaces. The materials were placed on a glassy carbon electrode to obtain a differential pulse voltammetric sensor for dopamine (DA). The electrochemical sensitivities are (a) 1.55 µA µM-1 cm-2 for the Pd/Cu pop-NP sensor in its linear range (15-300 µM), (b) 1.17 µA µM-1 cm-2 for the br-NP sensor in the linear range (15-200 µM), and (c) 0.97 µA µM-1 cm-2 for the Pd NC sensor in its linear range (15-100 µM). The best working potentials are near 0.10 V (vs. SCE) for all three sensors. The pop-NP-based sensor performs particularly well due to it selectivity over ascorbic and uric acid. Graphical abstract Pd/Cu popcorn nanoparticles (pop-NPs), nanoparticles with branches (br-NPs), and Pd nanocubes (NCs) were synthesized using seed-mediated growth methods and directly used on glassy carbon electrodes for non-enzymatic sensing of dopamine.

9.
J Nanosci Nanotechnol ; 18(8): 5558-5565, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-29458610

RESUMO

In this study, through silicon via (TSV)-less interconnection using the fan-out wafer-level-packaging (FO-WLP) technology and a novel redistribution layer (RDL)-first wafer level packaging are investigated. Since warpage of molded wafer is a critical issue and needs to be optimized for process integration, the evaluation of the warpage issue on a 12-inch wafer using finite element analysis (FEA) at various parameters is presented. Related parameters include geometric dimension (such as chip size, chip number, chip thickness, and mold thickness), materials' selection and structure optimization. The effect of glass carriers with various coefficients of thermal expansion (CTE) is also discussed. Chips are bonded onto a 12-inch reconstituted wafer, which includes 2 RDL layers, 3 passivation layers, and micro bumps, followed by using epoxy molding compound process. Furthermore, an optical surface inspector is adopted to measure the surface profile and the results are compared with the results from simulation. In order to examine the quality of the TSV-less interconnection structure, electrical measurement is conducted and the respective results are presented.

10.
Clin Sci (Lond) ; 130(9): 667-81, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26811540

RESUMO

Arthritis is a process of chronic inflammation that results in joint damage. IL (interleukin)-1ß is an inflammatory cytokine that acts as a key mediator of cartilage degradation, and is abundantly expressed in arthritis. Neovascularization is one of the pathological characteristics of arthritis. However, the role of IL-1ß in the angiogenesis of chondrocytes remains unknown. In the present study, we demonstrate that stimulating chondrocytes (ATDC5) with IL-1ß increased the expression of FGF (fibroblast growth factor)-2, a potent angiogenic inducer, and then promoted EPC (endothelial progenitor cell) tube formation and migration. In addition, FGF-2-neutralizing antibody abolished ATDC5-conditional medium-mediated angiogenesis in vitro, as well as its angiogenic effects in the CAM (chick chorioallantoic membrane) assay and Matrigel plug nude mice model in vivo. IHC (immunohistochemistry) staining from a CIA (collagen-induced arthritis) mouse model also demonstrates that arthritis increased the expression of IL-1ß and FGF-2, as well as EPC homing in articular cartilage. Moreover, IL-1ß-induced FGF-2 expression via IL-1RI (type-1 IL-1 receptor), ROS (reactive oxygen species) generation, AMPK (AMP-activated protein kinase), p38 and NF-κB (nuclear factor κB) pathway has been demonstrated. On the basis of these findings, we conclude that IL-1ß promotes FGF-2 expression in chondrocytes through the ROS/AMPK/p38/NF-κB signalling pathway and subsequently increases EPC angiogenesis. Therefore IL-1ß serves as a link between inflammation and angiogenesis during arthritis.


Assuntos
Condrócitos/citologia , Células Progenitoras Endoteliais/metabolismo , Fator 2 de Crescimento de Fibroblastos/metabolismo , Interleucina-1beta/farmacologia , Neovascularização Fisiológica/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Linhagem Celular , Galinhas , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Modelos Animais de Doenças , Células Progenitoras Endoteliais/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Humanos , Articulações/efeitos dos fármacos , Articulações/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Receptores de Interleucina/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
11.
Carcinogenesis ; 36(1): 104-14, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25330803

RESUMO

Chemokines modulate angiogenesis and metastasis that dictate cancer development in tumor microenvironment. Osteosarcoma is the most frequent bone tumor and is characterized by a high metastatic potential. Chemokine CCL5 (previously called RANTES) has been reported to facilitate tumor progression and metastasis. However, the crosstalk between chemokine CCL5 and vascular endothelial growth factor (VEGF) as well as tumor angiogenesis in human osteosarcoma microenvironment has not been well explored. In this study, we found that CCL5 increased VEGF expression and production in human osteosarcoma cells. The conditioned medium (CM) from CCL5-treated osteosarcoma cells significantly induced tube formation and migration of human endothelial progenitor cells. Pretreatment of cells with CCR5 antibody or transfection with CCR5 specific siRNA blocked CCL5-induced VEGF expression and angiogenesis. CCL5/CCR5 axis demonstrably activated protein kinase Cδ (PKCδ), c-Src and hypoxia-inducible factor-1 alpha (HIF-1α) signaling cascades to induce VEGF-dependent angiogenesis. Furthermore, knockdown of CCL5 suppressed VEGF expression and attenuated osteosarcoma CM-induced angiogenesis in vitro and in vivo. CCL5 knockdown dramatically abolished tumor growth and angiogenesis in the osteosarcoma xenograft animal model. Importantly, we demonstrated that the expression of CCL5 and VEGF were correlated with tumor stage according the immunohistochemistry analysis of human osteosarcoma tissues. Taken together, our findings provide evidence that CCL5/CCR5 axis promotes VEGF-dependent tumor angiogenesis in human osteosarcoma microenvironment through PKCδ/c-Src/HIF-1α signaling pathway. CCL5 may represent a potential therapeutic target against human osteosarcoma.


Assuntos
Neoplasias Ósseas/irrigação sanguínea , Quimiocina CCL5/metabolismo , Neovascularização Patológica/metabolismo , Osteossarcoma/irrigação sanguínea , Receptores CCR5/metabolismo , Microambiente Tumoral , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Western Blotting , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Movimento Celular , Proliferação de Células , Quimiocina CCL5/antagonistas & inibidores , Quimiocina CCL5/genética , Embrião de Galinha , Membrana Corioalantoide/metabolismo , Membrana Corioalantoide/patologia , Imunoprecipitação da Cromatina , Meios de Cultivo Condicionados/farmacologia , Citometria de Fluxo , Humanos , Técnicas Imunoenzimáticas , Masculino , Camundongos , Camundongos Nus , Osteossarcoma/metabolismo , Osteossarcoma/patologia , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase em Tempo Real , Receptores CCR5/química , Receptores CCR5/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise Serial de Tecidos , Células Tumorais Cultivadas , Fator A de Crescimento do Endotélio Vascular/genética , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Neurobiol Dis ; 76: 13-23, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25576397

RESUMO

The unique proline isomerase Pin1 is pivotal for protecting against age-dependent neurodegeneration in Alzheimer's disease (AD), with its inhibition providing a molecular link between tangle and plaque pathologies. Pin1 is oxidatively modified in human AD brains, but little is known about its regulatory mechanisms and pathological significance of such Pin1 modification. In this paper, our determination of crystal structures of oxidized Pin1 reveals a series of Pin1 oxidative modifications on Cys113 in a sequential fashion. Cys113 oxidization is further confirmed by generating antibodies specifically recognizing oxidized Cys113 of Pin1. Furthermore, Pin1 oxidation on Cys113 inactivates its catalytic activity in vitro, and Ala point substitution of Cys113 inactivates the ability of Pin1 to isomerize tau as well as to promote protein turnover of tau and APP. Moreover, redox regulation affects Pin1 subcellular localization and Pin1-mediated neuronal survival in response to hypoxia treatment. Importantly, Cys113-oxidized Pin1 is significantly increased in human AD brain comparing to age-matched controls. These results not only identify a novel Pin1 oxidation site to be the critical catalytic residue Cys113, but also provide a novel oxidative regulation mechanism for inhibiting Pin1 activity in AD. These results suggest that preventing Pin1 oxidization might help to reduce the risk of AD.


Assuntos
Doença de Alzheimer/metabolismo , Peptidilprolil Isomerase/química , Peptidilprolil Isomerase/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Anticorpos , Domínio Catalítico , Linhagem Celular Tumoral , Hipocampo/metabolismo , Humanos , Peptidilprolil Isomerase de Interação com NIMA , Oxirredução , Peptidilprolil Isomerase/imunologia , Proteínas tau/metabolismo
13.
Appl Opt ; 53(22): E56-60, 2014 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-25090355

RESUMO

A conventional handheld skin camera is suitable for 2D inspection of shallow skin. Due to its high resolution and noninvasiveness, optical coherence tomography (OCT) has become a popular medical-imaging technology. Among OCT schemes, full-field optical coherence tomography (FF-OCT) is suitable for rapid en face imaging, as it uses a 2D imaging device for pixel processing of a sample plane. Because of its wide bandwidth and long lifetime, an RGB LED was chosen in an FF-OCT system among three source candidates in this study. A full-color tissue image and real-time video were obtained from the system to demonstrate the potential of the RGB LED FF-OCT system in medical imaging. All devices used here can be integrated by micro-optoelectromechanical technology into a handheld model. Noninvasive, real-time, full-color handheld imaging capability contributes to advance dermatology and cosmetology.


Assuntos
Colorimetria/instrumentação , Dermoscopia/instrumentação , Aumento da Imagem/instrumentação , Iluminação/instrumentação , Semicondutores , Tomografia de Coerência Óptica/instrumentação , Sistemas Computacionais , Desenho de Equipamento , Análise de Falha de Equipamento , Miniaturização
14.
Front Cardiovasc Med ; 11: 1393440, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39105079

RESUMO

Introduction: Although angiotensin receptor-neprilysin inhibitor (ARNI) has shown promise in patients with heart failure and reduced ejection fraction (HFrEF), the treatment effect in HFrEF patients with end-stage renal disease (ESRD) undergoing dialysis is uncertain. This study aimed to examine the real-world effects of ARNI vs. angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) in this subpopulation. Methods: This multi-institutional, retrospective study identified 349 HFrEF patients with ESRD on dialysis, who initiated either ARNI or ACEI/ARB therapy. Efficacy outcomes included rates of hospitalization for heart failure (HHF) and mortality, as well as changes in echocardiographic parameters. Safety outcomes encompassed hypotension and hyperkalemia. Treatment effects were assessed using Cox proportional hazards models, with additional sensitivity analyses for robustness. Results: Out of 349 patients screened, 89 were included in the final analysis (42 in the ARNI group and 47 in the ACEI/ARB group). After 1 year of treatment, echocardiographic measures between the two groups were comparable. The primary composite rate of HHF or mortality was 20.6 events per 100 patient-years in the ARNI group and 26.1 in the ACEI/ARB group; the adjusted hazard ratio was 0.98 (95% CI: 0.28-3.43, P = 0.97). Their safety outcomes did not differ significantly. Sensitivity analyses, including repetitive sampling, propensity score matching, and extended follow-up, corroborated these findings. Conclusion: ARNI has proven effective in treating HFrEF patients; however, significant benefits were not observed in these patients with ESRD undergoing dialysis compared with ACEI/ARB in this real-world cohort. Future research employing a more extended follow-up period, larger sample size, or randomized design is warranted to investigate the treatment effects in this subpopulation.

15.
ScientificWorldJournal ; 2013: 571875, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24379746

RESUMO

To control hepatitis B virus (HBV) infection, a universal HBV vaccination program for infants was launched in Taiwan in 1984. The aim of this study was to investigate the role of B-cell and T-cell epitope variations of HBsAg and polymerase in HBV infection in vaccinated children. One hundred sixty-three sera from vaccinated children were enrolled randomly. HBV serum markers, including hepatitis B surface antigen (HBsAg) and antibodies to HBsAg (anti-HBs) and core antigen (anti-HBc), were detected by ELISA. Nucleotide sequences encoding the S and the pre-S regions of HBsAg were analyzed in all HBsAg positive sera. Five children were HBsAg positive. Sequence analysis of S, pre-S, and overlapped polymerase (P) genes showed that HBV isolates of HBsAg-positive vaccinees were variants; no G145R but G145A and other substitutions were found in the "a" determinant. Fifteen, six, and eight amino acid substitutions within B-cell and T-cell epitopes of S, pre-S, and P regions were detected, respectively. Several immune-epitope mutants, such as S45T/A, N131T, I194V, and S207N in S, were detected in all isolates. In conclusion, our results suggested that these naturally occurring immunoepitope mutants, which changed their immunogenicity leading to escape from immune response, might cause HBV infection.


Assuntos
Epitopos de Linfócito B/genética , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/genética , Epitopos de Linfócito T/imunologia , Vírus da Hepatite B/imunologia , Hepatite B/genética , Hepatite B/imunologia , Substituição de Aminoácidos , Criança , DNA Viral/genética , Mapeamento de Epitopos , Hepatite B/prevenção & controle , Antígenos de Superfície da Hepatite B/genética , Antígenos de Superfície da Hepatite B/imunologia , Vacinas contra Hepatite B/genética , Vacinas contra Hepatite B/imunologia , Vírus da Hepatite B/genética , Humanos , Mutação , Vacinação
16.
Guang Pu Xue Yu Guang Pu Fen Xi ; 33(7): 1863-7, 2013 Jul.
Artigo em Zh | MEDLINE | ID: mdl-24059190

RESUMO

As skin is the exterior organ of human body, cosmetic industry advances year by year. To reveal the details of skin tissue, threedimensional medical imaging is required. Based on the idea of "readout instead of write", a new scheme named spectral classification imaging (SCI) is proposed in the present study to reduce the invasiveness by applying the reflection spectra of the sample points for three-dimensional medical imaging. Broad-band light source and the spectrometer were employed to collect the spectra curves of scanned region, which were classified into several tissue types by their cross-correlations. A colorful tissue tomography can finally be obtained by filling in each image pixel the color indicating the corresponding tissue type. The lateral/longitudinal resolutions and penetration depth were analyzed to characterize the SCI system. The lateral resolution is based on the source's diffraction limit, the longitudinal resolution is by its depth-of-focus, and the penetration depth is equivalent to its skin depth. The imaging results of an amethyst of 0.6 mm (chi-direction) x 0.6 mm (y-direction) with a total of 120 x 120 pixels per frame and a guppy fish of 3.2 mm (chi-direction) x 2.4 mm (y-direction) of 160 x 120 pixels, are presented to show the image quality. The effects of the cross-correlation coefficient and the number of source wavelengths on the imaging results were explored. The value of cross-correlation threshold determines the required time for imaging, the resulted number of tissue groups, and the variety of tissue colors in the imaging result. Owing to its virtual noninvasiveness and easy configuration, the SCI system is highly promising for practical uses. RGB LEDs possess merits of broad bandwidth, low cost, long lifetime, small volume, and are ready to be integrated into a multi-color source module. Replacing the wide-band light source and the spectrometer module with a composite RGB LED with discrete wavelengths and a micro-spectrometer for spectra retrieval, the system has great potential to be minimized as a hand-held product for noninvasive medical imaging. It leads to reduced use of non-eco-friendly cosmetics and extended advance of cosmetic dermatology.


Assuntos
Imageamento Tridimensional/instrumentação , Pele/anatomia & histologia , Análise Espectral/instrumentação , Animais , Peixes , Microtecnologia , Poecilia , Pele/patologia , Análise Espectral/métodos
17.
IEEE Trans Biomed Eng ; 70(12): 3330-3341, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37327105

RESUMO

OBJECTIVE: Although many speech enhancement (SE) algorithms have been proposed to promote speech perception in hearing-impaired patients, the conventional SE approaches that perform well under quiet and/or stationary noises fail under nonstationary noises and/or when the speaker is at a considerable distance. Therefore, the objective of this study is to overcome the limitations of the conventional speech enhancement approaches. METHOD: This study proposes a speaker-closed deep learning-based SE method together with an optical microphone to acquire and enhance the speech of a target speaker. RESULTS: The objective evaluation scores achieved by the proposed method outperformed the baseline methods by a margin of 0.21-0.27 and 0.34-0.64 in speech quality (HASQI) and speech comprehension/intelligibility (HASPI), respectively, for seven typical hearing loss types. CONCLUSION: The results suggest that the proposed method can enhance speech perception by cutting off noise from speech signals and mitigating interference caused by distance. SIGNIFICANCE: The results of this study show a potential way that can help improve the listening experience in enhancing speech quality and speech comprehension/intelligibility for hearing-impaired people.


Assuntos
Implantes Cocleares , Aprendizado Profundo , Auxiliares de Audição , Perda Auditiva , Percepção da Fala , Humanos , Inteligibilidade da Fala
18.
N Z Med J ; 136(1580): 48-61, 2023 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-37536311

RESUMO

AIMS: Diabetes-related dementia (DRD) is a new dementia subtype associated with type 2 diabetes mellitus, first described in 2013. This study investigated data from a local New Zealand memory service to identify patients that met the criteria for DRD. METHODS: Using routinely collected data from 2013-2021, we selected a sample of people with dementia, diabetes, and no CT evidence of Alzheimer's disease (AD), vascular dementia, or frontotemporal dementia. We compared their socio-demographic, clinical, and cognitive characteristics with a sample of patients with diabetes and Alzheimer's disease. RESULTS: Forty (16%) of 249 patients with diabetes and dementia had "normal" CT scans (DRD subgroup), and 38 (15%) had AD (AD subgroup). Compared to NZ Europeans, disproportionally more Maori and Pacific Islanders (70.2%) were in the DRD subgroup. In the Pacific subgroup (n=31), the DRD subgroup had higher memory subscores than the AD subgroup (p=0.047), and the Kaplan-Meier plot suggested poorer survival (p=0.13). Maori patients with diabetes and dementia were more likely to meet all four criteria for DRD. CONCLUSION: We have replicated the findings of the 2013 DRD research and have demonstrated a higher risk for the DRD subtype of dementia among the Maori and Pacific Islander patients in our sample.


Assuntos
Demência , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Povo Maori , Nova Zelândia/epidemiologia , Dados de Saúde Coletados Rotineiramente , Demência/epidemiologia , Demência/etiologia
19.
Guang Pu Xue Yu Guang Pu Fen Xi ; 32(12): 3299-303, 2012 Dec.
Artigo em Zh | MEDLINE | ID: mdl-23427556

RESUMO

Collagen is one of the main structural proteins in human dermis. The lack and atrophy of collagen induces the appearance of wrinkles and beginning of aging. L-ascorbic acid has significant effects on skin-whitening and anti-oxidation, which helps keep skin beautiful and healthy, respectively. With auto-fluorescence, the amount of collagen is in proportion to the strength of its fluorescence spectrum. Therefore, a new method is proposed to determine the content of collagen and the health of skin through the analysis of fluorescence and reflection spectra. Compared with conventional chemical analysis, this method needs less time, and is much more noninvasive. Solutions of different concentration of external collagen and L-ascorbic acid were applied on healthy, spotted and wrinkled skin in this study. By the time dependence of fluorescence and reflection spectra, the effects of skin absorption and restoration of collagen and L-ascorbic acid were derived, respectively. The experiment shows that the collagen or L-ascorbic acid solution of adequate concentration is best for skin absorption. Admixed with suitable concentration of L-ascorbic acid, the collagen solution was well absorbed and results in effect of smoothing wrinkles; the effect of L-ascorbic acid to clear up the spots was also demonstrated. By scientific explorations shown above, the restoration effects of cosmetic materials were validated, and people's confusion and myth about skincare products were avoided. Consequently, this study helps advance cosmetic industry.


Assuntos
Ácido Ascórbico/análise , Colágeno/análise , Envelhecimento da Pele/efeitos dos fármacos , Pele/química , Espectrometria de Fluorescência/métodos , Administração Cutânea , Ácido Ascórbico/administração & dosagem , Colágeno/administração & dosagem , Humanos , Análise Espectral/métodos
20.
JASA Express Lett ; 2(5): 055202, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-36154065

RESUMO

Medical masks have become necessary of late because of the COVID-19 outbreak; however, they tend to attenuate the energy of speech signals and affect speech quality. Therefore, this study proposes an optical-based microphone approach to obtain speech signals from speakers' medical masks. Experimental results showed that the optical-based microphone approach achieved better performance (85.61%) than the two baseline approaches, namely, omnidirectional (24.17%) and directional microphones (31.65%), in the case of long-distance speech and background noise. The results suggest that the optical-based microphone method is a promising approach for acquiring speech from a medical mask.


Assuntos
COVID-19 , Auxiliares de Audição , Percepção da Fala , COVID-19/prevenção & controle , Desenho de Equipamento , Humanos , Máscaras , Fala , Vibração
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