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QUESTION: Pseudomonas aeruginosa (Pa) is a common pathogen that contributes to progressive lung disease in Cystic Fibrosis (CF). Genetic factors other than CF-causing CFTR variations contribute approximately 85% of the variation in chronic Pa infection age in CF according to twin studies, but the susceptibility loci remain unknown. Our objective is to advance understanding of the genetic basis of host susceptibility to Pa infection. MATERIALS AND METHODS: We conducted a genome-wide association study (GWAS) of chronic Pa infection age in 1037 Canadians with CF. We subsequently assessed the genetic correlation between chronic Pa infection age and lung function through polygenic risk score (PRS) analysis and inferred their causal relationship through bi-directional Mendelian Randomization analysis. RESULTS: Two novel genome-wide significant loci with lead SNPs rs62369766 (chr5p12; p-value= 1.98 ×10-8) and rs927553 (chr13q12.12; p-value= 1.91 × 10-8) were associated with chronic Pa infection age. The rs62369766 locus was validated using an independent French cohort (N=501). Furthermore, PRS constructed from CF lung function-associated SNPs was significantly associated with chronic Pa infection age (p-value=0.002). Finally, our analysis presented evidence for a causal effect of lung function on the chronic Pa infection age (Beta=0.782â years, p-value= 4.24 × 10-4). In the reverse direction, we observed a moderate effect (Beta=0.002, p-value=0.012). CONCLUSIONS: We identified two novel loci that are associated with chronic Pa infection age in individuals with CF. Additionally, we provided evidence of common genetic contributors and a potential causal relationship between Pa infection susceptibility and lung function in CF. Therapeutics targeting these genetic factors may delay the onset of chronic infections which accounts for significant remaining morbidity in CF.
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Controlling crystallization and grain growth is crucial for realizing highly efficient hybrid perovskite solar cells (PSCs). In this work, enhanced PSC photovoltaic performance and stability by accelerating perovskite crystallization and grain growth via 2D hexagonal boron nitride (hBN) nanosheet additives incorporated into the active perovskite layer are demonstrated. In situ X-ray scattering and infrared thermal imaging during the perovskite annealing process revealed the highly thermally conductive hBN nanosheets promoted the phase conversion and grain growth in the perovskite layer by facilitating a more rapid and spatially uniform temperature rise within the perovskite film. Complementary structural, physicochemical, and electrical characterizations further showed that the hBN nanosheets formed a physical barrier at the perovskite grain boundaries and the interfaces with charge transport layers, passivating defects, and retarding ion migration. As a result, the power conversion efficiency of the PSC is improved from 17.4% to 19.8%, along with enhanced device stability, retaining ≈90% of the initial efficiency even after 500 h ambient air storage. The results not only highlight 2D hBN as an effective additive for PSCs but also suggest enhanced thermal transport as one of the pathways for improved PSC performance by 2D material additives in general.
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Despite the recent progress in increasing the power generation of Anion-exchange membrane fuel cells (AEMFCs), their durability is still far lower than that of Proton exchange membrane fuel cells (PEMFCs). Using the complementary techniques of X-ray micro-computed tomography (CT), Scanning Electron Microscopy (SEM) and Energy Dispersive X-ray (EDX) spectroscopy, we have identified Pt ion migration as an important factor to explain the decay in performance of AEMFCs. In alkaline media Pt+2 ions are easily formed which then either undergo dissolution into the carbon support or migrate to the membrane. In contrast to PEMFCs, where hydrogen cross over reduces the ions forming a vertical "Pt line" within the membrane, the ions in the AEM are trapped by charged groups within the membrane, leading to disintegration of the membrane and failure. Diffusion of the metal components is still observed when the Pt/C of the cathode is substituted with a FeCo-N-C catalyst, but in this case the Fe and Co ions are not trapped within the membrane, but rather migrate into the anode, thereby increasing the stability of the membrane.
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PURPOSE: Cystic fibrosis (CF), caused by pathogenic variants in the CF transmembrane conductance regulator (CFTR), affects multiple organs including the exocrine pancreas, which is a causal contributor to cystic fibrosis-related diabetes (CFRD). Untreated CFRD causes increased CF-related mortality whereas early detection can improve outcomes. METHODS: Using genetic and easily accessible clinical measures available at birth, we constructed a CFRD prediction model using the Canadian CF Gene Modifier Study (CGS; n = 1,958) and validated it in the French CF Gene Modifier Study (FGMS; n = 1,003). We investigated genetic variants shown to associate with CF disease severity across multiple organs in genome-wide association studies. RESULTS: The strongest predictors included sex, CFTR severity score, and several genetic variants including one annotated to PRSS1, which encodes cationic trypsinogen. The final model defined in the CGS shows excellent agreement when validated on the FGMS, and the risk classifier shows slightly better performance at predicting CFRD risk later in life in both studies. CONCLUSION: We demonstrated clinical utility by comparing CFRD prevalence rates between the top 10% of individuals with the highest risk and the bottom 10% with the lowest risk. A web-based application was developed to provide practitioners with patient-specific CFRD risk to guide CFRD monitoring and treatment.
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Fibrose Cística , Diabetes Mellitus , Biomarcadores , Canadá , Fibrose Cística/complicações , Fibrose Cística/diagnóstico , Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/genética , Estudo de Associação Genômica Ampla , Humanos , Recém-NascidoRESUMO
Nanodiamonds (ND) have emerged to be a widely-discussed nanomaterial for their applications in biological studies and for medical diagnostics and treatment. The potentials have been successfully demonstrated in cellular and tissue models in vitro. For medical applications, further in vivo studies on various applications become important. One of the most challenging possibilities of ND biomedical application is controllable drug delivery and tracing. That usually assumes ND interaction with the blood system. In this work, we study ND interaction with rat blood and analyze how the ND surface modification and coating can optimize the ND interaction with the blood. It was found that adsorption of a low concentration of ND does not affect the oxygenation state of red blood cells (RBC). The obtained in vivo results are compared to the results of in vitro studies of nanodiamond interaction with rat and human blood and blood components, such as red blood cells and blood plasma. An in vivo animal model shows ND injected in blood attach to the RBC membrane and circulate with blood for more than 30 min; and ND do not stimulate an immune response by measurement of proinflammatory cytokine TNF-α with ND injected into mice via the caudal vein. The results further confirm nanodiamonds' safety in organisms, as well as the possibility of their application without complicating the blood's physiological conditions.
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Eritrócitos/efeitos dos fármacos , Nanodiamantes/toxicidade , Animais , Difusão Dinâmica da Luz , Ensaio de Imunoadsorção Enzimática , Eritrócitos/citologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microscopia de Fluorescência , Nanodiamantes/química , Oxigênio/química , Tamanho da Partícula , Ratos , Albumina Sérica/química , Albumina Sérica/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier , Análise Espectral Raman , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: Solar ultraviolet (UV) radiation causes various deleterious effects, and UV blockage is recommended for avoiding sunburn. Nanosized titanium dioxide and zinc oxide offer effective protection and enhance cosmetic appearance but entail health concerns regarding their photocatalytic activity, which generates reactive oxygen species. These concerns are absent in nanodiamonds (NDs). Among the UV wavelengths in sunlight, UVB irradiation primarily threatens human health. RESULTS: The efficacy and safety of NDs in UVB protection were evaluated using cell cultures and mouse models. We determined that 2 mg/cm(2) of NDs efficiently reduced over 95% of UVB radiation. Direct UVB exposure caused cell death of cultured keratinocyte, fibroblasts and skin damage in mice. By contrast, ND-shielding significantly protected the aforementioned pathogenic alterations in both cell cultures and mouse models. CONCLUSIONS: NDs are feasible and safe materials for preventing UVB-induced skin damage.
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Nanodiamantes , Protetores contra Radiação/farmacologia , Pele/efeitos dos fármacos , Pele/efeitos da radiação , Animais , Células Cultivadas , Dermatite/etiologia , Dermatite/prevenção & controle , Fibroblastos/efeitos dos fármacos , Fibroblastos/efeitos da radiação , Humanos , Hiperplasia/tratamento farmacológico , Hiperplasia/patologia , Queratinócitos/efeitos dos fármacos , Queratinócitos/efeitos da radiação , Leucócitos/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Protetores contra Radiação/química , Radiodermite/etiologia , Radiodermite/prevenção & controle , Pele/patologia , Titânio/farmacologia , Raios Ultravioleta/efeitos adversos , Óxido de Zinco/farmacologiaRESUMO
Red, green, and blue light InxGa1-xN multiple quantum wells have been grown on GaN/γ-LiAlO2 microdisk substrates by plasma-assisted molecular beam epitaxy. We established a mechanism to optimize the self-assembly growth with ball-stick model for InxGa1-xN multiple quantum well microdisks by bottom-up nanotechnology. We showed that three different red, green, and blue lighting micro-LEDs can be made of one single material (InxGa1-xN) solely by tuning the indium content. We also demonstrated that one can fabricate a beautiful InxGa1-xN-QW microdisk by choosing an appropriate buffer layer for optoelectronic applications.
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This paper introduces a novel approach to achieve multiple photon counting for Raman spectroscopy. The multiphoton counting process is made possible by recording and analyzing the photomultiplier tube response to each pulse of a pulsed laser in a time-resolved Raman spectroscopy system. Conventional Raman spectroscopy typically considers photon arrivals as binary events assessed by a single threshold. Hence, the conventional algorithm ignores the fact that multiple photons could arrive within the same response, sacrificing potential signal gain. In this work, a high-speed data acquisition system and multiple threshold digital signal processing counting algorithm are employed to facilitate multiphoton counting, a data processing approach that differentiates photon arrival events by amplitude and time and contributes to improved Raman detection sensitivity. The multiphoton counting algorithm enables lower concentration detection, greater sensitivity, shortens experiment duration, and improves noise rejection. Results from analyses of aqueous solutions of nitrate, isopropanol, and rhodamine 6G demonstrate the versatility and effectiveness of this algorithm. The algorithm increased system sensitivity by â¼ 2.0-, 2.0-, and 3.1-fold, compared to traditional single-threshold analyses of the same data for tests performed on nitrate, isopropanol, and rhodamine 6G, respectively. Results also demonstrated that the multiphoton counting algorithm increases the upper analysis limit for high Raman-yield compounds, shifting the saturation threshold to a higher concentration in typical concentration versus intensity calibration curves.
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Hybrid core-shell nanodiamond-gold nanoparticles were synthesized and characterized as a novel multifunctional material with tunable and tailored properties for multifunctional biomedical applications. The combination of nanostructured gold and nanodiamond properties afford new options for optical labeling, imaging, sensing, and drug delivery, as well as targeted treatment. ND@Au core-shell nanoparticles composed of nanodiamond (ND) core doped with Si vacancies (SiV) and Au shell were synthesized and characterized in terms of their biomedical applications. Several bioimaging modalities based on the combination of optical and spectroscopic properties of the hybrid nano-systems are demonstrated in cellular and developing zebrafish larvae models. The ND@Au nanoparticles exhibit isolated ND's Raman signal of sp3 bonded carbon, one-photon fluorescence of SiV with strong zero-phonon line at 740 nm, two-photon excited fluorescence of nanogold with short fluorescence lifetime and strong absorption of X-ray irradiation render them possible imaging agent for Raman mapping, Fluorescence imaging, two-photon Fluorescence Lifetime Imaging (TP-FLIM) and high-resolution hard-X-ray microscopy in biosystems. Potential combination of the imaging facilities with other theranostic functionalities is discussed.
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Nanopartículas Metálicas , Nanodiamantes , Nanoestruturas , Animais , Ouro/química , Peixe-ZebraRESUMO
Six nitriolotriacetic-acid-modified ordered mesoporous silicas (NTA-OMPSs) with different pore sizes and surface features for specific and reversible protein immobilization were fabricated and characterized. Specific immobilization of a genetically engineered undecaprenyl pyrophosphate synthase (UPPs) from cell lysate and a chemically modified His-tagged horseradish peroxidase (HRP) in these Ni-NTA-OMPSs through histidine coordination to the nickelated NTA was demonstrated and confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and sodium dodecyl sulfate polyacrylamide gel electrophoresis. Negligible leakage of these enzymes over a wide range of acidic conditions was observed. Moreover, histidine tags with different lengths (His6, His4, His3, and His2) applied to HRP were evaluated to find the minimum length for effective complexation. Enzymatic assessment studies indicated that the pore size of the OMPSs has minimal influence on the enzymatic activity, whereas chemical entities such as unreacted mercapto groups tailored on the interior surfaces of the OMPSs played certain roles in inhibiting the enzymatic activity and stability. On MCF-S-NTA, SBA-S-NTA, and film-S-NTA, which contained unreacted mercaptopropyl groups on the interior surface, immobilized His-tagged HRP showed lower catalytic activity and stability than on MCF-NTA, film-NTA, and SBA-NTA. Selective hydroxylation of optically pure L-tyrosine to (S)-2-amino-3-(3,4-dihydroxyphenyl)propanoic acid (L-DOPA) by the immobilized HRP was also demonstrated.
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Histidina/química , Proteínas Imobilizadas/química , Ácido Nitrilotriacético/química , Dióxido de Silício/química , Alquil e Aril Transferases/química , Catálise , Peroxidase do Rábano Silvestre/química , Peroxidase do Rábano Silvestre/metabolismo , Concentração de Íons de Hidrogênio , PorosidadeRESUMO
INTRODUCTION: Nanodiamond (ND) refers to diamond particles with sizes from few to near 100 nanometers. For its superb physical, chemical and spectroscopic properties, it has been proposed and studied with the aims for bio imaging and drug delivery. Many modalities on conjugating drug molecules on ND to form ND-X for more efficient drug delivery have been demonstrated in the cellular and animal models. AREA COVERED: Many novel drug delivery approaches utilizing nanodiamond as a platform have been demonstrated recently. This review summarizes recent developments on the nanodiamond facilitated drug delivery, from the ND-X complexes preparations to tests in the cellular and animal models. The outlook on clinical translation is discussed. EXPERT OPINION: Nanodiamond and drug complexes (ND-X) produced from different methods are realized for drug delivery; almost all studies reported ND-X being more efficient compared to pure drug alone. However, ND of particle size less than 10 nm are found more toxic due to size and surface structure, and strongly aggregate. In vivo studies demonstrate ND accumulation in animal organs and no confirmed long-term effect studies on their release from organs are available. Standardized nanodiamond materials and drug delivery approaches are needed to advance the applications to the clinical level.
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Nanodiamantes , Neoplasias , Preparações Farmacêuticas , Animais , Sistemas de Liberação de Medicamentos , Neoplasias/tratamento farmacológico , Tamanho da PartículaRESUMO
Titanium dioxide (TiO2) is considered to be a nontoxic material and is widely used in a number of everyday products, such as sunscreen. TiO2 nanoparticles (NP) are also considered as prospective agents for photodynamic therapy and drug delivery. These applications require an understanding of the potential effects of TiO2 on the blood system and its components upon administration. In the presented work, we analyze the interaction of TiO2 nanoparticles of different crystal phases (anatase and rutile) with individual rat Red Blood Cells (RBC) and the TiO2 influence on the oxygenation state and functionality of RBC, estimated via analysis of Raman spectra of Hemoglobin (Hb) and their distribution along individual RBC. Raman spectral signals also allow localization of the TiO2 NP on the RBC. No penetration of the NP inside RBC was observed; however, both kinds of TiO2 NP adsorbed on the RBC membrane can affect the Hb state. Mechanisms involving the NP-membrane-Hb interaction, resulting in partial deoxygenation of Hb and TiO2 photothermal effect on Hb under Raman laser excitation, are suggested. The possible influence on the safety of TiO2 use in advanced medical application, especially on the safety and efficiency of photothermal therapy, is discussed.
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Inserting a coverslip into half of a Gaussian laser beam at a suitable tilting angle can make the single-mode laser beam become closely spaced dual light spots at the laser focus. In this way, we can reform the conventional single-beam optical tweezers easily and construct a set of dual-mode split-beam optical tweezers, which can be used to manually rotate a trapped and twisted red blood cell around the optical axis. Furthermore, we demonstrate that the split-beam optical tweezers can also stably trap and orient a birefringent polystyrene micro strip particle, which otherwise will self rotate at a varying speed along the structural principal axes, fast spin about the optical axis in a tilting pose, or precess like a gyroscope, in the original linearly polarized single-beam optical tweezers.
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The quantitative evaluation of the three-dimensional (3D) morphology of porous composite materials is important for understanding mass transport phenomena, which further impact their functionalities and durability. Reactive porous paint materials are composites in nature and widely used in arts and technological applications. In artistic oil paintings, ambient moisture and water and organic solvents used in conservation treatments are known to trigger multiple physical and chemical degradation processes; however, there is no complete physical model that can quantitatively describe their transport in the paint films. In the present study, model oil paints with lead white (2PbCO3·Pb(OH)2) and zinc white (ZnO) pigments, which are frequently found in artistic oil paintings and are associated with the widespread heavy metal soap deterioration, were studied using synchrotron X-ray nano-tomography and unilateral nuclear magnetic resonance. This study aims to establish a relationship among the paints' compositions, the 3D morphological properties and degradation. This connection is crucial for establishing reliable models that can predict transport properties of solvents used in conservation treatments and of species involved in deterioration reactions, such as soap formation.
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The identification of genetic variation that directly impacts infection susceptibility to SARS-CoV-2 and disease severity of COVID-19 is an important step towards risk stratification, personalized treatment plans, therapeutic, and vaccine development and deployment. Given the importance of study design in infectious disease genetic epidemiology, we use simulation and draw on current estimates of exposure, infectivity, and test accuracy of COVID-19 to demonstrate the feasibility of detecting host genetic factors associated with susceptibility and severity in published COVID-19 study designs. We demonstrate that limited phenotypic data and exposure/infection information in the early stages of the pandemic significantly impact the ability to detect most genetic variants with moderate effect sizes, especially when studying susceptibility to SARS-CoV-2 infection. Our insights can aid in the interpretation of genetic findings emerging in the literature and guide the design of future host genetic studies.
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COVID-19/epidemiologia , Estudos de Casos e Controles , Genômica/métodos , Pandemias , Projetos de Pesquisa , SARS-CoV-2 , COVID-19/genética , Teste para COVID-19 , Simulação por Computador , Fatores de Confusão Epidemiológicos , Expossoma , Reações Falso-Negativas , Predisposição Genética para Doença , Variação Genética , Interações Hospedeiro-Patógeno/genética , Humanos , Projetos de Pesquisa/estatística & dados numéricos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Risco , Sensibilidade e EspecificidadeRESUMO
PURPOSE: Participation in cancer clinical trials (CCTs) for adolescents and young adults (AYAs) remains the lowest of any patient group with cancer. Little is known about the personal barriers to AYA accrual. The aim of this study was to explore AYA attitudes that influence CCT participation. METHODS: A mixed-methods approach was used. AYAs and non-AYAs (≥ 40 years) completed the Cancer Treatment subscale of the Attitudes Toward Cancer Trials Scales and 9 supplementary questions formed from interview analysis. Differences between AYA and non-AYA cohorts were analyzed using the Mann-Whitney U test, and logistic regression models were constructed to evaluate the effect of demographics on perceptions of CCTs. RESULTS: Surveys were distributed to 61 AYAs (median age, 29 years; range, 17-39 years) and 74 non-AYAs (median age, 55 years; range, 40-88 years). Compared with non-AYAs, AYAs perceived CCTs to be unsafe/more difficult (Personal Barrier/Safety domain; P = .01). There were no differences based on age in other domains. AYAs were also more concerned with CCT interference in their long-term goals (P = .04). Multivariable ordered logistic regression identified increased personal barriers in the Personal Barrier/Safety domain for AYAs (P = .01), in patients with English as a second language (ESL; P < .01), and in patients previously not offered a clinical trial (P = .03). Long-term goals were identified as a barrier in particular tumor types (P = .01) and in patients with ESL (P < .01), with a trend identified in AYAs (P = .12). CONCLUSION: Age-related differences in attitudes toward CCTs suggest that tailored approaches to CCT accrual are warranted. Patient-centered delivery of information regarding CCTs, particularly in patients with ESL and who are trial naïve, may improve accrual.
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Neoplasias/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Atitude , Ensaios Clínicos como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Waste liquid streams from distillery were a hurdle in conventional wastewater treatment due to extreme high chemical oxygen demand (COD) and fluctuating feed conditions. A recently commissioned full-scale external circulation sludge bed (ECSB) was applied at a malt whiskey distillery in northeast Taiwan. Start-up of the new ECSB system, which has a total volume of 490 m3 with diameter of 6.55 m (ø) and height of 15.9 m (H), was performed by gradual increasing influent flow rates from zero to the design value of 300 m3 day-1 in the first 90 days. In the subsequent 204 days, both influent flow rates (0-389 m3 day-1) and COD concentrations (2.8-18.1 kg L-1) were highly fluctuated due to diverse batches from the distillery. However, effective bioremediation (COD removal 95.1 ± 2.4%) and biogas production (1195 ± 724 L day-1) were achieved in this system. Intensively, the Imhoff tests were carried out and shown the settled solids concentration by 0.5 ± 0.4 mL L-1, while size distributions of granular sludge were analyzed and observed by SEM-EDS. In addition, developments of the anaerobic systems (including lab, pilot, and full scale from the simplest reactor to the latest ECSB) applied in whiskey wastewater treatment were reviewed with their operational parameters for comparing performances of various anaerobic systems. In general, real-time monitoring and feasible operation strategies were critical to successfully run the system by producing clean energy simultaneously. It provides more economically attractive and sustainable-to-adopt ECSB not only an end-of-pipe process but also a bioresource technology.
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Bebidas Alcoólicas , Eliminação de Resíduos Líquidos/métodos , Anaerobiose , Biocombustíveis , Análise da Demanda Biológica de Oxigênio , Reatores Biológicos , Esgotos , Taiwan , Águas ResiduáriasRESUMO
Using a specially designed apparatus, which collects simultaneous temperature and X-ray scattering data, we performed in situ measurements of the filament during MatEx 3D printing. The data show that the MatEx 3D printing extrusion process provides sufficient shear to form shish-kebab structures, which initially nucleate at the filament surface and spread into the filament core. Time-resolved measurements show that the kebab component near the surface relaxes after deposition of the second filament and enhances chain diffusion across the interface. SEM images indicate near complete interfacial merging of the filaments, which results in excellent mechanical properties.
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The National Health Insurance database to determine the treated prevalence and incidence of dementia in Taiwan was used in this study. A population-based random sample of 22 118 subjects aged 65 or older was obtained as a dynamic cohort. Those study subjects who had filed at least one service claim from 1996 to 2003 for either outpatient care or inpatient care with a principal diagnosis of dementia were identified. The annual treated prevalence increased from 0.71% to 1.92% from 1996 to 2003. The annual treated incidence rates were around 0.76% to 1.04% per year from 1997 to 2003. The annual treated incidence rates for the 5-year age groups, from 65 to 90 years and older, were 0.44%, 0.65%, 0.98%, 1.46%, 1.81%, and 1.80%, respectively. Both the treated prevalence and incidence rates of dementia in National Health Insurance were lower than those of community studies.