Trifolirhizin inhibits proliferation, migration and invasion in nasopharyngeal carcinoma cells via PI3K/Akt signaling pathway suppression.

Nasopharyngeal carcinoma (NPC) is a highly recurrent and metastatic malignant tumor affecting a large number of individuals in southern China. Traditional Chinese herbal medicine has been found to be a rich source of natural compounds with mild therapeutic effects and minimal side effects, making them increasingly popular for treating various diseases. Trifolirhizin, a natural flavonoid derived from leguminous plants, has gained significant attention for its therapeutic potential. In this study, we confirmed that trifolirhizin could effectively inhibit the proliferation, migration and invasion of nasopharyngeal carcinoma 6-10B and HK1 cells. Furthermore, our findings demonstrated that trifolirhizin achieves this by suppressing the PI3K/Akt signaling pathway. The findings of the present study provides a valuable perspective on the potential therapeutic applications of trifolirhizin for the treatment of nasopharyngeal carcinoma.

Deep learning-based method for non-uniform motion-induced error reduction in dynamic microscopic 3D shape measurement.

The non-uniform motion-induced error reduction in dynamic fringe projection profilometry is complex and challenging. Recently, deep learning (DL) has been successfully applied to many complex optical problems with strong nonlinearity and exhibits excellent performance. Inspired by this, a deep learning-based method is developed for non-uniform motion-induced error reduction by taking advantage of the powerful ability of nonlinear fitting. First, a specially designed dataset of motion-induced error reduction is generated for network training by incorporating complex nonlinearity. Then, the corresponding DL-based architecture is proposed and it contains two parts: in the first part, a fringe compensation module is developed as network pre-processing to reduce the phase error caused by fringe discontinuity; in the second part, a deep neural network is employed to extract the high-level features of error distribution and establish a pixel-wise hidden nonlinear mapping between the phase with motion-induced error and the ideal one. Both simulations and real experiments demonstrate the feasibility of the proposed method in dynamic macroscopic measurement.

Generic saturation-induced phase error correction for structured light 3D shape measurement.

Intensity saturation is a challenging problem in structured light 3D shape measurement. Most of the existing methods achieve high dynamic range (HDR) measurement by sacrificing measurement speed, making them limited in high-speed dynamic applications. This Letter proposes a generic efficient saturation-induced phase error correction method for HDR measurement without increasing any fringe patterns. We first theoretically analyze the saturated signal model and deduce the periodic characteristic of saturation-induced phase error. Based on this, we specially design a saturation-induced phase error correction method by joint Fourier analysis and Hilbert transform. Furthermore, the relationship among phase error, saturation degree, and number of phase-shifting steps is established by numerical simulation. Since the proposed method requires no extra captured images or complicated intensity calibration, it is extremely convenient in implementation and is applicable to performing high-speed 3D shape measurements. Simulations and experiments verify the feasibility of the proposed method.

Characterization of four polymorphic genes controlling red leaf colour in lettuce that have undergone disruptive selection since domestication.

Anthocyanins protect plants from biotic and abiotic stressors and provide great health benefits to consumers. In this study, we cloned four genes (Red Lettuce Leaves 1 to 4: RLL1 to RLL4) that contribute to colour variations in lettuce. The RLL1 gene encodes a bHLH transcription factor, and a 5-bp deletion in some cultivars abolishes its function to activate the anthocyanin biosynthesis pathway. The RLL2 gene encodes an R2R3-MYB transcription factor, which was derived from a duplication followed by mutations in its promoter region. The RLL3 gene encodes an R2-MYB transcription factor, which down-regulates anthocyanin biosynthesis through competing with RLL2 for interaction with RLL1; a mis-sense mutation compromises the capacity of RLL3 to bind RLL1. The RLL4 gene encodes a WD-40 transcription factor, homologous to the RUP genes suppressing the UV-B signal transduction pathway in Arabidopsis; a mis-sense mutation in rll4 attenuates its suppressing function, leading to a high concentration of anthocyanins. Sequence analysis of the RLL1-RLL4 genes from wild and cultivated lettuce showed that their function-changing mutations occurred after domestication. The mutations in rll1 disrupt anthocyanin biosynthesis, while the mutations in RLL2, rll3 and rll4 activate anthocyanin biosynthesis, showing disruptive selection for leaf colour during domestication of lettuce. The characterization of multiple polymorphic genes in this study provides the necessary molecular resources for the rational breeding of lettuce cultivars with distinct levels of red pigments and green cultivars with high levels of health-promoting flavonoids.

Return on Investment for Digital Behavioral Counseling in Patients With Prediabetes and Cardiovascular Disease.

INTRODUCTION: We calculated the health and economic impacts of participation in a digital behavioral counseling service that is designed to promote a healthful diet and physical activity for cardiovascular disease prevention in adults with prediabetes and cardiovascular disease risk factors (Prevent, Omada Health, San Francisco, California). This program enhances the Centers for Disease Control and Prevention's Diabetes Prevention Recognition Program. Participants completed a 16-week core program followed by an ongoing maintenance program. METHODS: Analysis was conducted for 2 populations meeting criteria for lifestyle intervention: 1) prediabetes (n = 1,663), and 2) high cardiovascular disease risk (n = 2,152). The Markov-based model simulated clinical and economic outcomes related to obesity and diabetes annually over 10 years for the 2 defined populations. Comparisons were made between participants and propensity-matched controls from the community. RESULTS: The return-on-investment break-even point was 3 years in both populations. Simulated return on investment for the population with prediabetes was $9 and $1,565 at years 3 and 5, respectively. Simulated return on investment for the population with cardiovascular disease risk was $96 and $1,512 at years 3 and 5, respectively. Results suggest that program participation reduces diabetes incidence by 30% to 33% and stroke by 11% to 16% over 5 years. CONCLUSION: Digital Behavioral Counseling provides significant health benefits to patients with prediabetes and cardiovascular disease and a positive return on investment.

Validation of a one-step genomics-based molecular classifier for endometrial carcinoma in a large Chinese population.

OBJECTIVE: The aim of this study is to delineate the molecular classification features within Chinese endometrial cancer (EC) patients and to evaluate the concurrence between two widely employed methods for diagnosing EC molecular subtypes. METHODS: This retrospective observational cohort study encompassed 479 cases of EC for analysis. Utilizing next-generation sequencing (NGS) panels targeting POLE, TP53, and microsatellite instability (MSI) status, four subtypes [POLE ultramutated (POLE mut), MMR-deficient (MMRd), p53 abnormal (p53abn), and no specific molecular profile (NSMP)] were classified. Immunohistochemistry (IHC) was employed to ascertain the expression of p53 and MMR proteins. RESULTS: Among the 479 patients, the distribution of EC subtypes was as follows: 28 (5.85%) POLE mut, 67 (13.99%) MMRd, 60 (12.53%) p53abn, and 324 (67.64%) NSMP. When compared to published findings on EC subtypes in the Caucasian population, our real-world data on Chinese ECs revealed a notably higher proportion of NSMP/CNL (copy number low). The evaluation of MSI/MMR status through NGS-based and IHC-based methods displayed substantial concordance (Kappa = 0.91). Slight discordance between the two techniques in identifying p53 abnormalities (Kappa = 0.83) might stem from TP53 truncating mutations, cytoplasmic p53 expression, null TP53 mutants, and well-documented challenges in interpreting p53 IHC. CONCLUSIONS: Chinese ECs exhibit distinctive molecular attributes. For accurate molecular subtyping of Chinese ECs, additional molecular markers that align with the Chinese population's characteristics should be incorporated into existing classifiers. The study's outcomes underscore a strong agreement between NGS and IHC in TP53/p53 detection and MSI assessment.

Miniature inverted-repeat transposable elements (MITEs) have been accumulated through amplification bursts and play important roles in gene expression and species diversity in Oryza sativa.

Miniature inverted-repeat transposable elements (MITEs) are predicted to play important roles on genome evolution. We developed a BLASTN-based approach for de novo identification of MITEs and systematically analyzed MITEs in rice genome. The genome of rice cultivar Nipponbare (Oryza sativa ssp. japonica) harbors 178,533 MITE-related sequences classified into 338 families. Pairwise nucleotide diversity and phylogenetic tree analysis indicated that individual MITE families were resulted from one or multiple rounds of amplification bursts. The timing of amplification burst varied considerably between different MITE families or subfamilies. MITEs are associated with 23,623 (58.2%) genes in rice genome. At least 7,887 MITEs are transcribed and more than 3,463 were transcribed with rice genes. The MITE sequences transcribed with rice coding genes form 1,130 pairs of potential natural sense/antisense transcripts. MITEs generate 23.5% (183,837 of 781,885) of all small RNAs identified from rice. Some MITE families generated small RNAs mainly from the terminals, while other families generated small RNAs predominantly from the central region. More than half (51.8%) of the MITE-derived small RNAs were generated exclusively by MITEs located away from genes. Genome-wide analysis showed that genes associated with MITEs have significantly lower expression than genes away from MITEs. Approximately 14.8% of loci with full-length MITEs have presence/absence polymorphism between rice cultivars 93-11 (O. sativa ssp. indica) and Nipponbare. Considering that different sets of genes may be regulated by MITE-derived small RNAs in different genotypes, MITEs provide considerable diversity for O. sativa.

The cost-effectiveness of the levonorgestrel-releasing intrauterine system for the treatment of idiopathic heavy menstrual bleeding in the United States.

OBJECTIVES: Heavy menstrual bleeding negatively impacts the health and quality of life of about 18 million women in the United States. Although some studies have established the clinical effectiveness of heavy menstrual bleeding treatments, few have evaluated their cost-effectiveness. Our objective was to evaluate the cost-effectiveness of the levonorgestrel-releasing intrauterine system (LNG-IUS) compared with other therapies for idiopathic heavy menstrual bleeding. METHODS: We developed a model comparing the clinical and economic outcomes (from a US payer perspective) of three broad initial treatment strategies over 5 years: LNG-IUS, oral agents, or surgery. Up to three nonsurgical treatment lines, followed by up to two surgical lines, were allowed; unintended pregnancy was possible, and women could discontinue any time during nonsurgical treatments. Menstrual blood loss of 80 ml or more per cycle determined treatment failure. RESULTS: Initiating treatment with LNG-IUS resulted in the fewest hysterectomies (6 per 1000 women), the most quality-adjusted life-years (3.78), and the lowest costs ($1137) among all the nonsurgical strategies. Initiating treatment with LNG-IUS was also less costly than surgery, resulted in fewer hysterectomies (vs. 9 per 1000 for ablation) but was associated with fewer quality-adjusted life-years gained per patient (vs. 3.80 and 3.88 for ablation and hysterectomy, respectively). Sensitivity analyses confirmed these results. CONCLUSIONS: LNG-IUS resulted in the lowest treatment costs and the fewest number of hysterectomies performed over 5 years compared with all other initial strategies and resulted in the most quality-adjusted life-years gained among nonsurgical options. Initial treatment with LNG-IUS is the least costly and most effective option for women desiring to preserve their fertility.

Lighting up RNA-specific multi-photon and super-resolution imaging using a novel zinc complex.

Ribonucleic acid (RNA) probes are critical for understanding the role of RNA dynamics in cellular function but are in short supply due to the lack of optimized imaging systems and excellent fluorescence emission performance. Here, the terpyridine Zn(II) complex (Zn-T) with D-π-A configuration and bright aggregation-induced fluorescence emission (AIE) has been fabricated for the selective detection and real-time monitoring of RNA. Impressively, Zn-T exhibits a large Stokes shift and three-photon absorption (3PA) activity and responds specifically through hydrophobic interactions with an RNA pocket. The combination of AIE-assisted two-photon fluorescence and stimulated emission depletion (STED) microscopy of Zn-T for imaging nuclear RNA has higher spatial resolution and brightness, thus providing an imaging platform for studying RNA-related physiological or pathological processes.

Maackiain inhibits proliferation and promotes apoptosis of nasopharyngeal carcinoma cells by inhibiting the MAPK/Ras signaling pathway.

Nasopharyngeal carcinoma (NPC) is the third most common malignancy with a high recurrence and metastasis rate in South China. Natural compounds extracted from traditional Chinese herbal medicines have been developed and utilized for the treatment of a variety of cancers with modest properties and slight side effects. Maackiain (MA) is a type of flavonoid that was first isolated from leguminous plants, and it has been reported to relieve various nervous system disorders and exert anti-allergic as well as anti-inflammatory effects. In this study, we demonstrated that MA inhibited proliferation, arrested cell cycle and induced apoptosis in nasopharyngeal carcinoma CNE1 and CNE2 cells in vitro and in vivo. The expression of the related proteins associated with these processes were consistent with the above effects. Moreover, transcriptome sequencing and subsequent Western blot experiments revealed that inhibition of the MAPK/Ras pathway may be responsible to the anti-tumor effect of MA on NPC cells. Therefore, the effects of MA and an activator of this pathway, tertiary butylhydroquinone (TBHQ), alone or combination, were investigated. The results showed TBHQ neutralized the inhibitory effects of MA. These data suggest that MA exerts its anti-tumor effect by inhibiting the MAPK/Ras signaling pathway and it has the potential to become a treatment for patients with NPC.

An Adaptive Image Segmentation Network for Surface Defect Detection.

Surface defect detection plays an essential role in industry, and it is challenging due to the following problems: 1) the similarity between defect and nondefect texture is very high, which eventually leads to recognition or classification errors and 2) the size of defects is tiny, which are much more difficult to be detected than larger ones. To address such problems, this article proposes an adaptive image segmentation network (AIS-Net) for pixelwise segmentation of surface defects. It consists of three main parts: multishuffle-block dilated convolution (MSDC), dual attention context guidance (DACG), and adaptive category prediction (ACP) modules, where MSDC is designed to merge the multiscale defect features for avoiding the loss of tiny defect feature caused by model depth, DACG is designed to capture more contextual information from the defect feature map for locating defect regions and obtaining clear segmentation boundaries, and ACP is used to make classification and regression for predicting defect categories. Experimental results show that the proposed AIS-Net is superior to the state-of-the-art approaches on four actual surface defect datasets (NEU-DET: 98.38% ± 0.03%, DAGM: 99.25% ± 0.02%, Magnetic-tile: 98.73% ± 0.13%, and MVTec: 99.72% ± 0.02%).

Host specificity and genetic diversity of Bartonella in rodents and shrews from Eastern China.

Bartonella are vector-borne gram-negative facultative intracellular bacteria causing emerging infectious diseases worldwide, and two thirds of known Bartonella species are carried by rodents. We captured rodents, shrews and rodent ectoparasitic mites in rural areas of Qingdao City, Shandong Province, China from 2012 to 2021 and used the animal spleen tissues for the PCR amplification of Bartonella gltA and rpoB genes. PCR showed 9.4% (40/425) rodents, and 5.1% (12/235) shrews were positive for Bartonella. Seven Bartonella species including three novel species were identified in five rodent species and one shrew species, indicating the abundance and genetic diversity of Bartonella in rodents and shrews. The infection rate of each Bartonella species in the animal species was as below: novel Candidatus Bartonella crocidura in shrews Crocidura lasiura (5.1%, 12/235); novel Candidatus Bartonella cricetuli in hamsters Tscherskia triton (20%, 9/45); novel Candidatus Bartonella muris in striped field mice Apodemus agrarius (4.2%, 7/168) and house mice Mus musculus (1.5%, 2/135); Bartonella fuyuanensis in striped field mice (8.9%, 15/168) and house mice (0.7%, 1/135); Bartonella rattimassiliensis and Bartonella tribocorum in brown rats Rattus norvegicus (6.7%, 3/45 and 4.2%, 2/45, respectively); Bartonella queenslandensis in Chinese white-bellied rat Niviventer confucianus (12.5%, 1/8). These results suggest that Bartonella infected a variety of rodent and shrew species with high infection rate, but each Bartonella specie is restricted to infect only one or a few genetically closely related rodent species. In addition, Candidatus Bartonella cricetuli, Candidatus Bartonella muris and Bartonella coopersplainsensis were found in chigger Walchia micropelta (33.3%, 3/9), and B. fuyuanensis were found in chigger Leptotrombidium intermedium (4.1%, 1/24), indicating chiggers may be reservoirs of Bartonella. In conclusion, abundant genetic diversified Bartonella species are found to infect rodents, shrews and chiggers, but each Bartonella species has a strict rodent animal host specificity; and chigger mites may play a role in Bartonella transmission.

SFTSV infection in rodents and their ectoparasitic chiggers.

SFTSV, a tick-borne bunyavirus causing a severe hemorrhagic fever termed as severe fever with thrombocytopenia syndrome (SFTS). To evaluate the potential role of rodents and its ectoparasitic chiggers in the transmission of SFTSV, we collected wild rodents and chiggers on their bodies from a rural area in Qingdao City, Shandong Province, China in September 2020. PCR amplification of the M and L segments of SFTSV showed that 32.3% (10/31) of rodents and 0.2% (1/564) of chiggers (Leptotrombidium deliense) from the rodents were positive to SFTSV. Our results suggested that rodents and chiggers may play an important role in the transmission of SFTSV, although the efficiency of chiggers to transmit SFTSV needs to be further investigated experimentally.

Bis-(ethanol-κO)bis(1-ferrocenyl-4,4,4-tri-fluoro-butane-1,3-dionato-κ2 O,O')nickel(II).

In the title compound, [NiFe2(C5H5)(C9H5F3O2)2(C2H6O)2], the central NiII ion is observed in an octa-hedral coordination environment. The chelating ß-diketonate ligands are substituted by ferrocene, a lipophilic organometallic moiety. The ferrocene groups have the normal geometry, with eclipsed cyclo-penta-diene rings. Coordinated ethanol mol-ecules are engaged in inter-molecular hydrogen bonds, and the crystal is further stabilized by weak C-H⋯F and C-H⋯π contacts.

SARS-CoV-2 ORF3a Induces Incomplete Autophagy via the Unfolded Protein Response.

In the past year and a half, SARS-CoV-2 has caused 240 million confirmed cases and 5 million deaths worldwide. Autophagy is a conserved process that either promotes or inhibits viral infections. Although coronaviruses are known to utilize the transport of autophagy-dependent vesicles for the viral life cycle, the underlying autophagy-inducing mechanisms remain largely unexplored. Using several autophagy-deficient cell lines and autophagy inhibitors, we demonstrated that SARS-CoV-2 ORF3a was able to induce incomplete autophagy in a FIP200/Beclin-1-dependent manner. Moreover, ORF3a was involved in the induction of the UPR (unfolded protein response), while the IRE1 and ATF6 pathways, but not the PERK pathway, were responsible for mediating the ORF3a-induced autophagy. These results identify the role of the UPR pathway in the ORF3a-induced classical autophagy process, which may provide us with a better understanding of SARS-CoV-2 and suggest new therapeutic modalities in the treatment of COVID-19.

Health care resource utilization and burden of disease in a U.S. Medicare population with a principal diagnosis of osteoarthritis of the knee.

AIMS: To assess the prevalence, health care resource utilization (HCRU), and economic burden of disease among Medicare beneficiaries with a principal diagnosis of osteoarthritis (OA) of the knee. MATERIALS AND METHODS: Patients with a principal diagnosis of knee OA were identified from the 5% noninstitutional sample file within 2009 and 2014 Medicare fee-for-service Limited Data Sets. A complete medical benefit record for each individual was generated by linking patient data across corresponding institutional claims from inpatient, outpatient, skilled nursing facility, and home health care services. The study revealed the prevalence and HCRU among Medicare knee OA patients, as well as the patient-level burden of disease by comparing HCRU and costs between knee OA patients and matched control patients. RESULTS: The prevalence of principal diagnosis of knee OA among Medicare beneficiaries increased from 5.9% in 2009 to 6.2% in 2014. Total disease-related claims for the knee OA population was approximately 8 million in 2009 and 9 million in 2014. The average Medicare reimbursement per claim was $12,085 in the inpatient setting, $5,563 in skilled nursing facilities, $2,742 in home health care, $264 in the outpatient setting and $147 in noninstitutional office visits in 2014. Overall, the average total expense per knee OA patient in 2014 was $15,558, an increase of $5,364 compared to the matched control patient. CONCLUSIONS: Many Medicare beneficiaries received care for knee OA, and these patients had significantly greater HCRU than those with the absence of knee OA, totaling over $34 billion in healthcare expenditures in 2014.

Ten-year Medicare budget impact of increased coverage for anti-obesity intervention.

Aims: To estimate the long-term budget impact of expanding Medicare coverage of anti-obesity interventions among adults aged 65 and older in the US. Materials and methods: This study analyzed a representative sample of Medicare beneficiaries from the combined 2008-2016 National Health and Nutrition Examination Surveys. Population characteristics, cost and effectiveness of anti-obesity interventions, and the sustainability of weight loss in real-life were modeled to project the budgetary impact on gross Medicare outlay over 10 years. Hypothetical scenarios of 50% and 67% increases in intervention participation above base case were used to model moderate and extensive Medicare coverage expansion of intensive behavior therapy and pharmacotherapy. Results: For each Medicare beneficiary receiving anti-obesity treatment, we estimate Medicare savings of $6,842 and $7,155 over 10 years under moderate and extensive coverage utilization assumptions, respectively. The average cost of intervention is $1,798 and $1,886 per treated participant. Taking the entire Medicare population (treated and untreated) into consideration, the estimated 10-year budget savings per beneficiary are $308 and $339 under moderate and extensive assumptions, respectively. Sensitivity analysis of drug adherence rate and weight-loss efficacy indicated a potential variation of budget savings within 7% and 22% of the base case, respectively. Most of the projected cost savings come from lower utilization of ambulatory services and prescription drugs. Limitations: Due to the scarcity of studies on the efficacy of pharmacotherapy among older adults with obesity, the simulated weight loss and long-term maintenance effects were derived from clinical trial outcomes, in which older adults were mostly excluded from participation. The model did not include potential side-effects from anti-obesity medications and associated costs. Conclusions: This analysis suggests that expanding coverage of anti-obesity interventions to eligible individuals could generate $20-$23 billion budgetary savings to Medicare over 10 years.

Where can obesity management policy make the largest impact? Evaluating sub-populations through a microsimulation approach.

BACKGROUND: There is a critical need to focus limited resources on sub-groups of patients with obesity where we expect the largest return on investment. This paper identifies patient sub-groups where an investment may result in larger positive economic and health outcomes. METHODS: The baseline population with obesity was derived from a public survey database and divided into sub-populations defined by demographics and disease status. In 2016, a validated model was used to simulate the incidence of diabetes, absenteeism, and direct medical cost in five care settings. Research findings were derived from the difference in population outcomes with and without weight loss over 15 years. Modeled weight loss scenarios included initial 5% or 12% reduction in body mass index followed by a gradual weight regain. Additional simulations were conducted to show alternative outcomes from different time courses and maintenance scenarios. RESULTS: Univariate analyses showed that age 45-64, pre-diabetes, female, or obesity class III are independently predictive of larger savings. After considering the correlation between these factors, multivariate analyses projected young females with obesity class I as the optimal sub-group to control obesity-related medical expenditures. In contrast, the population aged 20-35 with obesity class III will yield the best health outcomes. Also, the sub-group aged 45-54 with obesity class I will produce the biggest productivity improvement. Each additional year of weight loss maintained showed increased financial benefits. CONCLUSIONS: This paper studied the heterogeneity between many sub-populations affected by obesity and recommended different priorities for decision-makers in economic, productivity, and health realms.

RNA sequencing provides insights into the evolution of lettuce and the regulation of flavonoid biosynthesis.

Different horticultural types of lettuce exhibit tremendous morphological variation. However, the molecular basis for domestication and divergence among the different horticultural types of lettuce remains unknown. Here, we report the RNA sequencing of 240 lettuce accessions sampled from the major horticultural types and wild relatives, generating 1.1 million single-nucleotide polymorphisms (SNPs). Demographic modeling indicates that there was a single domestication event for lettuce. We identify a list of regions as putative selective sweeps that occurred during domestication and divergence, respectively. Genome-wide association studies (GWAS) identify 5311 expression quantitative trait loci (eQTL) regulating the expression of 4105 genes, including nine eQTLs regulating genes associated with flavonoid biosynthesis. GWAS for leaf color detects six candidate loci responsible for the variation of anthocyanins in lettuce leaves. Our study provides a comprehensive understanding of the domestication and the accumulation of anthocyanins in lettuce, and will facilitate the breeding of cultivars with improved nutritional value.

The cost-effectiveness of delayed-release dimethyl fumarate for the treatment of relapsing-remitting multiple sclerosis in Canada.

BACKGROUND: Multiple sclerosis (MS) causes significant disability and diminished quality-of-life. Delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) is a new oral treatment for relapsing-remitting MS (RRMS) approved in the US, Australia, Canada, and Europe. OBJECTIVES: A cost-effectiveness model was developed to compare the health economic impact of DMF against other disease-modifying therapies (DMTs) as first-line RRMS treatment from a Canadian Ministry of Health perspective. METHODS: A Markov cohort model was developed to simulate patients' progression through health states based on the Kurtzke Expanded Disability Status Scale (EDSS) over a life-time horizon. Patients entered the model based on a distribution of baseline EDSS scores, from which they could progress to higher or regress to lower EDSS state, or remain in the same state. Relapses could occur at any EDSS score. Results from a mixed-treatment comparison were used to inform model inputs for disease progression and relapse rates per treatment. Costs included direct medical costs stratified by EDSS score. Utilities were accrued based on time spent in each EDSS state. RESULTS: Compared with glatiramer acetate, DMF yielded 0.528 incremental quality-adjusted life-years (QALYs) at an incremental cost of $23 338 Canadian dollars (CAD), resulting in an incremental cost-effectiveness ratio (ICER) of CAD $44 118/QALY. The ICER for DMF compared with Rebif 44 mcg was CAD $10 672. Results were consistent across a wide range of one-way and probabilistic sensitivity analyses. CONCLUSIONS: Based on traditional cost-effectiveness thresholds in Canada (CAD $50 000-60 000), DMF can be considered a cost-effective option compared to other first-line DMTs.