5-hydroxytryptophan attenuates imiquimod-induced psoriasiform dermatitis probably through inhibition of IL-17A production and keratinocyte activation.

Psoriasis is a chronic autoimmune disease with keratinocyte activation and lymphocyte infiltration in the skin. Our previous study found that 5-hydroxytryptophan (5(OH)Trp), a tryptophan metabolite, alleviated collagen-induced arthritis and suppressed cytokine production. In this study, we evaluated the effects of 5(OH)Trp in a mouse model for psoriasiform dermatitis, induced by imiquimod (IMQ). We showed that 5(OH)Trp significantly reduced the cumulative scores, epidermal thickness and ki-67 expression in the skin. In addition, 5(OH)Trp decreased local and systemic inflammation. Moreover, 5(OH)Trp significantly inhibited keratinocyte activation with decrease in IL-6 production and p-Erk1/2 and p-STAT3 expression. 5(OH)Trp also inhibited the differentiation of IFN-γ- and IL-17A-expressing CD4+ T cells and related cytokine production (TNF-α, IL-6, IL-17A and IFN-γ) in splenocytes. In conclusion, 5(OH)Trp can inhibit imiquimod-induced psoriasiform dermatitis in mice and inhibit activation in keratinocytes and splenocytes.

Incidence of sicca syndrome is 3.6 fold higher in areas with farm soils high in chromium and nickel.

BACKGROUND/PURPOSE: Chromium and nickel are important soil pollutants in Taiwan. Previously, we showed that blood chromium levels correlated strongly with soil chromium levels. Our observation that many patients with dry eyes or a dry mouth came from areas where soils contain high chromium levels prompted us to investigate whether incidence and prevalence of SS are higher in areas where soils contain high levels of heavy metals. METHODS: We used a database from national health insurance (NHI) to study the epidemiology of SS. It was ascertained by at least 3 hospital visits with the diagnosis within 12 months. We then compared the results with the information about heavy metal contents in farm soils. RESULTS: The incidence of SS was significantly increased (3.6 fold) in the areas where soils contained high levels of chromium and nickel. In contrast, lead, copper, or arsenic did not show such a strong association. CONCLUSION: Both the prevalence and incidence of SS are significantly increased in areas where soils contain high levels of chromium and nickel. Whether heavy metal, particularly chromium or nickel is a novel environmental risk factor for sicca syndrome needs more studies to confirm.

Bayesian depth estimation from monocular natural images.

Estimating an accurate and naturalistic dense depth map from a single monocular photographic image is a difficult problem. Nevertheless, human observers have little difficulty understanding the depth structure implied by photographs. Two-dimensional (2D) images of the real-world environment contain significant statistical information regarding the three-dimensional (3D) structure of the world that the vision system likely exploits to compute perceived depth, monocularly as well as binocularly. Toward understanding how this might be accomplished, we propose a Bayesian model of monocular depth computation that recovers detailed 3D scene structures by extracting reliable, robust, depth-sensitive statistical features from single natural images. These features are derived using well-accepted univariate natural scene statistics (NSS) models and recent bivariate/correlation NSS models that describe the relationships between 2D photographic images and their associated depth maps. This is accomplished by building a dictionary of canonical local depth patterns from which NSS features are extracted as prior information. The dictionary is used to create a multivariate Gaussian mixture (MGM) likelihood model that associates local image features with depth patterns. A simple Bayesian predictor is then used to form spatial depth estimates. The depth results produced by the model, despite its simplicity, correlate well with ground-truth depths measured by a current-generation terrestrial light detection and ranging (LIDAR) scanner. Such a strong form of statistical depth information could be used by the visual system when creating overall estimated depth maps incorporating stereopsis, accommodation, and other conditions. Indeed, even in isolation, the Bayesian predictor delivers depth estimates that are competitive with state-of-the-art "computer vision" methods that utilize highly engineered image features and sophisticated machine learning algorithms.

Increased inflammation in rheumatoid arthritis patients living where farm soils contain high levels of copper.

BACKGROUND/PURPOSE: Heavy metal pollution in farm soils is a problem in some parts of Taiwan. Copper can be a factor associated with increased disease activities of rheumatoid arthritis (RA). Thus, the aim of this study was to investigate whether copper pollution in farm soils is associated with worsened RA. METHODS: Clinical parameters from 122 RA patients were collected from a medical center in central Taiwan. Levels of heavy metals in the blood were measured using inductively coupled plasma mass spectrometry. Levels of copper in farm soils were retrieved from a national survey. These data were analyzed to find the factors related to RA disease activities. RESULTS: RA patients living where farm soils contained high levels of copper had increased white blood cell counts, erythrocyte sedimentation rate, and disease activity score 28, compared with patients living where copper levels were low. Among the nine types of heavy metal measured in the study, blood levels of copper and nickel correlated with erythrocyte sedimentation rate. CONCLUSION: Our cross-sectional data suggest a correlation between RA disease activity and the level of copper at township farm soils samples. Further longitudinal studies using more rigorous methodologies are warranted to examine whether this correlation is causal.

Reduction in arsenic intake from water has different impacts on lung cancer and bladder cancer in an arseniasis endemic area in Taiwan.

BACKGROUND: Excessive arsenic intake has a detrimental effect on human health, as reflected in an increase in cancer incidence. In an area on the southwest coast of Taiwan, arsenic intake from well water since the 1920s had caused an exceptionally high mortality from cancer. Municipal water has become available to people living in the arseniasis endemic area since the early 1970s. This study explored the impacts of reduction in arsenic intake from water on lung cancer and bladder cancer in the arseniasis endemic area in Taiwan. METHODS: Chart records of 23,013 patients diagnosed with bladder cancer and 93,633 patients with lung cancer from 1979 to 2003 were retrieved from the Taiwan Cancer Registry Center. We used the age-period-cohort model to study the changes in the incidence of lung cancer and bladder cancer in the arseniasis endemic area and the rest of Taiwan. RESULTS: Three decades after municipal water supply to the arseniasis and black foot disease endemic area (BFDEA), we saw a marked decrease in the incidence of both bladder cancer and lung cancer in the area, especially for those in the later cohorts. The relative risk (RR) of getting a bladder cancer for people living in BFDEA when compared with those in the rest of Taiwan has dropped from 20 for the early cohorts to 5 for the late cohorts. As to lung cancer, the RR has decreased from 8 to between 1.5 and 2. CONCLUSION: Reduction in arsenic intake from water has a positive impact on the incidence of both lung and bladder cancer; however, while RR for lung cancer has dropped to below 2, RR for bladder cancer remained at around 5. The difference may be because (1) there are other risk factors beside the well-water intake or (2) bladder cancer may have longer latency period for excessive arsenic exposure than lung cancer. More studies are required to understand the causes behind the difference in RR for these two types of cancer.

A critical exploration of blood and environmental chromium concentration among oral cancer patients in an oral cancer prevalent area of Taiwan.

The growing incidence of oral cancer (OC) in Taiwan has become a crucial public health concern. In particular, Changhua, a county in central Taiwan, carries persistently high OC incidence rate, with an alarmingly high male/female ratio of OC incidence. Previous epidemiological studies had found that the incidence is spatially correlated with the level of soil content to certain heavy metals in the central Taiwan area. Soil and the human body both intake environmental heavy metals, which can be absorbed through various ways. The soil metal concentration is an index of possible environmental exposure to heavy metal, and the blood metal concentration somewhat reflects the level of the exposure on the human body. Metallic carcinogen is likely to generate free radicals and play a role in many cancers, and many studies had reported that environmental exposure to heavy metals is an important risk factor for developing cancer. Studies on animals showed that chronic intake of chromium (Cr) could induce OC. This study aims to explore the association between the Cr concentration in the farm soil and in the blood of OC patients. We recruited 79 OC patients from Changhua County, with their lifestyle being adjusted in regression analysis. The results showed that the Cr concentration in the blood of OC patients is significantly higher than the background value, and is positively associated with the Cr concentration in the soil surrounding their residence (p-value < 0.023). Because Changhua County is only with moderate prevalence of the known OC habitual risk factors, an environmental factor related to heavy metal Cr exposure is suspected. Future investigations may verify the causal relation between Cr and OC.

Increased prevalence of Parkinson's disease in soils with high arsenic levels.

INTRODUCTION: Exposure to arsenic (As)-containing pesticides was associated with an increased risk for Parkinson's disease (PD). Arsenic also induced in murine brains α-synuclein aggregates, a pathognomic feature of PD. OBJECTIVES: People living on farms irrigated with high As water in Taiwan are likely exposed to increased As. We addressed whether increased farm soil As levels correlate with an increased PD risk. METHODS: We used the information from several national surveys (1983-1986) on soil metal contents to study the relationships between soil metal contents and PD prevalence in Taiwan. PD prevalence (2009-2013) was calculated with a database from Taiwan's compulsory national health insurance. A patient is defined by a PD diagnosis and prescriptions of Levodopa in three or more office visits in twelve months. We used regression models to study the correlation between PD prevalence and soil metal contents. RESULTS: The PD prevalence ranged from 83 to 213 per one hundred thousand persons in different regions of Taiwan. Among the studied heavy metals, we found only As was significantly associated with the PD prevalence. The top three regions (Yunlin, Chiayi, Tainan) in the PD prevalence list correspond exactly with the top three in soil As levels. Soil As levels and PD prevalence had a strong correlation (r = 0.75). CONCLUSION: PD prevalence is statistically correlated with farm soil As levels in Taiwan.

Incidence of oral cancer in relation to nickel and arsenic concentrations in farm soils of patients' residential areas in Taiwan.

BACKGROUND: To explore if exposures to specific heavy metals in the environment is a new risk factor of oral cancer, one of the fastest growing malignancies in Taiwan, in addition to the two established risk factors, cigarette smoking and betel quid chewing. METHODS: This is an observational study utilized the age-standardized incidence rates of oral cancer in the 316 townships and precincts of Taiwan, local prevalence rates of cigarette smoking and betel quid chewing, demographic factors, socio-economic conditions, and concentrations in farm soils of the eight kinds of heavy metal. Spatial regression and GIS (Geographic Information System) were used. The registration contained 22,083 patients, who were diagnosed with oral cancer between 1982 and 2002. The concentrations of metal in the soils were retrieved from a nation-wide survey in the 1980s. RESULTS: The incidence rate of oral cancer is geographically related to the concentrations of arsenic and nickel in the patients' residential areas, with the prevalence of cigarette smoking and betel quid chewing as controlled variables. CONCLUSIONS: Beside the two established risk factors, cigarette smoking and betel quid chewing, arsenic and nickel in farm soils may be new risk factors for oral cancer. These two kinds of metal may involve in the development of oral cancer. Further studies are required to understand the pathways via which metal in the farm soils exerts its effects on human health.

Increased prevalence of Sjogren's syndrome in where soils contain high levels of chromium.

Previously, we showed that farm soil levels of chromium were strongly correlated with people's serum chromium levels and an increase (3.6 fold) in both the incidence and prevalence of sicca syndrome in areas where farm soil chromium was high. Because Sjogren's syndrome (SS) is the major disease causing a dry mouth and dry eyes, we aimed in the study to investigate whether these areas with high soil chromium have a high SS prevalence. We used a database from the authority in charge of catastrophic illness certificates. Heavy metal concentrations in farm soils were retrieved from nationwide surveys. We used spatial regression models to study the relationships between the SS prevalence and soil metal concentrations. There were 11,220 people, 1165 men and 10,055 women who received a SS certificate from 2000 to 2011. The SS prevalence was 31 per 105 people, 5.59 for men and 55.01 for women. The highest SS prevalence in Taiwan (53 per 105) was located in an area where farm soils contain the highest amounts of chromium. In contrast, other types of heavy metal did not show such a strong association. In conclusion, the SS prevalence is significantly increased in areas where soils contain high levels of chromium. Chromium is likely a risk for SS.

Tetrathiomolybdate, a copper chelator inhibited imiquimod-induced skin inflammation in mice.

BACKGROUND: Copper is an essential metal for maintenance of many biological functions; however, excessive amount can induce inflammation and oxidative stress. Tetrathiomolybdate (TM) is a copper chelator for treatment of Wilson's disease, and decreased the severity of autoimmune arthritis in mice. OBJECTIVE: In this report, we evaluated the effects of TM in a mouse model for psoriasis. METHODS: Imiquimod-induced psoriasis murine model was used. We applied immunohistochemistry staining and ELISA to determine levels of cytokines in the inflamed skin, splenocytes, and draining lymph nodes. In addition, we used keratinocytes and splenocytes to test the inhibitory effects of TM on cytokine production and activation of transcription factors. RESULTS: Our results showed that TM significantly reduced cumulative scores, epidermis thickness, and ki-67 expression in the inflamed skin. In addition, TM decreased skin cytokine levels and systemic inflammation. Moreover, TM suppressed activation in keratinocytes and splenocytes with reduction in phosphorylation of Erk1/2 and STAT3. CONCLUSION: These findings are strong evidence that TM can inhibit psoriasis in the model.

Distinctive features of oral cancer in Changhua County: high incidence, buccal mucosa preponderance, and a close relation to betel quid chewing habit.

BACKGROUND/PURPOSE: Oral cancer is one of the fastest increasing malignancies in Taiwan. Among the counties on the island, Changhua has been ranked in the top three in the list of oral cancer incidence. This study was performed to better characterize the epidemiology of oral cancer in Changhua county. METHODS: We used the complete registered records of oral cancer from the Department of Health databank, and studied the trends in incidence rate, age of distribution, and anatomic sites of oral cancer in Taiwan. In addition, we correlated the incidence rate with known risk factors (betel quid chewing, smoking, and alcohol drinking) by regression analysis. RESULTS: Among neoplasms, oral cancer is one of the fastest increasing malignancies in Taiwan. In the past two decades from 1982 to 2001, Taiwan had an alarming 5.3-fold increase in the incidence of male oral cancer. Among the 23 counties, Changhua has ranked top in oral cancer incidence in recent years. The incidence of male oral cancer in Changhua is also among the highest in the world (45.07/105/year in 2001). The most common site was the buccal mucosa, while it was the tongue in other counties. Finally, Changhua was the only outlier in our regression model, indicating that possible interference factors may interact with oral cancer incidence and prevalence of betel quid chewing in Changhua. CONCLUSION: We conclude that the high incidence and buccal mucosa preponderance of oral cancer in Changhua may have an exceptionally close relation with patients' betel quid chewing habit, and other unknown etiologic factors may also be present locally.

Environmental heavy metal as a potential risk factor for the progression of oral potentially malignant disorders in central Taiwan.

OBJECTIVE: Oral cancer (OC) is a leading cause of death from cancer in men between the ages of 25 and 44 years in Taiwan. The overall 5-year survival rates for the four OC stages (I-IV) in Taiwan are approximately 70%, 30%, 20%, and 10%, respectively, indicating the importance of the early diagnosis of oral potentially malignant disorders (OPMDs). Previous studies indicated an association between the OC incidence and certain environmental heavy metal concentrations. If these associations do exist for OC, they may also be observed for OPMD. The purpose of this study is to explore the association between the development of OPMD to OC and environmental heavy metals. Oral submucous fibrosis (OSF) and oral leukoplakia (OL) are two major types of OPMD in Taiwan. MATERIALS AND METHODS: A retrospective cohort study was conducted by Changhua Christian Hospital, the sole medical center in Changhua County, where 2725 male adult patients diagnosed with either OSF or OL between 2000 and 2014 were recruited. Data were analyzed by Cox regression and adjusted for smoking and betel-quid chewing. RESULTS AND DISCUSSION: OPMD patients who resided in areas with high nickel concentrations (polluted levels) exhibited hazard ratios of 1.8-2 for OC relative to those who lived in areas with low nickel levels (P<0.01). Meanwhile, smokers with OPMDs had a hazard ratio of 2.8-2.9 relative to non-smokers. Betel-quid chewers had a 2.2-2.3 hazard ratio relative to non-chewers. Smoking, betel-quid chewing, and environmental nickel exposure are associated with an increased risk of OC development in OPMD patients. This study provides valuable findings on the environmental effects of heavy metals on human health. Enhanced surveillance of the condition of OPMD patients who have been exposed to high nickel concentrations may be crucial for OC prevention.

Cordycepin and a preparation from Cordyceps militaris inhibit malignant transformation and proliferation by decreasing EGFR and IL-17RA signaling in a murine oral cancer model.

Cordyceps militaris (CM) and its active ingredient cordycepin have been reported to inhibit tumor growth, but the mechanisms are not fully understood. This study used a mouse model for oral cancer and a cell line, 4NAOC-1 derived from the model to study the mechanisms. Our results show that a CM preparation (CMP) can significantly inhibit tumor development and malignant transformation in the model. In vitro data indicate that CMP and cordycepin can inhibit 4NAOC-1 cell proliferation, either anchorage-dependent or -independent. Cordycepin can also increase cell apoptosis, and decrease cell mitosis and EGFR signaling. In accordance, CMP treatment can significantly decrease the levels of ki-67 and EGFR signaling molecules in cancer tissues. We also found that the levels of IL-17A in cancer tissues of control mice were significantly increased, and CMP inhibited these levels. IL-17A can stimulate cancer cell proliferation, which can be suppressed by cordycepin. Furthermore, cordycepin can reduce the expression of IL-17RA and its downstream signaling molecules. Moreover, CMP and cordycepin can significantly decrease IL-17A production in vitro and in vivo. Finally, CMP and its ingredients can enhance tumoricidal activities with increase in IFN-γ and TNFα, and decrease PD-L1 expression. In conclusion, CMP and its ingredient cordycepin can inhibit tumor growth and malignant transformation in a mouse model for oral cancer via inhibition of EGFR- and IL-17RA-signaling and enhancement of anti-tumor immunity.

CD30 is involved in inhibition of T-cell proliferation by Hodgkin's Reed-Sternberg cells.

CD30 is expressed on Hodgkin's Reed-Sternberg (H-RS) cells, the tumor cells in Hodgkin's disease. Increased levels of serum CD30 are observed in Hodgkin's disease patients and are a good marker for predicting a poor prognosis and a poor response to therapy. In this study, we addressed the effect of CD30 on T cells. We showed that CD30, either as a membranous protein on H-RS cells and Chinese hamster ovary cells or as a plate-bound chimeric protein, inhibited T-cell proliferation. Anti-CD3-stimulated T cells in the presence of CD30 failed to increase tritium uptake and failed to express CD25 and CD26 and to produce interleukin 2. The inhibition of T-cell proliferation was, however, reversed with addition of exogenous interleukin 2 or pretreatment of H-RS cells with anti-CD30. Inability of T cells to express CD25 and CD26 in cocultures with H-RS cells or a plate-bound CD30 chimeric protein is in accordance with the results of immunohistochemistry on disease-involved tissues. We conclude that H-RS cells are able to inhibit the proliferation and activation of T cells through CD30-related interaction. The outcome of CD30-related interaction is an ineffective antitumor immunity, which is clearly in favor of the growth and survival of the tumor cells.

Increased Prevalence of Esophageal Cancer in Areas with High Levels of Nickel in Farm Soils.

Background: Heavy metal pollution in farm soils is a grave concern in Taiwan. Previously, we found the incidence of oral cancer (OC) correlated positively with levels of nickel and arsenic in farm soils. Many OC patients have a second malignancy, among which esophageal cancer (EC) is the most common one in Taiwan. Objectives: We aimed to investigate whether these two cancers share some common risk factors. Methods: Taiwan began a compulsory national health insurance program in 1995. We used a database from this program to calculate the prevalence of EC and OC in Taiwan. We compared the prevalence of EC with prevalence of betel nut chewers in adults and the information of heavy metal in farm soils to look for any association. Results: The prevalence of OC and prevalence of EC were strongly correlated. The prevalence of betel nut chewing correlated with OC prevalence, but not with EC prevalence. An increased prevalence (1.9 fold) of EC was found where the farm soils contained high levels of nickel. Meanwhile, among the eight heavy metals studied, only the levels of nickel in the farm soils correlated statistically with the prevalence of EC. Conclusion: Nickel is probably a common environmental risk factor for esophageal cancer and oral cancer.

Supplement of 5-hydroxytryptophan before induction suppresses inflammation and collagen-induced arthritis.

BACKGROUND: Evidence is accumulating that a preclinical phase is present before the onset of clinical signs and symptoms of rheumatoid arthritis (RA). This phase represents an important therapeutic window within which interventions can dramatically modulate outcomes. An agent able to prevent RA for high risk individuals in this phase is therefore desired. In this study, we investigated whether tryptophan metabolite, 5-hydroxytryptophan (5-HTP) or 5-methoxytryptophan (5-MTP), can act as such an agent for primary prevention of collagen-induced arthritis (CIA). METHODS: Mouse splenocytes were pretreated with 5-HTP or 5-MTP and activated by anti-CD3 plus anti-CD28 antibodies in vitro. The percentages of interferon-γ (IFNγ)(+)CD4(+) T cells and interleukin-17 (IL-17)(+)CD4(+) T cells were measured by flow cytometry. The production of pro-inflammatory cytokines, serotonin and kynurenine was measured by enzyme-linked immunosorbent assay. A CIA model was used to investigate the in vivo effects of 5-HTP on the prevention of arthritis. RESULTS: 5-HTP decreased the percentages of IFNγ(+)CD4(+) T cells and IL-17(+)CD4(+) T cells and suppressed the production of IL-2, IL-4, IL-6, IL-17, tumor necrosis factor-α (TNFα) and IFNγ in activated splenocytes. 5-HTP administered before induction decreased the disease activities in CIA mice and suppressed the production of TNFα, IL-6 and cyclooxygenase-2 in arthritic joints. 5-HTP also increased serotonin, but decreased kynurenine in the CIA mice. CONCLUSIONS: 5-HTP suppresses inflammation and arthritis through decreasing the production of pro-inflammatory mediators. 5-HTP supplement before induction ameliorates arthritis in a CIA model.

Oriented correlation models of distorted natural images with application to natural stereopair quality evaluation.

In recent years, bandpass statistical models of natural, photographic images of the world have been used with great success to solve highly diverse problems involving image representation, image repair, image quality assessment (IQA), and image compression. One missing element has been a reliable and generic model of spatial image correlation that reflects the distributions of oriented and relatively oriented spatial structures. We have developed such a model for bandpass pristine images and have generalized it here to also capture the spatial correlation structure of bandpass distorted images. The model applies well to both luminance and depth images. As a demonstration of the usefulness of the generalized model, we develop a new no-reference stereoscopic/3D IQA framework, dubbed stereoscopic/3D blind image naturalness quality index, which utilizes both univariate and generalized bivariate natural scene statistics (NSS) models. We first validate the robustness and effectiveness of these novel bivariate and correlation NSS features extracted from distorted stereopairs, then demonstrate that they are predictive of distortion severity. Our experimental results show that the resulting 3D image quality predictor based in part on the new model outperforms state-of-the-art full- and no-reference 3D IQA algorithms on both symmetrically and asymmetrically distorted stereoscopic image pairs.

Color and depth priors in natural images.

Natural scene statistics have played an increasingly important role in both our understanding of the function and evolution of the human vision system, and in the development of modern image processing applications. Because range (egocentric distance) is arguably the most important thing a visual system must compute (from an evolutionary perspective), the joint statistics between image information (color and luminance) and range information are of particular interest. It seems obvious that where there is a depth discontinuity, there must be a higher probability of a brightness or color discontinuity too. This is true, but the more interesting case is in the other direction--because image information is much more easily computed than range information, the key conditional probabilities are those of finding a range discontinuity given an image discontinuity. Here, the intuition is much weaker; the plethora of shadows and textures in the natural environment imply that many image discontinuities must exist without corresponding changes in range. In this paper, we extend previous work in two ways--we use as our starting point a very high quality data set of coregistered color and range values collected specifically for this purpose, and we evaluate the statistics of perceptually relevant chromatic information in addition to luminance, range, and binocular disparity information. The most fundamental finding is that the probabilities of finding range changes do in fact depend in a useful and systematic way on color and luminance changes; larger range changes are associated with larger image changes. Second, we are able to parametrically model the prior marginal and conditional distributions of luminance, color, range, and (computed) binocular disparity. Finally, we provide a proof of principle that this information is useful by showing that our distribution models improve the performance of a Bayesian stereo algorithm on an independent set of input images. To summarize, we show that there is useful information about range in very low-level luminance and color information. To a system sensitive to this statistical information, it amounts to an additional (and only recently appreciated) depth cue, and one that is trivial to compute from the image data. We are confident that this information is robust, in that we go to great effort and expense to collect very high quality raw data. Finally, we demonstrate the practical utility of these findings by using them to improve the performance of a Bayesian stereo algorithm.

Progression of precancerous lesions to oral cancer: results based on the Taiwan National Health Insurance Database.

BACKGROUND: Oral cancer (OC) is the leading cause of death from cancer in men between the ages of 25 and 44 in Taiwan. The survival rate for the last stage of OC is <20% while that for the earliest stage is >75%, which suggests the importance of the diagnosis of oral precancerous lesions (OPLs) in reducing OC mortality. The aim of this study was to analyze the time to OC event after OPL diagnosis, and to suggest the surveillance period necessary according to OPL type. MATERIALS AND METHODS: This was a retrospective cohort study based on 1.0 million people randomly selected from the Taiwan National Health Insurance Database, which provided data on 3058 adult male patients aged ≥20 years who were diagnosed with OPL for the first time between 1996 and 2009. The patient population was divided into two groups according to the type of lesion: oral submucous fibrosis (OSF) or oral leukoplakia (OLE). Age-standardized incidence rate (ASIR) and hazards rate (HR) were then estimated. RESULTS: The ASIR for OPL showed an increasing trend over the study period, the main contributor to this being OSF. The OSF group demonstrated a higher OC incidence rate than the OLE group. CONCLUSION: Patients with both OLE and OSF carry a higher risk for OC than those with either OLE or OSF alone, and they may also experience malignant transformation at an earlier date (mostly within 5 years). The 5- and 10-year OC rate for both OLE and OSF was found to be 5% and around 10%, respectively. However, 10 years after the diagnosis of OPL, OSF carries a higher risk of developing into OC than OLE.

Risk of diabetes in patients with rheumatoid arthritis: a 12-year retrospective cohort study.

OBJECTIVE: The incidence of type 2 diabetes (T2D) in adults with rheumatoid arthritis (RA) was investigated, and the results were compared with non-RA controls to confirm whether RA is a risk factor for diabetes mellitus (DM) in Taiwan. METHODS: We used a databank of 1 million individuals randomly selected from 23 million Taiwanese citizens covered by the National Health Insurance plan in 2005. All persons older than age 20 years in 1998 and not diagnosed with either RA or T2D before 1998 were included. They were divided into 2 cohorts, 1 with RA and the other without. Those who had T2D before RA were excluded. Each patient in the RA cohort was followed from the RA diagnosis until the end of 2009, or until dropping out of the insurance coverage. RA was ascertained by at least 3 visits using ICD-9 code 714.0, plus at least 2 visits with prescription of antirheumatic drugs in a period of 12 months. T2D was ascertained by at least 3 visits with diabetes codes within 1 year, while hypertension (HTN) and disorders of lipid metabolism (DLM) were determined by at least 3 visits using corresponding ICD codes during the study period. Kaplan-Meier plots, log-rank tests, and Cox regression were used to study the effects of age, sex, glucocorticoid use, HTN, DLM, and RA on T2D risk. RESULTS: The subjects include 600,695 adults. Of these, 4193 were diagnosed with RA, and among them 799 were diagnosed with T2D. The RA to non-RA risk ratio for T2D was 1.68 (95% CI 1.53-1.84) in men and 1.46 (95% CI 1.39-1.54) in women. CONCLUSION: RA appears to be associated with an increased risk for T2D in Taiwan.