There is a heated debate on whether the prognostic value of SPARC is favorable or unfavorable. Thus, we carried out a meta-analysis evaluating the relationship between SPARC expression and the prognosis of patients with pancreatic cancer.We searched PubMed, EMBASE and Web of Science for relevant articles. The pooled hazard ratios (HRs) and corresponding 95%CI of overall survival (OS) were calculated to evaluate the prognostic value of SPARC expression in patients with pancreatic cancer. We also performed subgroup analyses.With 1623 patients pooled from 10 available studies, the incorporative HR showed an unfavorable prognosis of patients with pancreatic cancer in the multivariate analysis , but not in univariate analysis  and estimate . And this adverse impact could also be found in the subgroup analyses in multivariate analysis, especially in the stroma . However, the combined HR had the highly significant heterogeneity. No obvious publication bias was found.SPARC might be an unfavorable indicator in patients with pancreatic cancer, especially in the stroma. More and further researches should be conducted to reveal the prognostic value of SPARC. In spite of the advanced resection and chemoradiotherapy, pancreatic cancer, with the worst prognosis, has become a global challenge. And conSecreted protein acidic and rich in cysteine (SPARC), also termed osteonectin or BM-40, one of the eight members of the SPARC family, which are invovled in human development and disease–7.In human carcinogenesis, SPARC plays remarkable roles in altering the activity and the microenvironment of cancer cells, modulating cell growth, apoptosis, adhesion migration and invasion, regulating ECM and the activity of matrix metalloproteinases,8. HenceIn view of the heated controversy of SPARC, a systematic review of the available articles with meta-analysis is urgent to be performed to evaluate the prognostic value of SPARC in pancreatic cancer.We performed systematic literature search of Pubmed, EMBASE and Web of Science from their incipiency to August, 2015. The retrieval strategy was used as follow: (SPARC or "Secreted protein acidic and rich in cysteines" or osteonectin or BM-40) AND (pancreatic or pancreas*) AND (cancer or tumor or tumour or neoplasm or carcinoma or adenocarcinoma) AND . Reference lists of articles and reviews were hand-searched for additional studies. Manuscripts were also manually scanned to obtain potential articles most relevant to this review. Only studies published in peer reviewed journals were included. All articles were written in English. All the initially identified articles were scrutinized independently by two reviewers (Han W and Cao F). There was no protocol developed for this review.To be eligible for inclusion, the following criteria had to be fulfilled: (a) clinical studies researched patients with pancreatic cancer; (b) SPARC expression in pancreatic cancer was measured with methods such as immunohistochemistry (IHC) or Quantitative real-time polymerase chain reaction (qRT-PCR); (c) studies reported the association between SPARC expression and survival outcome; (d) studies contained HRs and 95% CI for OS according to SPARC status which either were reported or could be estimated from the relevant published data; (e) onlExclusion criteria were: (a) literature published as letters, editorials, abstracts, reviews, case reports and expert opinions; (b) experiment in vitro or in vivo but not based on patients; (c) articles without the HRs with 95% CI about overall survival, or the K-M survival curves; (d) repeated and similar studies.The following information from each article was extracted: (a) general information, including first author, publication year, country (area) of origin, age and gender of the study patients, sample size and the follow-up duration; (b) method to determine SPARC expression and number of patients stratified by SPARC expression; (c) clinical outcomes, including OS or DFS and its correlative HRs with 95%CI. When an article only had K-M curves,we used Engauge Digitizer, a digitizing program, that could translate curves into numbers to extract survival data from its curves, and then put the data into a spreadsheet, called Tierney table, by which the estimated HR and corresponding 95%CI were calculated immediately.The two independent reviewers (Han W and Cao F) assessed the quality of each study with the Newcastle-Ottawa Quality Assessment Scale (NOS). This sc2 test. A random or Fixed model was used according the heterogeneity analysis. A random effect model was applied if I2≧50%; the fixed effect model was selected if I2<50%. When I2≧50%, subgroup analyses would be carried out. A P < 0.05 indicates a significant factor contributing to the observed heterogeneity. The latent publication bias was assessed by a funnel plot and Egger’s linear regression test, and a value <0.05 indicated an inevitable significant publication bias[The primary outcome was OS associated with SPARC expression in patients with pancreatic cancer. HR and 95% CI were used to be the effect measure of interest. A combined HR>1, with its 95% CI did not overlap 1, indicated a worse survival for the group with high SPARC expression. The heterogeneity among studies was measured using the Q and Ition bias. All staA total of 218 articles were retrieved in the initial search of databases. In addition, 29 records were yielded by manual searching. After removing 98 duplicates, we read the titles and abstracts of the 149 studies left. 60 citations were excluded from analysis based upon abstracts or titles, leaving 89 studies for further full-text review. At the same time, one study could't be found anyway. After mThe basic characteristics of the 10 studies are summarized in None of these ten studies gained a NOS <6, suggesting that all of them had high levels of methodological quality in this meta-analysis .All of these ten studies showed the association between SPARC expression and overall survival of patients with pancreatic cancer. In spite of highly significant heterogeneity , the pooled HR for all of these seven studies with multivariate analysis was 1.55 . The left three studies were treated non-surgery, but their pooled HR had no significance (P = 0.35). Also, in the estimate, the pooled HR of surgical had no significance (P = 0.39). In the region of Caucasian, we can see that both the multivariate analysis and the estimate had significant pooled HR , and the estimate had a low heterogeneity with I2 = 5%. Then, we performed the subgroup analysis demixed by sample size, and I²being 0 and 8% were found in the studies with size <100, while the subgroup of the studies with size ≥100 still had heterogeneity. And only found a P<0.05 in the multivariate analysis , but not in the estimate. Thus, sample size might be the source of heterogeneity. As for the detection method and the scoring method, only found a pooled HR in IHC, and another one in EI had a P<0.05, still with a high heterogeneity. None of the other had no significance. In the univariate analysis, two were detected by IHC, but reported the HRs in the stroma and in the tumor, respectively, and the other was detected by qRT-PCR. Also, they all had a sample size>100. So, we didn’t carry out a subgroup analysis in the univariate analysis.In view of the heterogeneity, we conducted the subgroup analyses, presented in Due to only one study, we failTo value the stability of our results, a sensitivity analysis was performed. In the multivariate analysis and the univariate analysis, no significant changes were detected between the previous and new HRs, the latter pooled by the studies left when we deleted an individual study at a time. However, in the estimate, when deleting the study of Mao, we founDue to ten studies, we carried out the publication bias assessment of the ten eligible studies. There was no obvious asymmetry in these funnel plots , multivaSPARC, as a potential molecular marker of prognosis in malignant tumors, has generated remarkable interest in this crucial period of the high morbidity and mortality of malignancies. However, there is a heated controversy whether high or low SPARC expression is correlated with poor survival. SPARC expression is an unfavorable outcome in gastric, prostate and lung cancers ,34,35, wAs we all know, this meta-analysis, with a total 10 studies and 1632 patients, was the first systematic review which evaluated the role of SPARC in the prognosis of pancreatic cancer. The pooled HR of OS indicated that high expression of SPARC had a poor survival in patients with pancreatic cancer. This conclusion could be showed in subgroup analyses, especially in the subgroup of cell type, which showed that high SPARC expression in the stroma, but not in the tumor, was a strong prognostic indicator of lower OS. In addition, with their I² = 0, the sample size < 100, may be the sources of the heterogeneity. Furthermore, the funnel plots were established with no dissymmetry and a Egger’s test was performed gaining a P>0.05 in multivariate analysis, univariate analysis and estimate, indicating that our results were robust.SPARC is useful for the adjuvant chemotherapy of pancreatic cancer. Nab-paclitaxel (Nab-P) is active in pancreatic cancer refractory to gemcitabine and the With the most research and the deepest exploration among all of the members of this family, SPARC has been found to have many significant molecular mechanisms in malignancies, including modulating ECM and the tumor microenvironment (TME), anti-adhesive and regulating apoptosis, tumor growth, migration and invasion. SPARC wIn this meta-analysis, there were some limitations. Firstly, the sample size was still small. In spite of 1632 patients in total, most of whom come from healthcare centers or hospitals with sufficient follow-ups, there were only 829 patients pooled in the multivariate analysis of overall survival. Secondly, the HRs estimated from Kaplan-Meier curves were imprecise. These might influence our consequence. Thirdly, because most of studies were retrospective, selection bias, information bias and other biases were inevitable. Fourthly, none of these eligible studies divided patients into two groups by TNM stage. However, in another study investigating SPARC expression in patients with esophageal squamous cell carcinoma (SCC), the author evaluated the relationship between SPARC expression in the stroma and overall survival through two groups, stage-IIA/IIB and stage-III/IV esophageal SCC. And theIn this systematic review with meta-analysis, the elevated SPARC expression, especially in the stroma, was associated with a poor prognosis in patients with pancreatic cancer. Further studies should be performed to confirm our conclusion and explore its molecular functions.S1 PRISMA Checklist(DOC)Click here for additional data file.S1 Fig(DOC)Click here for additional data file.S2 Fig(DOCX)Click here for additional data file.S3 Fig(DOCX)Click here for additional data file.S1 Table(DOCX)Click here for additional data file.


Physical activity (PA) is important for healthy ageing. Better insight into objectively measured PA levels in older adults is needed, since most previous studies employed self-report measures for PA assessment, which are associated with overestimation of PA.This study aimed to provide insight in objectively measured indoor and outdoor PA of older adults, and in PA differences by frailty levels.Data were collected among non-frail (N = 74) and frail (N = 10) subjects, aged 65 to 89 years. PA, measured for seven days with accelerometers and GPS-devices, was categorized into three levels of intensity .Older adults spent most time in sedentary and light PA. Subjects spent 84.7%, 15.1% and 0.2% per day in sedentary, light and moderate-to-vigorous PA respectively. On average, older adults spent 9.8 (SD 23.7) minutes per week in moderate-to-vigorous activity, and 747.0 (SD 389.6) minutes per week in light activity. None of the subjects met the WHO recommendations of 150 weekly minutes of moderate-to-vigorous PA. Age-, sex- and health status-adjusted results revealed no differences in PA between non-frail and frail older adults. Subjects spent significantly more sedentary time at home, than not at home. Non-frail subjects spent significantly more time not at home during moderate-to-vigorous activities, than at home.Objective assessment of PA in older adults revealed that most PA was of light intensity, and time spent in moderate-to-vigorous PA was very low. None of the older adults met the World Health Organization recommendations for PA. These levels of MVPA are much lower than generally reported based on self-reported PA. Future studies should employ objective methods, and age specific thresholds for healthy PA levels in older adults are needed. These results emphasize the need for effective strategies for healthy PA levels for the growing proportion of older adults. According to the World Health Organization (WHO), by 2050 the percentage of people aged 65 years and older is expected to be doubled to the figure of 16%, and the number of people aged over 80 years will increase by 315% (double ageing) .Ageing comes with the loss of muscle mass and strength . This phAccording to the WHO, health benefits can be achieved by older adults aged 65 years and older, when they accumulate at least 150 minutes of moderate intensity aerobic PA (MPA), or at least 75 minutes of vigorous intensity aerobic PA (VPA), or an equivalent combination of both intensities .In addition, research has shown that also light PA (LPA)  and overMost studies investigating PA in older adults used self-report measures, which suffer from limitations such as recall bias, socially desirable responses, and the influence of factors as mood and cognition ,14. ManyMoreover, it is important to gain insight in locations where older adults are physically active. Previous studies have shown that older adults who are physically active outside, spend more time in MVPA than people who are only physically active inside . SpendinIn sum, more objectively collected evidence of PA levels in older adults is needed to provide a baseline for international comparisons, to inform public health policies , and to This cross-sectional study was part of ELANE (ELderly And their NEighborhood), a study that was conducted in a middle-sized city (Spijkenisse) in the Netherlands, to investigate associations between environmental characteristics and PA, functional loss, independent living and quality of life. ELANE employed the same research structure and methods as the Prevention and Reactivation Care Program study (PreCAP), that was conducted in the same study area . A more The flowchart in PA was measured objectively by using ActiGraph GT3X+  accelerometers. Participants were instructed to wear the accelerometer at the right hand side of the waist, during waking hours (except during water-based activities) for seven consecutive days. A manual was handed out, to read back instructions. The manufacturers software  was used to process accelerometer data. In this study population, sequences of 60 minutes or more of consecutive zero counts were excluded from each recording, as these were considered to be non-wear time , 16.In order to have sufficient data for a reliable estimate of PA, recommendations have been made to include only participants with sufficient data on a daily basis, and to have at least three valid days of data . In accoAccelerometer data were collected in ten second epochs and aggregated as counts per minute (cpm). After cleaning the data, counts per minute were classified in different intensities of PA. For older adults there is no consensus for cut-off values in cpm . Cut-offWHO PA recommendations  are met In order to calculate energy expenditure from accelerometer data, METs were derived from cpm using the following regression equation: 1.439008 + 0.000795*counts/min . These MRMS) of the distances of all GPS data points to the COG was calculated. Data points that were more than three dRMS away from the COG are eliminated from the data list and marked as outliers. Then the COG is calculated again and if it lies more than five meters from the first COG, the outlier removal procedure was repeated. Data points that were less than two dRMS away from the COG were marked as part of the cluster. All data points of the cluster corresponding to the home address were classified as ‘at home’.GPS receivers BT-Q1000X and BT-Q1000XT  were used to map geographical locations of participants. Participants were instructed to wear the GPS receiver on the same belt the accelerometer was placed on, at the right hand side of the waist, during waking hours (except during showering and swimming), for seven consecutive days. Locations were measured every ten seconds. GPS receiver data were mapped using the Qstarz QTravel software (v1.45 for Win XP/Vista/7) and it was date- and time-linked to the accelerometer data to create combinations of activity and location. In this study, PA at home was compared to PA at other locations (both indoors and outdoors), referred to as not at home. Identification of ‘at home’ and ‘not at home’ was performed using cluster detection on GPS data . In clusDaily transportation distances per active mode of transport were derived from GPS measurements. The mode of transport  was defined based on the speed that was registered by the GPS device. For every outdoor data point, the maximum speed was determined, calculated as the maximum during the two-minute time interval that starts one minute before and ends one minute after the time stamp of the data point . In thisInformation on age, sex, frailty and health status was collected during the interviews, using a questionnaire. Health status was measured using a question of the SF-12 questionnaire: ‘In general, would you say your health is’. Answer options were 1) Excellent, 2) Very good, 3) Good, 4) Fair, 5) Poor. Frailty status was determined using the ‘Identification Seniors At Risk—Hospitalized Patients’ questionnaire (ISAR-HP) to determine frailty, which has sufficient validity , 33. Thet-tests were used to analyze differences in mean time spent at home and not at home. Most of the dependent variables were not normally distributed and neither log transformations nor taking the square root of variables, led to normal distributions. Therefore, bootstrapped linear regression was used (number of samples set to 5000) to assess differences in PA behaviour between non-frail and frail older adults. PA measures were regressed on the frailty indicator and adjusted for age [Descriptive statistics were used to present baseline characteristics and to describe time spent at home and not at home in different PA levels per day. Paired samples  for age , 27, sex for age , 27, 34,On average, participants spent 9.8 (SD 23.7) minutes in MVPA per week . Non-fraTime spent in different levels of PA is shown in Time spent at home and not at home is shown in Older adults walked on average 2486.9 (SD 1707.6) meters per day, and they cycled on average 3915.1 (SD 5215.8) meters per day . WalkingThe present study found that older adults spent only 9.8 (SD 23.7) minutes per week on MVPA. Since there is no consensus in accelerometer cut-off values to determine levels of PA for older adults, results of this study should be compared to other studies with caution. For example, Gorman et al. 2014) found in their review eight different cut-off values that were used for the classification of MVPA in older adults [ found inBesides, the present study found that none of the older adults met WHO recommendations for aerobic PA. These findings are inconsistent with national figures of PA of Dutch older adults: 75% of men and 67% of women aged 65–75 years, and 45% of older adults aged over 75 years, were physically active for at least 30 minutes of MVPA per day, on five days of a week . HoweverAlthough older adults spent only little time in moderate-to-vigorous activities, a considerable amount of time is spent in light activities. Light intensity activities often include activities of daily life . No specific skills are required and therefore these activities can be easily integrated in older adults’ daily life’s. Current guidelines for PA have not yet integrated recommendations on LPA.Furthermore, this study showed that older adults spent most time per day sedentary (84.7%), and this confirms findings of previous studies which reported that adults spent on average 62% to 86% per day sedentary . Since sMoreover, the results indicate that sedentary behaviour is more performed at home than not at home, whereas MVPA is more performed not at home. Although in this study little time is spent in MVPA, our results seem to indicate that spending time not at home might contribute to an increase of time spent in moderate-to-vigorous activity. This is consistent with literature, which shows that spending time outdoors might contribute to the frequency, duration and intensity of PA . MoreoveIn this study, additional analyses were conducted to calculate weekly energy expenditure in MET minutes. This study provides insight in objectively measured weekly energy expenditure of non-frail and frail older adults, and we did not find differences between frail and non-frail older adults with regard to MET minutes. However, more research is needed to draw strong conclusions.This study showed that non-frail older adults had a higher daily walking distance than frail older adults, whereas the frail adults had a higher daily cycling distance. However, these differences were not statistically significant. In a previous study  it was sFindings of this study on cycling distances were comparable to previous findings in this age group in the Netherlands . The bicIn this study, the prevalence of frail older adults was 11.9%, which is in accordance with previous findings. According to the review of Collard et al. (2012), the average prevalence of frailty among adults aged 65 years and older, was 10.7% (with a range from 4.0% to 59.1%) . In thisA major strength of this study is the use of accelerometers and GPS devices, which supplies high quality data. Accelerometers and GPS devices provide objective information on PA and are used to overcome limitations of self-report  ,14. HoweTaraldsen et al. 2012) reported that most studies that used accelerometers, had small sample sizes (≤ 50 participants) . Althoug reportedParticipants were randomly approached for participation, but only 15.4% of those eligible for participation, participated in this study and wore an accelerometer and GPS-device. Therefore, this study population may not be representative for the Dutch population, and we cannot rule out selection bias. However, in terms of age and sex distribution, our final study sample is representative for the population of Spijkenisse and for the Dutch population. Mean age of our final study sample was similar to the mean age of the population of Spijkenisse and the Dutch population, aged 65 years and older. Also, participants of the final study population were homogeneously distributed over Spijkenisse. People who volunteer for participation in an exercise study are often healthier and fitter than non-volunteers . This miEthnicity and weather conditions  are sometimes taken into account as confounders in studies assessing PA , 23, 34.We conclude that PA levels of older adults aged 65 years and older were very low, and that most PA was of light intensity. In an ageing population health gains can be achieved by reducing sedentary behaviour and stimulating PA. More large scale population-based studies that use objective methods are needed to inform public health policy adequately. This study emphasizes the need for interventions aimed at stimulating healthy PA levels in older adults.S1 Dataset(XLS)Click here for additional data file.


We conducted a dose–response meta-analysis of prospective studies to summarize evidence of the association between tea consumption and the risk of breast, colorectal, liver, prostate, and stomach cancer.We searched PubMed and two other databases. Prospective studies that reported risk ratios (RRs) with 95% confidence intervals (CIs) of cancer risk for ≥3 categories of tea consumption were included. We estimated an overall RR with 95% CI for an increase of three cups/day of tea consumption, and, usingrestricted cubic splines, we examined a nonlinear association between tea consumption and cancer risk.Forty-one prospective studies, with a total of 3,027,702 participants and 49,103 cancer cases, were included. From the pooled overall RRs, no inverse association between tea consumption and risk of five major cancers was observed. However, subgroup analysis showed that increase in consumption of three cups of black tea per day was a significant risk factor for breast cancer .Ourresults did not show a protective role of tea in five major cancers. Additional large prospective cohort studies are needed to make a convincing case for associations. Camellia sinensis plant through several processes. Black tea is the main tea beverage in the United States, Europe, and Western Asia, while green tea is more popular in China, Japan, and Korea [Tea is a popular beverage consumed worldwide, generally in the forms of black and green tea. Tea is produced from the leaves of the nd Korea . Extensind Korea ,3.In some recent reviews, researchers have suggested that green tea, which contains abundant polyphenols and catechins, specifically epigallocatechin-3-gallate (EGCG) 5, might have a protective effect against cancers. Using multiple approaches, studies have shown that polyphenols, theaflavins (TF) and thearubigins (TR) in black tea might possess chemopreventive properties. However, most of the evidence showing a protective effect of tea on cancer has been generated in animal experiments but has not been demonstrated in human trials ,5.The World Cancer Research Fund report of 2007 concluded that the evidence for associations between the consumption of tea and risk of some major cancers was still limited and inconsistent . The resPrevious meta-analyses mainly focused on the relationship between the highest tea consumption level and either the lowest tea consumption level or non-drinkers. However, the range of tea consumption and the cut-offs for the categories differed between studies. Another drawback of the previous meta-analyses is the inclusion of retrospective case–control studies, which were sensitive to confounding variables and bias, especially recall bias. To quantitatively assess the relationship between tea consumption and risk of five major cancers, we conducted a systematic review and dose–response meta-analysis with prospective studies. The five major cancers we studied were liver, stomach, breast, prostate, and colorectal cancer.We performed a systematic literature search in PubMed, Embase, and Cochrane Library with a combination of the following terms: tea AND  AND (cancer OR cancers OR carcinoma OR carcinomas OR neoplasm OR neoplasms). No language restrictions were imposed. Reference lists of the identified publications were also reviewed for inclusion/exclusion. We also searched the conference abstract on the website of American Society of Clinical Oncology (ASCO) annual meeting from 2004 to 2013. Two reviewers (FY and CX) independently selected studies based on the titles and abstracts of the retrieved studies. Studies were included if they met the following criteria: (1) a prospective study assessing the association between tea consumption and at least one of the five selected cancers ; (2) a study considering at least three levels of tea consumption and providing a sample size for cases and non-cases in each exposure category ; and (3)Data extraction was performed according to the MOOSE  guidelines  see the by two rWe performed a two-stage dose–response meta-analysis to examine the relationship between tea consumption and five major cancer risks. First, we synthesized the RRs across categories of tea consumption in each study ,23. BecaP value for nonlinearity was calculated by testing the null hypothesis that the coefficient of the second and third spline was equal to zero.If a study did not report the median of the exposure category, we assigned the level of tea consumption to categories based on the calculated midpoint of tea consumption. When the highest category was open-ended, we assumed the dose as 1.2 times the lowest bound of this category . In studet al. pooled data from six cohort Japanese studies that studied the relationship between tea consumption and stomach cancer [2 test and I2 statistic were used to explore the heterogeneity among studies [Eight studies on colorectal cancer ,31,38-41h cancer . Results studies . The Egg studies ,48. As a studies . We cond studies ,42,49-52 studies ,27,33, o studies ,54, rathWe used Stata  for all analyses and all statistical tests were two-sided. P < 0.05 was considered statistically significant.As of December 28, 2013, 1,881 records were retrieved by using our search strategy. After reviewing the titles and abstracts, we excluded 1,668 articles and 213 articles were further evaluated by reviewing the full texts. Finally, we identified 41 articles assessing tea consumption and cancer risk, which satisfied the inclusion criteria for our meta-analysis. A flow diagram of study selection is provided as Figure P = 0.22, I2 = 21.2%). For colorectal cancer, the pooled RR for three cups increment per day was 0.98  with mild heterogeneity . For liver cancer, the overall RR for three cups increment per day was 0.91  with moderate heterogeneity . For prostate cancer, the overall RR for three cups increment per day was 1.02  with moderate heterogeneity . For stomach cancer, the overall RR for three cups increment per day was 0.98  with moderate heterogeneity .The associations between tea consumption and the risk of major cancers are shown in Figures As shown by Figure In the subgroup analysis, we pooled the studies into groups by sex, tea type, geographic region, and menopausal status for breast cancer. The results are shown in Table et al. [A sensitivity analysis omitting one study at a time and calculating the pooled RRs for the remainder of the studies suggested that no single study dramatically influenced the pooled RRs (results are not shown). After removing the studies that did not report tea consumption as cups per day, the results did not change significantly. On excluding a study by Inoue et al. , which hP = 0.59 and P = 0.60, respectively) and colorectal cancer , indicating no evidence of substantial publication bias . Subgroup analyses, stratified by sex, geographic regions, and type of tea, showed no significant associations with risk of cancer.et al. [P = 0.30, I2 = 17.1%), which suggests a preventive effect of tea drinking for liver cancer. However, large prospective studies are still needed to verify this preventive effect.The results of heterogeneity test suggested that most pooled effects had mild heterogeneity. However, moderate heterogeneity was seen in studies on liver cancer. Sensitivity analysis performed by omitting one study at a time, identified the main source of heterogeneity as the study by Inoue et al. , which iEleven previous meta-analyses have evaluated the association between green tea or black tea intake and the risk of the five selected cancers -16,70-75et al. presented conflicting results across cohort studies and case–control studies for breast cancer risk [et al. reported that the levels of circulating estrogens were higher in black tea drinkers than in non-tea drinkers [et al. reported that black tea consumption was positively associated with the risk of ER+/PR + breast cancer, suggesting a possible carcinogenic role involving sex hormones [Among the three meta-analyses examing the relationship between black tea consumption and cancer risk, Sun cer risk . The poocer risk . Wu et adrinkers , and Larhormones .et al. [et al. concluded that drinking four cups increment per day might be a risk factor for colon cancer. In addition, Zhang et al. also reported that the risk of colon cancer did not increase with a 250 g/day increment of tea consumption either in men  or women ; this is consistent with our current meta-analysis. Zhang et al. attributed the observed positive association to chance.Of the three meta-analyses exploring the association between tea consumption and colorectal cancer risk, Zhang et al.  found a It is notable that most epidemiological evidence for the inverse association between tea intake and cancer risk has come from retrospective case–control studies. Because information in case–control studies is collected after cancer is diagnosed, it reflects the past exposure history based on recall; therefore, recall bias is inevitable and cannot be ignored. This bias may partly explain the difference in the findings between prospective studies and retrospective case–control studies. Given the limitations of case–control studies, the conclusion that tea consumption has an inverse association with cancer risk is not convincing.When compared with previous meta-analyses, our meta-analysis has several strengths. First, we assessed the association of tea consumption with five major cancers. Second, only prospective studies were included in the meta-analysis, which greatly reduces the likelihood of selection and recall biases. Third, the dose–response analysis included a wide range of tea consumption, which allows a concrete and quantitative assessment of the dose–response relationship between tea intake and cancer risk.However, several potential limitations of our meta-analysis must be considered when interpreting the results. First, the temperature of tea is an important confounding factor when assessing the association between tea drinking and cancer risk. However, we could not analyze the effect of this factor because only one study reported the relationship between iced or hot tea and cancer; this study reported no significant association were observed between iced or hot tea and gastric cancers. Second, the methods of data collection differed across the included studies. Most of the studies assessed the exposure of the tea consumption via food frequency questionnaire, and the response rate varied among these studies. As is known, people in different countries have different traditions of tea consumption or drinking style, which presents difficulties in assessing tea consumption amounts accurately. In addition, people from the same country may also have different habits of drinking tea, such as strong or weak tea. In addition, tea consumption level is mostly assessed as the number of cups of tea consumed daily or weekly. However, cup size may vary considerably for different countries or areas and the dry tea leaves brewed in each cup may also be different. The cut-offs for the highest consumption level varied across different studies. Therefore, there might be some inevitable measurement errors and possible uncontrolled confounding factors when assessing tea consumption; this could prevent the detection of a modest association between tea consumption and cancer risk. However, we endeavoured to decrease these errors by unifying the unit of measurement and using a similar standard to calculate daily tea consumption. We also performed sensitivity analyses by removing the studies that did not report tea consumption as cups and performed subgroup analyses by geographic region, especially China and Japan (see Table There is insufficient information from epidemiologic studies to support the suggestion that tea intake plays a role in the prevention of cancer. Randomized controlled trials and large prospective cohort studies are needed to further explore this association.GTE: Green tea extract; RR: relative risk; 95% CI: 95% confidence intervals; HR: Hazard ratio; OR: Odds ratio; NOS: Newcastle-Ottawa Scale.The author’s declare that they have no competing interest.FY developed inclusion and exclusion criteria, drafted and revised the manuscript, contributed to the study design, analysis, and interpretation of the data. ZJ drafted the manuscript and contributed to the study design. HJ contributed to revising the manuscript, data analysis and interpretation of the data. CX developed inclusion and exclusion criteria, contributed to the data analysis and interpretation of the data. JT and TL contributed to the electronic search, hand-search of literature and the revision of the manuscript. JH contributed to the interpretation of the results and the conception of the study. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/14/197/prepubThe MOOSE checklist for this meta-analysis.Click here for file


Aims. To compare the clinical features of endometrial polyps (EPs) between patients with endometriosis (EM) (EM group) and without EM (non-EM group). Methods and Results. Seventy-six cases in the EM group and 133 cases in the non-EM group underwent laparotomy or hysteroscopy and laparoscopy; later, it was confirmed that the results by pathology from July 2002 to April 2008 in the Department of Gynecology and Obstetrics at the First Affiliated Hospital of Sun Yat-sen University. The recurrence of EPs was followed up after the surgery until 2013. The following parameters were assessed: age, gravidity, parity, infertility, and menstrual cycle changes, as well as polyps diameters, locations, number, association with the revised American Fertility Society (r-AFS) classification, and their recurrence. On review, 76 EPs cases of EM group histologically resembled EPs but the majority of EPs with EM occurred in primary infertility cases and in fewer pregnancy rate women who had stable and smaller EPs without association with the AFS stage. The recurrence rate of EPs in EM group was higher than that in non-EM group. Conclusion. It is important to identify whether infertile patients with EM are also having EPs. Removing any coexisting EPs via hysteroscopy would be clinically helpful in treating endometriosis-related infertility in these patients. Endometriosis (EM) is defined as functional endometrial glands and stroma tissue that are located outside the uterine cavity. It affects approximately 2–17% of women in their reproductive years, and it typically manifests as chronic pelvic pain, congestive dysmenorrhoea, heavy menstrual bleeding, and deep dyspareunia. It is suggested that 47% of infertile women have EM –6.EPs, the local hyperplastic growth of endometrial glands and stroma covered by epithelium, can affect between 7.8% and 34.9% of women, especially infertile women . OccasioIn cases of infertility, EM and EPs can be closely associated with each other in some respects. For example, some studies reported a higher frequency of EPs in EM patients , 4, 20. P = 0.90 and P = 0.67, resp.). The eutopic endometrial pathological types in the two groups were not different with respect to the menstrual cycle stage (P = 0.12). This study was approved by our hospital ethics committee.A retrospective comparison was conducted of the data from 76 patients (EM group) who had been diagnosed with EM with EPs and 133 patients (non-EM group) who had been diagnosed with EPs without EM based on pathology, all of whom had undergone laparotomy or hysteroscopy and laparoscopy between July 2002 and April 2008 in the Department of Gynecology and Obstetrics at the First Affiliated Hospital of Sun Yat-sen University. The recurrence of EPs was followed up after the surgery until 2013. The two groups of patients had no internal medicine complications and had not taken any steroid hormone medications within 3 months before the surgery. There was no significant difference between the two groups with respect to the presence of uterine fibroids and adenomyosis ], operative data , and pathological data were conducted. The EPs size was measured via preoperative vaginal ultrasound and confirmed during diagnostic hysteroscopy prior to resection or by gross appearance. The sizes were estimated using the largest polyp as a reference. The cases with prolonged operative times due to multiple operations for other indications or complications were excluded from the final analysis.The diagnosis of EPs was made by histopathological examination. Specifically, the diagnosis was made according to the presence of irregularly dilated endometrial glands and thick-walled vessels scattered within fibrotic stroma. The type of EPs was determined based on the angle between the polyp and the adjacent uterine wall. (1) Pedunculated-type polyps were defined when the angle of the polyp surface to the endometrium was <90 degrees. (2) Sessile-type polyps were those with an angle ≥90 degrees . The preU test for continuous variables and Fisher's exact test for categorical variables. The patients' polyps, along with infertility type, menstrual cycle changes, polyp location, and EM r-AFS stage, were compared with the Pearson chi-square test and Fisher's exact test for qualitative variables. A P value < 0.05 was considered to be statistically significant.Statistical analysis was performed using SPSS 13 Statistical Software . Multivariate logistic regression analysis was performed, in which the occurrence of EPs was used as the dependent variable, while the age, gravidity, and parity were used as independent variables. Quantitative data, such as age, polyp diameter, and number of polyps, are expressed as the means and 95% confidence intervals (95% CIs). Differences between the groups were assessed using the Mann-Whitney P > 0.05). After a follow-up period to 2013, 76 patients of EM and 133 patients of non-EM group were contacted for a phone interview. Two persons could not be reached by the phone.The average age of the EPs patients in the EM group was 38.37 ± 0.74 years, while that of the EPs in non-EM group was 40.0 ± 10.55 years ; specifically, the less the parity, the higher the incidence of EPs in EM group (P = 0.00), and the incidence of EPs in EM patients was significantly increased in primary infertility patients   and between the two groups in the same menstrual cycle    . Further = 0.15) . There w = 0.15) . The EPs = 0.15) , concent = 0.15) . The siz, resp.) .The recurrence rate of EPs in EM patients in our study was higher in EM patients with EPs, and there was a positive association between the recurrence rate and follow-up period; specifically, the 2-year recurrence rate was 23.08% postoperatively, whereas the 5-year recurrence rate was as high as 56.41% .The precise pathogenesis of endometriosis in patients with EPs is not clear. However, the most widely accepted characteristic mechanism for endometriosis is retrograde menstruation with the transport of endometrial cells, metaplasia of coelomic epithelium, and hematogenous or lymphatic spread of endometrial cells. Other factors, such as genetic, immunological, and inflammatory factors, are involved in this process, in which eutopic endometrial fragments become implanted in the pelvis or other organs. A combination of these theories is likely to characterize the features of endometriosis. Furthermore, because blood reflux is common when women are of reproductive age, the eutopic endometrial status in endometriosis patients is mainly considered to be abnormal at the same time –25.Previous studies , 18, 20,Furthermore, our results showed that the EPs associated with EM were in a relatively quiescent state; that is, there is little risk of the severity of menstrual disorders increasing, and the original menstruation pattern is often maintained. It is recommended for EM patients with infertility to have routine vaginal ultrasound and hysteroscopy examinations to assess EPs. At the same time, this examination should be conducted more carefully because polyps associated with EM are generally distributed in a similar manner with other polyps but have a smaller size. The recurrence rate of EPs in EM patients in our study was higher in EM patients with EPs, and there was a positive association between the recurrence rate and follow-up period; specifically, the 2-year recurrence rate was 23.08% postoperatively, whereas the 5-year recurrence rate was as high as 56.41%.There could be intrinsic factors that make EM more likely to occur in association with EPs, which should mainly be associated with infertility. Some authors found both EM and EPs that exhibited an overgrowth of the endometrium, a process that requires the support of estrogen. Additionally, previous research revealed that the expression patterns of estrogen receptor (ER) and aromatase are both altered in EM and EPs patients –28. AddiEPs formed when the local hormone and its receptor were abnormal. At the same time, it is possible that the vessel axis of the functional polyps could actually originate from the evolution of the vascular changes that are associated with endometritis. Inflammatory factors could play an important role in EPs formation in association with EM-related infertility. In the eutopic endometrium of EM patients, vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMP) 1, 2, and 9, and angiogenesis factors 1 and 2 levels were higher than those in normal endometrium –31. ThusBased on the clinical analysis, patients with EM combined with EPs have smaller polyps size, exhibiting unchanged menstrual cycle and higher recurrence rate and having high rates of primary infertility or fewer pregnancies in patient complaints. It is important to identify whether infertile patients with EM are also having EPs. Hysteroscopic polypectomy together with the removal of endometriotic foci will significantly increase the likelihood of achieving a pregnancy.


Drinking water, a fluid primarily for human hydration, is also a source of mineral nutrients. Groundwater, a drinking water source for more than 70% of inhabitants living in Asian deltas, has received much attention because of its naturally occurring arsenic, but the linkage of arsenic toxicity with other water constituents has not been studied. In addition, although nutrients are generally provided by food, in under developed rural settings, where people subsist on low nutrient diets, drinking-water-nutrients may supply quantities vital to human health thereby preventing diseases. Here, we show, using augmented datasets from three Asian deltas , that the chemical content of groundwater is such that in some areas individuals obtain up to 50% or more of the recommended daily intake (RDI) of some nutrients  from just two litres of drinking water. We also show some indications of a spatial association of groundwater nutrients and health outcome using demographic health data from Bangladesh. We therefore suggest that an understanding of the association of non-communicable disease and poor nutrition cannot be developed, particularly in areas with high levels of dissolved solids in water sources, without considering the contribution of drinking water to nutrient and mineral supply. Water is essential for all forms of life and plays an essential role in maintaining fluid and electrolyte homeostasis in humans. Sustaining hydration is necessary for thermoregulation and normal bodily function. Drinking water, although often rich in minerals, has rarely been considered in terms of its ability to supply essential mineral nutrients e.g., . It can etc.). Rarely has there been consideration of the positive health effects of mineral-nutrients . Medical hydrogeology, however, should not only consider the harmful elements but also those that influence the toxicity of harmful elements and those  that alter the groundwater characteristics during storage and treatment. For example, fluoride is harmful in drinking water if it is at a concentration above 1.5 mg/L. However, toxicity of fluoride can be reduced if the the groundwater and/or diet contain high levels of calcium e.g., [Medical geology is a branch of geology that studies the relationship between health and geological conditions e.g., ,4,5. Thium e.g., ,7.Around 300 million people living in Asian deltas rely on groundwater for their water supply. In these areas a nutrient rich diet is not widely affordable and many live on limited cereal based diets, which can lead to micronutrient malnutrition. At present >2 billion of people on the globe suffer from this, and many of them live in these delta areas . We haveWe also carried out a preliminary exploratory study in Bangladesh to assess the possible health benefits of these groundwater nutrients at a national scale. We would like to relate drinking water and health within a framework of “medical hydrogeology”, which links the hydrogeology of an area with certain diseases and health benefits due to presence, or shortage of certain nutrients in groundwater.Geologically, Asia is very diverse, characterised by highlands and mountainous terrains of igneous and metamorphic rocks and thick piles of unconsolidated to semi-consolidated sediments in mega-deltas formed along the coasts by the rivers draining the highlands and mountains, e.g., . Asian rca. 50 m. The sediments are sand, silt and clay with occasional gravel, and overlay older sediments of a similar origin. All these deltas experienced periodic eustatic changes leading to episodes of (ca. 100 ka) sub-aerial weathering and (ca. 10–20 ka) deposition [ca. 120 m drop in global sea level leading to groundwater flushing during the low stands. By contrast, at high stands increased sedimentation leads to the formation of new aquifers on top of the older well flushed, and often sub-aerially weathered, desposits [The current landforms in these deltas have been determined, during Late Quaternary time, by geological modifications ,12,13,14position . The subesposits ,17. The ca. 150 mbgl) depths is polluted by naturally occurring arsenic e.g., [In recent decades the discovery of, mostly naturally occurring, arsenic in shallow groundwater has led to a number of hydrogeological studies of these aquifers e.g., ,20,21,22ic e.g., , whereasic e.g., . In contic e.g., ,26.Although the use of groundwater as a source of drinking water in Asia has a long history, it was only during the period between 1970 and 2000 that it markedly expanded to its current extent ,28. The In addition to the widespread effects of high arsenic concentrations in these deltaic groundwaters, there are other potential health impacts from high levels of dissolved ions present in these waters. In particular, manganese, which, although an essential micro-nutrient, at high concentrations can hinder mental development in children . Also, e3), calcium (Ca), fluoride (F), iodine (I), iron (Fe), magnesium (Mg), manganese (Mn), nitrate (NO3), potassium (K), selenium (Se), sodium (Na), uranium (U), vanadium (V), and zinc (Zn). Analytical procedures and the actual data can be found in the cited literature sources.A comprehensive water quality dataset has been compiled for 5256 tube-wells using published literature ,35,36,37The RDI for different nutrients vary according to age group, as well as for special groups , however, for simplicity a fixed conservative value e.g.,  is consietc.) [For proper bodily function and hydration a person needs around 3.5 litres of fluid. Some of this comes from food, but a significant part of comes from drinking water and other drinks. A conservative assumption is made that a person living in an Asian delta drinks two litres of water from the same well, though some studies, e.g., ,41, haveetc.) . Howeverca. 95%) sourced from groundwater [Drinking water in Bangladesh, which occupies most of the Bengal delta, is almost entirely , some of which can be found in groundwater, as outlined below:Calcium (Ca) and Magnesium (Mg): Significant amounts, up to 50% RDI of Ca and Mg, can be derived from groundwater in some areas (me areas . Around Sodium (Na): Although the human body needs Na, it is generally assumed that this is met from food and added salt. However, in coastal deltas a significant amount of the daily Na requirement (as well as chloride—though not considered here) can be obtained from drinking water (ca. 80%) provide less than 10% of RDI, however around 4% wells, particularly in coastal areas, contain more than 500 mg/L of Na, which is more than 50% of RDI. The EPA guidance level for Na in drinking water is 20 mg/L and 65% of the wells exceed this concentration. In contrast, there is no health-based guideline provided by the WHO, however, it does, on the grounds of taste, recommend a limit of 200 mg/L. Around 12% of the wells have concentrations above this value.ng water . Most wePotassium (K): Groundwater generally contains limited amounts of K. In Asian deltas the contribution to the daily intake of K by groundwater is insignificant and, in most cases, less than 10% of RDI (% of RDI e. SimilaIron (Fe): Significant amounts of dissolved Fe are present in the analysed groundwaters, with 64% of the wells containing concentrations above 0.3 mg/L, the WHO recommended value, which is for aesthetic reasons and not a health-based guideline for Fe in drinking water. Around 32% of wells in the deltas provide more than 50% of RDI for Fe, while 17% provide more than the daily Fe requirement for an adult. The occurrence of high Fe in groundwater has a regionalised spatial pattern and is relatively higher in shallower aquifers (aquifers .3):Selenium (Se) and Nitrate : Like Se, a relatively small amount of F is needed for dental and bone health. Although excess F is a problem in some parts of Asia, in the deltas investigated the content of F in groundwater is insignificant. Only a few analyses for F are available for the Bengal delta  and these indicate that its presence is insignificant, and all are well below the 1.5 mg/L WHO guideline for drinking water (ng water i.Iodine (I), and Zinc (Zn): Iodine is widely present in the deltaic groundwaters, with a relatively high concentration in the Red River delta, where half of the wells can provide 50% or more of the RDI ( the RDI h. The pr the RDI g.Manganese (Mn): Manganese is an essential micro-nutrient but there is evidence that excessive intake can be harmful [ harmful . In the  harmful ). HoweveArsenic (As): Groundwater in Asian deltas over the last few decades has been extensively studied for naturally occurring As e.g., [ca. <100 m) groundwater contains excessive levels of As. In the sets of groundwater analyses for the three delta areas 44% of wells have As concentrations above the WHO guideline, 10 µg/L, for drinking water. The proportion of wells that satisfy the local regulatory standard , of 50 µg/L, is 71% : Some groundwaters contain U but rarely exceed the WHO guideline value of 30 µg/L.( 30 µg/L.a3):Bicarbonate , and wasting (ca. 12%) in under-five year old children . These underweight children are susceptible to chronic diseases in later life. Magnesium deficiency during pregnancy can lead to low birth weight [Despite considerable improvement in national health status, children and women in Bangladesh suffer from high levels of malnutrition and micro-nutrient deficiencies ,55. Thish weight ,57. In BDeficiency in Mg during pregnancy, as well as in adulthood has been linked to glucose intolerance potentially leading to type 2 diabetes ,59. The As well as a nutrient for bone health , Ca has also been (in association with Mg) linked with hypertension by number of previous studies e.g., . The Ca The widespread nature of “Ca undernutrition” almost certainly contributes to the emergence of rickets in Bangladesh and the prevalence of osteoporosis . In soutPrevious studies have shown that hard water  is good for blood pressure regulation in the body, and soft-water has been linked with cardiovascular diseases see . In Banghttp://www.dghs.gov.bd, accessed on 5 August 2014) indicates that the numbers of patients are low in areas where tube wells have a higher Fe concentration  located in different areas of the county (The Bangladesh Arsenic Mitigation Water Supply Project (BAMWSP) has undertaken field screening of around 5 million tubewells. This shows that, of the wells tested, 29% contained As above the Bangladesh standard of 50 µg/L . The BAMe county . Althouge county .The components in drinking water are generally analysed in order to avoid passing on chemicals harmful to human health. In contrast, little, if any, attention is given to constituents beneficial to health. WHO guideline values for drinking water reflect this and are essentially set for toxic elements, along with micro-nutrients that are essential at certain concentrations but become a health problem when in excess . No guidAlthough the groundwaters sampled contain some beneficial minerals, it is also found, for example, that wells containing high levels of Fe also may contain excessive levels of dissolved As. In addition, some of these wells also contain beneficial levels of Ca and Mg, thus further complicating the situation c. Human http://www.who.int/nutrition/topics/ida/en/, accessed on 20 August 2014). Most Asian deltaic groundwaters contain significant amounts of Fe, although the bioavailability of this iron is not fully understood [3, are at concentrations too low to have any serious impact on human health.Iron is the single micro-nutrient whose deficiency affects >2 billion people in the world and a great majority of these people are living in developing countries  lead to carbonate dissolution along with silicate weathering and therefore increased levels of Ca, Mg, HCOpe water .3 from the recharging water, leading to the release of Mn and Fe and, consequently, the release of adsorbed As on MnOOH and FeOOH minerals into solution [3 [i.e., within ca. 100 bgl). Deeper groundwater, which is typically a few thousand years old [ca. 100 m.The high organic content within these aquifers help drive microbial reduction, which removes any infiltrating dissolved oxygen and NOsolution . Among tution [3 . The redution [3 , they arution [3 . The difears old  rarely cWhere intake through food is insufficient, the addition of nutrients contained in drinking water may help those in such circumstances attain the daily required intake. Our exploratory research in Bangladesh indicates that the levels of nutrients in groundwater is so substantial that in some areas individuals can obtain up to 50% or more of the RDI  from just two litres of drinking water. Consumption of groundwater is therefore promoting better heath in some areas, whilst in other areas the lower nutrient content in groundwater may contribute to the prevalence of non-communicable diseases including anaemia, hypertension, glucose intolerance (diabetes), rickets and bone deformation.In view of the contribution that groundwater can provide to nutrient intake, this implies that an understanding of the total nutritional level of an individual in such cases cannot be properly determined without considering the contribution of the nutrients and minerals supplied by drinking water. However, there is no known protocol to incorporate drinking-water-derived nutrients in the framework of dietary assessment, and existing dietary assessments do not take into consideration the contribution from drinking water .i.e., tubewells are distributed over a large area with heterogeneous water quality and individually managed.There are no health-based guidelines for beneficial nutrients, though Rosbborg  has suggThis paper has demonstrated the potential health benefits of drinking water nutrients for those with nutrient poor diets, particularly in the case of calcium, magnesium and iron, using limited demographic health data from Bangladesh. The concentrations of beneficial nutrients in many areas of this and other deltas are such that these probably minimize the daily intake gap between the RDI and that obtained from the food. The results indicate a need for further studies with more rigorous quality-controlled health data to evaluate the health benefits. We anticipate the health benefit of groundwater would be similar to Bangladesh in other deltas and should be explored.Drinking groundwater may supply substantial amounts of nutrients beneficial to human health, even though their adsorption by the body and overall health benefits are yet to be fully determined.In addition, groundwater may also contain toxicants and therefore coupling or decoupling the toxicity with other constituents present in the water needs to be studied in an holistic manner.An understanding of the association of non-communicable disease and poor nutrition cannot be developed, particularly in areas with high levels of dissolved solids in water sources, without considering the contribution of drinking water to nutrient and mineral supply.From this exploratory work we would like to put forth the following conclusions:


Adherence is the result of the interaction of the macro, meso, micro, and patient level factors. The macro level includes full coverage of immunosuppressive medications as is the case in Brazil. We studied the correlates of immunosuppressive non-adherence in post kidney transplant patients in the Brazilian health care system.Using a cross-sectional design, adherence to immunosuppressives was assessed in a sample of 100 kidney transplant patients using a composite non-adherence score consisting of three methods . Multilevel correlations of non-adherence were assessed . Univariate and multivariate logistic regression was applied to assess the correlates of non-adherence.Our sample consisted primarily of male (65%), Caucasians (72%) with a mean age of 45.0 ± 13.5 years old, who received grafts from a living donor (89%), with a mean time after transplantation of 72.3 ± 44.4 months. Prevalence of non-adherence was 51%. Family income higher than five reference wages , and having access to private health insurance  were associated with non-adherence in univariate analysis. Only the higher family income variable was retained in the multiple logistic regression model .Higher family income was the only factor that was associated with immunosuppressive non-adherence. In Brazil, lower income recipients benefit from better access to care and coverage of health care costs after transplantation. This is supposed to result in a better immunosuppressive adherence compared to high-income patients who have experienced these benefits continuously. Kidney transplant (KTx) is considered the best therapeutic option for patients with chronic kidney disease (CKD), both from a clinical and economic point of view . In termWHO proposes that NA to treatments is a result of a complex, multidimensional, and multilevel interaction between socioeconomic factors, condition, treatment and patient related factors as well as health care team and health system characteristics . Yet, whPatient-level factors include, for instance, individual characteristics, self-efficacy, and attitudes. Micro-level factors refer to the quality of interpersonal relationships with health care professionals and social support. Meso-level factors encompass the characteristics of the health care organization where the patient is being treated . Macro-level factors refer to the characteristics of the health care system where the patient lives and includes local, state, and national laws and policies related to health such as insurance coverage and regulations on reimbursement for medication [dication ,13.Understanding risk factors for NA provides a basis for targeting modifiable factors through preventive and restorative interventions ,14. GiveBrazil is specific case in transplantation, both in volume and in overall health policy framework for transplantation. The number of transplants in Brazil has progressively increased in the last ten years. Although Brazil is ranked 2nd in the absolute number of kidney transplants performed worldwide, the rate of 28.5 kidneys transplants pmp is still far below the country´s requirement ,16. NeveGiven the inherent challenges of the Brazilian Health Care System in view of transplantation and their potential specific impact on NA levels, and given the limited evidence in the view of the magnitude and risk factors of NA to immunosuppressives in Brazil, this study aims to determine the prevalence of NA to immunossuppresives in a Brazilian KTx population, applying standardized methods and to explore multilevel risk factors of NA.The local Ethics in Research Committee  approved this study .We conducted a cross sectional study in a single kidney transplant center in Brazil between May to December 2010.We evaluated a convenience sample of 100 KTx patients followed up in the outpatient clinic of the Núcleo Interdisciplinar de Estudos, Pesquisas e Tratamento em Nefrologia of the Federal University of Juiz de Fora, in Brazil. Patients were included if they were at least 18 years old, more than a year post-transplant, and provided written informed consent. Exclusion criterion was retransplant.We retrieved demographic and specific clinical variables from the medical files.In the absence of a gold standard for the assessment of NA, triangulation of different diagnostic methods is favored ,20. A vaSelf-report: We used The Basel Assessment of Adherence Scale for Immunosuppressives (BAASIS), of which the Brazilian Portuguese version was recently validated by our group  . The fouCollateral report was provided by the nurse and the medical assistant directly responsible for the follow-up care of the KTx recipients. They categorized patients as good, fair, or poor adherers. NA was defined as a fair or poor upon evaluation by one or both clinicians .Assay: Patients´ adherence was also measured trough blood levels of the immunosuppressives drugs. Based on our service’s adopted guidelines, which consists of a therapeutic range of 100–150 ng/ml for cyclosporine, 5–10 ng/ml for sirolimus and tacrolimus, blood levels were analyzed in five time points: at the moment of the BAASIS interview and at the four prior outpatient clinic appointments. Patients with blood levels within the therapeutic range used by our center were categorized as adherent and those with levels below the accepted values were considered as non-adherent. The study staff performed clinical evaluations of patients with deviating values before they were categorized as non-adherent. Interpretation was based on the patient’s medical conditions as well as their medication blood levels [Composite adherence score: The findings from the self-report, collateral report, and blood assay were combined to calculate a composite adherence score . OverallPatient-level, factors included were Socio-economic factors: age (years and younger than 25 years old), gender, race , highest level of education , employment status (yes or no), marital status (married/steady partner or not), family income  [Micro-level, the patients evaluated the quality/satisfaction of their relationship with their health care providers (physician and nurse) by rating these as good, fair, or poor [Meso-level, city of origin (same or different from transplant´s center) and access to the center , were evaluated. At the Macro-level, private health insurance coverage (yes or no) was measured [Multilevel correlates of NA included were following. At ,100.00) , current or poor . At the measured .All patients attending routine visits between 1 May to 1 December 2010, who fulfilled the study inclusion criteria and did not have the exclusion criterion, were invited to participate in the study. They received written and oral information before signing the written informed consent form. Trained nurse interviewers who were part of transplantation team administered the BAASIS. Both the renal nurse and the physician treating the patient filled out the collateral report form. The blood assay was collected from the medical files. Correlates were assessed by interviewers or were collected from the medical files .Baseline characteristics were described as frequencies or as mean ± standard deviation and median/interquartile ranges as appropriate, after checking the level of measurement and distribution of variables using the Kolmogorov-Smirnov and Shapiro-Wilk tests. The T-Test, Chi-square, Mann-Whitney, or Fisher´s tests were used to compare adherent with non-adherent patients according to the assessed correlates.Multivariate Logistic Regression analysis was performed to assess the association between the variables with NA as the outcome. We only included the variables  with a p value of <0.20 in the univariate analysis in the model. Statistical analysis was performed using the SPSS software v.19.0 . A p value <0.05 was considered significant. All collected data is summarized in From a total of 154 patients, 133 were determined to be eligible for the study. We included the first 100 who accepted the invitation to participate . Given tThe composite adherence score showed that 51% of patients were non-adherent. In multivariate analysis, only having a family income higher than five reference wages was independently associated with NA outcome . Based on the triangulation of assessment methods for NA, this cross-sectional study involving Brazilian KTx patients, revealed that 51% of subjects were non-adherent to their immunosuppressive medications. This peculiar population is provided with free immunosuppressants and with a more favorable access to health care after transplantation, especially those patients with only public health insurance before KTx. Our study is one of the few that have assessed the multilevel correlates of NA in transplantation. It is the first, to our knowledge, to study the correlates of NA in Brazilian KTx patients. Through multivariate analyses, we found that patients with higher incomes showed more NA, an unexpected yet reasonable finding from the gift-exchange relationship . One hypThe high level of NA (51%) in our study can only be compared to a few other Brazilians reports ,26,27,28Considering the potential consequences, the frequency of NA of our study is somehow worrying. Overall, a median of 22% non-adherent recipients (varying from 1.4 to 66.7%) has been reported in cross-sectional studies . On the Based on the methodology of triangulation, applying three measurements tools, a unique study involving KTx patients found a similar percentage (60%) of NA . CompareHowever, our rates of NA can still be considered elevated, because immunosuppressive medications are freely provided to transplant patients in Brazil. In other countries with the same health policy of free access to immunosuppressives, the prevalence of NA was lower and varied from 34 to 45%, based on only one method of NA assessment ,32. ThisWe investigated many potential correlates, comprising the four levels of NA based on the Ecological Model. Some classic correlates associated with NA were not detected in our study, such as younger age and male sex) , 33. NA Our study has some important limitations. First, the convenience sample was relatively small and composed mostly of recipients of living donor grafts from a single center. Although the deceased donors’ recipient numbers are not representative of our study, recent substantial evidence favors living kidney allograft as a risk factor for NA in KTx . ConsistUsing appropriate methodology of triangulation, we studied prevalence and correlates of NA immunosuppressives in a population of Brazilian post adult KTx patients, who received full-access to immunosuppressives. High levels of NA were found and having a high income was the single variable associated with NA. These findings are unexpected for a population from a developing country, like Brazil, where the underprivileged conditions are more likely to be associated with NA behavior. They also reinforce the need for the evaluation of the correlates to NA in specific populations before designing strategies to reduce NA.S1 Appendix(SAV)Click here for additional data file.


Xanthogranulomatous inflammation is an uncommon form of chronic inflammation that is destructive to the normal tissue of affected organs. Although xanthogranulomatous endometritis and xanthogranulomatous salpingitis of the female genital tract has been described previously, to the best of our knowledge, this is the first report of xanthogranulomatous inflammation with infiltration into the uterine myometrium from the perimetrium without endometritis.A 68-year-old Japanese woman with intermittent lower abdominal pain and low-grade fever who was initially treated with antibiotics underwent hysterectomy due to abscess formation in the posterior wall of the myometrium and perimetrium . Histopathological findings revealed that the abscess was caused by xanthogranulomatous inflammation with the granulation tissue and chronic inflammatory cells that consisted of focal and sheets of foam cells. The inflammation destroyed the perimetrial elastic lamina, and the myometrium was deeply infiltrated by the xanthoma cells. Neither endometritis nor salpingitis was coexistent with the xanthogranulomatous inflammation.The patient was diagnosed as xanthogranulomatous inflammation, most likely arising from the perimetrium. Our findings suggest that the perimetrium, as well as the endometrium and adnexae, is one of the origins of xanthogranulomatous inflammation in female genital tract. Xanthogranulomatous inflammation (XGI) is an uncommon form of chronic inflammation that may destruct the normal tissue of affected organs. Histopathologically, it is characterized by a marked proliferative fibrosis, parenchymal destruction, and infiltration of foamy histiocytes intermixed with other inflammatory cells.XGI has been reported in multiple organs, most commonly in the kidney and gall bladder, and less commonly in the female genital tract ,2. XGI iA 68-year-old  post-menopausal woman presented to our hospital with vaginal bleeding. She had a history of multiple uterine fibroids over the past 20 years, but no history of endometriosis, pelvic inflammatory disease, use of an intrauterine device, or surgery. Her family history was unremarkable.Escherichia coli was detected in her vaginal culture. She was diagnosed with endometritis and treated with antibiotics (levofloxacin). In addition, the cytology of the endometrium showed atypical columnar cells with inflammation, for which further examination was recommended to rule out malignancy. After her symptoms improved, endometrial biopsy was performed under levofloxacin. Pathologically, inflamed endocervical mucosa and endometrium were observed, but no malignant cells were detected. The white blood cell count was 8.3 × 103/uL. Six weeks later, she visited our hospital again due to persistent low-grade fever and abdominal pain. Transvaginal ultrasonography revealed an irregularly shaped mass, 6 cm in diameter, in the posterior wall of the myometrium. Contrast-enhanced computed tomography (CT) scan suggested an intramural abscess besides multiple uterine fibroids. Magnetic resonance imaging (MRI) also revealed an irregularly shaped mass, 6 cm in diameter, which was localized in the posterior wall of the uterus  and abdominal pain. n Figure A. The cun Figure B. Microsn Figure C and D. XGI is a rare inflammatory disease, which may affect various organs, including the kidney and gallbladder ,2. XGI iOne of the primary differential diagnosis of XGI is malignancy ,13. IndeHere, we have reported a case of severe XGI, originating from the perimetrium into the deep posterior uterine myometrium. Our case highlights the need for careful assessment of the inflammatory diseases in female genital tract. Pelvic inflammatory diseases are commonly associated with sexually transmitted diseases, intrauterine devices, or previously experienced surgeries, and the inflammations commonly originate from the adnexae and the endometrium. However, our case indicated that the inflammation of the perimetrium might deeply infiltrate into the myometrium and cause dense adhesion with the colorectum. Thus, careful considerations are warranted to diagnose the origin of the inflammatory diseases and to appropriately treat the diseases in the female genital tract.Written informed consent was obtained from the patient for publication of this Case report and any accompanying images.XGI: Xanthogranulomatous inflammation; CT: Computed tomography; MRI: Magnetic resonance imaging; CRP: C-reactive protein.The authors declare that they have no competing interests.All authors have made substantial contributions to the diagnosis and treatment of this case. TI and KO: treated the case and wrote the manuscript. YT, DM and MF diagnosed the case pathologically. TS, TA, KK, YO, and TF contributed to the diagnosis, obtained informed consent, and determined the management of the case. All authors read and approved the final manuscript.Drs. TI (MD) and TS (MD) are obstetricians and gynecologists, and are graduate students of “Graduate Scool of Medicine, The University of Tokyo”. Drs KO  and KK  are gynecologic oncologists, and are associate professors of “Department of Obstetrics and Gynecology/Graduate School of Medicine, The University of Tokyo”. Dr. TA is a gynecologic oncologist, and a project assistant professor of “Department of Obstetrics and Gynecology, The University of Tokyo” Drs. YT  and DM  are pathologists, who have a specialty of gynecologic pathology. Dr. MF  is a professor of “Department of Pathology, The University of Tokyo”. Drs. YO  and TF  are professors of “Department of Obstetrics and Gynecology/Graduate School of Medicine, The University of Tokyo”.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6874/14/82/prepub


In 2005, Bangladesh, India, and Nepal joined forces to eliminate Visceral Leishmaniasis  from the region by 2015. In Bangladesh the elimination target is set at less than one new case per 10,000 population per year at upazila (sub-district) level. As the deadline approaches, we review the status of the elimination initiative in this country.We collected all available disease surveillance data at the Disease Control Unit of the Directorate General of Health Services, Government of Bangladesh from 1994 to 2013. Additionally, we retrieved data from the Civil Surgeon Office from the Mymensingh district, one of the most heavily affected areas in Bangladesh.Between 1994 and 2013, 109,266 kala-azar cases causing 329 deaths were reported from 37 endemic districts in Bangladesh. Only 16 districts reported cases every year. The Mymensingh district was the most affected with 53,582 (49.04%) cases. Between 2008 and 2013 only 16 upazilas showed incidence rates above the elimination target in which they ranged from 1.06 to 18.25 per 10,000 people per year.While clear progress has been made towards eliminating VL, 16 upazilas in Bangladesh had not yet reached the target in 2013, based on official notification data that probably suffered from under-reporting bias. The elimination initiative urgently needs to establish methods to ascertain and monitor the elimination target. Leishmania donovani, which is transmitted from man to man by the sand fly Phlebotomus argentipes, the only known vector On the Indian subcontinent, Visceral Leishmaniasis (VL), or kala-azar, is caused by L. donovani, (ii) Phlebotomus argentipes is the only vector, (iii) the disease is confined to a limited number of districts, (iv) a rapid diagnostic test allows easy diagnosis, and (v) effective oral treatment was available In 2005, Bangladesh, India, and Nepal joined efforts to eliminate kala-azar. Elimination was thought feasible in this region because (i) human beings are considered the only reservoir host of For any disease control program, proper epidemiological surveillance is a key issue. It allows for the establishment of the past and present disease burden, and will guide the program to take timely and appropriate action on case detection, patient management, vector control, and community awareness. In an elimination initiative, routine surveillance data are essential to keep track of the elimination target, though additional measures are required to ascertain the elimination status of given areas. As the set VL elimination target of 2015 is fast approaching, we have analyzed the available epidemiological information in Bangladesh to advise the national and regional disease control policy.Bangladesh is administratively divided into six divisions, namely: Chittagong, Barishal, Dhaka, Khulna, Rajshahi, and Sylhet. All of the divisions except Sylhet are reporting VL cases, but not to the same extent. Each division is further subdivided into districts , sub-districts, called upazilas or thanas , Union Parishads (UPs), and wards. The governmental health care system is structured along the same administrative divisions, with a national, divisional, district, upazila (sub-district), union, and ward level. Three levels in this system deliver VL treatment: (i) the Upazila Health Complex (UHC)  (ii) the District Sadar Hospital (DSH) , and (iii) Medical Colleges. A UHC caters to a population of 200,000 to 300,000, while a DSH covers approximately 2 to 5 million inhabitants.Disease surveillance is organized as follows. At the end of each month, the UHC and DSH send their morbidity and mortality reports to the Civil Surgeon Office at the district headquarters. The District Civil Surgeon transmits these reports to the Director of Disease Control at the Directorate General of Health Services (DGHS), who will notify country data to the World Health Organization. As is commonly the case in routine surveillance, these figures are an underestimation of the true number of VL cases. Medical colleges do not report although some VL patients get reported when they are referred back to the UHC or DHS after some days of treatment. This happens quite often, as VL drugs are provided for free in the public health services but are not always available in the medical colleges. Another important factor to consider when analyzing trends in the surveillance data is the recent change in drug policy. While the injectable Sodium Stibogluconate (SSG) was the only drug of choice for many years, since the middle of 2009, the oral drug Miltefosin was introduced as first-line drug (except for women of childbearing age and pregnant women). As this drug is not available in the local market, patients are now more motivated to attend a UHC to get this oral medication. The recent introduction of single-dose AmBisome therapy also attracts VL patients to the UHC, as does the recent involvement of one international Non-governmental organization (NGO), Médecins Sans Frontières (MSF), in VL care.We have collected all data on VL available at the central level (DGHS) for the years 1994 to 2013. We also collected district-level data for the Mymensingh district from the Civil Surgeon's Office in Mymensingh for the same period. As the VL elimination target is set at the upazila level “to reduce VL incidence rate below one per 10,000 population per year at upazila level,” From 1994 to 2013, the DGHS of Bangladesh reported 109,266 cases of VL and 329 VL-related deaths from 37 endemic districts. During this 20-year period, there were three years  with more than 8,000 reported cases. The highest number of cases was reported in 2006, and the annual number of cases diminished after that peak year . AltogetThe most affected upazilas are situated in the Dhaka division, reporting the highest number of cases of all the divisions . From 2008 to 2013, there were 16 upazilas in nine districts with an average IR exceeding the elimination target, ranging between 1.06 to 18.25 per 10,000 inhabitants .From 2011 to 2013 there were 409, 325, and 240 post kala-azar dermal leishmaniasis (PKDL) cases reported from the Mymensingh district. No country-wide PKDL data are available up to 2012, and 325 cases were reported country-wide in 2013.The VL elimination program was launched in 2005, and its target was set to reduce the number of cases at upazila level below one case per 10,000 people by 2015 About half of the total numbers of VL cases were reported from a single district (Mymensingh), where five upazilas are highly endemic. Therefore, the national program should intensify its efforts in these areas with high priority. Due to VL, there is a huge economic loss for the affected families in an endemic community In 2011, the Fulbaria upazila of the Mymensingh district reported 1,608 cases. The most likely explanation for this high figure is that in mid-2010 an international NGO (MSF) started a VL control program in this upazila through active case search and treatment with AmBisome. They also provided food during hospitalization, and compensation for transport and wage losses. This intervention attracted a high number of patients, including some living in nearby upazilas, who used the address of their relatives or friends in Fulbaria as their own address in order to get access to the best facilities.Passive surveillance records show 329 patients died in 20 years (1994–2013), which is probably an under-estimation, as there was drug scarcity before the introduction of Miltefosine as a first-line drug. Poor quality SSG was used during periods of drug scarcity, and there was a major incidence of the use of substandard Miltefosine for a certain period, which added to mortality The reporting of PKDL cases should be strengthened, as country-wide data are lacking up to 2013. A recent study from Bangladesh shows that the cumulative incidence of PKDL can be up to 17% within five years of being treated for kala-azar Effective progress towards VL elimination requires continuous surveillance  of mortaMeasure the past and present disease burden.Guide national program to take timely and appropriate action on:○Patient management○Vector control○Community awareness through IECPrevent unnecessary program expenditure, i.e., accurate surveillance record will provide guidance on specific areas in which to take necessary actions instead of in the whole upazila or union.Predict future burden.Human resources responsible for epidemiological surveillance, including data management, require intensive training and supervision.Effective surveillance is crucial to understand the real burden of disease and for taking timely action.It is essential to have a proper referral system for the VL patients so as to avoid the duplication of reporting.Community-level health staff needs training to identify the cause of death.The private sector clinics and practitioners should be involved in the reporting system for VL.Bern C, Chowdhury R (2006) The epidemiology of visceral leishmaniasis in Bangladesh and prospects for improved control. Indian J Med Res 123: 275–288.Mondal D, Alam MS, Karim Z, Hague R, Boelaert M, et al. (2008) Present situation of vector control in Bangladesh: a wake up call. Health Policy 87: 369–376.Ahluwalia IB, Bern C, Costa C, Akter T, Chowdhury R, et al. (2003) Visceral Leishmaniasis: Consequences of neglected disease in a Bangladeshi community. Am J Trop Med Hyg 69: 624–628.Ahluwalia IB, Bern C, Wagatsuma Y, Costa C, Chowdhury R, et al. (2004) Visceral Leishmaniasis: Consequences to Women in a Bangladeshi Community. J Womens Health (Larchmt) 13: 360–364.Anoopa Sharma D, Bern C, Varghese B, Chowdhury R, Haque R, et al. (2006) The economic impact of visceral leishmaniasis on households in Bangladesh. Trop Med Int Health 11: 757–764.


In the current and past decades, associations between sleep impairment and glucose control in individuals with diabetes have been unveiled. Sleep disorders and curtailment were shown to deteriorate glycemic control, while glycemic extremes impact sleep quality and melatonin secretion, forming a vicious circle.Our aim with the present study was to identify associations between glycemic control and parameters of the sleep-wake cycle, with emphasis on the sleep quality, of adults with type 1 diabetes mellitus (T1D), a population poorly studied in the sleep field.Eighteen non-obese adults with T1D , without chronic complications were studied. The following instruments were used during ten consecutive days: sleep diaries , actimeters, and a home fingertip glucometer (6.41±1.5 tests a day). The analysis was made using fitted inflated beta regression models with GAMLSS for the response variable sleep quality rate (SQR). Subject-level covariables in this dataset included: number of hyperglycemia and hypoglycemia episodes in the previous day, number of awakenings during the night, morning awakening type (spontaneous or not), sleep rate , and the corresponding interactions.The SQR was negatively associated with the sleep rate (p<0.001), and positively associated with spontaneous awakening (p=0.042). The relationships between the other variables with SQR were the following: the SQR rises with the increase of both, hypoglycemic events and sleep rate (p=0.002). On the other hand, when the hypoglycemic or hyperglycemic events are associated with non-spontaneous awakening, the SQR decreases (p=0.02 for both glycemic conditions). However, the SQR increases when both the number of hyperglycemia and the number of night awakenings increase (p=0.01).The present study contributes with a specific understanding that T1D, especially through its glycemic excursions, impacts the sleep-wake cycle in different ways, with emphasis on the sleep quality. Thus, the previously proposed vicious circle involving sleep and diabetes is reinforced. Considering that, health care professionals should be encouraged to pay attention to sleep patterns and complaints of patients, in order to identify and address hidden poor glycemic control, and, this way, help to improve this population's sleep and life quality.


Numerous studies have demonstrated that fasting serum glucose (FSG) levels and certain single-nucleotide polymorphisms (SNPs) are related to an increased risk of colorectal cancer (CRC); however, their combined effects are still unclear.Of a total of 144,527 men and women free of cancer at baseline, 317 developed CRC during 5.3 years of follow-up. A case-cohort study  was used, consisting of participants with a DNA sample available. Three well-known SNPs  were genotyped. Hazard ratios (HR) and 95% confidence intervals (CI) of CRC, colon and rectal cancer were calculated, with the Cox proportional hazard models.The crude incidence rates per 100,000 person-years were 41.1 overall, 48.4 for men, and 29.3 for women. Among participants with dysglycemia, SNPs rs3802842 and rs6983267 were both associated with an increased risk of CRC  and rectal cancer . The interaction effect of dysglycemia and SNPs was positive, that is, resulted in an elevated risk of CRC, but was not statistically significant.This study demonstrates that both high FSG and certain SNPs are major risk factors for CRC and rectal cancer but that they did not interact synergistically. The difference in effect size of the SNPs according to CRC subtype  and presence of dysglycemia merits further research. Colorectal cancer (CRC) is one of the most common cancers worldwide. In Korea, the standardized incidence of CRC has increased from 21.2/100,000 people in 1999 to 57.6/ 100,000 people in 2012 . In partAlthough colonoscopy plus biopsy is the gold standard for CRC screening and diagnosis, more than half of all patients do not want to undergo this procedure because of the invasive nature and intestinal discomfort of colonoscopy . CompareAlthough many epidemiologic studies of CRC have investigated diabetes and genetics as risk factors, there has been a limited exploration of their combined effects, reflecting limitations posed by the study population size and the exposure data available in the studies carried out to date. Detecting synergism among common risk factors would have substantial public health and clinical relevance because it would identify some individuals who are at extremely high risk. It is well known that early discovery of high-risk groups is beneficial in reducing CRC incidence and mortality by enabling management of risk factors .We have conducted a prospective cohort study of the causes of cancer in Koreans. Blood samples and information concerning diabetes were available for all participants in this large cohort. Follow-up was accomplished through record linkage at the national level and was complete except for emigrants. Here, we describe the risk for CRC in relation to fasting serum glucose (FSG) and SNPs over 5.3 years of follow-up, during which there were 234 diagnoses of CRC among our cohort of 117,258.Participants for this study were drawn from a pool of 270,514 individuals  who had voluntarily undergone health examinations in 11 centers located in Seoul and Kyunggi provinces in Korea from 1994 to 2010, which were used as the baseline. Of these individuals, 159,844 provided informed consent and were followed prospectively, forming the cohort of participants in the Korean Cancer Prevention Study-II (KCPS-II). A full description of KCPS-II has been previously published [Each participant was interviewed by using a structured questionnaire to collect the following details: smoking history , alcohol drinking , and regular exercise (yes or no). Participant’s height and weight were measured while the participants were wearing light clothing. BMI was calculated by dividing the weight (kg) by the square height (m2). Systolic and diastolic blood pressures were measured after a rest period of at least 15 minutes.For clinical chemistry assays, serum  was obtained from each participant after a minimum fasting period of 12 hours and stored at -70°C until the time of analysis. Levels of FSG, total cholesterol, triglyceride, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were measured by using a Cobas Integra 800  and a Hitachi-7600 analyzer .As genetic factors for the risk of CRC, three well-known SNPs  were selected from previous studies [Data regarding the incidence of CRC were obtained from the records of the National Cancer Registry. All incidence of CRC was confirmed by histological cell type. According to the International Classification of Diseases, 10th revision (ICD-10), CRC was coded as C18-C20 . Deaths Person-years were calculated from the baseline enrollment to December 2012 or the date of CRC diagnosis, death, or loss to follow-up. Crude incidence rates  were calculated from the person-years and number of cases of CRC. Hazard ratios (HRs) were calculated by using the Cox proportional hazard model, after adjusting for age, sex, BMI, smoking status, alcohol consumption, and regular exercise. These analyses were used after the FSG levels were divided into four categories on the basis of cut-offs at 100 mg/dL, 110 mg/dL, and 126 mg/dL. A chi-square goodness-of-fit test was used to assess whether the SNPs were in Hardy-Weinberg equilibrium and to identify differences in genotype frequencies between CRC cases and controls. All statistical tests were two-sided, and statistical significance was determined as p<0.05. SAS version 9.2  was used for all analyses.2 or above and 3.5% of the men and 1.6% of the women above 30 kg/m2. Both smoking and alcohol use were substantially more common in men than in women.The basic characteristics of the participants  are summarized in 95% CI, 1.6 to 7.1, respectively). The interaction effect of dysglycemia and SNPs was positive, resulted in an elevated risk of CRC, but was not statistically significant.In this large prospective cohort study of the Korean population, we found that high FSG and SNPs rs3802842 and rs6983267 were independent risk factors for CRC, colon, and rectal cancer. No interaction between these risk factors was observed.In particular, we found that hyperglycemia, including IFG, was associated with CRC incidence, indicating that pre-diabetic status might be related to colorectal carcinogenesis. This finding was consistent with those of several previous studies ,8, althoWhen considering early exposure to risk factors for a disease, genetic factors are obvious candidates because exposure begins before birth and continues for an entire lifetime. In the present study, the incidence of rectal cancer was associated with both SNPs rs3802842 and rs6983267 . Also, SOur study has several potential limitations that arise primarily from the use of data collected as part of routine medical examinations. The statistical power of the current study may have been too low, since genotyping was performed only in a limited sample. In addition, our study cohort was not necessarily representative of all Koreans because it included only employed persons and their families. However, follow-up should be almost complete because of our use of record linkage with unique personal identifiers to national databases; thus, any loss to follow-up is unlikely to have introduced bias.Our study has analyzed the possibility of a mutual interaction of diabetes and genetic factors as a potential predictor of CRC, and is of importance to the public health and health promotion sectors. Research efforts should continue to analyze the interactions between genetic factors, environmental risk factors, and prognostic factors that are associated with CRC.