Self-management is the cornerstone of diabetes control and prevention of complications; however, it is undetermined whether differences in intention to adopt healthy lifestyles and actual healthy behavior exist across race/ethnic groups. This study evaluated the differences across racial-ethnic groups in self-reported medical advice received and health intentions and behaviors among adults with type 2 diabetes mellitus.A cross-sectional analysis of the 2007 SHIELD US survey ascertained self-reported health intentions and behaviors for regular exercise, diet, and weight management among Non-Hispanic Caucasian (n = 2526), Non-Hispanic African-American (n = 706), and Hispanic (n = 179) respondents with type 2 diabetes.A similar proportion of respondents from each race-gender group (43%-56%) reported receiving healthcare advice to increase their exercise (P = 0.32). Significantly more minorities reported an intention to follow the exercise recommendation compared with Non-Hispanic Caucasians (P = 0.03). More Non-Hispanic African-American (29%) and Hispanic (27%) men reported exercising regularly compared with other race-gender groups (P = 0.02). Significantly more Non-Hispanic Caucasian women (74%) and Hispanic women (79%) reported trying to lose weight compared with other groups (P < 0.0001).Differences in health intentions and healthy behaviors were noted across race-gender groups. More Non-Hispanic African-American men reported an intention to follow advice on exercising and self-report of exercising regularly was also higher compared with other race-gender groups. More Hispanic men reported high physical activity levels than other groups. Despite an increased willingness to follow healthcare recommendations for diet, >50% of respondents were obese among all race-gender groups. In the United States, considerable variation by race and ethnicity exists in healthcare access and utilization for a number of diseases and conditions -4. It isStudy to Help Improve Early evaluation and management of risk factors Leading to Diabetes (SHIELD). SHIELD, a large US population-based survey, provides longitudinal data on healthcare providers' health recommendations, individuals' intention to follow the health recommendations, and actual health behaviors practiced by adults with type 2 diabetes. It is undetermined whether physicians provide similar health recommendations to their patients with type 2 diabetes who are Caucasian versus minorities and whether minority patients intend to and actually follow the recommendations compared with Caucasians.To investigate whether there are differences across racial-ethnic groups in the self-reported information provided to adults with type 2 diabetes mellitus by their healthcare providers or differences in the health intentions and behaviors among these individuals, we analyzed data from the A cross-sectional analysis of the 2007 SHIELD survey data was conducted to determine if differences exist across racial-ethnic groups for self-reported clinical advice from healthcare providers regarding diet and exercise and respondents' intention to follow the advice and their health behaviors among individuals with self-reported diagnosis of type 2 diabetes.SHIELD included an initial screening phase to identify cases of interest in the general population , a baseline survey to follow up identified cases with a questionnaire about health status, health knowledge and attitudes, and current behaviors and treatments, and annual follow-up surveys. A detailed description of the SHIELD methodology has been published previously ,17.In brief, the screening survey was mailed on April 1, 2004, to a stratified random sample of 200,000 U.S. households, representative of the U.S. population for geographic residence, household size and income, and age of head of household , identifThe baseline survey was mailed in September-October 2004 to a representative sample of individuals  who were identified in the screening survey as having self-reported type 1 diabetes mellitus or type 2 diabetes mellitus, no diabetes, or being at risk for diabetes. The baseline survey and the subsequent annual follow-up surveys were sent to the individuals of interest and not the original head of the household. Each respondent group was balanced to be representative of that population for age, gender, geographic region, household size, and income for the U.S. population, and then a random sample from each group was selected and sent the baseline survey. A response rate of 72% was obtained.Annual follow-up surveys were mailed to all individuals from the baseline survey who were still enrolled in the TNS NFO panel. To better understand the role that race and ethnicity may have on disease and lifestyle management, the mailing for the 2007 survey was increased with a targeted sample of minorities (African-Americans and Hispanics). Minority respondents from the 2004 screening survey who had not been selected for the baseline survey were invited to complete the 2007 survey. From the supplemental minority sample, 4,125 African-American and 1,674 Hispanic respondents completed the 2007 survey. This analysis used the combined survey responses from the core 2007 sample and the supplemental minority sample, with a total response rate of 69%. Only respondents with a diagnosis of type 2 diabetes (n = 706 African-American and 179 Hispanic) were included in the analyses. The SHIELD study was approved by the Quorum Review Board.Respondents were classified as having type 2 diabetes based upon their self-report of having been told by a doctor, nurse, or other healthcare professional that they had type 2 diabetes. Medical advice regarding exercise and diet, an individual's intention to follow the recommendations, and current exercise and weight management were assessed. For exercise, respondents were asked, "In the past 12 months, has a physician, nurse or other health professional recommended that you increase the amount that you exercise?" (yes/no) and "Do you intend to follow their recommendations?" (yes/no). To capture attitudes about the benefits of exercise, respondents were asked, "How likely do you think it is that increasing the amount of exercise you do will keep you healthy?" Response categories included very unlikely, unlikely, don't know, likely, and very likely. Current exercise behavior was captured by asking, "Which of the following statements best describes your current exercise routine?: 1) I currently do not exercise and I do not intend to start exercising in the next 6 months; 2) I currently do not exercise, but I am thinking about starting to exercise in the next 6 months; 3) I currently exercise some, but not regularly; 4) I currently exercise regularly, but have only begun doing so in the last 6 months; and 5) I currently exercise regularly and have done so for longer than 6 months." Additionally, the type and length of physical activity over the previous 7 days was assessed through the 7-item International Physical Activity Questionnaire (IPAQ) short form . The IPA2), overweight (BMI 25.0-29.9 kg/m2), and obese (BMI ≥ 30.0 kg/m2).For diet and weight management, respondents were asked, "In the past 12 months, has a physician, nurse, or other health professional recommended that you change what you eat?" (yes/no) and "Do you intend to follow their recommendation?" (yes/no). Weight management behavior was reported as the response to "have you tried to lose weight during the last 12 months?" (yes/no). Respondents were also asked, "In the past 12 months, have you tried to change anything in your diet or your physical activities in any way to improve your health?"(yes/no). Body mass index (BMI) was calculated based on self-reported height and weight. BMI scores were categorized as normal weight (BMI < 25.0 kg/mRace and ethnicity were self-reported as two separate questions: 1) "Are you of Spanish/Hispanic descent?" and 2) "Of what race do you consider yourself?" Individuals who reported that they were of Spanish/Hispanic descent were categorized as Hispanic regardless of the race reported. Respondents were categorized as "Caucasian, non-Hispanic" if they reported Caucasian race and no Hispanic descent. Likewise, respondents were categorized as "African-American, non-Hispanic" if they reported African-American race and no Hispanic descent. Asian or Pacific Islander, American Indian, Aleut Eskimo or other race respondents (n = 130) were excluded from the analysis due to small sample and heterogeneity of these groups. Annual household income was self-reported in categories of <$30,000, $30,000-$49,999, $50,000-$74,999, and ≥$75,000. Education levels were classified as high school degree or less, some college, college degree, and graduate work or degree.a priori as a P value < 0.05.Analyses were stratified by gender and household income to assess whether physician recommendations and actual behavior differed between men and women and across income levels. Education level was not used in the stratification because of the high correlation between income and education. Racial-ethnic groups were compared by chi-square test for proportions and ANOVA for means. Statistical significance was established A total of 3,604 respondents with type 2 diabetes completed the 2007 SHIELD surveys. Along with the 130 patients excluded for "other" race, an additional 63 respondents were excluded due to incomplete responses to the survey questions of interest. Among this final cohort  of type 2 diabetes, there were 2,526 (74%) non-Hispanic Caucasian, and 706 (21%) non-Hispanic African-American, and 179 (5%) Hispanic respondents.Comparison of sociodemographic characteristics across the 3 racial-ethnic groups indicated that there were significantly more African-American women (67%) compared with Caucasian (58%) and Hispanic (55%) women (P < 0.01). Hispanics were slightly younger (mean age of 59 years) than African-Americans (62 years) and Caucasians (63 years) (P < 0.05). There were also significantly more African-Americans with low household income  compared with Caucasians (39%) and Hispanics (41%) (P < 0.01). Education level was similar across the 3 groups (P > 0.05).Overall 47% of respondents reported that a healthcare professional recommended an increase in the amount of exercise. A similar proportion of respondents from each racial-ethnic and gender group reported that a healthcare professional had recommended that they increase the amount that they exercise (43%-56%) (P = 0.32) Table . Among tCurrent exercise behaviors differed significantly across racial-ethnic and gender groups (P = 0.02) Table . More AfAmong the subset of respondents who reported receiving medical advice to exercise and that they intended to follow the exercise recommendation (16-24% of each race-gender group), Hispanic men had the lowest proportion (19%) and Caucasian women had the highest proportion (36%) who reported intent to follow the recommendation and exercising regularly. Among men, 35% of Caucasians, 22% of African-Americans, and 19% of Hispanics reported intent to follow the recommendation and exercising regularly. For women, 36% of Caucasians, 28% of African-Americans, and 21% of Hispanics reported intent to follow the recommendation and exercising regularly.From 40% to 57% of respondents indicated that a healthcare professional had recommended that they change what they eat Table . A greatMore than 50% of each race-gender group reported trying to lose weight in the past 12 months  and fewer Hispanic men (49%) reported that they had tried to change their diet or physical activities to improve their health compared with the other race-gender groups  (P < 0.0001). For the subset of respondents who reported receiving medical advice to change their diet and reported that they intended to follow the diet recommendation (19-35% of each race-gender group), African-American men had the lowest proportion (73%) and Hispanic women had the highest proportion (87%) who reported intent to follow the recommendation and tried to lose weight. Among men, 82% of Caucasians, 73% of African-Americans, and 76% of Hispanics reported intent to follow the recommendation and tried to lose weight. For women, 86% of Caucasians, 80% of African-Americans, and 87% of Hispanics reported intent to follow the recommendation and tried to lose weight.Stratification by household income  did not change the associations observed in the race-gender groups. The associations that were similar (P > 0.05) across race-gender groups  were similar for both income levels, and associations that were significantly different across race-gender groups  remained significant for both income levels. Multivariable logistic regression model showed that after controlling for age, education, household income, and obesity, African Americans were more likely to report exercising regularly than Caucasian men but the association was only significant for African American women  indicated that 73% of adults with diabetes were told by a health professional to exercise more  which isThe present study has limitations that should be considered. The determination of type 2 diabetes and obesity were made based upon self-report rather than clinical or laboratory measures; therefore, there may be misclassification bias. However, all respondents were asked the same questions to assess diabetes and weight status. Medical advice, physical activity, diet, and weight management were also self-reported. However, the IPAQ for physical activity assessment is a validated and well-accepted physical activity instrument. Household panels such as the SHIELD study tend to under-represent the very wealthy and very poor segments of the US population and do not include military or institutionalized individuals. Thus, the study findings should not be generalized to these population segments. The survey was provided in English only, thus potentially excluding individuals who spoke other languages, especially among Hispanic households. Given that the supplemental minority sample that was added in 2007 was not part of the random, stratified sampling method at baseline, these minority respondents may not be representative of the African-American or Hispanic populations in the United States. This study examined health intentions and behaviors by race-gender groups which may not represent individual intent-behavior correlation.In conclusion, differences in health intentions and actual healthy behaviors were noted across racial and gender groups. More Non-Hispanic African-American men reported an intention to follow advice on exercising and they reported a greater frequency of exercising than other race-gender groups. More Hispanic men reported high physical activity levels than other groups. Despite an increased willingness to follow healthcare recommendations for diet, more than 50% of respondents were obese among all race-gender groups. More research is needed to better understand how to assist communities in translating intentions for lifestyle change into achievement of healthy behaviors.Dr. Gavin is an advisor to AstraZeneca LP. Dr. Fox received research funds from AstraZeneca LP to conduct the analysis. Dr. Grandy is an employee and stockholder of AstraZeneca LP.JRG participated in the conception and design of the SHIELD study, assisted in the interpretation of the study data, and critically reviewed and revised the manuscript. KMF participated in the design of the investigation, performed the statistical analysis and data interpretation, and drafted the manuscript. SG conceived of the SHIELD study, participated in its design and coordinated the acquisition of data, and critically reviewed and revised the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/11/533/prepub


A gluten-free diet is the only available treatment for celiac disease. Our aim was to investigate the effect of a gluten-free diet on celiac disease related symptoms, health care consumption, and the risk of developing associated immune-mediated diseases.A questionnaire was sent to 1,560 randomly selected members of the Swedish Society for Coeliacs, divided into equal-sized age- and sex strata; 1,031 (66%) responded. Self-reported symptoms, health care consumption , and missed working days were reported both for the year prior to diagnosis  and the year prior to receiving the questionnaire while undergoing treatment with a gluten-free diet. Associated immune-mediated diseases  were self-reported including the year of diagnosis.All investigated symptoms except joint pain improved after diagnosis and initiated gluten-free diet. Both health care consumption and missed working days decreased. Associated immune-mediated diseases were diagnosed equally often before and after celiac disease diagnosis.Initiated treatment with a gluten-free diet improves the situation for celiac disease patients in terms of reduced symptoms and health care consumption. An earlier celiac disease diagnosis is therefore of great importance. In celiac disease (CD), gluten triggers an autoimmune reaction in the small intestinal mucosa which results in inflammation, villous atrophy, and malabsorption. A gluten-free diet is the only effective treatment for CD, and it usually results in recovery of the small intestinal mucosa .During the last 30 years the clinical spectrum of CD has changed from mainly being comprised of young children with overt malabsorption to often affecting adults, with mild or atypical symptoms, and some of those diagnosed with the disease are even asymptomatic . DespiteThe aim of this study was to investigate the effect of a gluten-free diet on CD related symptoms, health care consumption, and the risk of developing associated immune-mediated diseases.A cross-sectional questionnaire survey among Swedish adults with CD was performed during 2009 . The queWe invited randomly selected members of the Swedish Society for Coeliacs to respond to a postal questionnaire administered by the Society, and when needed three reminders were sent. The Society represents about 60% of Swedish CD patients . A questpre-treatment, as well as the year prior to responding to the questionnaire, referred to as today. Regarding drug use, respondents were asked if their CD diagnosis and gluten-free diet had resulted in them being able to stop taking any medication.The questionnaire included sections covering self-reported symptoms, health care consumption, missed working days, and self-reported diseases. For each symptom , rheumatic disease, thyroid disease, vitiligo, alopecia areata, or inflammatory bowel disease. Regarding these diseases the respondents were also asked for the year of diagnosis. As respondents were asked about insulin or non-insulin dependent diabetes, we cannot with certainty differentiate between diabetes mellitus type 1 and 2.pre-treatment and today. Time between diagnoses was calculated as time from CD diagnosis to other disease diagnosis. When both diagnoses occurred during the same year, time was defined as 0 years. Differences in symptoms between members with a recent diagnosis (2005–2009) and members with earlier diagnosis were performed using Students t-test. Comparisons of health care visits, hospitalization days, and missed working days between the groups were performed using Wilcoxon rank-sum test. To test if a gluten-free diet might decrease the risk for associated diseases, the proportions of diagnoses of associated diseases before or during the same year as the CD diagnosis were compared with the proportions after CD diagnosis using Students t-test. We excluded comparisons for vitiligo and alopecia areata due to too few complete answers. Statistical significance was defined at the 5% level. Microsoft Access was used for data handling, while Stata 11.2  was used for statistical analysis and figures.Results are presented using descriptive statistics. The sign-test was used for comparisons between Pre-treatment, flatulence (64%) was the most commonly reported symptom, followed by fatigue (62%), soft stool (54%), and abdominal pain (53%). All investigated symptoms, except joint pain, improved after diagnosis and initiated treatment with a gluten-free diet , all investigated symptoms except vomiting and hair loss, which were rare in our study population, improved after diagnosis. The only differences between recently diagnosed and those with an earlier CD diagnosis was that weight loss and vomiting were less common in the former pre-treatment, joint pain was more common for recently diagnosed cases pre-treatment, and nausea was less common for recently diagnosed cases today.t Figure . Today, fatigue 6%, soft spre-treatment (5.4 visits during the year) than today (3.7 visits during the year) (p < 0.001), more hospitalization days (2.3 days during the year) pre-treatment compared to today (0.7 days during the year) (p < 0.001), and more missed working days pre-treatment (7.2 days during the year) than today (2.5 days during the year) (p < 0.001) (Table pre-treatment and today. For recently diagnosed patients (2005–2009) there were reductions in health care visits and missed working days, but not in hospitalization days. We observed significantly fewer hospitalization days pre-treatment and significantly fewer health care visits today for recently diagnosed patients as compared to patients earlier diagnosed. Thirteen percent of participants (n = 136) reported that they stopped taking at least one drug after their CD diagnosis.Participants reported more frequent health care visits At least one immune-mediated disease was reported by 256 (25%) of the study participants. Autoimmune thyroid disease, reported by 9.1%, was the most prevalent immune-mediated disease Table . There wCD patients suffer from more symptoms and consume more health care before diagnosis and initiated gluten-free diet than they do afterwards. However, we did not observe a difference in the risk of developing other immune-mediated diseases after initiated treatment with a gluten-free diet.This study is one of the largest of its kind and it has a high response rate. Its unique contribution is that it compares the situation before and after initiation of a gluten-free diet, including symptoms and health care consumption, which adds valuable information about individual and societal costs of untreated CD.Our retrospective approach involves the risk of recall bias. We observed a similar pattern for symptom relief, health care visits, and missed working days when restricting our analysis to screened and recently diagnosed 2005–2009) CD patients. There was not a significant reduction in hospitalization days for the recently diagnosed (2005–2009) CD patients. This could indicate an improved situation due to earlier diagnosis, which we have reported earlier in the same population [–2009 CD today, their health consumption was significantly lower today than prior to the CD diagnosis, indicating a decreased need for health care after initiated treatment with a gluten-free diet.Retrospectively reported symptoms prior to a CD diagnosis have been studied previously , as haveThere is a well-known association between CD and other immune-mediated diseases . A proteIn a previous publication based on the same study population and questionnaire, we reported that there is a long delay until CD diagnosis and that CD patients experience a poor health-related quality of life that is significantly improved after initiation of a gluten-free diet . ConsideRecent studies have indicated that the extent of symptoms that patients detected through a population-based CD screening might have may be similar to that of non-CD persons ,30. The In conclusion, CD patients profit from being diagnosed and treated with a gluten-free diet, since this reduces both symptoms and health care consumption. An earlier celiac disease diagnosis is therefore of great importance. The possible protective role of a gluten-free diet regarding the development of other immune-mediated diseases remains to be demonstrated.The authors declare that they have no competing interests.Study design by FN, AI, and LL. FN coordinated data acquisition. FN performed the analyses and the interpretation in collaboration with AI, LL, and OS. FN drafted the paper and all co-authors contributed actively. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-230X/12/125/prepub


Objective: To investigate changes of quality of life (QOL) of patients with adenocarcinoma of the esophagogastric junction (AEG) after gastric tube anastomosis.Methods: From January 2009 to December 2011, eighty-seven patients with Types II and III AEG were selected for gastric tube reconstruction after proximal gastrectomy. The QOL of the patients was assessed using the Chinese versions of the EORTC QLQ-C30 and the EORTC QLQ-STO22 preoperatively, as well as one and two years postoperatively.Results: The QLQ-C30 showed that the global health of the respondents decreased at one year after the surgery (P=0.02). The preoperative score for physical function was significantly better than the one- and two-year post-operation scores. The preoperative scores for pain, nausea and vomiting, and economic difficulties were worse than the one- and two-year post-operation scores (P<0.05). Diarrhea was worse at one year post-operation than during pre-operation (P = 0.00), but improved at two years after the operation. The QLQ-STO22 scales showed that the preoperative dysphagia score was better than one-year post-operation, and no significant differences were observed in terms of dysphagia between the pre-operation and two-year postoperative periods. Preoperative reflux and taste scores were better than those after the operation (P<0.05). The hair loss score at one-year post-operation was worse than at either pre-operation or two-year post-operation.Conclusions: Most QOL scales worsened after surgery, particularly at postoperative year one. However, the scales can be gradually recovered to preoperative levels. The physical function, nausea and vomiting, reflux, taste, and financial difficulties did not fully recover two years after the operation. AEG is currently divided into three types according to Siewert’s classification.3 Total or proximal gastrectomy has been recommended for Type II or Type III AEG, with direct anastomosis between the remnant stomach and the esophagus being recommended after proximal gastrectomy. However, direct anastomosis is followed by some severe complications, such as gastrointestinal reflux and reflux esophagitis. To reduce such postoperative complications, researchers have proposed a new technique, namely, gastric tube reconstruction, which involves shaping the gastric remnant into a tube after proximal gastrectomy followed by anastomosis.4,5 Researchers have concluded that this technique can reduce the number of complications at the early postoperative stage. However, to our knowledge, very little research has addressed the longitudinal changes of QOL resulting from this new digestive tract reconstruction procedure.The adenocarcinoma incidence of the esophagogastric junction (AEG) has evidently increased in recent years.6 QOL measurement provides relevant information on long-term postoperative cancer survival. With the increasing overall survival rate for gastric cancer patients, physicians have become more interested in the QOL of gastric cancer patients. A number of questionnaires, such as the Spitzer index, the SF-36 health survey questionnaire, the European Organization for Research and Treatment of Cancer Quality of life Questionnaire Core-30 (EORTC QLQ-C30), and the EORTC QLQ-STO22 (stomach module) are widely used for QOL measurement.7-10 Of these questionnaires, the QLQ-C30 is usually used in combination with the stomach module to evaluate gastric cancer patients’ QOL because these questionnaires can obtain more concrete and valuable information. These two QOL questionnaires have already been converted into different versions.11,12With the increasing concern regarding postoperative recovery, we need to examine the available information needs and sources regarding cancer patients after surgery.In this study, we used the Chinese version of the EORTC QLQ-C30 and QLQ-STO22 to evaluate the QOL of Type II and Type III AEG patients who had undergone the new gastric tube reconstruction after proximal gastrectomy.Participant Recruitment: The protocol was approved by the institutional review board and committee of West China Hospital of Sichuan University. All the patients gave their written consent to undergo the procedure. We analyzed the data obtained from patients with Type II or Type III AEG who underwent curative proximal gastrectomy with gastric tube reconstruction between January 2009 and December 2011 at the Department of Gastrointestinal Surgery, West China Hospital, Sichuan University. All patients underwent laparotomy. Age, gender, tumor diameter (cm), hospital stay (days), histological type, Siewert type, Borrmman type, depth of invasion (T), lymph node metastasis (N), and tumor TNM stage13 were obtained from the patients’ medical records ( records .Inclusion criteria: (1) Patients diagnosed with AEG (Siewert Type II/III) through gastroscope biopsy and upper gastrointestinal barium examination. (2) No clear proof of distant metastasis or adjacent tissue invasion shown by routine preoperative examination, such as chest radiography, abdominal CT scan, or endoscopic ultrasonography. Exclusion criteria: Patients with evidence of recurrence, metastasis, or death during the follow-up period were excluded from this study. Accordingly, 87 patients with Type II or Type III AEG who had undergone curative surgery were enrolled in this study. All of the patients or their family members were informed of the new technique and the follow-up for postoperative QOL measurement. Operation Procedure: The surgical procedure was started with a midline upper abdominal incision under general anesthesia. Proximal gastrectomy and distal esophagectomy were then performed through this incision. All patients underwent standard treatment according to the criteria of the Japanese Gastric Cancer Association (JGCA), and the proximal gastrectomy, vagectomy, and D2 or greater D2 lymphadenectomy were included. The remnant stomach volume was approximately 40% to 70% of its original size. Linear-stapling devices were used to shape the lesser curvature that lay at approximately 3 cm above the pylorus of the gastric remnant into a tube with approximately 4 cm to 5 cm in width and 30 cm in length (n length . The reaData Collection and Assessment of QOL: Patients or their family members were asked to complete the questionnaires (Chinese version of EORTC QLQ-C30 and QLQ-STO22) preoperatively, at one post-operation, and at two years’ post-operation.9 The EORTC QLQ-STO22 is composed of five multi-item scales  and four single items .10 Once all of the scales were scored, the raw scores for each scale were linearly transformed to scores ranging from 0 to 100, according to the Scoring Manual. For the global health status and functional scales in the QLQ-C30, a high score represents a better quality of life. However, high scores in the symptom scale and single items represent poor quality of life. For the QLQ-STO22, a high score represents low quality of life.The EORTC QLQ-C30 is composed of five functional scales , three symptom scales , six single items , and a global health statusStatistical Analysis: Quantitative data were expressed as means ± SD, repeated measured ANOVA was used to compare the score of each scale before and after surgery. P<0.05 was considered statistically significant. Statistical analysis was conducted using SPSS 17.0 for Windows.Clinical Outcomes: Of the 87 patients, 16 were lost during the follow-up, 17 cases died, and 8 patients experienced tumor recurrence or distant organ metastasis during the follow-up period. Finally, we got 71 and forty-two eligible QOL questionnaires at one post-operation, and at two years’ post-operation, respectively. All patients completed the QOL questionnaires preoperatively.EORTC QLQ-C30: The global health status of EORTC QLQ-C30 decreased at one year after surgery when compared with pre-operation (P = 0.02). However, no statistically significant difference was observed between pre-operation and two-year postoperative status (P = 0.76). The preoperative physical function scores were significantly better than those at one and two years’ post-operation, indicating that the patients had poor physical fitness after their operations. The preoperative scores for pain, nausea and vomiting, and economic difficulties were worse than either the one- or two-year post-operation scores (P < 0.05). No statistical differences were observed between the one- and two-year post-operation scores for these three scales. The diarrhea score increased in the one-year post-operation group (P = 0.00), but decreased two years after surgery. However, no statistically significant differences were observed before and after the operation in terms of role function, emotional function, social function, cognitive function, fatigue, and so on, during the study period. The score for all scales are shown in EROTC QLQ-STO22: In the EORTC QLQ-STO22, the patients scored worse for dysphagia at one year after surgery (P = 0.00) than during pre-operation, whereas no statistically significant difference was observed between the pre-operation and two-year post-operation scores (P = 0.28). The eating restriction score significantly increased at one year post-operation (P < 0.05), but decreased at two years after surgery, with no statistically significant difference from the preoperative score (P = 0.17). Changes observed, such as those in the QLQ- C30 pain scale, indicated that surgery or other postoperative treatment can alleviate stomach pain (P < 0.05). The preoperative reflux and taste scores were better than those of post-operation (P < 0.05). The hair loss score was worse at one year after surgery, possibly as a result of the post-surgery chemotherapy. No statistically significant difference was observed in terms of anxiety or dry mouth scale before and after the surgery  and QLQ-STO22 (a gastric cancer-specific module) in 1993 and 1998, respectively. In this study, we used the Chinese version of the EORTC QLQ-C30 and QLQ-STO22,16,17 to assess QOL.AEG patients who undergo proximal gastrectomy have their anatomic anti-reflux barriers destroyed. Meanwhile, gastric acid secretion does not completely abate,18,19 In the present study, many functional scales and global health status scores at one year post-operation are worse than the pre-operation and two-year post-operation scores. Some potential correlative factors of QOL such as education level, marriage, employment status, and poor lifestyle habits , may make a difference in QOL. Moreover, we notice that most AEG patients (Type II/III) were diagnosed at advanced or terminal stage, and these patients may take a longer time to recovery. We have found no obvious differences in the preoperative and one-year postoperative social and cognitive function scores, indicating that the patients recovered to baseline status at one year post-operation. Using EORTC QLQ-C30, past studies have observed that most functional scales recover to preoperative levels at 6 to 12 months after operation.18 Many patients suffered from postoperative diarrhea because of denervation resulting from truncal vagotomy. Kobayashi et al.20 showed that postoperative diarrhea does not fully recover during the first year of progress. In the present study, the diarrhea score was worse at one year after surgery, but recovered one year later, indicating that diarrhea resulting from proximal gastrectomy improved to preoperative levels at two years after surgery. The scales for financial difficulties and nausea/vomiting did not fully recover at two years after the operation. Zhou et al.21 pointed out that these two scales cannot recover to the level of healthy people at three years’ post-operation.These results are consistent with those of previous studies.18 found no statistically significant difference in the pain scale at pre- and post-operation, attributing this peculiar result to pain score reaching the maximum level rapidly and recovering quickly before the first postoperative questionnaire survey is conducted. By contrast, the patients enrolled in the present study exhibited quite a different pattern. All of the respondents reported substantial pain relief at one and two years after surgery. Moreover, a lengthier investigation in Korea observed that gastric cancer patients who had undergone a curative distal subtotal gastrectomy still suffered from financial difficulties and nausea/vomiting on their fifth annual follow-up visit. Perhaps a return to baseline will take a much longer time. Thus, it is essential to conduct further follow-ups to verify whether or not the patients can fully recover or not. Kong et al.Hence, it is reasonable and logical to assume that patients with medium or advanced cancers often experience more pain than early cancer patients. In addition, this study involved more patients at advanced TNM stages in that of Kong et al. Thus, the baseline pain score in this study was much higher. However, the pain score in our study was not much different from that of Kong et al. at one year after surgery, which may be the reason for the significant pain relief after operation exhibited in the present study.22 This result may be the adverse outcome of gastrectomy; however, different surgical procedures may have different effects on recovery time and mode. Patients’ decreased stomach pain after surgery should be attributed to the removal of the tumor and rational postoperative treatment, such as postoperative chemotherapy or supportive treatment. No difference was observed between the pre-operation and post-operation anxiety scores. The patients may have had a degree of concern about their diseases or the potential risks of operation prior to surgery. They are also worried about their future health on account of specific postoperative complications and discomforts, which could explain why there are no significant differences in the anxiety scale during the study. Moreover, the scores of dry mouth and body image scales at one year after surgery were slightly poorer than those prior to the operation, but did not reach statistical significance. This result indicates that patients had reverted to the baseline for these two scales one year post-operation.For EORTC QLQ-STO22, the dysphagia, eating restriction, and hair loss scales recovered to baseline within two years. However, reflux and taste did not fully recover at two years’ post-operation. Another investigation showed a marked difference between gastric cancer patients and the healthy population in terms of reflux scale at five years’ post-operation.Some scales varied in recovery time, which may be associated with different surgical procedures, methods of anastomosis, tumor location, and application of postoperative chemotherapy. The type of surgery can also provide more information to a surgeon or patient in the future. Therefore, we plan to explore the relationship between QOL and these factors in future studies.This study showed that patients with Type II or Type III AEG who underwent gastric tube reconstruction after proximal gastrectomy experience problems involving nausea and vomiting, reflux, taste, and financial difficulties. These differences exist for at least two years. However, most scales worsened after surgery, and then recovered to preoperative levels. For the scales that did not recover over the course of the study, further follow-ups would be carried out to confirm whether or not the patients can return to baseline or not. Accordingly, countermeasures should be taken to treat these discomforts and improve the QOL of the patients.


Team-based learning (TBL), a new active learning method, has not been reported for neurology education. We aimed to determine if TBL was more effective than passive learning (PL) in improving knowledge outcomes in two key neurology topics - neurological localization and neurological emergencies.We conducted a modified crossover study during a nine-week internal medicine posting involving 49 third-year medical undergraduates, using TBL as the active intervention, compared against self-reading as a PL control, for teaching the two topics. Primary outcome was the mean percentage change in test scores immediately after (post-test 1) and 48 hours after TBL (post-test 2), compared to a baseline pre-test. Student engagement was the secondary outcome.Mean percentage change in scores was greater in the TBL versus the PL group in post-test 1  and post-test 2 . After adjustment for gender and second year examination grades, mean percentage change in scores remained greater in the TBL versus the PL group for post-test 1  and post-test 2 , indicating further score improvement 48 hours post-TBL. Academically weaker students, identified by poorer examination grades, showed a greater increase in scores with TBL versus strong students (p < 0.02). Measures of engagement were high in the TBL group, suggesting that continued improvements in scores 48 hours post-TBL may result from self-directed learning.Compared to PL, TBL showed greater improvement in knowledge scores, with continued improvement up to 48 hours later. This effect is larger in academically weaker students. TBL is an effective method for improving knowledge in neurological localization and neurological emergencies in undergraduates. TBL wThere are few studies comparing TBL to other educational methods. These studies vary in their study designs , measuring knowledge as the primary outcome and self-reported student engagement as a secondary outcome.Our study population comprised third year medical undergraduates from the National University of Singapore. In the third year, students undergo a nine-week posting in internal medicine, where they are rotated into various medical subspecialties including neurology; teaching of all subspecialties runs concurrently. We obtained ethics approval from the institutional ethics committee.We performed a controlled study of TBL versus PL, using a modified crossover design ,20. We sTBL was administered as the active learning intervention in two cohorts of students. The first cohort was randomly assigned to receive TBL in NE; the second cohort received TBL in NL Figure . Both coAs we aimed to compare TBL against PL, we have depicted the groups being compared (TBL versus PL) in Figure The pure application of TBL ,8 involvPhase 1: Students read preparatory material independently outside of classPhase 2: Students complete an Individual Readiness Assurance Test (IRAT) to assess their grasp of the knowledge and concepts learned in Phase 1. The same test is then re-administered to the students in pre-assigned groups of 5-7 students; each student was randomly assigned to a group. The team then forms a consensus about each answer in a Group Readiness Assurance Test (GRAT)Phase 3: Students work in groups on assignments that allow them to apply knowledge gleaned in Phases 1 and 2 to clinical problems.The TBL method allows flexibility on the part of the teachers to selectively use one or more of the phases, depending on the context and demands of the course. Given the constraints of medical education, such flexibility has previously been exercised ,15,17,23We first prepared the students by meeting them to explain the purpose and learning objectives of TBL . The stuPhase 2 was conducted in a conference room over 2 hours Figure  with twoAfter IRAT, the class formed into 4 to 5-student teams for GRAT; students were randomly assigned to teams . Each teStudents undergoing the PL topic were also provided lectures notes on the topic at TBL Phase 1 and told to do advance reading. However, the students were unaware which topic (NE or NL) would be used for the TBL Phase 2 until the start of IRAT. By doing so, we aimed to ensure that they read equally diligently for both topics before TBL Phase 2. Prior knowledge of the TBL topic may introduce bias as the students may opt to read the TBL topic more diligently.We performed three closed-book tests to assess knowledge Figure  as our pEach test consisted of 40 true/false questions, covering 10 clinical scenarios . Questions were designed such that the correct answers required both recall and application of Phase 1 knowledge. Post-tests 1 and 2 consisted of the same scenarios as the pre-test, but with the order of scenarios and questions randomly scrambled. The maximum score was 20 each for NE and NL sections. Students were allotted 20 minutes for each test.For the primary outcome, we measured the change between each student's post-test score (both post-test 1 and 2) and the baseline pre-test score, and expressed it as a percentage of the total score for that section (NE or NL). For a student who scored 10/20 in the NL section of the pre-test, then 12/20 for post-test 1, and 15/20 for post-test 2, the outcomes would be represented as: 0% (baseline), +10% (post-test 1), +25% (post-test 2).We measured self-reported student engagement as a secondary outcome, using a modified version of a validated tool . EngagemWe collected data on students' gender and their second year examination grades. Students who failed (< 50% of maximum score) were graded 'F' by the university. Students who passed (50-100% of maximum score) were graded from 'A' to 'D' by quartiles ; there was no 'E' grade. We used examination grade as a proxy measurement of each student's baseline medical knowledge.The students were blinded to the nature, number and timing of the pre-post tests. They were also blinded to the TBL topic until Phase 2. Between post-test 1 and 2, students underwent teaching in internal medicine by non-neurology tutors who were unaware of our study.2 test; differences in means were tested using two-sample t-test if normality & homogeneity assumptions were satisfied otherwise the non-parametric Mann-Whitney-U test was applied. A mixed model ANCOVA  was performed, taking into account that each student was used twice, to determine differences between TBL & PL groups in the primary outcome, adjusting for gender and examination grades. We also looked for interaction between TBL and gender, TBL and topic, and TBL and examination grades; interaction effects were deemed significant if p < 0.05. Statistical evaluations were performed using SPSS 17.0 based on 2-sided tests; p < 0.05 was considered as significant.Differences in proportions between TBL and PL groups were tested using the χForty-nine students participated in our study  table . No studComplete data for all three pre-post tests were obtained. Mean baseline pre-test scores in both groups were not significantly different (p = 0.13); these scores were not significantly different in males compared to females (p = 0.71), but was higher in those who had examination grades of A or B, compared to those who were graded C or D .After TBL, the unadjusted mean scores for both post-test 1 and post-test 2 increased in both groups; however, the increase was significantly greater in the TBL group. The proportion of students getting ≥ 90% of the questions correct was significantly higher in the TBL versus the PL group.After adjusting for gender and examination grades Figure , for posWe found no significant interaction of gender or TBL topic with the effect of TBL on the primary outcome. However, the effect of examination grades on improvement in test scores was significant from baseline to post-test 1 (p = 0.007), but was not significant from baseline to post-test 2 (p = 0.22). We dichotomized the students into 'strong' (A-B examination grades) versus 'weak' (C-D grades) students. In both strong and weak students, the TBL group showed a larger increase in the primary outcome compared to the PL group Figure . The effMeasures of engagement were high in the TBL group table ; most stWe used a novel study design to explore the effect of TBL as an active learning method compared to PL, measuring knowledge outcomes immediately and 48 hours after intervention. Students receiving PL showed initial improved scores, which fell 48 hours later. Conversely, scores increased immediately after TBL and increased further 48 hours later. In addition, this effect of TBL is larger in academically weaker students compared to strong students.An earlier randomized controlled trial  comparinOur finding that TBL improves knowledge immediately compared to PL is not surprising, as TBL has been shown to reinforce concepts and aid application . TBL utiHowever, the additional improvement 48 hours later was striking, particularly when compared to the score decrease in the PL group. This interesting finding leads us to hypothesize that TBL encouraged self-directed learning ,31 via pDuring the GRAT, we found enthusiastic student participation and interaction. The students also reported high levels of engagement by themselves and the class, consistent with previous TBL studies ,17,19,33Our finding that TBL has a greater effect in academically weaker students is consistent with extant literature ,34. We bThe strengths of our study include learner homogeneity, use of a PL comparator, matching of TBL and PL groups and mitigation of the carryover effect using our study design, blinding of students to study design and testing, relevance of topics ,22, measWe selected self-reading as the PL comparator, although previous studies have compared TBL with lectures ,18, tutoOur study has several limitations. Firstly, our sample size is small as only 49 students were involved; a larger study would be helpful to confirm our findings. Secondly, post-test 2 was similar to post-test 1; new questions added to post-test 2 may have allowed learners to apply newly-obtained knowledge to fresh questions. Our tests therefore predominantly assess retention of knowledge at 48 hours, rather than the ability to apply knowledge to new clinical scenarios at the end of their nine-week posting. True/false questions also have inherent limitations .a priori defined subgroup, confirmation with formal testing for interaction, statistical significance and lack of multiple subgroup testing [Thirdly, due to time constraints in a busy nine-week internal medicine posting, we conducted a modified TBL focusing on Phases 1 and 2 instead of a full programme . However testing  in our sTBL improves knowledge scores in undergraduate neurology education, with sustained and continuing improvement up to 48 hours later. This effect is greater in academically weaker students. Students taught by TBL report high engagement which may promote greater self-directed learning. With increasing emphasis on active learning in neurology , our resANCOVA: Analysis of Covariance; ARS: Audience Response System; GRAT: Group Readiness Assurance Test; IRAT: Individual Readiness Assurance Test; NE: Neurological emergencies; NL: Neurological localization; PL: Passive learning; TBL: Team-based learning.The authors declare that they have no competing interests.NCK Tan had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study conception and design: NCKT, KT, NK. Acquisition of data: NCKT, KT, SHL, TU. Analysis and interpretation of data: NCKT, YHC, KT, NK. Drafting of manuscript: NCKT, YHC. Critical revision of manuscript for important intellectual content, and final approval of manuscript: All authorsThe pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6920/11/91/prepub


AKI is common following liver transplantation and is associated with significant morbidity and mortality. Biomarkers of AKI have not been well established in this setting but are needed to help guide patient care and facilitate development of novel therapeutics.Serum creatinine, cystatin C, IL-6, and IL-8 and urine IL-18, NGAL, IL-6, and IL-8 were measured before and within 24 hours after liver transplantation in 40 patients. AKI was defined as a ≥50% sustained increase in creatinine above pre-operative values occurring within 24 hours of transplantation and persisting for at least 24 hours.Seven patients met criteria for AKI (17.5%), with mean creatinines of 0.81 mg/dL pre-operatively and 1.75 mg/dL post-operatively. While pre-operative biomarker levels in patients with AKI were similar to those in patients without AKI, differences were seen between the groups with regard to median post-operative serum IL-8 (pg/mL)  and urine NGAL (ng/mL) , IL-6 (pg/mL) , IL-8 (pg/mL) , and IL-18 (pg/mL) . The areas under receiver operating characteristic (ROC) curves were 0.749 for urine IL-18, 0.833 for urine NGAL, 0.745 for urine IL-6, 0.682 for serum IL-6, 0.773 for urine IL-8, and 0.742 for serum IL-8. Post-operative cystatin C was not significantly different between AKI and no AKI groups.Serum IL-8 and urine IL-18, NGAL, IL-6, and IL-8 are elevated in AKI within the first 24 hours following liver transplantation. Orthotopic liver transplantation (OLT) is the definitive treatment for end-stage liver disease (ESLD), but the procedure has a significant morbidity and mortality. One of the most significant complications of OLT is AKI, which has been reported in 17 to 95% of OLT patients depending on the definition of AKI . These mGiven the unfavorable outcomes associated with AKI (in the setting of OLT and otherwise), there has been considerable interest in developing therapies to improve renal dysfunction. However, interventional approaches have been limited by the shortcomings of the conventional approach to the diagnosis of AKI. Measurement of serum creatinine remains the commonest diagnostic tool for assessment of renal function, but this long-used marker suffers from its insensitivity to small changes in renal function, its lack of specificity for renal function given the influence exerted by a variety of non-renal factors (such as muscle mass and diet), and its long lag-time in response respond to kidney injury. These problems can be particularly pronounced in the setting of ESLD, where creatinine has been shown to be an especially unreliable marker of renal function . The inaHowever, the role of biomarkers for detection of AKI in patients undergoing OLT has been explored in only a few prior studies that were limited to urinary and serum NGAL levels -18. UrinAll patients aged 18 to 90 years old who underwent a first-time OLT at the University of Colorado (N=11) and University of Washington (N=29) were eligible for the study. Patients were excluded if they were pregnant, incarcerated, unable to provide consent, received dialysis before or during OLT, or received a kidney transplant simultaneously with their liver, had pre-renal AKI (a more than 50% rise in serum creatinine that was not sustained for 24 hours). All the patients received either tacrolimus or cyclosporine as immunosuppressive therapy. All study enrollment procedures and subsequent data collection and acquisition was approved by the Colorado Multiple Institutional Review Board. All eligible patients who were consented according to proper procedures in a consecutive fashion over an 18 month period were enrolled at the 2 hospitals.Pre-operative blood and urine samples  were collected from each patient within 24 hours of OLT. Additional samples of the same volumes were collected within 24 hours after OLT , and a standard calibration formula was used to estimate glomerular filtration rate from the result . Urine ISerum creatinine levels were measured daily by the hospital’s central laboratory as part of routine peri-operative care, and these values were recorded. A combination of retrospective and prospective chart reviews was performed to collect demographic and pertinent clinical data. AKI was defined as an increase in serum creatinine by 50% or greater compared to pre-operative values that occurred within 24 hours of OLT and that was sustained for at least 24 hours. Patients who developed a 50% rise in serum creatinine that was not sustained for 24 hours were removed from analysis as their kidney injury was thought to be pre-renal in nature. The definition of AKI was based on the Risk, Injury, Failure; Loss, End-Stage Renal Disease (RIFLE) classification and Acute Kidney Injury Network (AKIN) classification where Risk or AKIN stage 1 represents an increase of serum creatinine to 1.5 times baseline . In a set test. Two-tailed p-values are presented. Mean and standard deviation calculations were performed for the measured levels of serum creatinine and serum cystatin C. Mean pre-operative values were compared to mean post-operative values among patients who developed AKI and separately among patients who did not develop AKI using two-tailed paired t tests. At each of the two timepoints (pre-operative and post-operative), mean creatinine and cystatin C values among patients who developed AKI were compared to those in patients who did not develop AKI using two-tailed unpaired t tests. For serum and urinary biomarkers, medians and interquartile ranges were calculated, and median values of the AKI group were compared to those of the no AKI group using the Mann–Whitney test with two-tailed p-values. We defined statistical significance as a p-value of <0.05. InStat software was used for statistical analysis.Demographic data was compared between patients who developed AKI and those who did not using either the Fisher’s exact test or the unpaired Table Table To determine whether low albumin or systemic inflammation contributed to the lower pre-operative creatinine in the AKI group, serum albumin and serum IL-6 was compared between the AKI and no AKI groups. There was no difference in serum albumin or serum IL-6 pre-op between the AKI and no AKI groups suggesting that malnutrition or systemic inflammation is not the cause of the lower serum creatinine in the AKI group: Serum albumin (g/dL) pre-op was 3.15 in the AKI group and 3.08 in the non-AKI group (P=NS). Serum IL-6 (pg/mL) pre-op was 20.2 in the AKI group and 15.0 in the non-AKI group (P=NS).Table Table The absolute change in serum creatinine (mg/dl) from pre-operative to 24, 48, 72, 96 and 120 hrs post-operative in AKI patients is shown in Table Figure Finally, we repeated the biomarker analysis using a different definition of AKI. Seven patients met the criteria of AKI as defined by a >50% increase in serum cystatin C level at 24 hours. These seven patients had no statistical differences from the non-AKI patients in terms of age, sex, race, pre-operative MELD score, or baseline serum creatinine level, or pre-operative serum creatinine level. As shown in Table In this study, we sought to evaluate the performance of a variety of biomarkers of AKI in the setting of OLT when examined within 24 hours of surgery. We used serum creatinine in our definition of AKI because of its prominence in standard AKI definitions and because data on the superiority of cystatin C in the setting of OLT is conflicting. Some studies have shown that cystatin C may be a better assay for GFR estimation in the setting of cirrhosis  and a 20As established by our definition, post-operative serum creatinine levels were higher in the AKI group than in the non-AKI group. Interestingly, however, we found that pre-operative serum creatinine levels were significantly lower in the AKI group than in the non-AKI group. A similar pattern was seen with respect to cystatin C . While these differences were not expected, they supported the notion that AKI patients did not harbor any manifest renal dysfunction prior to transplantation, and the similarities seen in the pre-operative biomarker levels between the groups further supports this hypothesis.Using serum creatinine elevations to define AKI, we found statistically significant elevations in post-operative urine IL-18, urine NGAL, urine IL-8, and serum IL-8 in patients with AKI compared to those without AKI, and both serum and urine IL-6 levels were higher in AKI patients despite failing to achieve statistical significance. ROC curve analysis showed that urine NGAL had the best diagnostic performance and that the IL-6 measures performed the worst amongst those we tested. We also examined the biomarkers using an alternative, cystatin C-based definition of AKI. With AKI defined as a >50% increase in serum cystatin C levels at 24 hours, we found that post-operative urine NGAL, IL-6, and IL-8 levels were all significantly elevated above non-AKI controls. We did not normalize urinary biomarker concentrations to contemporaneous urine creatinine concentration because urinary creatinine excretion in the setting of AKI is dynamic and its inclusion in the assessment of urinary biomarkers has been challenged .While a few previous reports have documented elevations in NGAL levels in post-liver transplant patients who develop AKI, the utility of other biomarkers that have been proven indicators of AKI has not yet been established in the setting of OLT. In 2009, Niemann et al. evaluated plasma NGAL levels in 59 patients undergoing OLT and found that elevations in NGAL levels measured two hours after reperfusion was predictive of AKI . Among tDespite this data on NGAL’s role as a predictor of AKI, other biomarkers have not been evaluated in the setting of OLT. The need for studying other biomarkers in AKI is underscored by a closer examination of the previous studies on urinary NGAL that reveals some limitations of its diagnostic ability. When ROC curves were constructed in these prior studies, the AUC’s did not indicate superior diagnostic capabilities (AUC’s for urinary NGAL ranged from 0.693 to 0.800). Thus, urinary NGAL may be an imperfect tool in the early detection of AKI, and defining the diagnostic characteristics for other biomarkers may prove useful in designing future studies to determine whether multiple biomarkers are early predictors of AKI .Our goal was to expand the current panel of biomarkers that has been studied in the setting of OLT from NGAL alone to include urine IL-18, serum and urine IL-6, and serum and urine IL-8. These various biomarkers have been established in other settings. IL-18, a proinflammatory cytokine, has been identified as a mediator of ischemic injury in the kidney and has been demonstrated to be a reliable marker of and contributor to AKI through animal studies -30. FurtIt has been reported that worst pre-orthotopic liver transplant hepatic function is associated with an increased incidence of post- orthotopic liver transplant AKI ,43. In tOur study has limitations. First, the overall sample size was small and the incidence of post-operative AKI was significantly lower than that reported in the literature, resulting in a small pool of patients for analysis. This shortcoming may have diminished our statistical power and precluded a more robust calculation of our biomarkers’ predictive abilities. Second, it is likely that some of these biomarkers would have been elevated earlier than 24 hours post-operatively. Thus biomarkers that rise quickly in response to AKI may have already peaked and began normalizing by the time we measured them at 24 hours post-operatively. The degree of elevation may have underestimated the peak degree of elevation and thereby diminished our diagnostic power. Additionally, we may have missed transient elevations that had fully resolved by the time we collected our samples. In the present study, biomarkers were measured at the same time as serum creatinine and were elevated at the same time as serum creatinine in AKI patients. Our previous studies in AKI patients post cardiac surgery demonstrate that urine IL-18 and NGAL peak at 6 hrs post op . Thus itIn conclusion, the present study establishes the utility of measuring a wider selection of cytokines and chemokines  as biomarkers of AKI post liver transplantation. The present study should prompt further research into using these biomarkers with urine NGAL to detect AKI prior to randomization to therapeutic strategies in clinical studies. Given the prevalence of AKI associated with OLT and its associated morbidity and mortality, therapeutic studies based on the diagnosis of AKI using a panel of biomarkers including kidney injury molecule-1 (KIM-1), may be possible in the future. The development of novel therapies for AKI may lead to better outcomes.There are no conflicts of interest to declare.JS and AW randomized patients, collected samples, set up database, analyzed data, wrote manuscript. SF and AJ analyzed data, wrote paper. KM did statistical analysis. PD measured NGAL and data analysis. CD randomized patients, collected samples, advised on data analysis. CE data analysis, wrote paper. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2369/14/17/prepub


Eleutherococcus senticosus root, Schisandra chinensis berry, and Rhodiola rosea root as well as several constituents individually, namely, eleutheroside E, schizandrin B, salidroside, triandrin, and tyrosol. A common feature for all tested adaptogens was their effect on G-protein-coupled receptor signaling pathways, i.e., cAMP, phospholipase C (PLC), and phosphatidylinositol signal transduction pathways. Adaptogens may reduce the cAMP level in brain cells by down-regulation of adenylate cyclase gene ADC2Y and up-regulation of phosphodiesterase gene PDE4D that is essential for energy homeostasis as well as for switching from catabolic to anabolic states and vice versa. Down-regulation of cAMP by adaptogens may decrease cAMP-dependent protein kinase A activity in various cells resulting in inhibition stress-induced catabolic transformations and saving of ATP for many ATP-dependant metabolic transformations. All tested adaptogens up-regulated the PLCB1 gene, which encodes phosphoinositide-specific PLC and phosphatidylinositol 3-kinases (PI3Ks), key players for the regulation of NF-κB-mediated defense responses. Other common targets of adaptogens included genes encoding ERα estrogen receptor (2.9–22.6 fold down-regulation), cholesterol ester transfer protein (5.1–10.6 fold down-regulation), heat shock protein Hsp70 (3.0–45.0 fold up-regulation), serpin peptidase inhibitor (neuroserpin), and 5-HT3 receptor of serotonin (2.2–6.6 fold down-regulation). These findings can be reconciled with the observed beneficial effects of adaptogens in behavioral, mental, and aging-associated disorders. Combining two or more active substances in one mixture significantly changes deregulated genes profiles: synergetic interactions result in activation of genes that none of the individual substances affected, while antagonistic interactions result in suppression some genes activated by individual substances. These interactions can have an influence on transcriptional control of metabolic regulation both on the cellular level and the level of the whole organism. Merging of deregulated genes array profiles and intracellular networks is specific to the new substance with unique pharmacological characteristics. Presumably, this phenomenon could be used to eliminate undesirable effects  and increase the selectivity of pharmacological intervention.Gene expression profiling was performed on the human neuroglial cell line T98G after treatment with adaptogen ADAPT-232 and its constituents – extracts of  It is taken for decreased body performance such as fatigue and weakness , which in turn affects the production and function of active small molecules. Gene expression profiles aid in tracing molecular interactions and signal transduction pathways and to predict the pharmacological effect a drug will have on various cellular functions.R. rosea, S. chinensis, and E. senticosus.Recently, the so-called “-omics” technologies have been established for the analysis of pharmacological effects . We also compared these two fixed-composition mixtures to individual active compounds isolated from these plants, namely, salidroside, triandrin, tyrosol, eleutheroside E, and schizandrin B Figure . This phR. rosea L. roots, E. senticosus (Rupr. et Maxim) Harms roots, and S. chinensis (Turcz.) Baill. berries, were manufactured in accordance to ICH Q7A and EMEA guidelines for Good Agricultural and Collecting Practice (GACP) and Good Manufacturing Practice (GMP) of active pharmaceutical ingredients (API). We have previously described the detailed composition and chemical characterization of ADAPT-232 and ADAPT-232 forte . Triandrin was isolated in Swedish Herbal Institute (SHI) Research and Development , and identified by comparison  with the authentic reference sample kindly provided by Prof. Zapesoznaya . Pharmaceutical grade standardized extracts of R. rosea-derived salidroside in human blood plasma, where we measured concentrations of ∼1 μg/mL = 3 μM  is based on the results of a recent pharmacokinetic study of The concentrations of the total extracts of three herbal ingredients and their active constituents are compatible is all test samples: e.g., final concentration of salidroside is the same – 3 μM (900 μg/L) in all test samples containing salidroside, namely in Rhodiola extract, ADAPT-232, and ADAPT-232 forte. Similarly – schizandrin B, eleutheroside E triandrin, and tyrosol, their concentrations were calculated based of the results of HPLC analysis of their content in genuine extracts and their combinations. The concentrations of genuine extracts have been calculated using specifications of their combinations (ADAPT-232 and ADAPT-232 forte) to ensure that they corresponds to therapeutically effective doses.2. All experiments were conducted using cells in the logarithmic growth phase.The human neuroglial cell line T98G was purchased from the American Type Culture Collection . Cells were grown in DMEM + GlutaMAX-I  with 10% fetal bovine serum  and 1% penicillin/streptomycin . They were passaged twice a week and maintained in a 37°C incubator in a humidified atmosphere with 5% COT98G cells were seeded 24 h before treatment on 6-well plates in a density of 150,000 cells per well. The next day, old medium was removed and cells were treated in a final volume of 3 mL (Table The ethanol content was 0.8% for cells treated with isolated compounds and vehicle-treated control cells (test sample Z). Two technical replicates were performed for each sample. Cells were incubated with the test substances for 24 h at 37°C and then subjected to RNA isolation.Cells were harvested after 24 h of treatment. Total RNA was isolated using InviTrap Spin Universal RNA Mini kit  and dissolved in RNAse free-water. The RNA of the two technical replicates was pooled (1:1) resulting in one sample for each treatment/control. The quality of total RNA was checked by gel analysis using the Total RNA Nano chip assay on an Agilent 2100 Bioanalyzer . All samples were of highest quality with RIN values of 10.860K Agilent) were used for gene expression profiling. Probe labeling and hybridization procedures were carried out following the One-Color Microarray-Based Gene Expression Analysis ProtocolMicroarray hybridizations were performed at the Institute of Molecular Biology . Whole Human Genome RNA chips  values for the genes in samples were obtained by dividing the tC values of genes in drug-treated samples by tC values of RPS13 gene and multiplying with the tC value of RPS13 in the control. Fold changes were calculated with the ΔtC (Standardized tC of the gene in drug-treated sample – tC of the gene in untreated sample) method where the fold change is equal to Validation of the microarray data was done by real-time RT-PCR for five selected genes which were tested for two drug-treated samples Tables  and 3. PR = 0.81 (Pearson Correlation Test), Table The correlation coefficient between mRNA expression values determined by microarray hybridization and real-time RT-PCR was p < 0.05) by means of Chipster software analysis. Ingenuity Pathway analyses were performed with data sets of significantly up- or down-regulated genes: 536 genes for ADAPT-232 forte, 777 genes for ADAPT-232 forte tested at the low concentration, 534 genes for ADAPT-232 at the higher concentration, 591 genes for Eleutherococcus extract, 599 genes for Schisandra extract, 561 genes for substance Rhodiola extract, 567 genes for eleutheroside E, 620 genes for schizandrin B, 640 genes for salidroside, 601 genes for triandrin, and 562 genes for tyrosol. The Venn diagrams in Figure A microarray-based transcriptome-wide mRNA expression analysis was performed to identify possible targets of the tested substances in T98G cells. T98G cells were treated with test substances for 24 h in two technical replicates before total RNA was isolated and pooled for microarray hybridization. Significantly deregulated genes were identified compared to untreated controls p < 0.0 by meansR = 0.81, indicating a high degree of concordance between results obtained by both methods.To exemplarily validate the microarray-based mRNA expressions, real-time RT-PCR reactions were performed for five genes using each two different pairs of treated and untreated samples. The expression of these genes were quantified and the ratios between treated and untreated samples were calculated and compared to the ratios obtained from microarray experiments Table . The corBased on the analysis of results obtained in this study, we can draw several conclusions discussed in detail below.A common feature of all drugs tested is their effect on G-protein-coupled receptor (GPCR) signaling pathways. All tested adaptogens significantly deregulated the expression of a large number of genes encoding (a) GPCRs Table  and (b) Regulation of behavior and mood including binding of neurotransmitters such as serotonin, dopamine, GABA, and glutamate.Sympathetic and parasympathetic nervous systems, which are regulated by GPCR pathways, and are responsible for control of many automatic body functions such as regulating blood pressure, heart rate, and digestive processes.Regulation of immune system activity and inflammationNeuroendocrine homeostasis modulation.G-protein-coupled receptors Gilman,  are invoAll of these physiological processes are associated with stress and adaptogen activity, which increases stress tolerance.The regulation of GPCRs is thought to play a fundamental role in maintaining physiologic homeostasis during stress  and peripheral nervous systems opens the membrane channels, which in turn leads to an excitatory response and anxiety ,suppression of the immune system and spontaneous tumors promotion,decrease in liver detoxification,CNS malfunction (loss of memory and learning ability), and the development and progression of cardiac insufficiency, and hypercholesterolemia.G-protein-coupled receptor expression and G-protein-mediated signal transduction are affected by age and play an important role in the development of the major human pathologies associated with aging, cancer, neurodegenerative disorders, and cardiovascular diseases  inhibiting adenylate cyclase (inhibiting synthesis of cAMP) and (b) stimulating phosphodiesterase  acts in a cAMP-dependent manner  production in all tested tissues.Mitochondrial decay is a major cause of aging, leading to the subsequent death of aerobic organisms including humans. Impairments in mitochondrial antioxidant status were invariably associated with in vitro and in vivo  prolonged the duration of exhaustive swimming in comparison with control rats  with schizandrin B  enhanced mitochondrial ATP-generation capacity in various tissues  during aging and mitigated age-dependent impairments in mitochondrial antioxidant capacity and functional ability, thereby retarding the aging process in mice, particularly during early aging, up to the age of 120 weeks  into diacylglycerol (DAG) and inositol-1,4,5-triphosphate , which is involved in the development and function of the nervous system  and high-density lipoproteins , a nuclear receptor belonging to a large family of transcription factors, transducing hormonal signals, and regulating expression of target genes  resulted in quite different gene expression profiles, including some instances of dose-dependent reversal effects on the same gene, e.g., the adenylate cyclase-encoding gene Table .In can be concluded that cellular sensitivity/reactivity is decreasing at higher doses of adaptogens resulted in increased cellular tolerance to other stressors. Some effects of individual ingredients on gene expression were neutralized when the ingredients were combined in mixtures. In general, only the most common effects attributed to the individual ingredients were observed in the complex mixtures. Interestingly, rather than potentiating gene expression levels, the combination of these components resulted in somewhat of a “smoothing effect” on gene expression level.any isolated cell line can not reflect all of those in entire organism, because of numerous interactions with circulating hormones and mediators of immune system. However, these in vitro experiments can be helpful in finding of possible key mechanisms of action of adaptogens, particularly when they are considered in the context of huge body of evidences obtained in clinical and preclinical studies. It is just the first step in order to define a realistic hypothesis. Further studies can be focused on evidences supporting this hypothesis. It is not excluded that plant extracts are metabolized in the liver thus, their metabolites may also compete with precursors. However, relevance of this in vitro model to the results of clinical studies is supported by pharmacokinetic studies of salidroside, tyrosol, eleutheroside E, and schizandrin. The half-life (t1/2) was 4.662 h for eleutheroside E  and CNS functions. These results can be reconciled with beneficial effects of adaptogens in behavioral, mental, and aging-related disorders.We conclude also, that blending two or more active substances in one mixture significantly changes deregulated genes profiles: synergetic interactions result in activation of genes that none of the individual substances affected, while antagonistic interactions result in suppression some genes activated by individual substances. Consequently, these changes can have an influence on transcriptional control of metabolic regulation both on the cellular level and the level of the whole organism. As a result, the pharmacological profile of the combination may differ from the profiles of the ingredients. Similarly, pharmacological profiles of purified compounds might differ from the pharmacological profile the total plant extract. Presumably, this phenomenon could be used to eliminate undesirable effects  and increase the selectivity of pharmacological intervention.Rebecca Hamm, Thomas Efferth, and Alexander Panossian declare no competing financial interests. Georg Wikman is a stockholder in the Swedish Herbal Institute (SHI).http://www.frontiersin.org/Neuroendocrine_Science/10.3389/fnins.2013.00016/abstractThe Supplementary Material for this article can be found online at


There is debate as to whether the association between C-reactive protein (CRP) and insulin resistance is independent of body fatness, particularly central obesity. Therefore, the association among CRP, insulin resistance and obesity was analyzed in Chinese patients with type 2 diabetes.The study included 520 Chinese patients diagnosed with type 2 diabetes with CRP levels not exceeding 10 mg/L. The degree of insulin resistance was determined with the homeostasis model assessment of insulin resistance (HOMA-IR). The CRP levels were categorized into quartiles from the lowest to the highest concentrations (Q1-Q4).Body mass index (BMI) and waist circumference (WC) were both higher in Q4, Q3 and Q2 than those in Q1. HOMA-IR was higher in Q2, Q3 and Q4 than that in Q1 . Log CRP was significantly correlated with log HOMA-IR  and BMI  and WC  by Spearman correlation analysis. Multiple linear regression analysis adjusting for age, gender and components of metabolic syndrome, log CRP was also independently associated with log HOMA-IR  and WC .These findings showed that insulin resistance was associated with CRP levels independent of abdominal obesity in Chinese patients with type 2 diabetes, suggesting that abdominal obesity could only partly explain the link between subclinical inflammation and insulin resistance. C-reactive protein (CRP), an easily measured marker of systemic inflammation, is stimulated by other cytokines, especially interleukin-6 (IL-6). Insulin resistance is fundamental to the pathogenesis of type 2 diabetes mellitus. During the last few years, insulin resistance has been shown to be strongly associated with CRP and body fat, particularly visceral fat. However, the relationships among obesity, CRP, and insulin resistance are complex. There is debate as to whether the association between CRP and insulin resistance is independent of body fatness, particularly central obesity . SeveralData were obtained from a cross-sectional study undertaken to evaluate the prevalence of diabetic complications in Chinese patients with type 2 diabetes, aged over 30 years and living in downtown Shanghai -14. TwenBody height and weight were measured from the subjects wearing light clothing without shoes . Body mass index (BMI) was calculated from weight in kilogram divided by height in meter square. Waist circumference was measured to the nearest 0.1 cm, using a calibrated plastic tape measure at the umbilical level in the late exhalation phase while standing. The average of the last two measurements of systolic and diastolic blood pressure was obtained from the patients.Using the Hitachi 7600-020 clinical analyzer , serum cholesterol was determined by the cholesterol oxidase-paraaminophenazone method , serum triglycerides by the glycerol phosphate oxidase-para-aminophenazone method , high-density lipoproteincholesterol (HDL-C) by the International Reagents Corporation method , low-density lipoprotein-cholesterol (LDL-C) by the catalase method , and serum creatinine by the sarcosine oxidase-para-aminophenazone method . Blood urea nitrogen levels were measured using the UVGLDH Method , and uric acid was measured using the uricase-peroxidase coupling method  according to the manufacturer's instructions.Glycosylated haemoglobin (HbA1c) was determined by high-pressure liquid chromatography using an automated HLC-723G7 analyser . Serum insulin was evaluated by radioimmunoassay, after fasting and then following a 2-h oral glucose tolerance test . Plasma glucose levels were measured by the glucose oxidase method  using a Hitachi 7600-020 clinical analyser. Insulin resistance was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR) as follows: fasting serum insulin (mIU/ml) × fasting plasma glucose (mmol/l)/22.5. Serum CRP levels were measured by a chemiluminescence assay using an automatic analyser . This assay has a sensitivity of 0.162 mg/L. Inter- and intraassay coefficients of variation were <5% for the measurements. For the purposes of this analysis, patients were divided into strata according to quartiles of baseline CRP values(Q1~Q4).Quantitative variables were described as mean ± S.D. One-way ANOVA (multiple comparisons: LSD method) was used for quantitative variables comparisons among the four subgroups according to quartiles of CRP . Chi-square test was used for enumeration data comparisons among the four subgroups according to quartiles of CRP . The distribution of CRP and HOMA-IR levels were highly skewed. Logarithmically transformed values of CRP and HOMA-IR were used. Spearman correlation analysis was performed to determine the relationship among CRP, HOMA-IR, BMI and waist circumference. To explore the relationship between CRP and HOMA-IR independent of obesity, the association between CRP and HOMA-IR was tested by linear regression analysis with log CRP as the dependent variable. All statistical analyses were conducted with the SPSS statistical package for Windows version 16.0 .A total of 520 patients including 194 male patients and 326 female patients were analyzed in this study. The mean age of these 520 patients was 65.14 ± 12.11 years and the duration of diabetes 7.11 ± 6.73 years.Table Table To explore the relationship between CRP and insulin resistance, spearman correlation between log CRP and log HOMA-IR was analyzed. Log CRP was significantly correlated with log HOMA-IR . To explore the relationship between CRP and abdominal obesity, spearman correlation between log CRP and BMI, waist circumference was analyzed. Log CRP was significantly correlated with BMI  and waist circumference .To explore the relationship between CRP and insulin resistance independent of obesity, the association between CRP and the parameters of insulin resistance was tested by linear regression analysis with log CRP as the dependent variable Table . The folAll previous studies confirmed that abdominal fat distribution was significantly associated with insulin resistance. Chavez AO showed that simple morphometric measurements of adiposity/obesity,  could explain 59% of total insulin mediated glucose uptake, and provided a feasible method to screen and identify insulin resistant in baboons . MiyazakHow do we evaluate the role of low-grade systemic inflammation in the association between insulin resistance and obesity? Previous studies that examined the relationships among insulin resistance, CRP, and obesity were inconsistent. Several studies demonstrated that insulin resistance, as expressed by HOMA-IR, was significantly correlated with CRP concentrations in nondiabetic general populations. However, this correlation was abolished after adjusting for the parameters of obesity ,8. SimilHowever, some studies concluded that the relationship between CRP concentrations and insulin resistance was independent of obesity. In the Insulin Resistance Atherosclerosis Study, Festa et al showed that CRP was strongly associated with insulin sensitivity, as assessed by a frequently sampled intravenous glucose tolerance test; and this association was independent of BMI . AnotherRecently Nayak S et al revealed that adiponectin was not correlated with inflammatory marker . And amoOur study has several strengths. The subjects we included were all of population-based Han-Chinese patients diagnosed with type 2 diabetes. Besides, we used a uniform protocol, including standardized clinical assessments, anthropometric measurements, and biochemical measurements in a centralized core laboratory. However, some possible limitations of our study should be mentioned. First, because of the study's cross-sectional nature, our results do not establish causality. Second, subjects taking some antidiabetic and statin agents were not excluded from our study, which might have influenced the association of CRP levels and might have also affected the association of CRP with insulin resistance in the multivariable analysis.In conclusion, our findings showed that insulin resistance was associated with CRP levels independent of abdominal obesity in Chinese patients with type 2 diabetes, suggesting that abdominal obesity could only partly explain the link between subclinical inflammation and insulin resistance.The authors declare that they have no competing interests.BL, YY and RH contributed to design of the study, analysis and interpretation of data, and drafting of the manuscript. ZY contributed to interpretation of data and critical revision of the manuscript. All authors have given the final approval of the version of the manuscript to be published.