Injuries pose a considerable threat to the health of children and adolescents, and childhood injuries cause substantial economic loss for families and society. Many injuries are preventable. To provide a theoretical basis and empirical support for injury prevention interventions, we studied the epidemiological characteristics, risk factors, and burden of injuries among elementary and secondary school students in Xiamen, China.Participants were enrolled through multi-stage stratified cluster random sampling of elementary and secondary students in Xiamen in 2010. Questionnaires were completed by students’ parents or guardians to assay students’ basic information, family background, occurrence of injuries in the past year, and burden of injuries. Chi-square tests and logistic regression were performed to identify the key factors of injuries.A total of 2,816 usable questionnaires reported 365 injury incidents in 303 students over 1 year. The incidence of injuries was 10.8%. Students who were male, extroverted, suburban, had sibling(s), studied in grades 4–9, or whose parents were divorced or separated were more likely to suffer from injuries. Most injuries occurred during the summer months (from June to August), and in the afternoon. The main affected body parts were limbs, fingers or toes. Unintentional falls, collisions/strikes, sprains, and cuts/sharp instrument injuries were the predominant causes of injury. The overall economic burden of the 365 injury incidents was 1,014,649.1 RMB  total, 3,348.7 RMB (490.65 USD) per capita, and 2,779.9 RMB (407.31 USD) per incident.The injury incidence among elementary and secondary students in Xiamen, China is lower than Guangdong and Zhejiang but higher than Beijing and Shanghai. Injuries caused substantial economic and family burdens and threatened students’ health and life. Childhood and adolescent injuries have become a serious public health problem that requires the urgent attention of the government, society, schools, and families. Injury control and prevention among elementary and secondary school students is essential and will help in multiple ways to reduce the burden on the family to build a harmonious family and society. Some injuries require urgent attention and are the leading cause of death for children and adolescents throughout the world -5. AccorInjuries are a considerable threat to the health of children and adolescents and cause substantial economic loss for families and society . The numConsiderable evidence demonstrates that effective interventions can prevent the majority of childhood injuries. For example, setting minimum drinking age laws, lowering the blood alcohol concentration limit for drivers and reducing driving speeds around schools can effectively reduce childhood road traffic injuries ,11. A reBecause of the substantial epidemiological and economic burden of childhood injuries and because injuries are preventable, a study on the epidemiological characteristics and risk factors of childhood injury was necessary. While there were previous studies on this topic in China focusing on specific regions and populations, research on childhood and adolescent injuries in Xiamen, China had just begun and no relevant data sets were established. To provide a theoretical basis and empirical support for interventions, we aimed to (1) establish the prevalence and the major causes of injuries among elementary and secondary students in Xiamen, China; (2) identify the key indicators related to disparities in childhood and adolescent injuries; and (3) measure the economic and family burden of childhood and adolescent injuries. To accomplish these, we conducted an epidemiological study to understand the socio-demographic characteristics, risk factors and burden of injuries among elementary and secondary students in Xiamen, China.In our study, we considered 14 types of injuries: traffic and road injuries, unintentional falls, collisions and strikes, sprains, cuts and sharp instrument injuries, crush injuries, drowning, suffocation, electrocution, burns and scalds, explosions, poisonings, animal attacks, and medical complications. Injury was defined following Wang SY (1998) [Subjects in our study were students in elementary (grades 1–6) and secondary (grades 7–12) schools in Xiamen, China. Multi-stage stratified cluster random sampling was performed to recruit students in 2010. Recruiting was performed by district. Xiamen is one of five special economic zones in China, and it has six districts: Huli, Siming, Haicang, Jimei, Xiang’an and Tong’an. According to economic conditions, the first two districts are classified as urban, the middle two districts as suburban, and the last two districts as exurban. At the first sampling stage, one urban, suburban, and exurban district was randomly selected. At the second stage, two elementary schools and two secondary schools were randomly selected from each selected district. At the third and last stage, we randomly chose one class from each grade in each school. Randomization was performed using simple random sampling in SPSS 17.0. All of the students in the sampled classes were enrolled in our study. Participants received a paper questionnaire and were asked to bring it home for their parents or guardians to answer the questions.The content of the questionnaire included the following. (1) Students’ basic information: sex, age, height, weight, health status , personality , and number of siblings. (2) Students’ family background: parents’ age, education, occupations, marital status , and incomes. (3) Occurrence of injuries in the past year: number of injuries, time and location of injury, injury type, events, and affected part of the body. (4) Burden of injuries: economic and family-related.The economic burden of injuries was measured by direct economic burden, including medical and other expenses directly related to treatments for injuries; indirect economic burden, which refers specifically to family income loss due to parents’ or families’ absence at work caused by the children’s injuries; and intangible economic burden, measured by the amount of money the family is willing to pay to avoid injuries. The family’s burden of injuries was measured using the Family Burden Scale of Diseases (FBS) , which iInformed consent was acquired on the first page of the questionnaire. All respondents participated voluntarily and provided informed consent. This study was approved by the ethical review committee of the School of Public Health, Xiamen University.α coefficient was used to measure the internal consistency and reliability of the FBS. The six FBS dimensions were assessed as follows: (1) calculate the dimension scores by averaging the item scores within each dimension for each student; and (2) obtain the thresholds for each dimension by averaging all the students’ dimension scores. There was considered to be no impact if the dimension score for an individual student is 0, moderate impact if larger than 0 but less than the threshold, and serious impact at or above the threshold. We summarize the distributions of each dimension by reporting the frequency and relative frequency of each response. All statistical analyses were conducted using SPSS 17.0. Data was double-entered and validated by two trained research assistants using Epidata 3.1.A chi-square test was used to analyze the association between the incidence of injury and impact factors. A multivariate logistic regression model was used to analyze significant variables from the chi-square test. Cronbach’s A total of 2,960 questionnaires were issued and 2,918 finished questionnaires were received. The response rate was 98.6%. Of the finished questionnaires, 2,816 (96.5%) were complete therefore usable. Table The characteristics of injury events are shown in Table As Table The direct economic burden of the 365 injuries among 303 students was 258,219.6 RMB  total, 852.2 RMB (124.86 USD) per capita, and 707.5 RMB (103.66 USD) per incident. The outpatient expenses were 91,396.6 RMB  (35.4%) and the hospitalization expenses were 147,885 RMB  (57.3%). The expenses for travel, care, nutrition and rehabilitation supplies were 18,938 RMB  (7.3%). The indirect economic burden of the 365 injuries was 88,948RMB  total, 293.6 RMB (43.02 USD) per capita, and 243.7 RMB (35.71 USD) per incident. The intangible economic burden was 667,481.5 RMB  total, 2,202.9 RMB (322.77 USD) per capita, and 1,828.7 RMB (267.94 USD) per incident. Altogether, the total economic burden  of the 365 injuries amounted to 1,014,649.1 RMB  total, 3,348.7 RMB (490.65 USD) per capita, and 2,779.9 RMB (407.31 USD) per incident.The economic burden of injuries with different characteristics is presented in Table α for the six dimensions (FM1–FM6) were 0.889, 0.912, 0.907, 0.926, 0.902, and 0.892, respectively, and 0.961 for the FMS overall.Table Injury has become a public health problem that threatens elementary and secondary students’ health and causes substantial economic burden. Our study shows that the incidence of injuries in elementary and secondary students in Xiamen, China was 10.8%, lower than in Guangdong and Zhejiang provinces -20, but The incidence of injuries for the students living in suburban areas (12.0%) was higher than those in urban areas (8.3%). This may be because urban students had better living and learning environments and were well supervised and protected by their guardians. The incidence of injuries among boys (12.9%) was higher than girls (8.7%), which is consistent with other regional research results -22. BoysIn addition, students in grades 4–9 were more likely to suffer injuries than those in grades 1–3 or 10–12. One possibility is that the students in grades 4–9 were more playful but lacked the self-awareness of protection, while the younger students were closely supervised by both teachers and parents, and the older students were too busy with their courses and preparing for the college entrance examination to participate in outdoor activities. Furthermore, the senior students were less likely to get injured because they had better physical coordination and greater awareness of self-protection. However, when injuries occurred, the economic burden for older students was higher, which indicates that their injuries were more serious. Students whose parents’ educational levels were lower had a higher risk of injuries. Parents have an integral role in their children’s growth, and in general, more highly educated parents provide better education and supervision for their children to avoid injuries.Almost all (97.0%) injuries were unintentional. More than one third of the students’ injuries occurred from June to August, likely because students engaged in outdoor activities more frequently in summer, with less protection from clothing and with more of their body exposed. In addition, more than half of the injuries occurred in the afternoon, the peak time for outdoor sports activities.Most injuries of elementary and secondary school students occurred at school (35.1%), at home or in dormitories (20.8%), and on the road (17.3%), which were the major places where students spent their time. In all areas and grades investigated, the school was where most injury occurred, so it is essential that schools provide a safe environment with high-quality education and living facilities to prevent and control student injuries. Arms/legs and fingers/toes were the main affected body parts, which relates to the top three causes of injury: unintentional falls (30.7%), collisions/strikes (18.8%), and sprains (17.3%).Multivariate stepwise logistic regression analysis showed that the incidence of injuries varied significantly among areas, sexes and grades. The results suggest that injury prevention and control interventions should focus on male elementary and secondary school students in suburban and exurban areas. Second, student injuries varied by health condition and personality. Students in fair or poor health were more likely to be affected by various levels and types of injuries. Extroversive students had more exposure to injury risk factors because they were more physically active. Therefore, we suggest that the primary aim of injury prevention and control interventions be to strengthen students’ physique, cultivate their safety awareness, and improve their self-protection abilities. Third, students’ injuries might be caused by their domestic situation. A child with sibling(s) may receive less concern and care from parents compared with a single child. Consequently, a child with sibling(s) is more likely to be ignored, and their risk of injury is accordingly higher. The odds of injury were higher in single-parent families. In addition, more people living together increased the chances of friction between students and others, thereby increasing the risk of injuries.As our study indicated, the direct economic burden of student injury was 258,219.6 RMB  in total, 852.2 RMB (124.86 USD) per capita and 707.5 RMB (103.66 USD) per incident from 365 injury incidents in 303 elementary and secondary school students in Xiamen in one year. This economic burden was higher than in Haidian District and Pinggu District in Beijing [This study found that the intangible economic burden of injury accounted for nearly 70% of the total economic burden. Injuries not only wasted money for individuals, families, and society but also were a burden on the emotional wellbeing of individuals and families. Because elementary and secondary students are the hope of each family and of society in general, the psychological loss for families caused by injuries is substantial. Therefore, the overall costs saved for society by effective prevention and control measures to reduce the occurrence of injuries in elementary and secondary students will be far greater than the actual material goods and money saved on treatment.Injuries cause both the burden of disease and severe psychological pressure and life consequences for members of the family. The impacts of injuries on elementary and secondary school students are pervasive and multi-dimensional. Injuries are undoubtedly preventable with appropriate prevention and control measures. According to our research results, we provide the following suggestions for the government, the local Centers for Disease Control and Prevention (CDC), schools and families to develop effective measures to control the incidence of injuries.First, the government should focus and invest more on injury control and prevention within the school sector, especially in suburban and exurban areas. Secondly, schools should practice safety management strictly and do their best to eliminate the risk factors of injuries. Third, besides helping students to obtain academic achievements, schools should work together with parents on strengthening student physique, cultivating safety awareness, and improving self-protection abilities. For instance, Bjӧrklund et al. introduced a school-based intervention program, “Together at school”, in Finland to promote elementary school students’ socio-emotional skills and mental health . FinallyBecause of time and man-power limitations, our study collected fewer than 3,000 usable questionnaires and conducted analyses based on these data. Therefore, our results might not be representative of all the elementary and secondary school students in Xiamen, China. Although the randomly chosen schools appared to be representative and we do not believe that the sample size has biased our results, closer investigation about their representation needs to be done in the future. We were aware of this limitation, and we encourage scholars and practitioners to conduct more extensive surveys to obtain more representative results.The injury incidence among elementary and secondary students in Xiamen is lower than Guangdong and Zhejiang but high er than Beijing and Shanghai. Injuries cause enormous economic and familial burdens and threaten students’ health and life. Childhood and adolescent injuries have become a serious public health problem and require the urgent attention of the government, society, schools, and families.


Introduction: The refugee crisis is a great challenge to the social and healthcare system in European countries, especially in Germany. An abundance of data has been published on the refugees’ health problems  and their prevention . However, data on prevalences of multidrug-resistant organisms (MDRO) in refugees are scarce, although it is known that most refugees are from or travelled through countries with high prevalences of MDRO. This paper presents current data on MDRO colonization of refugees admitted to hospitals, and the impact of screening upon admission and infection control in hospitals is discussed.Methods: Anonymous data obtained by screening upon hospital admission were reported by hospitals in the Rhine-Main region of Germany to the local public health department. Screening and microbiological analyses were performed from December 2015 to March 2016 according to standardized and validated methods.Results: 9.8% of the refugees screened (32/325) exhibited colonization with methicillin-resistant Staphylococcus aureus (MRSA), and 23.3% of the refugees (67/290) were colonized with Gram-negative bacteria with extended spectrum beta-lactamases, and/or enterobacteria with resistance against 3 or 4 groups of antibacterials, so-called 3MRGN  and 4MRGN . Carbapenem-resistant Gram-negative bacteria (CRGN) were detected in 2.1% (6/290) of the refugees.Conclusion: The data confirms the studies published between 2014 and 2016, encompassing refugees tested in Germany, the Netherlands and Israel, with prevalences of MRSA and CRGN up to 13.5% and 5.6%. The MDRO prevalences are higher than those of “risk groups” for MRSA, such as hemodialysis patients and patients depending on outpatient home-nursing care or residing in nursing homes. Therefore, screening and special infection control in hospitals is strongly suggested when refugees are admitted to hospitals, in order to ensure best medical practice and safety for all hospital patients regardless of their country of origin. With the refugee crisis, thousands of refugees are migrating to Europe, many of them coming as asylum seekers to Germany . In 2015To combat possible communicable disease risk imported to Europe with the movement of these refugees, the European Center for Disease Prevention and Control (ECDC) has published a rapid risk assessment , arguingRates of tuberculosis in refugees are a matter of concern, especially in those arriving from Somalia and East Africa, whereas the tuberculosis incidence of refugees originating from Asian countries are lower . Some cases of louse-borne diseases, cutanueous diphtheria, malaria, and leishmaniosis have been published ; these aAn abundance of data show that many refugees suffer from diseases such as the common cold, respiratory infections, diabetes etc., and especially from psychiatric disorders , 9], , , 11], , , 13], , , 15], , , 17], , , [19], , Compared to these issues, the potential risk of importing multidrug-resistant organisms (MDRO) has almost been neglected, although reports dating back to 2014 have shown high prevelances in Syrian war-injured children and adults , 24] ob ob24] obStaphylococcus aureus (MRSA) or multi-drug-resistant Gram-negative bacteria (MRGN).The present paper reports on a multicenter study on screening refugees admitted to hospitals for MDRO, such as methicillin-resistant Acinetobacter spp. and Pseudomonas spp. are classified as 3MRGN or 4MRGN according to the phenotypic definition of the German Commission on Hospital Hygiene and Infection Prevention (KRINKO). 3MRGN refers to Enterobacteriaceae resistant to 3 of 4 antibiotic groups  and 4MRGN with additional resistance to carbapenems, with imipenem and/or meropenem as surrogate substances . . 27]. In spite of earlier data indicating high prevalences of MDRO in refugees , 24] an an24] anAt the request of the public health department in Frankfurt am Main, Germany, the hospitals screened refugees upon hospital admission and reported the anonymous data to the public health department. Thus, this is a multicenter study with data from 5 hospitals in the Rhine-Main region and one hospital outside that region. All refugees were screened upon admission. In cases where the country of origin was possible to determine, most of the patients came from Syria (40–50%) and Afghanistan 20–30%), reflecting the refugees’ nationalities in the surrounding camps. Although various hospitals with different prevalences of MDRO were the source, the data obtained in winter 2015/2016 solidly confirm that from June-December 2015 in the Rhine-Main region, with 9.8% and 5.6% MRSA and 2.1% carbapenem-resistant Gram-negative bacteria (CRGN) %, reflec.Despite potential methodological differences in microbiological protocols, we compared the Frankfurt – Rhine-Main data with other recently published studies.Steger et al.  reportedE. coli, 4 Klebsiella pneumonia, 1 M. morganii, and 1 E. cloacae). Thirteen of these  were resistant to fluoroquinolones as well, i.e., 3MRGN according to the KRINKO definition  an an35] anE. coli, 1 Klebsiella spp, and 1 Shewanella putrefaciens) and 4 (8.3%) with Pseudomonas species with meropenem resistance. Another study performed MRGN screening in young, healthy, unaccompanied refugee minors (<18 years old) in Frankfurt/Main in October/November 2015 , , , 41]. . 41]. Given this data on MDRO in refugees in various settings, which consequences should be drawn?With respect to refugee camps, in October 2015, the Robert Koch Institute, Germany, recommended not to screen refugees in asylum centers . AlthougWith respect to the hospital setting, the German Commission of Hospital Hygiene and Infection Prevention (KRINKO) has published guidelines for prevention and control of MRSA  and MRGNUp to now, the KRINKO has not published a special recommendation for screening and infection control of refugees. The refugees’ MRSA prevelances shown in Table 1 Systematic data on 3MRGN and 4MRGN in the hospital setting are lacking in Germany. On May 1, 2016, a mandatory reporting system for CRGN was implemented in Germany . In the The authors declare that they have no competing interests.


Prolonged aerobic exercise, such as running a marathon, producessupraphysiological stress that can affect the athlete's homeostasis.Some degree of transient myocardial dysfunction ("cardiac fatigue")can be observed for several days after the race.To verify if there are changes in the cardiopulmonary capacity, andcardiac inotropy and lusitropy in amateur marathoners after running amarathon.The sample comprised 6 male amateur runners. All of them underwentcardiopulmonary exercise testing (CPET) one week before the SãoPaulo Marathon, and 3 to 4 days after that race. They underwentechocardiography 24 hours prior to and immediately after the marathon.All subjects were instructed not to exercise, to maintain theirregular diet, ingest the same usual amount of liquids, and rest atleast 8 hours a day in the period preceding the CPET.-1 .min-1;19.4 and 18.1 mL.btm, respectively). The echocardiography showed asignificant reduction in the s' wave (inotropic marker), but nosignificant change in the E/e' ratio (lusitropic marker).The athletes completed the marathon in 221.5  minutes. In thepost-marathon CPET, there was a significant reduction in peak oxygenconsumption and peak oxygen pulse compared to the results obtainedbefore the race (50.75 and 46.35 mL.kgIn amateur runners, the marathon seems to promote changes in thecardiopulmonary capacity identified within 4 days after the race, witha reduction in the cardiac contractility. Such changes suggest thatsome degree of "cardiac fatigue" can occur. Transthoracic Dopplerechocardiography performed after prolonged endurance exercise has shown changesin contractility, relaxation, and systolic and diastolic left ventricularfunction, such as changes in left ventricular internal diameter, an increase inA wave and a reduction in the E/A ratio5.Transient myocardial dysfunction ("cardiac fatigue") can be observed over severaldays following prolonged exercise. It can be evidenced in healthy individuals byuse of specific imaging tests and analysis of cardiac biomarkers in peripheralblood3.Stickland et al.6 havesuggested that the change in pulmonary gas exchange following vigorous andprolonged exercise is influenced by the cardiovascular system. However, thatrelationship is yet to be established6.Impairment in pulmonary gas exchange and a reduction in pulmonary diffusingcapacity observed after vigorous and prolonged aerobic exercise suggest that itcan induce persistent respiratory functional impairment, even in thepost-exercise periodDespite the increasing interest in the effects of a marathon on the cardiovascularand pulmonary systems, few studies using the cardiopulmonary exercise test(CPET) as a tool for that assessment have been published. Thus, this study aimedat assessing whether changes in the cardiopulmonary capacity of amateur athletes(pilot study) occur after a marathon.This is a case series of six athletes participating in the same São PauloInternational Marathon edition, who were assessed at the Sports Cardiologyoutpatient clinic at Instituto Dante Pazzanese de Cardiologia. They signed thewritten informed consent, which, along with the study protocol, had beenpreviously approved by the Committee on Ethics and Research of the institution,abiding by the rules of the Declaration of Helsinki.This study included only male Caucasian runners participating in at least onemarathon in the last five years and in a half marathon in the last year. Allwere healthy and reported no cardiopulmonary disease.®, APEX 200 model, SãoPaulo, Brazil), and the heart rate was obtained by using aTEB® equipment (APEX 1000 model) and following a stepprotocol, initiating with an 8 km/h velocity and an 1 km/h increment every 1minute, aiming at leading the individual to exhaustion.The first CPET was performed in the week preceding the marathon (3 days), and thesecond, 3 to 4 days after the event. The individuals refrained from trainingfrom the marathon day to the day of the second CPET after the marathon, andreceived written instructions to maintain a routine regarding liquid and foodingestion and rest over the post-marathon period. All exercise tests wereperformed on a treadmill  with sensors, allowing abreath-by-breath analysis, was used. The room conditions were controlled andmaintained as follows: temperature, between 21°C and 23°C; relative air humidityregistered in a thermo-hygrometer, 61%; and pressure registered in a Torricellibarometer, 703 mm Hg.For the expired gas analysis, a CardiO2 System analyzer  was quantified in the 30seconds preceding the end of exertion and the 30 seconds after exertion. Afterdata collection breath by breath, means were determined every 15 seconds, thehighest value in the period being considered. In the last CPET stage, therunners pointed in the Borg scale, the value corresponding to their perceptionof exertion.Peak exercise oxygen consumption  with digital imagestorage capacity was used, equipped with a M4S sectorial transducer.The athletes underwent echocardiography 3 days before the marathon and immediatelyafter the event. The exam was performed in a tent located 100 meters after thefinish line. The image acquisition time was of up to 10 minutes. A Vivid 7device .Complete echocardiographic study with single- and two-dimensional, conventionalDoppler and tissue Doppler was performed according to the American Society ofEchocardiography recommendationsThe SPSS software, version 22.0  was used forstatistical analysis. The results were expressed as medians andinterquartile ranges, because the data were not normally distributedaccording to the Kolmogorov-Smirnov test. To assess the impact of themarathon on the two predetermined occasions (pre- and post-marathon), thenonparametric Wilcoxon test was used, and Spearman test was used tocorrelate the delta of the variables. The significance level adopted was5%.The São Paulo International Marathon was held in springtime, in a sunnyday. The environmental conditions at the beginning of the race were as follows:temperature, 17.8°C; air humidity, 55%; and wind velocity, 1 m/s. At the end,they were 22.8°C, 59% and 2 m/s, respectively.This pilot-study included six athletes. All athletes showed good cardiopulmonary capacity, in both the pre- andpost-marathon CPET, achieving practically the same peak velocity in bothtests . All tests were maximum, witha respiratory quotient (R) greater than 1.1, and associated with intensefatigue, characterized by a Borg rating of perceived exertion scale of 19or 20.2 peak and in peak oxygen pulse(PO2) was observed in post-marathon CPET. In addition, areduction was observed in the ventilation/carbon dioxide production(VE/VCO2) slope, but with no difference in the maximumventilation values between the tests. A significant reduction in VOOn echocardiography, the athletes showed ejection fraction within the normalrange, but they differed at rest after the marathon, mainly due to heartrate increase.Regarding the echocardiographic variables, a significant reduction in thevalues of E wave, s' wave and E/A ratio, as well as a concomitant increasein heart rate were observed .Cardiac lusitropy was assessed by use of the E/e' ratio, which showed nosignificant change after the marathon. Cardiac inotropy was assessed by useof the s' wave, which represents myocardial contractility. The s' waveshowed a significant reduction after the marathon, suggesting a reductionin contractility, and, thus, in cardiac inotropy.2 as compared to the pre-marathon period. This happenedalthough the athletes maintained the same performance on CPET, meaning that theyreached the same mean maximum velocity in both tests.The major finding in this study was the significant reduction in post-marathonpeak VO2 in astudy published in 2006, reported a reduction in peak VO2 andsuggested that it could have resulted from a deceleration in the muscle oxygenkinetics after prolonged exercise2. Similarly, Miles et al.8 have reported a reduction in pulmonarydiffusing capacity after prolonged exercise, and that persisted for a a certainamount of time. However, the changes in the system of oxygen delivery to tissuesoccurring after exercise have not been clarified.Some changes identified in our study are in accordance with the results ofprevious studies carried out in athletes completing endurance events.Kasikcioglu et al.,2 and PO2can suggest some degree of "cardiac fatigue". With the PO2 drop onthe post-marathon test, the reduction in cardiac inotropism seems to play asignificant role in the VO2 drop in that same period. This might havebeen the factor contributing most to VO2 drop, because the peak heartrate was similar in both tests. In addition, despite the partial benefitdemonstrated by pulmonary compensation, with greater ventilatory efficiency andoptimization in O2 use to produce the same exertion, a reduction incardiac output is evidenced in the post-marathon period. Based on thosefindings, one can speculate a worsening of myocardial performance after themarathon stress.In that context, the post-marathon drop in peak VO2 and peak VO2 on CPET, support thehypothesis that athletes can have some degree of "cardiac fatigue", mainly dueto the changes in cardiac inotropism, with no change in lusitropy. However, thevariables of diastolic function assessment had no change.Those hypotheses are supported by both echocardiographic and CPET post-marathonfindings. The modifications in contractility on echocardiography, along with thedrop in peak PO2 slope showed a significant reduction from the pre-marathonto the post-marathon period. No plausible explanation for this finding wasfound, but the small absolute variation of that variable makes us believe thatthere is no physiological relevance for that difference.The VE/VCOThis study's limitations include the small and selected sample , which can have caused a bias in the results obtained, inaddition to hindering any extrapolation regarding external validity. It is worthnoting the lack of control regarding the previous training of the athletes.Similarly, there was no control about possible interventions performed in therecovery period (3-4 days), which can have interfered with the results observed. New studies are required to supportour findings.In amateur athletes, marathon seems to cause changes in the cardiopulmonarycapacity identified up to four days after the event, with a reduction incontractility, and, thus, in cardiac inotropy. Such modifications suggest thatsome degree of "cardiac fatigue" can occur.


Background. Chronic obstructive pulmonary disease (COPD) is a common respiratory condition characterized by progressive dyspnea and acute exacerbations which may result in emergency department (ED) presentations. This study examines monthly rates of presentations to EDs in one Canadian province. Methods. Presentations for COPD made by individuals aged ≥55 years during April 1999 to March 2011 were extracted from provincial databases. Data included age, sex, and health zone of residence . Crude rates were calculated. Seasonal autoregressive integrated moving average (SARIMA) time series models were developed. Results. ED presentations for COPD totalled 188,824 and the monthly rate of presentation remained relatively stable . Males and seniors (≥65 years) comprised 52.2% and 73.7% of presentations, respectively. The ARIMA × 12 model was appropriate for the overall rate of presentations and for each sex and seniors. Zone specific models showed relatively stable or decreasing rates; the North zone had an increasing trend. Conclusions. ED presentation rates for COPD have been relatively stable in Alberta during the past decade. However, their increases in northern regions deserve further exploration. The SARIMA models quantified the temporal patterns and can help planning future health care service needs. Chronic obstructive pulmonary disease (COPD) is a common and disabling condition usually caused by cigarette smoke exposure and characterized by progressive symptoms of dyspnea. Acute exacerbations of COPD (AECOPD) are characterized by an increase in the ongoing symptoms of cough, sputum production, sputum purulence, and/or shortness of breath which usually require changes in baseline medical management , 2. OverPatients with COPD often experience exacerbations and some exacerbations are severe enough to require emergency department (ED) management. Treatment guidelines for AECOPD exist and prolonged treatment may occur in the ED, some exacerbations result in complications including pneumothorax, pneumonia, need for noninvasive ventilation, intubation and mechanical ventilation, and death. Due to the advanced age of patients, associated severe comorbidities, and severity of many presentations, hospital admission is a common outcome in severe exacerbations  to EDs for COPD during a 12-year period  and provides time series models to quantify the temporal patterns.This project is a secondary analysis of existing population-based, administrative databases.Alberta is a Western Canadian province, which operates under a single health authority, providing government funded health care services to more than 4.1 million residents. All visits to Alberta's more than 100 EDs are tracked in the provincial Ambulatory Care Classification System  (ACCS). All COPD ED visits for patients 55 years or older between April 1, 1999, and March 31, 2011 , were extracted from ACCS, where COPD was defined by either the first or second diagnosis field containing any of the diagnostic codes 490.x, 491.x, 492.x, 494.x, and 496.x (ICD-9-CM) or J40.x, J41.x, J42.x, J43.x, J44.x, and J47.x (ICD-10-CA). The date and time of the ED visit were extracted as well as the mode of release from the ED .Two age groups were formed with patients classified as either 55–64 or 65+ based on age at time of ED visit. Alberta is comprised of five geographical and administrative health zones   was usedp, d, q) × S where d is the order of nonseasonal differencing, p and q are the order of nonseasonal autoregressive (AR) and moving average (MA) terms, respectively, D is the order of seasonal differencing, P and Q are the order of seasonal AR and MA terms, respectively, and S is the order of seasonality  [To estimate parametric models for monthly rates of COPD ED visits over time, seasonal autoregressive integrated moving average (SARIMA) models were considered. SARIMA models can be denoted by ARIMA(ly data) . Additioly data)  and KPSSly data) , respectly data)  (AIC) amSAS version 9.4 for Linux  and R version 3.2.0 for Windows (including the “stats” and “forecast” packages) were used to carry out all statistical analyses.The study was approved by the University of Alberta's Health Research Ethics Board and patients were not contacted during this study. The data are reported in aggregate, and small cell sizes are suppressed to protect anonymity.There were a total of 188,824 ED visits for COPD between April, 1999, and March, 2011 , of which most (76.5%) listed COPD as the primary diagnosis. Average monthly rates of COPD ED visits per 100,000 individuals were higher for males than females (218.6 versus 180.2), higher for ages 65 and over compared to ages 55–64 (278.1 versus 109.5), and varied by geographic zones, ranging from a low of 108.6 in the Calgary zone to a high of 463.9 in the North zone .Each time series is shown in Despite similar seasonality across each series, there existed different patterns of long term trend. The trend component for the overall rate of COPD ED visits was relatively flat, with a 0.4% decrease from April, 1999, to March, 2011. The differences in sex were small but opposite in direction . For females, the age 65+ group increased by 20.2% compared to only 8.6% for age 55–64, while for males both age groups saw small decreases (3.5% for age 65+ and 1.8% for age 55–64). Three of the zones saw only small changes over the time period, including the urban zones of Edmonton (4.1% increase) and Calgary (6.5% decrease), as well as the South (6.9% decrease). The Central zone, however, had a decrease of 17.6% and the North zone had an increase of 40.6% over the time period .12, with AIC 1337.9, although several models had similar values of AIC suggesting other similar models are likely equally appropriate. The resulting optimal models for each series are shown in Tables To parametrically model the ED visit rates for COPD over time, SARIMA models were fit for each series. The OCSB test suggested seasonal differencing was not required for any of the series, and the KPSS test suggested nonseasonal differencing was required only for the North, Central, and South zones to achieve stationarity. For the overall series, the model that resulted in the smallest AIC was ARIMA × To evaluate the predictive ability of the optimal model for the overall series, the model parameters were estimated using the first 11 years of monthly data  and then used to predict the last year of our period , including 95% prediction intervals. The estimated model performed well, with the 95% prediction interval containing the actual values for all of the 12 time points . The MAPWe described the monthly rates of presentations to the ED for COPD during 12 years in a Canadian province and used time series modeling techniques to quantify the patterns. With over 188,000 ED visits for COPD during the study period, we demonstrated stable presentation rates, variations across age, sex, and location, and a consistent pattern reflecting the influences of environmental conditions. These findings were similar to our earlier investigation of ED visits for COPD in Alberta during 1999 to 2005 .The stable presentation rates observed in this study are similar to those seen in other jurisdictions, where stable temporal trends were observed during 1999 to 2010 (adults aged ≥25 years)  or 2001 Relatively few studies have used time series analysis methods to investigate patterns of COPD presentations. In Australia, COPD mortality rates during 1922–2005 were used to create functional time series models and forecast age- and sex-specific mortality rates for 2006 to 2025 . COPD, bThe study has several strengths and limitations. The large sample size, 12-year time frame, the use of population-based databases, and time series methods are all strengths of the study. In addition, the use of diagnostic codes assigned by trained medical records nosologists strengthens the validity of the work.Study limitations include the lack of linked data on treatment or contact with other health care services before the ED treatment; our focus on ED visits did not identify patients with COPD who used alternative sources for the delivery of acute care. In addition, the diagnosis of COPD is notoriously difficult to validate without supplemental records such as pulmonary function testing, simple imaging , or advanced imaging . While the diagnosis was not confirmed and this may both over- and underestimate COPD cases, ED-based research suggests that the diagnosis of COPD is valid and underestimates the problem . FinallyIn summary, rates of presentations to the ED for COPD have been remarkably stable and demonstrate a consistent pattern reflecting the influences of a cold-weather environment. During the cold winter months, indoor exposure, seasonal viral infections, and use of enclosed spaces predispose patients, and especially those with COPD, to upper respiratory tract infections, influenza, and pneumonia complications. SARIMA models fit the overall and subgroup data well and subgroups have similar parameter estimates. Such models can be helpful for forecasting and future health care planning.


Obesity is a chronic disease associated with excess morbidity and mortality. Clinical treatment, however, currently offers disappointing results, with very high rates of weight loss failure or weight regain cycles, and only two drugs (orlistat and sibutramine) approved for long-term use. Drugs combinations can be an option for its treatment but, although widely used in clinical practice, very few data are available in literature for its validation. Our review focuses on the rationale for their use, with advantages and disadvantages; on combinations often used, with or without studies; and on new perspectives of combinations being studied mainly by the pharmaceutical industry.  This isIn recent years, obesity has been considered a metabolic and neuroendocrine disease, which results from the interface between an obesogenic environment and an intrinsic genetic predisposition. Despite this, lifestyle changes proposed in the treatment of obesity are essential and may be effective, but the rates of long term success tend to be low.In this context, obesity pharmacotherapy plays an important role. The major limitations of obesity pharmacotherapy are the modest efficacy seen with the medications currently available and the limited availability of medications (orlistat and sibutramine) for long term treatment ,5, althoIn a recent meta-analysis, it was shown that both sibutramine and orlistat alone lead to placebo-subtracted weight loss on average of 3–5%, although the proportion of individuals with weight losses greater than 5% was of 54 and 55%, compared with 27 and 33% for placebo [This modest efficacy contrasts with the maintained weight loss and the low rates of therapeutic failure achieved in patients submitted to bariatric surgery, resulting in a significant reduction of comorbidities and increased life expectancy . Sibutramine Cardiovascular OUtcomes Trial (SCOUT) [In addition, sibutramine was taken off the European market in 2009 due to the results of the Therefore, at the same time new drugs are being tested, it seems attractive to use different strategies, such as combination of medications. Considering that obesity is a multifactorial disease, with environmental factors linked to genetic factors, it is expected that drug monotherapy may result in unsatisfactory outcomes. In analogy to the treatment of hypertension, where a combination of antihypertensive agents with different mechanisms of action is widely used to control blood pressure, obesity treatment using combinations of medications, working synergistically or in parallel , can resAlthough little data exists for the use of combinations, in a questionnaire answered by obesity specialists in the US, 85% prescribed combinations of drugs, and 65% of them prescribed combinations not approved for obesity treatment. This result is very relevant and shows us how important is to study and publish more about this issue . In this review, anti-obesity drug combinations in general will be discussed, covering those already studied, those still awaiting final results to be released and also those which are used empirically in clinical practice. It is worth noting that with regard to the drugs in initial studies, much of the information and clinical outcomes are from the pharmaceutical companies own websites, since they have not been yet submitted to peer-review in medical journals. Therefore, these results are subject to potential conflicts of interest. (1)Increased efficacy of treatment through synergic or additive action;(2)Promotion of endogenous synergism;(3)plateau during the effort to lose weight or combination of medications with opposite side effects, such as a medication associated with insomnia with another to drowsiness, could increase the tolerability of the treatment.Medications with different pharmacodynamic actions and that act on different pathways may “beat” the compensatory mechanisms involved in homeostasis and thus prevent or delay the formation of the (4)Combination of low doses could reduce the risk of adverse effects;The possible advantages of combination drug therapy are as follow :(1)Incr(1)Increased incidence of side effects, due to additive action and interaction of medications;(2)Inflexibility of dosing in combo drugs prescribed in a single agent;(3)Cost of treatment.The disadvantages include:Some drug combinations have already been studied in the past and stopped being used. It is worth remembering that the suspension of the commercialization of these combinations was on account of side effects of one of their components and not due to any negative interaction between the drugs. Phentermine is a catecholaminergic substance that increases the release of noradrenaline in the central nervous system (CNS), available for obesity treatment in the United States of America (USA) since 1959 (in doses of up to 37.5 mg/day) ,14. WeigFenfluramine raises the synaptic levels of serotonin in the CNS by stimulating the secretion and inhibiting the reuptake of serotonin. Dexfenfluramine is a highly selective D-isomer, which also leads to increased levels of serotonin and stimulates the hypothalamus . A randoThe combination of fenfluramine and phentermine resulted in a reduction of side effects and increased efficacy, even in lower doses, when compared to use of either medications by itself . This coEphedrine is a nonspecific beta-adrenergic agonist which promotes weight loss through increasing thermogenesis. Cafeine and acetylsalicylic acid reduce the degradation of ephedrine, potentiating its action . The useSibutramine and its metabolites act in the CNS inhibiting the reuptake of serotonin and norepinephrine, resulting in reduction of appetite, increase in satiety and possible increase of thermogenesis ,15,24.Orlistat is a synthetic hydrogenated derivative of lipstatin which partially inhibits the gastric lipase, pancreatic lipase and carboxyl ester lipase enzymes. These enzymes work hydrolyzing the dietary triglycerides into fatty acids and monoglycerides, which are subsequently absorbed by the mucosal cells of the gastrointestinal (GI) tract. Orlistat reduces the absorption of ingested fat by 30%, increasing its excretion in the feces . versus placebo for 16 weeks did not result in greater weight losses [Since the mechanisms of action of these two medications are very distinct, their combined use was evaluated in some studies. In obese women who had already been using subutramine for one year, the combination of orlistat t losses . vs. 6.9% placebo). It is noteworthy that this clinical trial, like many others in the obesity field, had a run-in phase which required weight loss of 2.5 kg, a method highly criticized by authors in the field [Two studies were conducted at different centers in Turkey, with similar results ,28. In ahe field .Another study involving 89 obese women, showed a mean weight loss of 5.5%, 10.2% and 10.6% with orlistat alone, sibutramine alone and combined therapy, respectively, once again with no statistical difference between the latter two groups. Despite these disappointing results, around 14% of obesity specialists reported to use this combination in clinical practice .A large clinical series done by our group was developed to evaluate the efficacy of the combination of sibutramine and orlistat in 446 individuals for six months, with concomitant dietary counseling . Weight In summary, studies of combinations that are safe and widely used in clinical practice worldwide are still very scarce. It is our belief that this combination appears to provide satisfactory results, although this was not confirmed in randomized controlled studies. In contrast with our opinion, some specialists in the obesity field believe that concomitant use of drugs acting on the gastrointestinal tract with centrally acting drugs does not result in additional weight compared to the latter by itself .Only one study evaluated orlistat in combination with metformin , an insu®) has been studied for some years by the pharmaceutical company Orexigen Therapeutics Inc. as a potential agent in the treatment of obesity [The combination of bupropion with naltrexone  leads to increased β-endorphin levels in the hypothalamus. With this data, it is assumed that the release of opioids has a role in the expression of food palatability, and ce-versa . Some ance-versa . The synce-versa .A double-blind phase 2 randomized study with a 24-week duration, with 419 patients, compared three different doses of immediate release (IR) naltrexone , in combination with bupropion sustained release (SR), 400 mg/d, with placebo, bupropion SR, 400 mg/d, and naltrexone IR, 48 mg/d, in monotherapy [Patients receiving bupropion alone or the three doses of the combination were followed for an additional 24 week-extension. In 24 weeks the weight loss by intent-to-treat analysis (ITT) was 5.4%, 5.4% and 4.3% for the combination of bupropion with naltrexone, 16 mg (NB16), 32 mg (NB32) and 48 mg (NB48) respectively, against 2.7% for bupropion, 1.2% for naltrexone and 0.8% for placebo. The lower weight loss seen in the patients receiving NB48 was justified by the higher dropout rate (63%) due to side effects in this group. After 24 weeks, there was no sign of a plateau in any of the three combination groups, and in the final analysis of 48 weeks, the NB32 combination reached a higher success rate with an average weight loss of 6.6%. It was also found in other phase 2 studies that naltrexone SR resulted in fewer side effects compared to the IR formulation .vs. 16%) and in COR II (56 vs. 17%).Based on these results, phase 3 studies were designed accordingly, using naltrexone SR in doses of 16 and 32 mg/d and bupropion SR, 360 mg/d, on a twice-daily basis (bid). The COR-I trial randomized 1.742 patients for NB16, NB32 or placebo, with four weeks of titration of medication and a duration of 56 weeks . The plaDropout rates were high for both studies , with around half of the cases being directly related to side effects. The most commonly observed side effect was nausea, around 30%, compared to 5 and 6% in the placebo group. The incidence occurred mainly in the initial weeks of treatment, still within the titration phase, with a tendency to fall after the fourth week. Other side effects significantly more common than placebo, in order of frequency were: Constipation, headache, dizziness, vomiting and dry mouth. There was no significantly higher incidence of adverse effects on the cardiovascular system, nor in relation to depressive disorders or suicidal ideation. BP of patients using the combination remained unchanged after 56 weeks, with a slight decrease of 2 mmHg in the placebo group, and a negligible increase of one beat per minute in the heart rate of the treated patients. Three serious events were reported, possibly related to the use of one component of the combination: seizure (one), paresthesias (one) and palpitations with dyspnea and anxiety (one).In vitro evidence has also shown that this drug leads to an increase in serotonergic and dopaminergic activity. It is assumed that this mechanism explains, at least in part, its effects as a weight-reducing agent. Another property of zonisamide is the relatively weak inhibition of carbonic anhydrase activity. This evidence highlights previous reports of taste alteration with other carbonic anhydrase inhibitors , thus possibly leading to an anorectic effect. Although in earlier stage of development, the combination of bupropion/zonisamide also seems promising as an anti-obesity drug. Zonisamide has been used as an antiepileptic drug in Japan since 1989, being approved for such use in the United States (USA) and in some European countries in the early 2000s. In some short-term studies of treatment of epileptic patients with zonisamide, weight loss was observed as a side effect . The mecvs. 1.0% of for zonisamide in monotherapy  and placebo, respectively, in association with a hypocaloric diet with a 500 kcal/d deficit [vs. 1.8% reduction of the initial weight. The drug was well tolerated in this study, with fatigue being the only side effect reported with a higher incidence in the active group than in the placebo. As seen in other studies of epileptic patients, there was a significant increase of serum creatinine of 0.13 mg/dL in the treated group compared to 0.03 mg/dL in the placebo group. In a subsequent study with obese patients with binge eating disorder (BED), zonisamide (in doses up to 600 mg/day) also proved effective both in reducing weight and in controlling bingeing episodes [A double-blind randomized pilot study with 60 patients, showed after 16 weeks a weight loss of 6.0%  deficit . An openepisodes .However, this study raised concerns regarding its tolerability, since eight out of 30 patients using the drug abandoned the study due to side effects, which included psychological complaints (two), cognitive changes (two) and even accidental injury with bone fracture (two). ®). In the phase 2 studies conducted so far, it has chosen to test lower doses of zonisamide (120 and 360 mg/d) with doses of bupropion the same as of Contrave® (360 mg/d), bid [Orexigen Therapeutics Inc. also decided to register the patent of zonisamide with bupropion (Empatic/d), bid . A 24-we/d), bid . The mosTopiramate is a medication originally approved for the treatment of epilepsy, which currently is also widely prescribed for migraine prophylaxis. Some studies in the early 2000s proved the efficacy of this drug to reduce the weight of obese patients (in tested doses of 64 to 384 mg/d) , a fact However, despite showing promising efficacy, the enthusiasm with the drug diminished considerably due to the elevated incidence of side effects, such as paresthesias, memory changes, concentration impairment and mood swings. While it is known that it exerts its anti-epileptic activity through blocking sodium and calcium channels, enhancing the action of the GABA and carbonic anhydrase inhibition, its mechanism of action as a weight-loss agent is still poorly understood. In animal models, topiramate reduces both appetite and interferes with the efficiency of energy use, by increasing thermogenesis and fat oxidation, probably through stimulation of lipoprotein lipase in brown adipose tissue and skeletal muscle .®) were tested: low (phentermine IR 3.75 mg/topiramate SR 23 mg), medium (phentermine IR 7.5 mg/topiramate SR 46 mg) and high (phentermine IR 15 mg/topiramate SR 92 mg). The EQUATE phase 2 study evaluated 776 patients for a period of 28 weeks (including a 4-week titration phase), where the patients were randomly selected for placebo, phentermine or topiramate in monotherapy in the medium and high doses and Qnexa® in medium and high doses [® both in medium and high doses lost significantly more weight than phentermine or topiramate high dose in monotherapy or placebo, proving, therefore, the synergistic effect of the combination .By combining lower doses of topiramate with phentermine, which act by different pathways, the pharmaceutical company Vivus Inc. aimed to increase the positive results and minimize the chance of side effects. Supposedly, the light stimulative effect of phentermine on the CNS could overcome the negative effects of topiramate on memory and cognition. Three doses of this combination  [2 with two or more comorbidities. By ITT analysis, the results were similar, with loss of 10.4%, 8.4% and 1.8% for Qnexa® high dose, medium dose and placebo, respectively. (PSWL of 8.6% for high dose and 6.6% for medium dose) [The results from phase 3 studies, with 56 weeks of duration, were recently reported. The EQUIP trial, involving 1.267 obese patients with BMI > 35 kg/mow dose) . The CONum dose) . There w® and 47% for the patients on placebo. Eighteen per cent of patients taking Qnexa® high dose discontinued the study because of side effects compared to 9% for the placebo group. Clinically significant changes in cognitive function, depression and anxiety, or effects on psychomotor skills were not reported in greater frequence by patients taking the medication. It is unclear if the lower incidence of adverse effects with Qnexa® compared to earlier studies involving topiramate is related to the use of lower doses of this drug or because of its SR formulation.The most common side effects, in order of frequency, were: dry mouth, paresthesias, constipation, upper respiratory tract infection, taste alteration and insomnia. The dropout rate ranged from 31 to 43% for patients taking QnexaThe control of energy homeostasis and body weight involves complex interactions between the CNS and peripheral neurohormonal signals from the adipose tissue, pancreas and GI tract ,37,47.These interactions include the integration of long-term adiposity signals, like insulin and leptin, and short-term satiety signals, such as amylin, peptide YY, incretins and cholecystokinin. Insulin and leptin show tonic secretion by the pancreas and adipose tissue, respectively, while the others are episodically secreted in response to the presence of food in the GI tract ,49.Amylin is a 37-amino acid peptide hormone co-secreted with insulin by pancreatic β-cells, which binds to receptors in the hindbrain, leading to increased satiety and a reduction in food intake . In prevet al. elegantly demonstrated that, after metreleptin administration, energy expenditure, skeletal muscle work efficiency, sympathetic nervous system tone, and circulating concentrations of thyroxine and triiodothyronine returned to pre–weight-loss levels [Leptin is a neurohormone secreted predominantly by adipocytes which bind to receptors in the hypothalamus, presenting a key role in the regulation of long-term energy homeostasis ,47,48. Is levels . Diet-induced leptin fall also contributed to reduce the anorexigenic effect of the satiety signals in the hindbrain. On the other hand, there is growing recognition that hindbrain signals may exert important effects on leptin signaling in the hypothalamus ,47,48.Preclinical studies in rats with diet-induced obesity showed that combined treatment with amylin and leptin led to a pronounced response and synergy in the reduction of food intake (up to 45%) and of body weight (up to 15%) .It was proven that weigh loss was fat-specific and not accompanied by reductions of energy expenditure and fat oxidation normally seen with caloric restriction. These figures corroborated, therefore, the hypothesis that the combination of pramlintide with metreleptin would have a potential role in the treatment of obese humans.2 (81%), or overweight patients with BMI between 27–30 kg/m2, with increased waist circumference  [The first clinical trial with this combination involved 177 obese patients with BMI between 30–35 kg/m> 88 cm) . The stuThe commonest side effects reported were adverse reactions at the site of injection  and nausea (12.5%). Other side effects were much less frequent, occurring in up to 5% of the cases, and included nasopharyngitis, headache, constipation, and diarrhea. Dropout rates were indifferent between the groups, ranging from 30–34%. One patient in each group left due to adverse reactions at the site of injection and one patient in the combined treatment group abandoned due to nausea. Four patients had already left the study due to nausea in the initial weeks of pramlintide titration. A randomized controlled trial compared the safety and efficacy of pramlintide alone or in combination with either oral sibutramine or phentermine . FollowiAt the end of the study, weight loss was similar for the combinations of pramlintide/sibutramine (11.3 ± 1.2 kg) and pramlintide/phentermine (11.3 ± 0.9 kg) and significantly greater than that observed for pramlintide alone (3.6 ± 0.7 kg) and placebo (2.1 ± 0.9 kg). PSWL was 1.5% for pramlintide alone, 8.9% for pramlintide/sibutramine and 9.1% for pramlintide/phentermine . Treatme®), when administered sc bid, leads to moderate and discreet weight loss in patients with T2DM [Glucagon-like peptide 1 (GLP-1) is a gut hormone rapidly secreted in response to food intake . GLP-1 iith T2DM . Moreoveith T2DM . Peptideith T2DM ,59. Intrith T2DM . Some stith T2DM .5-Hydroxytryptophan (5-HTP) is the precursor of serotonin  and is kThe combination of orlistat with noradrenergic drugs is frequently used in clinical practice, albeit the safety and efficacy of this combination has not been assessed in randomized controlled studies. Considering they act on different pathways ,6,13,14 Topiramate use as monotherapy for obesity treatment is not recommended as its usual side effects greatly reduce the tolerability and safety of the medication. However, for specific groups of patients, such as those who present associated conditions which indicate the need for treatment with topiramate , the combination of orlistat for an additive effect of weight loss seems reasonable, since they have distinct mechanisms of action and apparently there is no interaction between these two medications.Anxiety disorders, depression and eating disorders are considered risk factors for obesity. The treatment of these illnesses with antidepressants many times results in weight variation, depending on the drug class that is used ,34,64,65Sibutramine and topiramate act on the CNS, through different mechanisms of action. Both led to sustained weight loss in studies carried out with the drugs in monotherapy ,44. TherObesity is a chronic, multifactorial disease, still very challenging for the clinician to treat. Lifestyle modifications, such as diet and physical activity, are very often difficult to achieve and maintain in the medium to long term. Medical therapy appear as an important treatment modality, but drugs most studied to date show modest results for sustained weight loss when compared with bariatric surgery, which is, however, still reserved for a selected group of patients. As the obesity epidemic progresses worldwide in an alarming scale, development of new therapeutic strategies, in which combination of drugs are included, is of crucial importance. Although combining drugs may increase the risk of side effects, the use of medications which act in different pathways, or which have synergistic actions, can help overcome regulatory mechanisms which prevent continued weight loss.Most of the combinations used in clinical practice do not have, or have few studies which support them, but may be carefully used in clinical practice, customizing their use according to patients’ characteristics, while new studies or new drugs are not available.It is encouraging that a number of drugs which individually lead to modest weight loss, have positive results when used in combination, even though currently released studies are in initial stages and/or still linked to pharmaceutical industries.


Individuals with 45,X/46,XY karyotype are at increased risk for germ cell tumor development. We report a case with a diagnosis of 45,X/46,XY gonadal dysgenesis who presented with short stature, physical stigmata of Turner syndrome. Her pubertal development was at Tanner stage 3. At follow-up, bilateral prophylactic gonadectomy was performed when considering the risk factors. Pathological assessment was consistent with gonadoblastoma in the left gonad, and dysgerminoma and gonadoblastoma in neighboring areas in the right gonad. The karyotype analysis of the right and left gonadal tissues reveled 45,X/46,XY and 45,X/46,XY/47,XYY  mosaic, respectively. The clinical management of such patient should be individualized according to the present risk factors. Additionally, signs of estrogenization like advanced breast development always suggest the possible presence of germ cell tumor. Patients with gonadal dysgenesis, particularly those carrying Y chromosomal material in the gonadal tissue, are at an increased risk for germ cell tumor development.In this context, AZFc gene deletion on peripheral blood lymphocytes DNA detected in our patient  may contribute to germ cell tumour development as a risk factor. This can be expected when considering the role of AZF genes in gonadal cell differentiation by providing Y-chromosome stability during early embryogenic development.Gonadal dysgenesis (GD) is characterized by the abnormal development of the foetal gonads due to structural or numerical anomalies of the sex chromosomes or mutations in genes involved in the formation of the urogenital ridge and in sex determination of the bipotential gonad . PatientHere, we report a phenotypically Turner-like patient who had a 45,X/46,XY karyotype with a Yq microdeletion. The patient developed two different types of GCTs at each gonad.A 13-year-old female patient presented to our endocrinology clinic for evaluation of short stature. She had been shorter than her peers throughout her life. She was the third child of non-consanguineous parents and her two siblings were normal.Adjunct to short stature, her examination revealed physical stigma for Turner syndrome (TS) such as a short/webbed neck, cubitus valgus, and short 4th metacarpal bones. She stood 139.3 cm [-2.57 standard deviation (SD)] and weighed 41.2 kg (+2 SD). Both breast and pubic hair development were consistent with Tanner stage 3. Her external genitalia appeared completely female. Bone age determined by Greulich and Pyle atlas was 13 years.She had a follicle-stimulating hormone level of 121 IU/L, luteinizing hormone (LH) level of 28.8 IU/L, and an estradiol level of 28.6 pg/mL. Complete blood count, celiac markers, thyroid function tests, insulin-like growth factor-1, and insulin-like growth factor-binding protein-3 were all within normal range. She had a uterus of 9x14x33 mm in size, but her ovaries could not be visualized by ultrasonography. Further magnetic resonance imaging to evaluate internal genital organs revealed a right gonad with a size of 22x14x19 mm, an invisible left gonad, and a hypoplastic uterus. The chromosomal study of peripheral blood lymphocytes (PBL) with GTG-banding analysis of 55 metaphases showed a 45,X[30]/46,XY[25] karyotype. Y-derived sequences  were analysed by polymerase chain reaction (PCR); they were all present except for microdeletions in AZF regions  on PBL DNA.Due to an increased malignancy risk to the gonads, an explorative laparotomy and bilateral gonadectomy were performed. During explorative laparotomy, she was found to have a streak gonad on the left side and a 3-cm irregular nodule in the ovarian fossa on the right. The capsules of the gonadal tissues were intact, and the gonads were successfully removed. The frozen sample of the right nodule was consistent with dysgerminoma. On inspection, the uterus and fallopian tubes were normal, and there was no evidence of malignancy or abnormality in the pelvic organs. Histopathological examination of the left streak gonad revealed a gonadoblastoma. In the right gonad, together with a normal ovarian stroma, centrally located dysgerminoma and gonadoblastoma in neighbouring areas were identified. Twenty-three metaphases were analysed in each gonad. The karyotype of the right and left gonadal tissues were 45,X/46,XY and a 45,X/46,XY/47,XYY mosaic, respectively. The microdeletion in the AZF region was detected by using PCR analysis.The patient was discharged one week later, after an uneventful postoperative course. She then consulted with paediatric oncology. Based on their recommendations, computed tomography scans of the chest, abdomen and pelvis were performed for metastatic evaluation and did not reveal an abnormality. GCT markers  were measured, and all were within normal limits. After the first oncological evaluation, a follow-up plan was designed for every 3 months during the first year and every 6 months thereafter. At the same time, hormone replacement therapy was started to maintain secondary sexual characteristics and to prevent bone loss.The patient and especially her parents had numerous questions regarding fertility and gender identity, and therefore, she was referred to an adolescent psychiatrist and a gynaecologist. Her gender identity was that of a woman, and she was worried about having children. Future fertility treatment options, such as adoption and oocyte-donor in-vitro fertilization (IVF), were also discussed.Her regular follow-up has been ongoing in outpatient clinics of related departments nearly for the past postoperative 2 years and no complications have been noted.The mosaicism of 45,X/46,XY is an important component of sex chromosome disorders of sexual development (DSD) and occurs with an incidence of 1.5 per 10,000 ,8,9. ItsGCTs most often occur in a subgroup of DSD patients. The risk among subgroups of DSD is heterogeneity, and DSD can also be classified into different levels as high, intermediate, low, and unknown. GCT is associated with gonadal dysgenesis, hypervirilisation in 46,XX individuals, and undervirilisation  in 46,XY individuals ,10.The presence of the Y chromosome or molecular evidence of a Y-derived sequence serves as the risk factor for the origin of GCTs in those who have a dysgenetic gonad. This has been particularly related to the presence of a specific part of the Y chromosome that is known as the gonadoblastoma region of the Y chromosome (GBY) and candidate genes that are located in this chromosomal fragment . Of thesBesides the aforementioned genetic risk factors, AZFc gene deletion on PBL DNA detected in our patient  may contribute to GCT development as a risk factor. This can be expected when considering the role of AZF genes in gonadal cell differentiation by providing Y-chromosome stability during early embryogenic development ,16,17. AIt ıs well known that patients with 45,X/46,XY GD have a high incidence of Y-chromosome microdeletions and that there is a possible association with the severity of the phenotype . HoweverIn 45,X/46 XY Turner girls without signs of virilisation, tumour risk is low and tumour development is generally expected in postpubertal ages ,20,21. ODue to the increased risk of GCT development and the high prevalence of this tumour in mosaic patients, prophylactic gonadectomy has recently been recommended. However, new guidelines recommend a more conservative approach because of the decreased risk of GCT development in a histologically more mature gonad. Therefore, maturation stage and functionality of the gonad are of fundamental importance in the decision for gonadectomy ,4. In feConsequently, there are several potential genetic risk factors for GCT development in cases with mosaic karyotype. The risk for malignant transformation may also occur early in life and may increase with age. Therefore, in the event of detection of any genetic disorder involved in cell differentiation and/or of a clinical suspicion for GCT development, gonadectomy should not be postponed in girls with a mosaic karyotype despite the low risk of GCT development in such cases.


Sus scrofa L. (Artiodactyla: Suidae), carcass as a model, adult flies were collected immediately after death and in the early stages of carcass decomposition. To confirm actual colonization of the carcass, insects that completed their larval development on the resource were also collected and reared until adult stage. A diverse assemblage of dipterans composed of at least 28 species from seven families with necrophagous habits was observed within minutes after death. Besides Calliphoridae and Sarcophagidae, species from forensically-important families such as Phoridae, Anthomyiidae, and Fanniidae were also registered. Eleven species were shown to complete their development on the carcass. The majority of individuals emerged from larvae collected at the dry stage of decomposition. Hemilucilia segmentaria Fabricius , H. semidiaphana (Rondani), and Ophyra chalcogaster (Wiedemann) (Muscidae) were the dominant species among the colonizers, which supports their importance as forensic evidence in Brazil.This study aimed to provide the first checklist of forensically-important dipteran species in a rainforest environment in Northeastern Brazil, a region exposed to high rates of homicides. Using a decomposing pig,  The temporal pattern of arrival of necrophagous insects at a cadaver is a key feature in the estimation of the minimum post-mortem interval, which is the most widespread contribution of forensic entomology. Information on abiotic factors combined with the time interval taken by the larvae to reach each developmental stage can provide reliable estimates of the time elapsed between cadaver colonization by insects and the discovery of the body .In forensic studies, decomposition is divided into stages, the number and duration of which vary according to the region, climate, and other environmental factors. The changes in a cadaver that occur immediately following death are often more rapid than those that take place later during the decomposition . TherefoIt is a widely accepted assumption that dipteran species of the families Sarcophagidae (flesh flies) and Calliphoridae (blow flies) are able to reach cadavers within a few hours of death and are the first colonizers of a corpse , 2005. TThe development of forensic entomology in Brazil has been sustained by an increasing number of field surveys of necrophagous species, comprising ecosystems located mainly in the Amazon and in central and southern states of the country. Areas with high rates of homicides, such as cities located in the Northeastern region, have been neglected . In thisThe study was carried out in Recife, one of Brazil's largest cities (population 3.7 million), located on the Northeastern coast. It ranks among the most violent cities in the country, with a rate of 57.9 homicides/100,000 inhabitants, and many of the homicides are unsolved .The field study took place in a preserved rainforest fragment (Dois Irmaos State Park) in Recife . The park has a total area of 388 ha, with an altitude ranging from 30 to 80 m a.s.l. The local climate is hot and humid, with mean rainfall ca. 2,500 mm/year, an average annual temperature ca. 25.6° C, and two well-defined seasons, namely dry (October-February) and rainy (March-September). Vegetation is classified as dense, ombrophylous forest composed mainly of Fabaceae, Lauraceae, Moraceae, Sapotaceae, and Euphorbiaceae species . The areSus scrofa L. (Artiodactyla: Suidae) (ca. 15 kg) was used as the model. The pig was killed in loco with a gunshot to the occipital region, a procedure performed by experts according to the Ethics Committee of the Federal University of Pernambuco. Immediately after death, the carcass was placed in a metal cage (0.9 m × 0.6 m × 0.5 m) to prevent disturbance by large scavengers. Around the cage, a metal frame (2 m high × 1 m long × 1 m wide) covered with a fine white mesh fabric was placed in order to trap insects that visited the carcass. A 30 cm gap between the bottom of the net and the soil was left, through which insects could gain access to the carcass. The field experiment took place in July 2007, in the rainy season. The average temperature throughout the experiment was 25.2° C, and the mean relative humidity was 84%.A pig, Death occurred on day 1 at 13:00. For the collection of early species, samples were taken at seven timepoints, which combined are referred to hereafter as “immediately postdeath”: 5, 30, 60, 90, 120, 150, and 180 min post-mortem. At each of these timepoints, the adult flies trapped in the mesh structure were collected using an entomological net (20 cm diameter), sweeping for 5 min each time To determine which species would continue to visit the resource, an additional collection of dipteran adults on the carcass was performed at 24, 48, and 72 hr postmortem using the same procedure. Collected insects were killed using ethyl acetate, mounted, and identified using taxonomical keys . All speth day, from which point the tray was retrieved every 48 hr until the 17th day post-mortem. This was due to previous observational studies that indicated that the majority of pupation occurred in that time interval .In order to collect larvae at the post-feeding stage, i.e., insects that completed the larval stage on the carcass but were yet to pupate, a 60 cm × 30 cm × 15 cm plastic tray containing sawdust was placed under the cage, onto which insects would fall, as they typically pupate on the soil. Starting on the fourth day postmortem, the tray was removed daily until the 11All immature insects recovered from the tray on each day were placed in plastic containers (31 cm × 18 cm × 10 cm) covered with fine nylon mesh and containing a Petri dish with ca. 20 g of minced beef to guarantee that the larvae completed their development cycle. Rearing conditions in the glasshouse emulated field conditions . Insects were observed daily, and emerged adults were identified to the lowest taxonomie level. The frequency of occurrence of each species at each decomposition stage was calculated. Chi-square tests using the significance level of 5% were performed to check for differences in the abundance of necrophagous species according to the stage of decomposition.Oxysarcodexia  was the most abundant species  at the period immediately after death. Only nine species with no previous record of necrophagy were registered in this time interval  (Sarcophagidae), Oxysarcodexia modesta Lopes, O. fluminensis Lopes, , O. avuncular (Lopes), O. excise (Lopes), and Peckia  in gen s ; Hemilucilia segmentaria (F.) , H. semidiaphana (Rondani); Morellia humeralis (Stein) (Muscidae); Piophila casei L. (Piophilidae), Piophilidae sp.; Fannia obscurinervis (Stein) (Fanniidae), Fannia sp.l; and Anthomyia punctipennis (Wiedemann) (Anthomyiidae). From that moment on, necrophagous species continued to visit the carcass for at least 72 hr post-death, while the diversity of non-necrophagous  diminished throughout time  corresponded to Calliphoridae, followed by specimens from Phoridae (25.6%) and Muscidae (11.6% of the emerged adults) (H. segmentaria (34.4% of emerged adults) and H. semidiaphana (27.2%). Ophyra chalcogaster (Wiedemann) (Muscidae) and M. scalaris (Phoridae) also composed a significant proportion of the emerged adults.A total of 18,469 adults emerged from the samples collected at the post-feeding stage. Adults began to emerge from the fourth day post-death (when the carcass was at the bloated stage) until skeletonization of the carcass, which occurred on the 17 adults) . Two Cal2 = 5,757; p < 0.0001, df = 3). The diversity of emerged adults differed little according to the stage in which the larvae were retrieved, with the exception of Piophila sp., whose larvae were only collected at the dry stage. The temporal pattern of emergence varied. While the majority of H. semidiaphana and M. scalaris adults emerged when larvae were collected at dry stage, the numbers of O. chalcogaster larvae retrieved decreased with decomposition , bloated (48–96 hr), decay (96–120 hr), and dry stage (120-ca. 410 hr post-death). After that period, virtually no insects were found on the carcass. The amount of emerged adults differed according to the decomposition stage at which larvae were recovered: 15.5% of the adults emerged from larvae collected at the bloated stage, 18.4% at the decay stage, and 66.1% of the adults emerged from larvae collected at the dry stage, and this difference was statistically significant  were detected on the carcass just two hours after its exposure in the field.The amount of time after death affects the structure of the assemblage of insects attracted to a carcass , a featuM. scalaris (Phoridae), P. casei (Piophilidae), F. obscurinervis (Fanniidae), and M. humeralis (Muscidae), among others, can reach the carcass as quickly as five minutes after death. This is, to our knowledge, the documentation of the earliest arrival of these and other species , at later stages of decomposition was previously demonstrated by Pujol - Luz et al.  have been associated with both cadavers (cadavers  and carccadavers , especiacadavers .Despite the richness of species reported throughout the first days post-death, Sarcophagidae was classified as an accessory group, as they represented only 0.18% of all emerged adults. The high diversity associated with low abundance of Sarcophagidae observed in the rainforest fragment of Dois Irmaos State Park has also been found in other field studies . The othIn tropical regions with high rates of unsolved homicide, such as the case of Northeast Brazil, forensic scientists should be aware of the fact that decomposition-related processes occur at a fast rate, increasing the difficulty in establishing definite chronological stages and, consequently, the insect community associated with them. This reinforces the necessity of an immediate involvement of the forensic scientist in search for entomological evidence, preferably at larval stage, because a shorter window for data gathering is available.H. segmentaria, H. semidiaphana, O. chalcogaster, F. obscurinervis, and M. scalaris. The Neotropical Hemilucilia species in particular deserve further studies as useful forensic indicators, especially considering their recent use in the estimation of minimum post-mortem interval in Brazil (Despite the limitations of using a single carcass as model, due to logistical and ethical restraints, this study provides the first evidence of at least 10 species completing their larval cycle on carrion in rainforest fragments in Northeastern Brazil, which include n Brazil . Because


Whether retroperitoneal fat should be included in the measurement of visceral fat remains controversial. We compared the relationships of fat areas in peritoneal, retroperitoneal, and subcutaneous compartments to metabolic syndrome, adipokines, and incident hypertension and diabetes.We enrolled 432 adult participants (153 men and 279 women) in a community-based cohort study. Computed tomography at the umbilicus level was used to measure the fat areas.Retroperitoneal fat correlated significantly with metabolic syndrome (adjusted odds ratio (OR), 5.651, p<0.05) and the number of metabolic abnormalities (p<0.05). Retroperitoneal fat area was significantly associated with blood pressure, plasma glycemic indices, lipid profile, C-reactive protein, adiponectin , and leptin , but not plasma renin or aldosterone concentrations. During the 2.94±0.84 years of follow-up, 32 participants developed incident hypertension. Retroperitoneal fat area (hazard ration (HR) 1.62, p = 0.003) and peritoneal fat area , but not subcutaneous fat area (p = 0.14) were associated with incident hypertension. Neither retroperitoneal fat area, peritoneal fat area, nor subcutaneous fat areas was associated with incident diabetes after adjustment.Retroperitoneal fat is similar to peritoneal fat, but differs from subcutaneous fat, in terms of its relationship with metabolic syndrome and incident hypertension. Retroperitoneal fat area should be included in the measurement of visceral fat for cardio-metabolic studies in human. Metabolic syndrome (MS) is a combination of risk factors mainly related to abdominal obesity and insulin resistance, according to the National Cholesterol Education Program’s Adult Treatment Panel III report (ATP III) In the abdominal cavity, there are 3 different compartments of fat: omental, mesenteric, and retroperitoneal fat. Blood from fat tissue in the peritoneal region, including omental and mesenteric fat, is drained through the portal vein into the liver, while the blood from fat in the retroperitoneal region is drained into the kidney, pancreas, or directly to the vena cava The study was approved by the Institutional Review Board of the National Taiwan University Hospital, and complied with the Helsinki Declaration. Written informed consent was obtained from each patient before enrollment.rd visit was defined as the follow-up visit. The new diabetes or hypertension was defined by comparing the status between baseline and follow-up visit. Written informed consent was obtained from every participant. The study was review and approved by the Institutional Review Board.From 2006 to 2012, residents from the Yunlin county, Taiwan, aged ≥18 years, who did not report the presence of diabetes during an interview, were invited to join this prospective study, named the Taiwan Lifestyle Study A questionnaire was administered by trained nurses in order to obtain data on the demographic characteristics, medical history, and health habits of the participants. Body height and weight were recorded to the nearest 0.5 cm and 0.1 kg, respectively. BMI was calculated from body weight in kilogram divided by the square of body height in meters. Waist circumferences were measured according to the method by the World Health Organization and the International Diabetes Federation to the nearest 0.1 cm Plasma glucose and fasting serum total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol concentrations were measured using an automatic analyzer . Plasma hemoglobin A1c (HbA1c) concentrations were measured using another automatic analyzer . Hepatitis B surface antigen and hepatitis C virus antibody were measured by the AxSYM System . The laboratory attends and is qualified by an external quality assurance program by the Taiwan Society of Laboratory Medicine twice a year. The HbA1c assay was certified by the National Glycohemoglobin Standardization Program Diabetes was diagnosed according to the American Diabetes Association (ADA) recommendations in 2010 (HbA1c concentration ≥6.5% (48 mmol/mol), fasting plasma glucose (FPG) concentration ≥126 mg/dL, or OGTT 2h plasma glucose (OGTT-2h-PG) concentration ≥200 mg/dL). MS was diagnosed using the criteria defined in the ATP III, with a modification of waist circumference for Asians Abdominal adiposity was assessed using a 16-slice multidetector CT scanner  in the supine position . Image analysis software  was used to quantify the subcutaneous and visceral adipose fat areas, on one cross-sectional scan obtained at the level of umbilicus and expressed in millimeters squared. 2 in MS group and 4000 mm2 in non-MS group with a SD of 2500 mm2. The MS to non-MS group ratio was set at 1∶3 according to a prevalence of MS at around 25–30%. Accordingly, a sample size of 400 patients (100 patients in MS group and 300 patients in non-MS group) was calculated.The sample size estimation was based on the following assumptions that was modified from a previous study(18): a 2-sided α level of 0.05 and power of 95% and retroperitoneal fat area of 5000 mmt-tests and Pearson’s chi-square tests were used to compare the demographic and metabolic parameters between participants with and without MS. The different fat areas were logarithmically transformed to approximate normal distributions. Logistic regression models were used to evaluate the relationship between MS and different fat areas using age, gender, and BMI as potential confounders. We also performed this analysis with standardized fat areas as follows: standardized fat area = (log fat area – mean of log fat area)/(SD of log fat area). Pearson’s correlation coefficients were used to assess the relationship between metabolic parameters and different fat areas. Partial correlation coefficients were calculated after adjusting for age and gender. Bootstrap resampling was used to compare the correlation coefficient of each metabolic variable and the retroperitoneal fat area with the correlation coefficient of each metabolic variable and the subcutaneous or peritoneal fat area. The differences in numbers of metabolic abnormalities were assessed by analysis of variance. The relationship between adipokines and the retroperitoneal fat area was expressed by Pearson’s correlation coefficients. Cox proportional hazard models were used to assess the relationship of abdominal fat areas and the development of incident hypertension or incident diabetes during follow-up, adjusted for age, sex, and family history of hypertension or diabetes. The fat areas in the Cox regression models were normalized by the standard deviation, to show the hazard ratios for every 1 standard deviation increase in fat areas. Kaplan-Meier failure curves were used to estimate the cumulative incidence of hypertension and diabetes in participants with fat areas above and below the median value. A two-tailed p value <0.05 was regarded as significant. Statistical analyses were performed with Stata/SE 11.0 for Windows .All variables are expressed as the mean and standard deviation (SD). Two-sample 2 and 19,659 mm2, respectively, of subcutaneous fat area (p<0.001); 7,187 mm2 and 4,855 mm2, respectively, of peritoneal fat area (p<0.001); and 5,233 mm2 and 3,784 mm2, respectively, of retroperitoneal fat area (p<0.001). As shown in A total of 432 participants (153 men and 279 women), with a mean age of 52.6±12.0 years, were enrolled in this study. Of the 432, 125 participants fulfilled the criteria for MS. The mean fat areas in men and women were as follows: 14,757 mmAs shown in Of the study population, 353 participants did not take any medication for hypertension, diabetes, or dyslipidemia. In these participants, there were significant correlations between metabolic variables and the retroperitoneal as well as peritoneal fat area . The retAfter a mean duration of 2.94±0.84 years, 297 (69%) of the 432 participants were followed successfully. Among the 199 participants who did not have hypertension at baseline and have been followed successfully, 32 participants developed incident hypertension. Among the 236 participants who did not have diabetes at baseline, 18 patients developed incident diabetes. Participants with retroperitoneal fat area above the median showed higher risk for incident hypertension, compared with participants with retroperitoneal fat area lower than the median , and visceral obesity as a marker of dysfunctional adipose tissue leading to ectopic fat deposition Taken together, these data suggest that differences exist in the biologic functions of retroperitoneal fat and peritoneal fat. However, compared to subcutaneous fat, retroperitoneal fat and peritoneal fat behave more similarly. Therefore, when the visceral fat area is measured by CT or MRI in human studies for cardiovascular and metabolic diseases, the retroperitoneal fat area should be included.To the best of our knowledge, the present study is the first comprehensive research to investigate if retroperitoneal fat should be included in the measurement of visceral fat in humans. We analyzed the relationship between retroperitoneal fat, MS, each metabolic abnormality, adipokines, a marker of systemic inflammation, and incident hypertension and diabetes. We also compared the pattern of these relationships among retroperitoneal fat, peritoneal fat, and subcutaneous fat. In addition, the use of CT to measure abdominal adiposity enabled us to compare different compartments of abdominal fat in detail. By contrast, the present study was limited in its follow-up rate of 69%. Although it is not likely that the relationships of retroperitoneal fat to incident hypertension and diabetes will be different in subjects who lost of follow-up, we cannot exclude the possibility completely.Retroperitoneal fat is associated with MS, plasma adipokine concentrations, systemic inflammation, and incident hypertension. Retroperitoneal fat is similar to peritoneal fat, but differs from subcutaneous fat, in its relationship with metabolic syndrome, adipokines, and incident hypertension. Our results indicate that the retroperitoneal fat area should be included in the measurement of visceral fat area. In addition, since the relationships between these factors and different compartments of abdominal fat are different, further research is needed to explore the pathophysiologic implications of these findings.Dataset S1Cross sectional dataset.(XLSX)Click here for additional data file.Dataset S2Longitudinal dataset.(XLSX)Click here for additional data file.