In Brazil, descending thoracic aorta disease (TAD), including aneurysms and dissection, are preferentially managed by endovascular treatment (TEVAR) due to the feasibility and good results of this technique. In this study, we analyzed endovascular treatment of isolated TAD (ITAD) in the public health system over a 10-year period in São Paulo, a municipality in Brazil in which more than 5 million inhabitants depend on the governmental health system.Public data from procedures performed between 2008 and 2019 were extracted using web scraping techniques. The following types of data were analyzed: demographic data, operative technique, elective or urgent status, number of surgeries, in-hospital mortality, length of hospital stay, mean length of stay in the intensive care unit, and reimbursement values paid by the government. Trauma cases and congenital diseases were excluded.vs. 14.31%, p=0.031). A total of R$ 24.766.008,61 was paid; an average of R$ 17.222,98 per elective procedure and R$ 18.558,68 per urgent procedure. Urgent procedures were significantly more expensive than elective surgeries (p=0.029).A total of 1,344 procedures were analyzed; most patients were male and aged ≥65 years. Most individuals had a residential address registered in the city. Approximately one-third of all surgeries were urgent cases. There were 128 in-hospital deaths (9.52%), and in-hospital mortality was lower for elective than for urgent surgeries (7.29% Over a 10-year period, the total cost of ITAD interventions was R$ 24.766.008,61, which was paid from the governmental system. Elective procedures were associated with lower mortality and lower investment from the health system when compared to those performed in an urgent scenario. Thoracic aortic disease (TAD) encompasses aneurysms and dissections. An aneurysm is defined as a localized and permanent dilatation of an artery by at least 50% of its normal diameter -3. DisseAneurysms of the thoracic aorta may develop in any combination of its four segments: the aortic root, the ascending aorta, the aortic arch, and the descending aorta.The estimated incidence of TAD is six cases per 100,000 person-years . In BrazCurrently, therapeutic alternatives for descending TAD include open surgical repair, and endovascular treatment (TEVAR) for large aneurysms >5.5 cm) (.5 cm (5)Although differences in mortality rates of TAD are likely to exist between nations, current knowledge is limited to a few isolated studies from individual countries based on the results of specialized centers. In a study by Sidloff et al., which aimed to examine trends in mortality from thoracic aneurysms in several countries, the age-standardized mortality of TAD ranged from 0.5% in Japan to 9.7% in the Netherlands . AlthougData from high-volume centers indicate an in-hospital mortality of 7.8% for conventional thoracic aortic aneurysm repair  and apprnd in the country's human development index (0.783)  . In 2016 (0.783) , of whic (0.783) .To the best of our knowledge, there have been no studies published in Brazil that have focused on the evaluation of the outcome of endovascularly treated TAD in a large urban center over a long period of time and including several variables. This information is relevant for the understanding of the real-life scenario, as opposed to being restricted to those published by highly specialized centers.In this study, we aimed to evaluate the endovascular management of isolated TAD  in 1,344 patients treated in the public health system in São Paulo between 2008 and 2019. We assessed the procedure type, frequency (elective or urgent), mortality, length of hospital stay, intensive care stay, and procedure costs.This study was approved by the Institutional Ethics Committee under protocol 3067-17.Public data concerning endovascular surgery procedures for isolated TAD (ITAD) repair performed from 2008 to 2019 were extracted from the TabNet platform of the Municipal Health Secretary of São Paulo. TabNet belongs to the Department of Informatics of the Unified Health System (DATASUS) (Sistema Único de Saúde (SUS) that are qualified to perform procedures of specific medical specialty, and ultimately represents an invaluable tool for the financial decision-making process. SIGTAP accreditation is a prerequisite for receiving government remittances for the procedures performed. For the purpose of this analysis, only SIGTAP accredited hospitals of “high complexity” in vascular surgery were considered.A Unified Procedure Table Management System (SIGTAP) systemizes sanitary institutions linked to the Unified Health System The DATASUS platform allows 22 possible selections for rows, 16 for columns, and 8 for content, providing 2,816 possible formatting combinations, separated into monthly periods. In this study, the variables selected were sex, age group, city of residence, number of surgeries performed by establishment, in-hospital mortality, length of hospital stay, mean length of intensive care unit (ICU) stay, and reimbursement values paid by the SUS over the study period.All endovascular procedures that were performed for the treatment of thoracic aortic aneurysms were analyzed. Procedures were identified using the SUS System of Procedures and Medicines coding for endovascular aneurysm repair/thoracic aortic dissection with a straight/conical stent graft (code: 04.06.04.017-6). Unfortunately, the system coding for both the diagnosis (ICD classification) and treatment procedure  are superimposed for aneurysms and dissections, rendering the separation of cases infeasible.Procedures classified as “Q25” by the ICD were rejected in order to avoid the inclusion of procedures for correction of congenital malformations of the great arteries. Hospitalizations due to trauma (ICDs starting in ‘S’) were also excluded.The selected cases were divided into two groups according to the hospitalization regimen reported: the elective group, consisting of patients who underwent surgery on an elective basis, and the urgent group, consisting of patients who underwent urgent hospital admissions.All information was obtained from public access websites through content access programs using web scraping codes. Manual data collection processes, although technically feasible, would have been too time-consuming. Automatic navigation codes with programming assistance were used to facilitate and expedite data collection. These codes were programmed in Python language  using the Windows 10 Single Language operating system. The stages of data collection, platform field selection, and subsequent table adjustments were performed using the Selenium WebDriver packages  and pandas . The web scraping code has a 14-search phase main structure (Appendix), which is adaptable to the different filters available on the platform. The Mozilla Firefox browser  and WebDriver GeckoDriver  were used during data collection.® software . The tables were formatted so that the procedure type groups were placed side by side, and contained, for each group, the following subdivisions: The number of procedures performed in each of the establishments, the total number of operated patients, the in-hospital mortality (absolute and percentage), the length of hospital stay, the average length of ICU stay, and the remittance values paid by the SUS. All values are shown in Reais , which underwent a 68.75% inflation between 2008 and 2019, in accordance with data from the “ĺndice de Preços para o Consumidor Amplo” (IPCA). The included hospitals were numbered in descending order according to the total number of procedures that they performed. In our study, we were able to use the available public data in a simpler and quicker fashion to analyze a larger number of procedures and years.After data collection and cleaning, all data were organized and grouped in spreadsheets using Microsoft Office Excel 2016p=0.05.The following tests were used for statistical analysis: The chi-square test to investigate whether there was a change between the number of patients treated in an elective or emergency setting over the study period (trend test); the Mann-Whitney test to compare, between the elective and urgent groups, the ordinal or continuous variables not normally distributed, the mortality rates, the hospitalization length, and the remittance values paid. The average length of ICU stay, given as the mean, was compared between groups using a generalized estimation equation with normal distribution and identity link function, assuming first-order autoregressive correlation between years in the same hospitals. For all tests, the level of statistical significance was set at In total, 1,344 endovascular procedures were performed in the city of São Paulo to correct ITAD between 2008 and 2019. The majority of patients treated were male  and <65 years of age . Nearly half of the patients treated for ITAD in São Paulo migrated from a different city , and the provenance was unknown for 58 patients.p<0.001), this was not observed, especially in the final years. Two-thirds of the total procedures were performed in elective scenarios and one-third were performed in urgent scenarios, as shown in The number, distribution percentage, and type of procedures (elective or urgent) per year are shown in p=0.029). The hospital with the highest number of surgeries (n=323) had the lowest in-hospital mortality (5.26%).The mortality per procedure type by hospital is presented in p=0.098).The length of hospital stay is shown in p=0.142). The distribution throughout the years was statistically similar for both groups (p=0.141), and there was no tendency for a shift between the average length of ICU stay of the procedure type groups during the study interval (p=0.735).The average length of ICU stay (in days) by patient group per year is shown in p=0.029).The reimbursement values paid by the public health system, by hospital establishment, in US dollars, are presented in Approximately 75% of the Brazilian population is dependent on the SUS, a universal, equitable, and comprehensive tax-funded government system . The remThe city of São Paulo strays from this national pattern of distribution, mainly due to its financial status . In São Our analyzed population consisted mainly of male patients , with 60.56% of the procedures (n=814) performed in individuals aged 65 years or older. The overall predominance of male patients aged over 65 years is in accordance with the expected population of TAD patients -25.The studies of Howard et al. and Clouse et al. estimated a worldwide incidence between 5.6 and 10.4 cases per 100,000 patient-years for TAAs ,27. Consp<0.001), which points to an undesirable distribution. However, in the last evaluated year, the proportion is anomalously re-inverted, demonstrating a possible improvement in medical conduct. This observed distribution is in accordance with the international pattern, in which elective procedure rates range from 68.4% to 80%  demonstrates an inclination for the centralization of health resources in a single urban center. Although the patients were not analyzed by procedure type based on provenance, we believe that the large number of patients whose treatment depended on being referred to and accepted by a larger center may have influenced the large proportion of cases that progressed to need urgent procedures.vs. 7.29%, p=0.021). This finding is in accordance with a large study by Wang et al., who evaluated thoracic aortic aneurysm in the North American National Inpatient Sample, and found that elective status was protective against inpatient mortality   .The mortality rate of the elective group 7.29%) was similar to that described in a large series of cases by other authors , althoug% was simp=0.098)  ,33. In ap=0.098) ,25,34.p=0.142). A retrospective analysis of the American College of Surgeons database published in 2019 found that emergency surgery was associated with longer ICU stays, as well as other factors such as aneurysm rupture or postoperative pneumonia . However, this analysis is restricted by the fact that the public health system compensation table is often lower than the actual amount spent on the procedures, meaning that the true expenditure per procedure by the hospitals may in fact have surpassed the values documented by the public database.The reimbursement values paid for urgent procedures were significantly higher than those paid for elective cases , but as a result of multisystemic or high-energy trauma. Conversely, the results relating to elective procedures are unlikely to be overestimated, as non-accredited hospitals are not reimbursed for operations, and very few (if any) elective cases were operated in hospitals that were not reimbursed for the procedure.Due to databank information anonymization, patient follow-up was not possible, and all mortality data discussed refers exclusively to in-hospital deaths. As a result, we were unable to contribute information with respect to long-term mortality rates. Another consequence of data anonymization is the inability to individualize cases with regard to the length of ICU and hospital stay. Because patients were grouped in the database by fixed intervals , a more detailed representation through time medians was rendered impossible.Lastly, we were unable to provide input with regard to the need for reinterventions, which are relatively more frequent in the context of endovascular procedures. This secondary limitation is also attributable to the anonymization necessary for data availability from public and governmental sources.These limitations notwithstanding, this is a comprehensive analysis of the public health systems management of TAD in the largest urban center in Brazil. Moreover, this study covers a 10-year period and includes over 1300 procedures; thus, we consider that this is a representative assessment of a real-world sample of TAD patients. The results of this study provide useful information on a public system and guidance for the allocation of health funds.In São Paulo, TAD interventions required a governmental investment of over R$ 24.766.008,61 over a 10-year period. Elective procedures were performed almost twice as frequently as their urgent counterparts, while urgency procedures were more expensive and associated with a longer time of hospitalization. This pioneering study design permits initial examination of the profile of TAD treatment in the city of São Paulo, and may provide evidence to guide monetary resource allocation by the health system.Portugal MFC was responsible for the manuscript composition, critical revision, manuscript approval and study accountability. Teivelis MP and Wolosker N were responsible for the manuscript conception, composition, critical revision, approval and study accountability. Silva MFA, Stabellini N, Amaro-Junior E and Szlejf C were responsible manuscript conception and approval, data collection, and study accountability. Fioranelli A was responsible for the manuscript conception, critical revision, approval and study accountability.


The aim of this study is to describe the prevalence and mortality of bladder cancer (BCa) using data obtained in the Global Burden of Disease study performed in 2017 (GBD 2017).Data on BCa for 2017, including prevalence, mortality, and disability-adjusted life years (DALYs), were obtained from GBD 2017 at the global, regional, and national levels. We also analyzed the association of BCa burden with the country development level.P < 0.0001 and ρ = 0.68 for ASP, and P = 0.0048 and ρ = 0.20 for ASDR). In addition, 33.72% deaths and 36.80% DALYs caused by BCa could be attributed to smoking globally.There were 2.63 million BCa cases estimated from the GBD 2017 data, with 200,000 persons dying of BCa, resulting in 3.60 million DALYs in 2017. The age-standardized prevalence (ASP) of BCa was 32.91/100,000 persons, and age-standardized death rate (ASDR) was 2.57/100,000 persons. The ASP and ASDR of BCa were higher in males than in females, and higher in people older than 60 years. The ASP and ASDR of BCa were higher in Western Europe and Central Europe than in South Asia, Andean Latin America, and Central Latin America, and higher in countries with a higher sociodemographic index (SDI). Correlation analysis identified that the ASP and ASDR of BCa were positively correlated with the country SDI (The prevalence and mortality of BCa were very high in 2017, especially in high-SDI countries. Smoking-cessation strategies should be strengthened to control the burden associated with BCa.The online version contains supplementary material available at 10.1186/s12889-020-09835-7. Bladder cancer (BCa) is one of the most-common urological malignancies, and is among the leading causes of cancer deaths worldwide. Approximately 3.0% of all new cancer diagnoses and 2.1% of all cancer deaths are due to BCa . MoreoveRichters A, et al. systematically described the epidemiological characteristics of BCa. They concluded the burden of BCa exhibits obvious regional, sex, and age variations . SpecifiThe Global Burden of Disease study performed in 2017 (GBD 2017) estimated the burdens of diseases, injuries, and risk factors at the global, regional, and national levels, and how they varied with sex and age [Ebrahimi H, et al.  and Dy Ghttp://www.healthdata.org/gbd/). Users can retrieve data on different aspects of a disease by choosing the appropriate selection boxes [The results obtained in GBD 2017 are now available via an interactive data-downloading tool using the GHDx  software  and the number of persons (or weight wi) in age subgroup i of the selected reference standard population, then dividing by the sum of the standard population weights: ASR The age-standardized rates (ASRs) in GBD 2017 were obtained for the global age-standardized population [P < 0.05 considered indicative of statistical significance.The SDI is a composite indicator of development status that is strongly correlated with health outcomes, and is calculated as the geometric mean of 0 to 1 indices of the total fertility rate among those younger than 25 years, the mean education level among those aged at least 15 years, and the lag distributed income per capita. GBD 2017 divides both countries and regions into the following five SDI quintiles: high, high-middle, middle, low-middle, and low. We compared the burden of BCa among these five SDI quintiles. In addition, we explored the factors influencing ASR by evaluating the associations of ASR with the SDI in 2017 at the country level using Pearson correlation analysis, with https://www.r-project.org/) based on data obtained in GBD 2017.All of the figures were made through the R package  and East Asia , as were the numbers of deaths due to BCa  and DALYs of BCa . Meanwhile, Oceania had the smallest numbers of cases , deaths , and DALYs   and Central Europe , as were the ASDR  and the ASR of DALYs . The ASP of BCa was lowest for South Asia  and Andean Latin America . The ASDR was lowest for Central Latin America  and for Andean Latin America , as was the ASR of DALYs  , followed by Italy, and lowest in Kenya , followed by Bangladesh. Egypt showed the highest ASDR of BCa  and ASR of DALYs , followed by Poland. Kenya had the lowest ASDR of BCa , followed by Bangladesh. Bangladesh showed the lowest ASR of DALYs  , ASDR , and ASR of DALYs , followed by countries with high-middle and low-middle SDIs. Low-SDI countries had the lowest ASP , while middle-SDI countries had the lowest ASDR  and ASR of DALYs   deaths and 36.80% (95% CI = 28.49–43.66%) DALYs caused by BCa could be attributed to smoking. These varied by SDI quintiles, with high-middle-SDI countries showing the highest percentage of smoking-attributable BCa deaths  and DALYs of BCa , and low-SDI countries showing the lowest percentages . Globally, 9.87% (95% CI = 2.06–21.20%) deaths and 8.91% (95% CI = 1.81–19.27%) DALYs caused by BCa could be attributable to high fasting plasma glucose. There were few variations in the percentages of deaths and DALYs caused by high fasting plasma glucose among the five SDI quintiles.We have presented the latest data and patterns of global prevalence, mortality, and DALYs of BCa based on GBD 2017. Overall, the prevalence and mortality of BCa were higher in males , and also showed geographical variations, being higher in Western Europe and Central Europe, and lower in Andean Latin America, Central Latin America, and South Asia. In addition, the prevalence and mortality of BCa were positively associated with the SDI, with high-SDI countries showing the highest prevalence and mortality rates of BCa. Smoking was the main risk factor for the BCa burden.https://ourworldindata.org/grapher/life-expectancy-at-birth-total-years). That is, the number of people aged 70–74 years old may be less than the number of people aged 65–69 years old.The prevalence and DALYs rate of all age groups over 70 years old was higher than that of 65–69 years old group. However, the number of patients and DALYs of those groups were less than those of 65–69 years old group. These indicated that the number of people in each age group over 70 years old was smaller than that of 65–69 years old group, which is consistent with the World Bank’s survey results. According to the World Bank’s data, the mean life expectancy of the world population in 2016 is 72.04 years old (http://gco.iarc.fr), which indicates that the prevalence of BCa is higher in Western Europe, Central Europe, North America, Turkey, Egypt, and Mali, while the mortality rate of BCa is higher in Western Europe, Central Europe, North Africa, Mali, and Turkey. The differences in the prevalence and mortality rates of BCa between North America and North Africa could be due to differences in medical conditions. One-third of BCa patients had muscle-invasive disease, which is more serious and has a higher mortality rate than non-muscle-invasive BCa [The prevalence of BCa appears to vary across world regions, which might be correlated with the distribution of its risk factors: smoking and occupational exposures to carcinogens in developed countries, and chronic bladder urothelial irritation from Schistosoma haematobium infection in Africa and the Middle East . In genesive BCa . There wsive BCa . HoweverThe burden of BCa also differs markedly between regions with different economic and social development statuses. Especially for prevalence, a previous study found that more than half of all BCa cases occur among the 20% of the world population living in countries with a very high Human Development Index , while only 5% of all diagnoses occur in those with a low HDI. In terms of mortality, there is somewhat less variation between parts of the world with different HDIs . The preTobacco smoking is the main identified risk factor for BCa, accounting for 50–65% of the urothelial cell carcinoma cases in males and for 20–35% of those in females . A largeSeveral articles also describe the global burden of BCa. Richters et al. provided an overview of the burden of BCa worldwide using published data and some public database . The maiBased on GBD 2017 data, we have described the burden of BCa across countries and regions globally, which may facilitate the understanding of the disease status. However, this study had some limitations. Firstly, muscle-invasive BCa is more serious and is the main type responsible for BCa-related deaths. The data of its burden are more clinical meaningful, but GBD 2017 did not provide detailed information. Secondly, as several African countries undergo social and economic development and changes, the histological subtype of BCa may gradually shift from squamous cell carcinoma to transitional cell carcinoma , 22. MorIn summary, in 2017 BCa remained a cancer that is diagnosed predominantly in males. The burden associated with BCa mainly occurs in people older than 60 years, varies across the world, and is significantly associated with development level. The prevalence and mortality rates of BCa are higher in developed regions. Smoking-cessation strategies are the most-effective way to control this burden, and policymakers should therefore strengthen these strategies.Additional file 1. The prevalent cases, death number and DALYs and their age-standardized rate of bladder cancer in 2017.


Female genital mutilation/cutting (FGM/C) is a common practice in developing countries, including the UAE, and presents a major health problem.A questionnaire-based cross-sectional study was conducted among 1035 participants: 831 (80.3%) females and 204 (19.7%) males.p-value < 0.001) and was mostly performed during infancy and childhood. Among the participants, 13.7% reported that their daughters had undergone FGM/C, with Type I being the most common, and 25% of them planned to have their future daughters undergo Type I FGM/C. While FGM/C was mostly performed by ritual circumcisers (74.4%), in 25 and 36.7% of the cases, it was performed by health professionals and in the clinic setting, respectively. About 69% of the participants considered FGM/C a custom, 72.8% were against the practice, and only 17.4% believed in its legality. Complications occurred in 30% of cases. The type of FGM/C was associated with the occurrence of complications: bleeding, difficulties in sexual life, and delivery-related problems . One-fifth of the male participants expressed plans to circumcise future daughters .The number of women with FGM/C was 344; hence the prevalence of FGM/C in our study was 41.4%. Type I was the most prevalent (62.8%), followed by Type II (16.6%) and Type III (5%). FGM/C was less prevalent among educated and employed women (FGM/C remains a prevalent practice in the UAE and has a negative association with the general health of Emirati women. The lack of clear legislation to criminalize this practice is a problem to be addressed. In this context, national-level educational and legal strategies should be a priority. Female genital mutilation/cutting (FGM/C), defined by the World Health Organization (WHO) as “all procedures involving partial or total removal of the female external genitalia or other injury to the female genital organs for non-medical reasons,” is internationally recognized as a violation of the fundamental rights of women and girls . FGM/C cFGM/C is a controversial topic in the Arab world, and there is no consensus on whether it is an Islamic requirement or a tribal tradition. However, the influential Egyptian Muslim institution Dar Al-Ifta Al-Misriyyah recently confirmed in a press statement that FGM/C is religiously forbidden owing to its negative impact on physical and mental well-being. Sheikh of Al-Azhar reconsiders unreliable fatwas released by some members of the faculty of Al-Azhar University (Egypt) who claim FGM/C is a religious necessity based on weak Hadith (Prophet Mohammad’s teachings) through the following statement: “This act has no religious origin, it only dates back to inherited traditions and customs and the biggest evidence for not being a religious duty for women is that the Prophet Muhammad had not circumcised his daughters.” Nevertheless, this practice is widely prevalent in many Muslim countries, especially Sudan , Iran 66, and EgFGM/C affects more than 125 million women and girls, predominantly across central Africa, parts of the Middle East and South Asia, and diaspora communities . In a reFGM/C has no medical benefits and is associated with severe health complications. In fact, it poses a serious health problem in some parts of the Arab world and is considered a harmful procedure that causes many complications during pregnancy and childbirth. During labor, FGM/C can impede delivery and cause infection and inflammation, as well as making intrapartum vaginal examination or catheterization difficult or even impossible . MoreoveIn 2008, the WHO, together with nine other United Nations partners, issued a new statement to advocate for the abandonment of FGM/C. The 2008 statement provides evidence about the practice collected over the past decade. It highlights the human rights and legal dimensions of the problem and provides data on the frequency and scope of FGM/C. It also summarizes research on why FGM/C continues, how to stop it, and its detrimental effects on the health of women, girls, and newborns. The new statement builds upon the 1997 original issued by the WHO, UNICEF, and United Nations Population Fund .As UAE-specific data regarding FGM/C prevalence and attitude are scarce; the only single report is in a newspaper, Hence, the aim of this study was to explore the prevalence of FGM/C, attitudes toward FGM/C, and medical and social consequences of FGM/C in the UAE.This study was conducted in Al Ain, Abu Dhabi city, from October 2016 to June 2017. Al Ain is located in the eastern region of Abu Dhabi Emirate and is considered the fourth largest city in the UAE with a population of 766,936 . At 30%, Al Ain has a high Emirati national population. The recruitment sites included Al Ain Hospital (AAH) (10 outpatient clinics plus pharmacy): paper copy of questionnaire; three Fatima College of Health Sciences (FCHS) campuses (student and staff): online questionnaire; and United Arab Emirates University (UAEU) : online questionnaire. This study was approved by the Al Ain Medical District Human Research Ethics Committee in February 2016. All participants provided written or electronic informed consent for participation before the interview.The sample size for this cross-sectional study was 1035. Separate structured/semi-structured questionnaires for female and male participants, available in both English and Arabic, were used, ensuring inclusion of both Arabic and non-Arabic speakers. The questionnaire was developed by the principal investigator by combining various similar questionnaires and validated through a small pilot study with students at the UAEU’s College of Medicine and Health Sciences. The process of development factored in social acceptance, ethnic and gender sensitivity, and applicability (supplements). The questionnaire was pre-tested on clerkship students to improve the relevance and appropriateness of the questions to the social context and subsequently revised. The interviewers underwent a two-hour training session before commencing the study. Participants answered the questionnaire in an approximately 10-min interview.The participants were recruited from three sites—UAEU, FCHS, and AAH—and included patients, students, and university staff. Particular sites were chosen because of the high numbers of Emirati nationals and Arabs working or studying there, as well as owing to the logistics of obtaining ethical approval to recruit the appropriate sample size.P = 30%), e = margin of error = 3%; *prevalence of FGM/C in Africa and Asia = 30%. Considering a non-response rate of 10%, the desired sample size was (588/0.9) or 653 respondents.Of the 1150 individuals initially approached, the 1035 who provided complete responses were included in the study. Hence, the non-response rate was 10%. Sample size calculation was based on Kish’s formula (n0 = Z2 p q/e2)  by a research assistant or interns/residents and nurses, who also offered assistance to any illiterate participants. The online questionnaire was distributed via an email link to UAEU graduates and FCHS students and staff. Consent was implied by voluntary completion of the questionnaire, following provision of study information to participants. This approach was chosen over obtaining written informed consent as it allowed completely anonymous participation and facilitated a better response rate.Collected variables in the structured/semi-structured questionnaire included sociodemographic characteristics such as age, education, religion, marital status, ethnicity, and income, as well as FGM/C-related knowledge, attitude, practices, and complications.The sample, which included both males and females, consisted of UAE citizens as well as non-UAE citizens. Adults aged 18 years and above, who resided in the UAE, regardless of religion, were included. The data were collected over eight months. Although the originally intended sample size was at least 2000, owing to difficulties in recruitment because of social restraints and cultural barriers, we ultimately analyzed the data of 1035 participants.The primary objectives of the study were to determine the prevalence of FGM/C in the UAE as well as the attitudes toward the practice. The secondary objectives were to evaluate the medical and social aspects of FGM/C among women living in the UAE.Statistical analysis was performed using SPSS version 20 . Simple frequency tables were used to describe the sample’s sociodemographic characteristics and related attitudes. Frequencies and proportions of categorical variables were compared using Pearson’s χ2 test, where appropriate. A Z-score calculator was used to measure whether two populations (circumcised women and their daughters) differed significantly on some single or categorical characteristic. The level of statistical significance was set at p-0.05.This study was conducted between 2016 and 2017. The 1035 participants included 831 (80.3%) females and 204 (19.7%) males. The sample’s sociodemographic characteristics are depicted in Table n = 216; 62.8%), followed by Type II (moderate)  and Type III . Surprisingly 1.4% of the participants were unaware of the type of FGM/C they had undergone and 14.2% did not want to answer the question  was the most common, followed by Type II . None of the daughters had undergone Type III  and in most cases, the FGM/C procedure was performed in a private hospital/clinic   was the most prevalent n = 16; 62.8%n = 90; 78.9%) had undergone FGM/C during infancy. The most recent daughter circumcision was performed in private hospitals/clinics . In contrast, among mothers, FGM/C had mostly been performed by ritual/traditional circumcisers , followed by health professionals/at private clinics , with only 117 (36.7%) reporting having been circumcised in a clean/sterile environment.Among all respondents, the total number of circumcised daughters was 114 (13.7%), most of whom  were against the practice of female circumcision, and regarding their opinion on the legality of the practice in the UAE, only 180 (17.4%) reported that they considered it legal , and about 20% considered it a sunna/recommended act. Most respondents  reported that they would have voluntarily undergone FGM/C. Only 40 women (12.9%) had undergone genital repair after delivery . There was an inverse association between circumcision status and literacy level: with increasing educational levels, there was a decrease in the proportion of women with FGM/C. The association between women’s circumcision status  and employment status was also statistically significant , as the highest rates of FGM/C were among housewives and unemployed women . Moreover, the association between circumcision status  and nationality was statistically significant , where the highest rate of FGM/C was among women from the Gulf Cooperation Council (GCC) nations and UAE , and the lowest rate was among women from other non-African Arab countries (10.1%)  was statistically significant  . In addition, we observed direct trends regarding the occurrence of complications such as bleeding and delivery-related problems as the rate of complications increased from minimal-type I to moderate-type II to major pharaonic-type III of FGM/C . However, the relationship between age at circumcision and individual complications such as pain, infection, bleeding, difficulties in sexual life and urination, and emotional distress, as well as all complications combined, was not significant . Despite the absence of significant associations, we observed direct trends in the context of difficulties with urination, emotional distress, and all combined complications and age at circumcision, and it is worth mentioning that the highest rate of all complications was among those who were circumcised in adolescence  was among women who were circumcised in adolescence (12–19 years) . However, there was no significant association between men’s attitude toward refusing to marry uncircumcised woman and their wish to have their future daughters circumcised   (3) Table .Table 9While, at 41.4%, there was a high prevalence of FGM/C among our study participants, only 13.7% of the participants’ daughters had undergone FGM/C, which may indicate a decrease in the prevalence of the practice. This decrease, which has also been reported in other recent studies , 17, mayType I  (62.8%) was the most prevalent, followed by Type II (moderate) (16.6%) and Type III (5%). While our data are in concordance with some studies , they coWe found that employed and educated women were less likely to have undergone FGM/C, pointing to the high importance of female education in plans to eradicate the practice of FGM/C. Educational programs and guidelines on the management of FGM/C for health professionals  and the About 69% of the participants considered FGM/C a custom and most respondents were against the practice. We noticed that in the context of FGM/C, there is a lack of clarity regarding the stance of religious leaders and scholars across the Muslim world. Some deny its status as a religious ritual, while others forbid Type III while accepting Type I. Nevertheless, when it comes to women, given the opportunity, the majority would neither wish to experience it themselves nor expose their daughters to the practice. This, in line with previous studies, reflects how FGM/C trends are changing . HoweverIn the majority of the cases, FGM/C was performed during infancy  and childhood . What is alarming is that, as per the self-reports of the female respondents, they were mostly circumcised by ritual/traditional circumcisers (74.4%), with only a quarter of the women having been circumcised by a health professional/at a private clinic. Even among such cases, only a third of the circumcisions had been performed in a clean/sterile environment. These facts should be enough to alarm the authorities into taking action to ensure the safety of those who undergo this procedure secretly and in unhealthy conditions. However, we found that this trend changed over a generation, as the reverse pattern was observed among daughters: they were mostly circumcised by professionals/at private clinics Table . This hiWe found that the type of FGM/C was associated with complications such as bleeding and difficulties in sexual life and delivery, with Type I being associated with the most complications. Our results are in concordance with a recent systematic review and other reports concluding that FGM/C leads to increased pain and impaired sexual satisfaction and desire , 23.p-value = 0.007). This was also reported in Egypt [Additionally, we found that factors associated with the occurrence of complications, especially delivery-related difficulties, included age at FGM/C, with the greatest complications (33.3%) reported among women in the adolescent age group (12–19 years) . However, an apparent weakness of our study is the fact that by being limited to Al Ain city, its results cannot be generalized to all of the UAE. In addition, not all participants answered all questions; apart from demonstrating that the topic of FGM/C is still considered a taboo, this limited our ability to procure all the necessary data. Further, women’s self-reports of having undergone FGM/C and the specific type were not verified through physical examination. Moreover, face-to-face and email interviews may have their own advantages and disadvantages, which might have contributed to the results. While we attempted to conduct the most rigorous study possible, in future research, we hope to improve the methodology and overcome the abovementioned limitations.Even though there have been many studies in areas where the prevalence of FGM/C is high, little is known about the GCC region. Given the multinational, multicultural structure of the population in the context of the country’s legislation and advanced educational and medical system , the UAE is a unique mix of tradition and modernity.We believe that to eradicate FGM/C in the UAE, there should be a strong and coordinated approach implemented at all levels, with an emphasis on mothers, along with the male population, health care providers, religious authorities, and legislative institutions. Of the utmost importance is the development of a national strategic plan, supportive educational programs, and targeted training programs implemented at multiple levels, such as schools, universities, and especially among health care providers and scholars in religious studies and legislation, who are uniquely positioned to support the eradication of FGM/C but are unfortunately likely to lack the necessary awareness and knowledge. We hope this study will contribute to spreading awareness about the prevalence of FGM/C and the related attitudes in the UAE. In addition, it can indicate and highlight the projected medical and social impact.FGM/C is a common practice among women in developing countries. Although there is a high prevalence of FGM/C among older generations of women in the UAE, there is a decrease in its prevalence among younger generations, especially that of Type III. Most of our participants were against FGM/C and would not prefer to undergo it if they had the choice. However, a small proportion of men still prefer to marry women with FGM/C. Urgent actions are needed to eradicate this practice. The lack of clear legislation to criminalize this practice is an important issue to be addressed, and a national educational and legal strategy to eradicate this problem should be a priority.Additional file 1. Female Circumcision Study Questionnaire. FEMALE Arabic version.Additional file 2. Female Circumcision Study Questionnaire FEMALE English version.Additional file 3:. Female Circumcision Study Questionnaire, MALE English version.Additional file 4. Female Circumcision Study Questionnaire, MALE Arabic version.Additional file 5. Map 1 UAE map ((Import from wikitravel.org/shared)


The application of DT may result in improvements only in back extensor endurance among individuals with CNLBP. This finding suggests that DT controls the processes that lead to back muscle fatigue.Evidence suggests that the application of Kinesio Tape (KT) on patients with chronic non-specific low back pain (CNLBP) is inconclusive. Dynamic tape (DT) is a relatively new treatment technique, which is increasingly being used as an adjunctive method to treat musculoskeletal problems. To our knowledge, no study has investigated the application of DT in individuals with CNLBP. To compare the immediate and short-term effects of DT versus KT and no tape among patients with CNLBP on pain, endurance, disability, mobility, and kinesiophobia. Forty-five patients with CNLBP were randomly assigned to 1 of 3 groups. Outcomes were measured at baseline, immediately, and on the third day post-application of tapes. The primary outcomes of pain, endurance, and disability were measured through the visual analog scale (VAS), Biering–Sorensen test, and Oswestry disability index (ODI), respectively. Secondary outcome measures of mobility and kinesiophobia were measured using the modified–modified Schober test and the Tampa Scale of Kinesiophobia, respectively. No significant immediate and short-term differences were found between DT and KT in pain, disability, mobility, and kinesiophobia. Improved back extensor endurance was observed for the DT group than KT ( Low back pain (LBP) is a critical public health condition that is associated with a high rate of absenteeism from work, disability, and the frequent use of health services . The mosThe current literature supports several options for the treatment of LBP that vary according to the duration of symptoms  and the Taping is one of the therapeutic interventions practiced by physical therapists and other members in the rehabilitation team. Sports injuries, different type of clinical conditions and disorders in the spine are prevented or managed by taping techniques , 18. NumDT is a relatively new treatment technique that is increasingly becoming an adjunctive method to treat musculoskeletal problems. In 2009, musculoskeletal physiotherapist Ryan Kendrick created DT, which is made up of a visco-elastic nylon and lycra blend material and can stretch in four directions, has strong elastic resistance and recoil, as well as a high degree of stretch (more than 200%) with no rigid endpoint and visco-elastic properties. The primary mode of action of DT is mechanical , while the second mode of operation is neurophysiological .KT was developed in 1973 by the Kenzo Kase and is applied in an elastic taping method to the patients’ skin under tension. It can be longitudinally extended up to 140% of its original length, producing a lesser mechanical restraint and less mobility restriction than conventional tape. KT has been reported to correct joint malalignment, provide support for muscles, activate the endogenous analgesic system, and eliminate congestion fluids .Studies have extensively analyzed the effectiveness of KT application in CNLBP, with mixed results –25. A syThus, we hypothesized that the immediate and short-term effects of DT are better than KT and no tape in terms of the reduction of pain and the improvement of endurance, disability, mobility, and kinesiophobia. However, no research has evaluated the impact of DT on LBP, and thus, the present study aims to determine the effect of DT on the treatment of CNLBP.A randomized controlled trial was conducted at the out-patient physical therapy clinic, King Khalid University located in Saudi Arabia.www.isrctn.com (ISRCTN12043220).Over 2-months, male patients referred from an orthopedic surgeon to physical therapy in the out-patient physical therapy department were screened for eligibility. Inclusion criteria were as follows: patients between 18 to 60 years of age, referred to physical therapy with a diagnosis of LBP, with a minimum duration of symptoms of more than 12 weeks, minimum pain intensity score of 3 and above on a 10 cm long visual analog scale, and a disability rating of at least 20% on the Oswestry disability index (ODI)  at the thttp://randomizer.org/ , participants were randomly assigned into the DT group (n = 15), KT group (n = 15), and control group (n = 15). Concealed allocation was performed using a computer-generated block randomized table of numbers  created before the start of data collection by a researcher (Researcher 1) who was not involved in the recruitment or treatment of patients. After that, the random numerical sequence was placed in sealed opaque envelopes. Another researcher (Researcher 2), blinded to the baseline examination, opened an envelope and proceeded with treatment according to the group assignment. An independent assessor who not known the study’s hypothesis and methods was blinded to the treatment group assessed the outcome measures before the tape application, 15 minutes after tape application and on the third day of post-tape application. A flow chart of the participants during the selection, follow-up, and analysis phases is provided in Following the baseline examination, by using the method on the website In the study protocol, we had mentioned earlier that the immediate post-measurement would be done 2 hours after the tape application. The authors changed the study protocol to only 15 minutes duration between the tape application and immediate post-application outcome measurement because patients were unwilling to wait for 2 hours post taping. A 15 minutes rest interval was sufficient to measure the outcomes among subjects with LBP after tape application, according to a study done by Velasco-Roldan et al. .Due to the presence of a group without tape, it was not possible for the participants to be blinded to the treatment. However, before any analysis was performed, the data were coded by another researcher (Researcher 4), as well as statistical analysis being performed by one more researcher (Researcher 5), who was also blinded.Baseline evaluation included demographic data, medical history, and physical examination. Demographic data included patients’ age, body weight (kg), height (cm), and body mass index (weight in kilograms divided by height in meters squared), marital status, education, employment status, smoking, duration and recent episode of the condition, as well as regular exercise. The routine physical examination performed to determine the subject did not include LBP with a neurological origin.The outcomes were assessed prior to tape application, 15 minutes after tape application with tape in situ, and on the third day of post tape application without tape. The primary outcome measures were pain, back extensor endurance, and disability. Pain was assessed with self-report measures of visual analog scale , which is a reliable and valid instrument to measure pain among patients with chronic LBP .Back extensor endurance was measured in seconds by using the Biering–Sorensen test, which is considered to have sufficient test–retest reliability (intraclass correlation coefficient (ICC) = 0.88)  for asse0 of extension and 50 of flexion in the inclinometer was permitted. The test ended when any part of the participant’s upper limb touched the table or when they were unable to recover the test position even with verbal encouragement. At this point, the timer was stopped and the test was finished [At the initiation of the test, the second table was lowered, and the subject was asked to place their arms across their chest and maintain a neutral spinal position. The timer was started as soon as their arms were positioned across their chest, and the participant maintained this position without assistance. However, at no point was either the researcher or participant aware of the amount of time that had passed, as this is a factor that directly influences test results. During the test, between 5finished .r = 0.83–0.99) and interclass correlation coefficient (0.84–0.94) are high [Participants’ disability was assessed using the English  or Arabiare high , while tare high .r = 0.67) and excellent reliability  [The secondary outcome measures were mobility and movement fear-avoidance (kinesiophobia). The mobility of the spine  was measured using the modified–modified Schober’s test (MMST). The measurement was done with the participant standing erect, knees extended, arms relaxed at the sides, and body weight centered. The inch tape and marker were used to make three markings on the skin overlapping the lumbosacral spine. The first mark (middle line) was made at the lumbosacral junction, as specified by the midpoint between the two posterior superior iliac spines (PSIS) at the S2 level. The second point mark (superior line) was made 10 cm above the lumbosacral junction. Finally, the third point mark (inferior line) was made 5 cm below the lumbosacral junction. The participant was instructed to bend forward as much as possible, and the additional distance between the second and third marks was measured. The original length (15 cm) was subtracted from the final length of trunk flexion to obtain the extent of trunk flexion . The MMS = 0.91)  to measuThe movement fear-avoidance (kinesiophobia) was assessed using the Tampa scale of kinesiophobia (TSK). This is a self-reported questionnaire consisting of 17 items, using a 4-point Likert scale, which was developed to measure the fear of movement or (re)injury among patients with LBP. The total score ranges between 17 and 68, while a high score on TSK indicates a high degree of kinesiophobia . Both thAfter completing the screening procedures to include the study participants, a piece of DT & KT was applied on the right and left side forearm, respectively. The absence of an allergic reaction was confirmed after 24 hours of tape application, and the participants were excluded from the study if any allergic reaction was present. After completing the baseline measurement, the participants were randomized into three groups. Participants were taped according to their group allocation by the same researcher. Once the participant was standing in a comfortable position, the PSIS and T12 (thoracic) vertebrae were carefully marked on the body’s surface. The participants were asked to extend the back as far as possible; during this time, two DT “I” strips were applied parallel to the spine without any stretch, both right and left, from the PSIS to T12 vertebrae . ParticiA priori power analysis was performed using GPower 3.1.9.4 software. Prior randomized trials [d trials , 45, 46 p2, which reports the proportion of the total difference within the dependent variables. When the effect of the test was significant, a Tukey post hoc test was used to identify the difference, while the p-value <0.05 was considered significant.Data were analyzed with SPSS Version 21.0 . The normality of distribution of all variables was verified using the Shapiro–Wilk test. The demographic and baseline characteristics between groups were compared by the one-way analysis of variance (ANOVA) for parametric variables and the chi-square test for nonparametric variables. A mixed-methods ANOVA (3 x 3) was used to analyze the main effect (group effect and time effect) and time x group interaction. All statistics were conducted using pre-protocol and intention-to-treat analyses. The effect size was calculated using ηth, 2019 to February 15th, 2020. The final sample included 45 subjects with a mean age of 37.2 ± 8.97 (range 20–53 years). No losses to follow-up were recorded during the data collection and analysis phase. In the demographic and baseline comparison between groups, no differences were found among the participants (p> 0.05)  .Mixed methods ANOVAs showed a significant difference between groups and time for pain, endurance, mobility, and kinesiophobia, whereas the disability showed a significant difference only in time intervals . The timp<0.001) and KT (p = 0.008) significantly decreased pain than no tape. The DT significantly helped increase back extensor endurance than KT (p = 0.023) and no tape (p = 0.006). There is no significant difference noticed in disability among all three groups (p>0.05). The DT revealed a significant improvement in spinal mobility than no tape (p = 0.005) and no significant improvement seen with KT (p = 0.072). Both DT and KT did not significantly improve than no tape (p>0.05) in kinesiophobia. No harmful or adverse effects were observed in any of the groups throughout the study and every patient in all three groups completed the study.As stated, we used mixed methods ANOVAs and employed the Tukey post hoc criterion for significance. Our findings indicated that both the DT  and kinesiophobia (movement fear avoidance). LBP patients often have reduced ROM/mobility in the lumbar spine . It has Pain-related fear of movement/kinesiophobia is significantly associated with restricted physical performance among patients with chronic LBP . CliniciThe present study also reports several limitations. First, we assessed the immediate and short-term effects of the DT application. Therefore, the effects of long-term or repeated use of DT remain unknown. Second, only male patients participated in this study due to the country’s cultural norms where it took place. Third, the amount of stretch in the KT was determined at 10–15%, and the same was achieved or not known by the therapist during the tape application. Fourth, the sham taping was not included in this trial which may help compare the therapeutic effects of both DT and KT with sham taping. Future research should assess DT’s effects on long-term outcomes for individuals with CNLBP and should address these limitations.This randomized controlled trial showed that the DT does not have a significant additional effect on pain, disability, mobility, and kinesiophobia among individuals with CNLBP compared to KT. However, the participants experienced significant improvement in back muscular endurance after the application of DT. This finding suggests that DT controls the processes that lead to back muscle fatigue. Therefore, more studies are required to examine the therapeutic benefits of DT in treating patients with CNLBP.S1 Protocol(DOCX)Click here for additional data file.S1 Checklist(PDF)Click here for additional data file.S2 Checklist(PDF)Click here for additional data file.


We aimed to evaluate a potential change in liver function in NASH patients and to evaluate the diagnostic power of ABT to detect NASH. We performed a retrospective analysis on patients suspected of NAFLD who underwent a liver biopsy and ABT. 440 patients were included. ABT did not decrease in patients with isolated liver steatosis but decreased significantly in the presence of NASH without fibrosis and decreased even further with the presence of significant fibrosis. The predictive power of ABT as a single test for NASH was low but improved in combination with ALT and ultrasonographic steatosis. We conclude that microsomal liver function of patients with NASH is significantly decreased, even in the absence of fibrosis. The ABT is thus a valuable tool in assessing the presence of NASH; and could be used as a supplementary diagnostic tool in clinical practice.The incidence of non-alcoholic fatty liver disease (NAFLD) is rising across the globe, with the presence of steatohepatitis leading to a more aggressive clinical course. Currently, the diagnosis of non-alcoholic steatohepatitis (NASH) is based on histology, though with the high prevalence of NAFLD, a non-invasive method is needed. The  Together with the obesity epidemic, incidences of non-alcoholic fatty liver disease (NAFLD) are rising across the globe. NAFLD is defined as an accumulation of fat in >5% of hepatocytes ocurring in the absence of significant alcohol consumption or any other cause of so-called “secondary” liver steatosis or disease. NAFLD includes two pathologically distinct conditions with different prognoses: isolated steatosis or non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH), which implies the presence of cell damage and inflammation. The latter covers a wide spectrum of disease severity, including fibrosis, cirrhosis and hepatocellular carcinoma .13C-aminopyrine breath test (ABT) has been widely used to evaluate microsomal hepatocellular function. Historically, it was the first breath test proposed for the assessment of patients with liver disease and is one of the most frequently utilized and most extensively validated tests for investigating microsomal liver function. The principle of the ABT is based on the selective metabolism of 13C-aminopyrine in the liver by the cytochrome P450 mono-oxygenase system of the microsomes .In the NASH-noF group, there was a trend for a decreased ABTpeak and ABTcum between patients with borderline NASH and definite NASH, though these differences did not reach statistical significance . In this group, there was no correlation between fibrosis stage and ABTpeak (p = 0.803) or ABTcum (p = 0.833).The correlation between fibrosis stage and ABTcum in this group without significant fibrosis is most likely due to the confounding effect of NAS score, which was, as might be expected, lower in the NAFL and noNAFLD groups which consisted of less patients with fibrosis stage 1. When analysing this NASH-noF group, no difference of ABT could be observed between patients with fibrosis F0 or F1 [F0 8.4 (6.1–11.6) and F1 8.6 (6.3–10.2), p < 0.05) could be found between the presence of NASH and age (0.155), waist (0.156), AST (0.227), ALT (0.268), ABTpeak (−0.174), ABTcum (−0.202) and USS (0.425). When separating ABTpeak and ABTcum, a remaining significant correlation could be found after logistic regression for ALT, USS and ABTpeak; and for ALT, USS and ABTcum. ALT and USS were significantly correlated with the NAS score . USS and ALT were significantly higher in the group of definite NASH compared to the group of borderline NASH.In the combined groups of noNAFLD, NAFL and NASH-noF, a significant correlation  + (0.909 x USS) + (−0.094 × ABTpeak)PredABTcum for NASH = −1.457 + (0.025 × ALT) + (0.901 × USS) + (−0.075 × ABTcum)p < 0.01) than ABTpeak, ABTcum and ALT individually for the prediction of NASH and definite NASH, but not significantly better than USS (p > 0.05).AUROCs for the prediction of NASH and definite NASH for ABTpeak, ABTcum, ALT, USS as single tests and for the predictive models are represented in Based on the predictive model of the ABTcum which showed a slightly higher AUROC than ABTpeak, we proposed cut-off values to determine the presence of NASH or definite NASH in p = 0.258 and rho −0.072, p = 0.435, respectively) nor to the NAS score . In this population, fibrosis stage has a stronger (inverse) correlation with ABTpeak  and ABTcum . Fibrosis stage is, however, inversely correlated to the NAS score .This group consisted of 121 patients with 38.8% F2, 33.9% F3 and 27.3% F4 ; 28.1% did not have NASH, borderline NASH was present in 19.8% and definite NASH in 52.1% of these cases. In patients with significant fibrosis, ABTpeak and ABTcum are no longer significantly correlated to the presence of NASH  and the presence of NASH .In our entire population, both ABTpeak and ABTcum were independently positively correlated with smoking and serum albumin concentration and negatively correlated with BMI, the presence of NASH and fibrosis stage. Fibrosis was positively correlated with NAS  and 13.40  for F0–1; 7.80  and 11.50  for F2; 6.70  and 9.50  for F3; and 3.50  and 5.00  for F4, respectively. Differences of ABTpeak and ABTcum for each fibrosis stage are represented in ABTpeak showed an AUROC of 0.612 (0.559–0.666), 0.674 (0.618–0.731), 0.718 (0.648–0.788) and 0.782 (0.682–0.882) for the prediction of NASH, significant fibrosis, advanced fibrosis and cirrhosis, respectively. ABTcum showed an AUROC of 0.616 (0.0566–0.673), 0.676 (0.619–0.732), 0.719 (0.650–0.788) and 0.769 (0.667–0.872) for the prediction of NASH, significant fibrosis, advanced fibrosis and cirrhosis, respectively.Based on the ABTcum which showed a slightly higher AUROC than ABTpeak, we proposed cut-off values to determine the presence of significant fibrosis, advanced fibrosis or cirrhosis in 13C-aminopyrine breath test has traditionally been used to estimate functional liver reserve in advanced liver disease. In this study, we demonstrate that non-alcoholic steatohepatitis, even in the absence of significant fibrosis, is associated with a significant impairment of hepatic microsomal function as measured by the 13C-aminopyrine breath test. In the fibrotic NAFLD population, the effect of fibrosis on ABT excretion was more important than the effect of inflammation. The ABT can be used as a tool in the prediction of the presence of NASH or fibrosis in the appropriate setting.The Fibrosis has been shown to be the strongest predictor of outcome in NAFLD, which does, however, not equal that it is as such the driver of disease progression . ProgresMultiple serum biomarkers have been evaluated for the prediction of the presence and/or severity of NASH, though most biomarkers failed to demonstrate accuracy. Plasma cytokeratin 18 fragment levels are a marker of hepatocyte apoptosis and represent the most extensively evaluated biomarker of steatohepatitis, although the accuracy is modest. To date, non-invasive tests cannot reliably be used solely for the diagnosis of NASH ,35. MoreThe ABT has mostly been studied in the setting of cirrhosis and end stage liver disease. Smaller studies have previously shown a significant decrease of liver function in NASH patients, measured by isotope breath tests, though these studies were confounded by a limited population size and the inclusion of patients with significant fibrosis to cirrhosis in the NASH groups ,13,14,15In this study, we included a large population of patients at risk of NAFLD, by the presence of overweight or obesity, allowing us to investigate the effect of NASH in patients without significant fibrosis and thus isolating the steatohepatitis effect. We observed a significant decrease of microsomal liver function in patients with NASH compared to patients with NAFL and overweight patients without liver steatosis. Liver function was not different between the latter two groups indicating that isolated steatosis does not significantly decrease microsomal liver function. Within the NASH population there was a trend of a decreased ABT excretion between patients with borderline NASH and definite NASH, though these differences did not reach statistical significance. Overall, this indicates that steatohepatitis as such is associated with a significant decrease in microsomal hepatocyte function, which is relevant for our understanding of the pathophysiology of NASH.Although extraction of aminopyrine seems to be independent of portal blood flow, a role for changes in the microcirculation that have shown to occur early in the development of NASH, even in the non-fibrotic stage, might indirectly play a role ,37,38,39People with overweight or obesity and other components of the metabolic syndrome are at risk of developing fatty liver which is characterized by the presence of large vacuoles of lipids within the cytosol. In addition to macrovacuolar steatosis, NASH implies the presence of cell damage and inflammation and is histologically characterized by microvesicular steatosis, portal and lobular inflammation, and the presence of hepatocyte injury in the form of ballooning and apoptosis. All these processes ultimately stimulate fibrogenesis. At least three major events are involved in the progression of fatty liver to NASH, including overproduction of ROS (reactive oxygen species) and RNS (reactive nitrogen species), lipotoxicity and increased release of proinflammatory and profibrogenic cytokines . These cSince NASH seems to be the driving force for fibrosis development, its diagnosis is paramount, and the ABT could potentially help by discriminating isolated steatosis from NASH. The rising prevalence of NAFLD and the known disadvantages of liver biopsy  illustrate the need for new non-invasive diagnostic techniques. Our current results suggest that ABT can indeed be helpful in the differentiation between patients with NASH and those with NAFL in patients without significant fibrosis. This test is non-invasive, innocuous, easy to administer and samples are transportable, which allows its use in primary and secondary care. In our group without significant fibrosis, the ABT as a single test had rather poor predictive power, though when including ALT and USS into a predictive model, the predictive power strongly increased. A potential limitation of the use of this model in clinical practice could, however, be hampered by the absence of reliable tools to exclude significant fibrosis. Liver steatosis and ALT have both been related to the presence of NASH. Previous research has shown a correlation between the extent of steatosis  and the presence of NASH ,46,47. ITribonias et al. found similar results with a substantial impairment of hepatic microsomal function as assessed by a simple non-invasive ABT in NASH patients including, however, patients with significant fibrosis in the NASH group . CompareIn our study, we observed, apart from the effect of NASH on microsomal function, a decreasing ABT excretion with each fibrosis stage, which is in line with current literature. Previous reports support this observation and show that ABT results are associated with the severity of liver disease, and that they have a prognostic role in predicting death from liver failure in cirrhotic patients ,51. MoreIn our entire population, the predictive power of the cumulative ABT value was mostly higher than the peak ABT value, though not statistically significant. ABT proved to be a poor predictor of significant fibrosis as a single test with an AUROC of 0.676 for ABTcum. The power increased to a fair test to predict the presence of advanced fibrosis and cirrhosis with an AUROC of 0.719 and 0.769 for ABTcum, respectively.Our findings clearly indicate that both steatohepatitis and fibrosis are associated with impairment of microsomal function. This implies that both these aspects should be taken into account when assessing the accuracy of the ABT as a non-invasive marker of disease. The mixing-up of both aspects may in part explain overall low accuracy and conflicting results in the literature.13C breath tests can explore either microsomal, cytosolic or mitochondrial hepatocellular subfunctions [13C breath tests are also capable of distinguishing patients with various degrees of liver disease from normal subjects, as well as distinguishing patients with compensated cirrhosis from those with decompensated cirrhosis. Banasch et al. used a 13C-methionine breath test to evaluate mitochondrial dysfunction. They showed in patients without significant fibrosis a difference of mitochondrial function between borderline and definite NASH, which was no longer present in patients with significant fibrosis [ABT is not the only breath test used to investigate hepatic function. unctions . Previoufibrosis . In the 13C-octanoate breath tests (OBT) in patients with NAFLD and demonstrated the relationship between the presence of fibrosis and the impairment of liver function, expressed by lower OBT results than those of controls [13C-caffeine breath test, another test for microsomal function, reflected the extent of hepatic fibrosis in NALFD and was an independent predictor of significant fibrosis in these patients. They showed impaired liver function in NASH patients, but induced by the presence of significant fibrosis, as they found no correlation with steatosis or inflammation [Miele et al. performed controls . Park etammation .In our study, ABT results were found to have an inverse correlation with BMI, which is consistent with previous findings as increasing BMI has been repeatedly shown to be associated with worse liver histologic lesions in the NAFLD patients ,54.A weakness of our study is the fact that the majority of patients were obese, but the sample included relatively few diabetic patients. The generalizability of the findings to NAFLD patients with a different metabolic profile hence needs to be studied. Furthermore, there is the confounding effect of patient characteristics on the ABT and the cross-sectional nature of the study. Enzymatic functions explored by the ABT may be influenced by hormones, malnutrition, heart or renal failure, sex or xenobiotics such as medication or smoking . No dataTo confirm our results, more studies should be performed in large patient groups without the confounding factor of significant or advanced fibrosis. Other compounds than aminopyrine can be used to assess the decreased microsomal function in NASH patients, such as caffeine, phenacetin or methacetin.The observations in this study open new possibilities for the use of the ABT in NAFLD. The ABT can be incorporated in the diagnostic toolset for NASH  or fibrosis assessment. A decreased microsomal liver function in patients with NASH might indicate a decreased metabolism of xenobiotics, which has a major impact considering the high global prevalence of NASH. Future studies of NASH medication should take this into account. The ABT could be used to monitor disease progression of inflammation in the absence of fibrosis. Furthermore, the ABT could be an additional tool the evaluate the potential improvement upon (new) therapeutic interventions. The present study shows a decreased microsomal function in NASH patients without significant fibrosis compared to patients with simple steatosis, as assessed by ABT. Fibrosis, when present, has a stronger impact on ABT excretion compared to inflammation and decreases ABT excretion with each fibrosis stage. ABT might be a useful tool for the decision to conduct a liver biopsy in the NAFLD patients and potentially also for the prospective monitoring of disease progression or of the potential benefits after therapeutic interventions.


WC increased by 0.71 cm, 1.21 cm after adjusting the covariates compared with the unexposed group among the total subjects and the female subjects in urban areas . The female subjects had a significantly higher prevalence of obesity and central obesity, with ORs of 1.34  (p = 0.022), 1.28  (p = 0.008) respectively. Our results suggest that fetal exposure to the Chinese famine increased obesity risk in adulthood, and the association was stronger in female and urban subjects.Fetal exposure to famine may have long-term consequences in adulthood. The purpose of the present study was to explore the association between famine exposure in fetal life (Chinese famine in 1959–1961) and obesity risk in adulthood. A total of 8054 subjects  were recruited from the cross-sectional 2010–2012 China National Nutrition and Health Survey (CNNHS). The subjects born in 1960 and 1961 were selected as the exposed group, while the subjects born in 1963 were selected as the unexposed group. Multiple linear or logistic regression was performed to examine the association between fetal exposure to famine and risk of obesity (body mass index (BMI), waist circumference (WC), obesity, central obesity) adjusting for gender, education level, economic status, physical exercise, sedentary time, smoking, drinking, the intake of livestock and poultry and the intake of cereal and beans. Compared with the unexposed group, WC increased by 0.52 cm after adjusting the covariates  One study presented that the combined prevalence of overweight and obesity rose by 27.5% for adults between 1980 and 2013, and the number of overweight and obese individuals increased from 857 million in 1980 to 2.1 billion in 2013 . MoreoveMI range .Increasing evidence has indicated that nutrition status in early life has a long-term impact on chronic diseases in adulthood. Fetal undernutrition lead to metabolic and structural changes which have been found beneficial for early survival, but might increase some diseases in adulthood ,33,34,35The CNNHS was a nationally representative cross-sectional study conducted by the National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention . The 2010–2012 survey covered all regions throughout China except for Taiwan, Hong Kong, and Macao. The country was divided into four strata: big cities, medium and small cities, ordinary rural areas and poor rural areas by economy and social level. A total of 150 surveillance sites were selected, and in each site six villages/communities (75 households were then randomly sampled from each village/community) were randomly selected. Questionnaires were used to collect information on the demographic characteristics. Height was measured using a stadiometer after removing shoes, body weight was measured with light clothes using a beam scale and WC was measured using a waist circumference tape only after breathing out. The accuracy of the height, weight and WC were 0.1 cm, 0.1 kg and 0.1 cm, respectively. All anthropometric measurement staff were trained according to the standard procedure .The Chinese famine lasted for three years in 1959–1961. There was data on the mortality rate in China (1956–62) that showed that the mortality rate in 1959–61 was higher than that in 1956–58, and in 1962 the mortality decreased to a lower level . TherefoInformation about demographic characteristics, dietary factors, smoking and drinking status, exercise data and anthropometric data were derived from the questionnaires by trained investigators. Self-reported education levels were classified as illiteracy to primary school, junior middle school, senior high school and higher. Current economic status was assessed by the per capita annual income of households in 2011, and was divided into three levels: low, middle and high. Smoking, drinking and physical exercise in leisure time were classified as “yes” or “no”. The sedentary time included the time spent watching TV, using computers, playing video games and reading in leisure time.A validated semi-quantitative food frequency questionnaire and a 24-h recall method for the last 3 consecutive days (2 weekdays and 1 weekend day) were used to collect the dietary intake. In the present study, we only considered the intake of cereal and beans and the intake of livestock and poultry as confounders, as they had been found to associate with obesity ,45,46. T2). According to the criterion of weight for adults (WST 428-2013) [BMI was calculated as the weight in kilograms divided by height in meters squared (kg/m28-2013) , we defiThe statistical software package SAS version 9.4  was used for data analysis. Chi-squared and nonparametric tests were used for the comparison of difference between the exposed and unexposed groups. We used multiple linear or logistic regression to estimate the association between fetal exposure to famine and risk of obesity indicators  adjusting for gender, education level, economic status, physical exercise, sedentary time, smoking, drinking, the intake of livestock and poultry and the intake of cereal and beans. Model 1 was adjusted for gender, education level and economic status. Model 2 was adjusted for the variables in Model 1 and some lifestyle factors including smoking, drinking, physical exercise and sedentary time. Model 3 was adjusted for the variables in Model 2 and dietary factors including cereal and beans intake as well as livestock and poultry intake.A total of 8054 subjects  were included in the present study, with the median age of 49.6 years. General characteristics of participants between the exposed and unexposed groups are shown in p = 0.019, p = 0.021), which was consistent with the results among female subjects. Females in the exposed group had a significantly higher prevalence of central obesity with odds ratios (ORs) of 1.16, 1.16 and 1.15 in Model 1, Model 2 and Model 3 respectively. No other significant difference of the remaining indicators was observed in unadjusted and adjusted models. We did not find significant results among the male subjects.p = 0.021). The increased WC was significantly associated with the fetal famine exposure before and after adjusting for the confounding factors in females . Compared with the unexposed group, the female subjects had a significantly higher prevalence of obesity and central obesity with ORs of 1.34 (p = 0.022) and 1.28 (p = 0.008). We did not find significant results between fetal famine exposure and obesity risk among the male subjects.Our results suggest that fetal exposure to the Chinese famine increased obesity risk in adulthood based on the national samples. A study among 1339 adults conducted in Nigeria indicated that fetal-infant exposure to famine was associated with WC and overweight as compared to people born after the famine . ResultsThe association was stronger in female subjects, which was consistent with some previous studies ,38,49,50In the present study, the areas were classified into urban and rural areas based on residence, not on birthplace. We performed an areas-stratified analysis, and the only significant association was found in urban areas, not in rural areas. As urbanization happened throughout China in the last century, the results did not represent the prevalence of obesity in the early 1960s. According to the proposals referred by Gluckman, people currently live in evolutionarily novel environments, and the mismatch between the evolved physiological capabilities and contemporary exposures can lead to ill health. This mismatch is especially relevant to food preferences and consumption and to energy expenditure, which have changed greatly over several decades in some countries undergoing socioeconomic improvement ,53,54. IThe current study indicates that exposure to famine during the prenatal period may be a risk factor of obesity, and our sample came from a large national survey, which covered the majority of the regions throughout China. We considered some lifestyle factors, including smoking, drinking, diet and physical activity. However, the present study also has some limitations, namely, that the subjects of child exposure to famine were not included and the nutrition status of childhood was not collected, as our study is a retrospective study.Our results confirmed that fetal exposure to famine was associated with obesity risk in adulthood and the association was stronger in female and urban subjects. The data suggest gender-specific and long-term consequences of maternal undernutrition.