Lactococcus, Alistipes, or Subdoligranulum abundances were positively correlated with systolic blood pressure (SBP) or diastolic blood pressure (DBP) in hypertensive patients with treatment-naive hypertension (n = 63). In hypertensive patients undergoing anti-hypertensive treatment (n = 104), the abundance of Megasphaera or Megamonas was positively correlated to SBP. In the hyperlipidemia group, some of the top 35 genera were significantly correlated to triglyceride, total cholesterol, and fasting blood glucose levels. This study analyzed the characteristics of the gut microbiota in patients with hypertension and/or hyperlipidemia, providing a theoretical basis for the prevention and control of hypertension and hyperlipidemia in this region.Human gut microbiota can be affected by a variety of factors, including geography. This study aimed to clarify the regional specific characteristics of gut microbiota in rural residents of Xinxiang county, Henan province, with hypertension and hyperlipidemia and evaluate the association of specific gut microbiota with hypertension and hyperlipidemia clinical indices. To identify the gut microbes, 16S rRNA gene sequencing was used and a random forest disease classifier was constructed to discriminate between the gut microbiota in hypertension, hyperlipidemia, and the healthy control. Patients with hypertension and hyperlipidemia presented with marked gut microbiota dysbiosis compared to the healthy control. The gut microbiota related to hypertension and hyperlipidemia may consist of a large number of taxa, influencing each other in a complex metabolic network. Examining the top 35 genera in each group showed that  Hypertension is a very common chronic medical condition, historically defined by sustained systolic blood pressure (SBP) above 140 mmHg or diastolic blood pressure (DBP) above 90 mmHg. Despite a variety of community-based efforts to influence lifestyle and recent pharmacological and surgical advances in the management of hypertension, its prevalence has doubled globally from 1990 to 2015 . In receNotably, recent studies have suggested that the gut microbiome participates in BP regulation and the pathogenesis of hypertension. The rationale for examining the association between the gut microbiome and hypertension is based on the following: first, the gut is the single most important organ for adsorption of nutrients and ions, which greatly impacts BP ; second,Human gut microbiota can be affected by a variety of factors, including geography and diet. Geography in particular exerts a strong effect on human gut microbiota ,15. GeogThis study was approved by the Ethics Committee of Xinxiang Medical University for Human Studies  and all subjects gave written informed consent. To investigate the characteristics of the gut microbiota of hypertensive patients, 63 hypertensive patients with treatment-naive hypertension (NH group), 104 hypertensive patients undergoing anti-hypertensive treatment (AH group), 26 subjects with normal BP but with hyperlipidemia (HLD group), and 42 healthy subjects with normal DBP, SBP, fasting blood glucose, cholesterol, and triglyceride levels (control group) in the rural area of Henan Province, central China were randomly recruited in this study. For the hypertensive patients in the AH group, nifedipine, metoprolol, statins, diuretics and angiotensin-converting enzyme inhibitors, and angiotensin II receptor antagonists were the most commonly used drugs. Hypertensive and/or hyperlipidemic patients with other chronic diseases including cancer, heart failure, diabetes mellitus, renal failure, chronic respiratory disease, peripheral artery disease, metabolic disorders, and inflammatory bowel disease were excluded. The healthy controls had no history of chronic diseases and were not taking any medicine that might disrupt gut microbiota, such as antibiotics, probiotics, and anti-inflammatory agents. The participants were older than 18 years, met the inclusion criteria, and were competent and willing to provide written consent.All on-site examinations were performed at the local medical stations or community clinics that usually provided clinical services for the participants from April to June 2017. Medical information was recorded according to standard procedures. BP was measured by trained medical students with an electronic sphygmomanometer  on the right arm positioned at heart level in a seated position. The participants were required to rest for at least 5 min before BP measurement. An appropriately sized cuff was selected based on the circumference of the right upper arm of the participants to avoid overlapping. BP was measured three times during one visit, and the mean of the three readings was used in the analysis. Hypertension was defined as SBP ≥ 140 mmHg, DBP ≥ 90 mmHg, or by self-reported use of antihypertensive medications in the last 2 weeks irrespective of BP values. Levels of fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) were measured with a SIEMENS ADVIA 2400 auto analyzer . In accordance with the Chinese guideline on the prevention and treatment of hyperlipidemia in adults, hypercholesterolemia was defined as TC > 5.72 mmol/L, high LDL as LDL > 3.64 mmol/L, hypertriglyceridemia as TG > 1.70 mmol/L and low HDL as HDL < 0.91 mmol/L. Hyperlipidemia was defined as the presence of one or more abnormal serum lipid concentrations. Waist circumference (WC), height, and body weight were measured according to the standard protocols. Body mass index (BMI) was calculated as weight in kilograms divided by height in meters squared. The validated interview questionnaire [® High-Fidelity PCR Master Mix . Sequencing libraries were generated using the Ion Plus Fragment Library Kit 48 rxns  following the manufacturer’s instructions. Library quality was assessed on a Qubit® 2.0 Fluorometer . Finally, the library was sequenced on an Ion S5™ XL platform and 600 bp single-end reads were generated.Fresh fecal samples collected from each participant were immediately frozen at −20 °C, transported to the laboratory and then stored at −80 °C until further analysis. Bacterial DNA was extracted at Beijing Novogene Bioinformatics Technology Co., Ltd. using the Cetyltrimethyl Ammonium Bromide/Sodium Dodecyl Sulfonate method. The V3–V4 regions of the 16S rRNA genes were amplified using specific primers . All PCR reactions were carried out with PhusionSingle-end reads were assigned to samples based on their unique barcode and truncated by cutting off the barcode and primer sequence. The raw reads were filtered with conditions to obtain high-quality clean reads according to the Cutadapt quality controlled process. The reads were compared to the reference database using the UCHIME algorithm  to detecp values are from two-tailed tests. A p value of less than 0.05 in a two-tail test was considered to be statistically significant. Statistical analyses were conducted using the R platform. Distance-based redundancy analysis was performed on normalized taxa abundance matrices with the R vegan package according to the Bray-Curtis distance. Random forest models were trained with the R random Forest package  to predict hypertension status according to genera abundance profiles. The performance of the predictive model was evaluated with cross-validation error. Receiver operator characteristic (ROC) analysis was performed using the R pROC package. The p-value was calculated to evaluate the false discovery rate and was corrected for multiple comparisons. We analyzed the Spearman’s correlation between the top 35 enriched gut bacteria genera in the NH, AH, HLD and control subjects and clinical indices of hypertension at the genus level. The p values were corrected for multiple testing with the Holm method by R vegan.Continuous data are presented as mean ± SD. Categorical variables are presented as proportions. Data entry and management were performed using SPSS 22.0 and all p = 0.019 and 0.027 respectively). There were significant differences in both DBP and SBP between the NH and HLD groups, NH group and control, AH and HLD groups, and AH group and control (p = 0.000). The HLD group had significantly higher levels of FBG than the NH, AH, and control groups . The levels of TG in the NH, AH, and HLD groups were all significantly higher than that in the control group . The levels of LDL and WC have the same trend .As described above, 234 rural residents in Xinxiang county, Central China, were recruited to identify the differences in gut microbiome between the NH, AH, HLD, and control groups. The demographic characteristics and clinical indices of the four groups of subjects are shown in We acquired a total of 20,235,921 raw reads. After filtering to obtain the high-quality clean reads in accordance with the Cutadapt  quality controlled process, 18,785,481 high-quality clean reads were obtained. Sequences with ≥97% similarity were clustered into the same OTU, the representative sequence for each OTU was screened for further annotation. Taxonomically, 18 bacterial phyla and 789 bacterial genera were detected in the four groups. The top 10 phyla and genera present in the four groups are listed in Blautia (8.68%), Bacteroides (7.74%), and Faecalibacterium (6.47%). Contrastingly, in the AH group, the dominant bacteria genus was Prevotella 9 (9.40%), which was more abundant than in the other three groups. Compared with the NH group, the relative abundance of Blautia (7.81%) was lower, however, the relative abundance of Faecalibacterium (8.76%) was higher. In HLD group, the dominant bacterial genera were Bacteroides (11.77%) and Faecalibacterium (10.50%), were more abundant than in the NH and AH groups. In the control group, the dominant bacterial genera were Bacteroides (9.81%), and Faecalibacterium (9.84%), which were the same genera seen in the HLD group, however, their relative abundances were lower than in the HLD group, but higher than in the NH group. The differential enrichment of gut microbiota in the hypertension and control groups demonstrated the dysbiosis of gut microbial in hypertension.As depicted in To explore the genera contributing to the differences between pairs of the four groups, we constructed a random forest disease classifier using the samples from the AH, NH, HLD, and control groups. Fivefold cross-validation was repeated five times and ROC curves for distinguishing any pair of the four groups were developed.As shown in Tyzzerella, Flavonifractor, Faecalitalea, Dorea, and Phascolarctobacterium were the common contributors for distinguishing the control group from both the AH and NH groups . Fecal microbial genera were significantly associated with many clinical indices of the hypertension tested.Lactococcus, Alistipes, or Subdoligranulum were positively correlated to SBP and DBP  with lower specificity and sensitivity. This confirmed that subjects in the HLD and NH groups had similar gut microbiome compositions, although both DBP and SBP are significantly different in the NH, and HLD groups. Correlation analyses of hypertension-related clinical indices and gut microbiome demonstrated that serum levels of HbA1c, HDL, TG, TC, and WC, the putative risk factors for hypertension, in the subjects in the HLD group, were significantly higher than those in the control group but were comparable to those in the NH group. These findings suggest that for early BP control, attention should be paid to previously neglected populations with hyperlipidemia since these people have hypertension-related gut microbiota dysbiosis. Early gut microbiome management for individuals with hyperlipidemia may have a strong clinical implication for disease intervention.Bifidobacterium in the AH group (7.55%) was much higher than in the NH group (5.18%), showing that antihypertensive medicine may increase the relative abundance of some beneficial bacteria. Medicine-induced shifts of the gut microbiome have been observed during the treatment of multiple diseases, inducing metformin therapy for type 2 diabetes [ROC analysis of the disease classifiers using 30 bacterial genera produced AUCs for AH vs. HLD 0.831), NH vs. the control (0.823), AH vs. the control (0.776), HLD vs. the control 0.756), NH vs. AH (0.708), and HLD vs. NH (0.686). We achieved reliable discrimination between AH and HLD, NH and the control, AH and the control, and between HLD and the control. This discriminatory power is higher than that from the prediction models based on genomic markers identified by GWAS ,28, and , NH vs. diabetes  and athe6, NH vs.For most patients with hypertension, measuring blood pressure is a common usage for hypertension diagnosis. According to the Guideline for the prevention, detection, evaluation and management of high blood pressure in adults, patients with blood pressure ≥130 mmHg and/or diastolic pressure ≥80 mmHg are diagnosed with hypertension, and given recommendations to receive treatment . HoweverOn the other hand, as high-risk factor and common comorbidity, hyperlipidemia diagnosis is highly dependent on blood samples . AlthougAs numerous studies proved, gut microbiota may exert a great influence on the functionality and pathophysiology of human diseases, including obesity, type II diabetes, cardiovascular diseases, and some psychiatric disorders, while a deluge of research utilized it to identity patients . It was Although our study reveals the important roles of the gut microbiome in hypertension, it has several limitations. First, the sample size is limited due to the high cost of sequencing and sample availability. Study subjects were recruited from a single clinic within a small geographic area and were divided based on BP alone, without consideration for possible confounding factors such as diet, culture, or demographics. Second, the influence of different kinds of hypertension drugs on the gut microbial community in the AH group was not considered. Therefore, our data need to be interpreted with caution. Generally, hypertension is a highly complex and heterogeneous disease, it is still infeasible to draw any conclusions about the causal relationships between the gut microbiota and hypertension.This study showed that a large number of gut microbiota taxa may be related to hypertension, influencing each other in a complex metabolic network, and is not solely a single player or a limited number of species. Collectively, the findings of this study expand on previous knowledge of the correlation between gut microbiota and hypertension, and provide a range of genomic biodiversity signatures for the hypertensive gut microbiome.


Snail control is an important component in the national schistosomiasis control programme in China, by application of chemical molluscicides, forestry projects, agriculture projects and water conservancy projects in recent decades. However, there are still wide areas of snail inhabited in China which remains a great challenge to achieve the goal of schistosomiasis elimination by 2025. Therefore, a SWOT  analysis on snail control measures is required for precision schistosomiasis control.The SWOT approach, which is a well-known structured analysis tool, was used to identify and evaluate the specific characteristics of four types of snail control measures in China, including chemical mollusciciding, forestry, agriculture, and water conservancy projects. The analysis were carried out based on the information collection from literature review, of research papers, books, annual report database of national schistosomiasis control programme in China, reports from the academic forums, and so on.For chemical mollusciciding, application strategy needs to focus on specific local settings, such as stage of schistosomiasis control, environmental factors, and limitations from external policies and internal deficiencies. Regarding forestry projects, the optimal strategies are to cooperate with other national forestry programmes to share the investment costs and pay attention on wetland protection. In agriculture projects, it is necessary to develop related cash crop industries and combine with national farmland consolidation projects simultaneously to increase the total economic benefits. Concerning water conservancy projects, the main purpose is to control snail migration from snail area to snail-free areas nationwide.Integrated strategies for various measures application and a top-level designed cooperation mechanism will be the necessary to eliminate snail and schistosomiasis in China.The online version of this article (10.1186/s40249-019-0521-0) contains supplementary material, which is available to authorized users. Please see Additional file Schistosomiasis is an endemic disease mostly in several provinces around the Yangtze River basin and lakes in China . By the Oncomelania spp. is the unique snail intermediate host of Schistosoma japonicum distributed in Asia, which is an amphibious snail, so snail control is the essential factor in the process of schistosomiasis elimination, which requires a multidisciplinary cooperative mechanism and integrated implementation strategy [The sixty-fifth World Health Assembly passed resolution WHA65.21, which proposed to eliminate schistosomiasis, a neglected tropical disease, in low-transmission areas of the world . The conOncomelania snail distribution area increased from 351 885.06 ha to 373 596.18 ha from 2002 to 2010, respectively, representing a growth rate of 6.17% [of 6.17% . The maiof 6.17% , 13. By of 6.17% –28. The In addition, Chongqing and Henan are potential regions at risk of schistosomiasis transmission because of the Three Gorges Dam Project and the South-to-North Water Diversion Project. Large-scale hydraulic projects and human cultivation may have contributed to the snail spreading because the hydrologic conditions resulting from such projects create marshland areas where suitable for snail survival . The inclink.springer.com), China Academic Journals Full-text Database (cnki.net) and Wanfang Database (wanfangdata.com.cn), and books related to schistosomiasis prevention [This study used published information from literatures to analyze the specific characteristics of four snail control measures of chemical molluscicides application, forestry, agriculture and water conservancy projects. The information for this study was based on the 88 published literatures from 1990 to 2018 in the databases including Springer Link Database  is easy to use for immersion or spraying methods. The powder formulation is useful for application in water-deficient areas. Niclosamide suspensions perform better in complex environments, due to their stability. Molluscicides can kill snails in a short period, ranging from 24 h to several days. The application of 1 mg/L WPN or 0.5 mg/L for 24 h of immersion can kill all snails in one experiment . The lowThe impermanence of snail control effectiveness is the main disadvantage of the chemical mollusciciding. Due to the influence of external factors, the internally active components of molluscicides are quickly reduced, and their effect on snail control lasts only for 5–7 days . AlthougThe dispersed distribution of snails and complex environmental conditions have made snail control a long-term and arduous challenge in China. One document of National Action Plan to Eliminate Schistosomiasis 2016–2025) has been co-issued by several ministries of Chinese government, including National Health Commission, Ministry of Agriculture, Ministry of Water Conservation, and Ministry of Forest, etc., which will sustain the investment of schistosomiasis elimination activities . In the 016–2025 In China, the main limitation of molluscicides use is from strict laws and regulations of environmental protection. In 2015, the State Council of the People’s Republic of China issued the Water Pollution Control Action Plan aiming to control agricultural non-point-source pollution and promote the low-toxicity chemicals , which wBased on systematic research on the characteristics and background of chemical molluscicides application, the relevant factors were classified into the internal factors of strengths and weaknesses and, the external factors of opportunities and threats representing influential environmental factors. This classification identified positive factors representing advantages and negative factors representing disadvantages Fig. .Fig. 2SWA total of four strategies were listed and described in Table In China, forestry projects aimed at snail control have been developed into a systematic project referred to as the Forestry Schistosomiasis Control Program. Forestry projects have been a durable and effective method for controlling snails based on altering the ecological conditions which is beneficial to snail survival . AccordiPterocaryastenoptera, Sapiumsebiferum, Cinnamomumbodinieri, Leonurusartemisia, and others


Methylmalonic acidemia (MMA) and propionic acidemia (PA) are two kinds of diseases caused by inborn errors of metabolism. So far, the epidemiological data on them are limited in China. The aim of our study is to investigate the proportion and characteristics of hospitalized pediatric patients with MMA and PA in China.The data in this study were obtained from the Hospital Quality Monitoring System, a national inpatient database in China, with information on the patients hospitalized during the period from 2013 to 2017. We identified the data related to the patients who were under 18 years old and were diagnosed with MMA/PA, and extracted the information on demographic characteristics, hospital location, total cost and other related clinical presentations from the data.Among all hospitalized pediatric patients with liver diseases, there were increasing trends in the proportion of individuals diagnosed with MMA or PA during the period from 2013  to 2017 . For both MMA and PA, children under 2-year-old accounted for the highest proportion. The median of total cost per hospitalization was relatively high . Moreover, most patients hospitalized in tertiary class A hospitals ; and a majority of pediatric patients admitted in the hospitals in Shanghai and Beijing are from outside districts. Manifestations of nervous system-related symptoms, and metabolic acidosis or anemia in laboratory findings were more common during hospitalization.The study is the first nationwide one in providing epidemiological and clinical information on hospitalized pediatric patients with MMA/PA. An increasing hospitalization with various presentations and a heavy financial burden were observed. In addition, geographically, the medical resources in China have been unevenly distributed. Methylmalonic acidemia (MMA)  and propionic acidemia (PA) OMIM #606054), two diseases caused by inborn errors of metabolism, are the most common organic acidurias . The age06054, twMMA and PA are both rare disorders of propionate catabolism among children. Compared with PA, MMA has been commonly reported with higher prevalence rate, but the incidence varies greatly worldwide –14. HoweSince China is a country with a huge population and MMA/PA are increasingly recognized diseases, the two diseases may pose a potential challenge to China’s national health system. Hence, to obtain information about the epidemiology and clinical presentations of MMA/PA is critical to the comprehensive perception of both of them and will be conducive to early diagnosis and even prognosis. Considering the low incidence and the cost of epidemiological survey, analyzing existing big data is a more rational way. Therefore, the purpose of this study was to 1) provide epidemiological information and financial burden status; 2) evaluate frequency of different clinical manifestations and laboratory results of MMA and PA hospitalizations among pediatric patients in China based on a large national database.The database we used is the Hospital Quality Monitoring System (HQMS) , a mandaPhysicians were in charge of completing the data on the front page of records, and the diagnosis was coded based on the International Classification of Diseases, revision 10 (ICD-10) coding system by certified professional medical coders at each participating hospital. Data quality was controlled automatically at the time of data submission.The study included all hospitalizations of patients who were under 18 years of age with a primary or secondary diagnosis of underlying liver disease , liver neoplasms, autoimmune liver disease, drugs/toxin-induced liver injury, trauma, biliary atresia, metabolic liver disease, other congenital diseases, hepatic vascular/anatomical abnormalities and idiopathic portal hypertension) using ICD-10 from 1 January 2013 to 31 December 2017. Among these diseases, MMA and PA were defined with the following ICD-10 codes: MMA (E71.102), PA (E71.101), all of whose hospital discharge data were extracted and analysed retrospectively. Other diagnosis related to MMA and PA  for highly skewed variables. Categorical variables were presented as frequency and percentage (%). Cochran-Armitage test for trend was performed to assess the trend of the proportion of MMA or PA pediatric patients.P values were 2-tailed. A P value less than 0.05 was considered to be significant. All analysis was performed using SAS software, version 9.4 . The maps were drawn by JMP software, version 14 .All n = 282 (0.76%)) to 2017 (n = 716 (1.61%)) with statistical significance (Ptrend < 0.001). There was also a relatively slow upward trend in the proportion of individuals diagnosed with PA from 2013 (n = 49 (0.13%)) to 2017 (n = 143 (0.32%)) .During the period from 2013 to 2017, total frequency of hospitalizations of the pediatric patients identified, with MMA and PA were 2610 and 538 in the database respectively. Among all hospitalized pediatric patients with liver diseases, the proportion of hospitalized pediatric patients with MMA showed an increasing trend from 2013 , Tianjin (80.0%) and Heilongjiang (72.4%)  were hospitalized in the highest level of hospitals, namely, tertiary class A hospital. Moreover, the hospitals located in Beijing, Chongqing, Shanghai and Jiangsu, admitted a majority of MMA or PA pediatric patients from other districts. This may be related to the unbalanced distribution of medical resources including experienced, specialized pediatricians and advanced equipment. For instance, measurement of serum/urine organic acid and genetic analysis has been generally available only in tertiary hospitals and rarely available in primary health care settings in China. These two diseases also require multidisciplinary team for nutritional, biochemical, neurodevelopmental and psychological assessment. Regular monitoring of metabolic parameters, developmental delay, long-term complications, compliance with therapy, along with overall nutritional status are strongly advised . Our stuIt has been already known that symptoms of MMA/PA may vary considerably and are nonspecific especially in childhood since multiple organ systems are affected , 31, 36.There are several limitations to our study. Firstly, the HQMS database is not able to distinguish each patient with repeated admissions, since ID numbers for children on the front page of medical records are usually unavailable. Secondly, we relied merely on ICD-10 codes for case identification, since we had no access to all medical records of studied population. This could have led to a less precise estimation of burden of hospitalized pediatric patients with MMA and PA to some extent. Thirdly, there were lack of follow-up outcomes for these pediatric patients in this study, as the study was based on sequential cross-sectional data.Despite these limitations, our study provides epidemiological and clinical information of MMA and PA hospitalizations based on a nation-wide database, which would help us better understand the general profile of these two rare diseases in China.In conclusion, this study is the first one to provide epidemiological, health economic and clinical presentation information on hospitalized pediatric patients with MMA and PA in China based on a national database. An increasing hospitalization with various presentations and a heavy financial burden per hospitalization were observed, while the medial resources were still relatively centralized in only several districts, such as Beijing, Chongqing, Shanghai and etc.


The intake by CD patients was significantly higher than healthy volunteers for: sweeteners and sugars with low content of FODMAP (p = 0.0007), fruits, dried fruits, and vegetables high in FODMAP (p = 0.003) and low in FODMAP (p = 0.04) when compared to controls. CD patients had a lower intake of cereals and sweets with a high content of FODMAP (p = 0.00001). Healthy volunteers consumed significantly higher alcoholic beverages and fats high in FODMAP (both p < 0.044). The mean daily intake of other food categories did not differ between both groups. Even though CD patients had a low intake of gluten-free cereals high in FODMAP, they still consumed a significant amount of fruits and vegetables high in FODMAP. The clinical effect of a concomitant gluten-free diet and low-FODMAP diet should be prospectively evaluated as a supportive therapy in CD patients.Our aim was to evaluate the intake of foods containing fermentable oligo/di/mono-saccharides and polyols (FODMAP) as a possible factor that induces gastrointestinal symptoms in treated celiac disease (CD) patients. We collected seven-day weighed food records for 104 CD patients and 91 healthy volunteers. All evaluated food items were from sources with high and low content of FODMAP, which were divided into cereals and sweets, sweeteners and soft drinks, fruits, dried fruits, and vegetables. Nutrient intake was calculated using the food database of the European Institute of Oncology. The symptoms reported were assessed by a Rome IV Irritable bowel syndrome (IBS) diagnostic questionnaire and by specific questions for the evaluation of functional gastrointestinal disorders (FGIDs). The 12% of CD patients met IBS symptoms criteria as opposed to 6% of controls ( Celiac disease (CD) is a chronic autoimmune enteropathy triggered by dietary exposure to gluten and is characterized by villous atrophy. CD is considered the most common chronic enteropathy in Western countries with an estimated prevalence ranging from 0.5 to 1% . An alteGluten is a complex of high molecular-weight proteins found in the endosperm of grass-borne grains including wheat, barley, and rye . The treThe criteria for diagnosing gastrointestinal disorders have been revised by the Rome Foundation in their latest update . The pathogenesis of IBS is multi-factorial and may be connected to visceral hyper-sensitivity, alterations of the gut-brain axis and the microbiota, post infectious consequences, and environmental and genetic factors . IBS canIn recent years, data supporting that the dietary restriction of fermentable oligo/di/mono-saccharides and polyols (FODMAP) for the management of IBS symptoms have emerged ,18,19. S2 and CH4 production and causes pain in the lumen. This gas production can be measured with a breath test, which shows an increase between 0–5 h after the ingestion of FODMAP [The main dietary sources of FODMAP include fructose in honey, apples, and pears, fructans in wheat, rye, onion, and garlic, galactans in cabbage and legumes, lactose in milk and dairy products, and polyols including sorbitol and mannitol in stone fruits, mushrooms, and artificial sweeteners . Among Ff FODMAP . As propf FODMAP . Zhou etf FODMAP  reportedNowadays, it is of great interest to evaluate if persistent gastrointestinal symptoms in celiac patients, classified as FGIDs and IBS, can be provoked by the ingestion of FODMAP. We aimed to evaluate the intake of foods containing FODMAP in a group of patients with CD compared with the intake of healthy volunteers.The participants were recruited among patients referred to the Center of Prevention and Diagnosis of Celiac Disease Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy. All the subjects were recruited between October 2012 and August 2014 and the data were collected during the same period. Over that time, during their annual medical examination, the patients were screened for their adherence to GFD by using the celiac diet adherence test (CDAT) .The enrolment process of CD patients and healthy individuals has been previously described ,35. All ClinicalTrials.gov (ID NCT01975155).The final sample included 104 celiac patients and 91 healthy controls. All the participants who agreed to participate signed a written informed consent and were enrolled in the study. The local Ethics Committee for Human Research of the City of Milan approved the protocol. The study was registered at The total food and beverage consumption was assessed by using a food diary filled in daily for a total of seven days, which was previously described . The parThe nutrient intake was calculated by using a Microsoft Access application  linked to the European Institute of Oncology’s food database, which covered the nutrient composition of 900+ Italian foods , integraFood items of interest for the FODMAP intake evaluation were grouped into the following food categories  was used in all the analyses. Statistical significance was set at a 5% α-level.Data were accordingly described as mean ± SD or median (with interquartile range), according to variables’ distribution . The Pearson chi-square test was used to compare the number of individuals reporting IBS and FGIDs in between both studied groups. The daily nutrient intake data of energy, water, and FODMAP-containing foods were computed and tabulated. To reduce the effect of implausible extreme values on the analysis, we checked that the ratio of total energy intake determined from the food record to the basal metabolic rate (determined by the Harris-Benedict equation) of each participant was not in the first or the last percentile of the distribution. The dietary data were compared between the control patients and the celiac disease patients by using the independent sample Student’s p = 0.0002) and there was a higher percentage of females in both groups . Both groups were comparable regarding their mean BMI  and daily energy intake  and 2044.7 kcal (329.3)), respectively. When analyzing the prevalence of gastrointestinal symptoms in both groups, we found out that 12% of CD patients suffered from IBS when compared with 6% of the controls (p = 0.09) while 27% of CD patients suffered from FGIDs symptoms  against 22% of controls (p = 0.42). Approximately 10.5% of CD patients did not suffer from either IBS, functional dyspepsia, or functional bloating (Patients in the CD group were older (bloating .p < 0.001) while a higher intake of foods with low FODMAP content was observed in CD patients (p < 0.001). Regarding the dietary intake, a slightly higher total food intake was observed in the CD group, but the energy and water intake were similar between both groups . A highep = 0.0001), high-FODMAP sweets (p = 0.0001), high-FODMAP alcoholic beverages (p = 0.0001), and high-FODMAP fats (p = 0.0447) was observed in the control group when compared to celiac patients. Instead, the CD group consumed significantly higher amount of cereals with low FODMAP content (p = 0.0001), low-FODMAP sweets (p = 0.0001), low-FODMAP sweeteners (p = 0.0099), fruit both high and low in FODMAPs (respectively p = 0.001 and p = 0.0158), and low-FODMAP juices (p = 0.0228). The mean daily intake of the other food categories did not differ between the two groups  while CD patients showed significantly higher consumption of fruits, dried fruits, and vegetables with high FODMAP content (p = 0.003). In addition, other large categories of foods with low FODMAP content were significantly more consumed by the CD patients as compared to the control group , a higher consumption of cereals and sweets with high FODMAP content was present in the control group  levels of them. We recorded all the foods and beverages consumed during a week and then consumed foods that were classified as being high or low in FODMAP content. We used such an approach since the direct measurement of FODMAP content by means of reliable analytical methods in common foods is unavailable yet. As expected, CD patients had a lower intake of cereals and sweets containing high FODMAP levels (including the gluten-containing grains forbidden to celiac patients) as compared to healthy volunteers. Conversely, patients had a higher intake of low FODMAP cereals including cereals allowed in GFD such as rice, corn, and pseudo cereals. Interestingly, a significantly higher intake of fruits (both high and low in FODMAP) was found in the CD patients. Moreover, when all vegetable foods, i.e., fruits, dried fruits, and vegetables were grouped together, we observed a significantly high intake of both categories in CD patients when compared to healthy volunteers. This suggests a greater level of attention about a healthy diet paid by CD patients than controls. However, since cereals contain fructans, fruit and vegetables are two food categories with a high content of FODMAP. This high intake of fruits rich in FODMAP might partly explain the tendency to a higher number of CD patients reporting IBS and FGIDs symptoms when compared to controls. When comparing sweeteners intake, both groups had a comparable low intake of high-FODMAP foods. This suggests that fructose as a sweetener was not commonly used by all the volunteers. In fact, only 12 out of 91 controls and 11 out of 104 CD patients made use of it (data not shown). By contrast, CD patients consumed more low-FODMAP sweeteners such as sugar and aspartame than controls. Lastly, the results suggest that patients with CD did not exclude or limit dairy products with a high content of FODMAP, which shows a pattern similar to that of the control group. Of note, milk and its derivatives provide important nutrients due to its content of vitamins, minerals, and macronutrients essential for the growth, development, and maintenance of tissues . On the Currently, little is known about the level of FODMAP intake in different population groups. Nevertheless, it is of great interest to confirm a potential relationship between specific dietary carbohydrates and gastrointestinal symptoms . FODMAP For the first time, this study evaluated the intake of low or high-FODMAP foods in CD patients affected by IBS and FGIDs symptoms. As limitations, we would like to mention that our results were obtained through food diaries in a seven-day period, which is a period of time that is short and does not allow conclusions about the long-term impact of this dietary pattern. Even though the recording period is short, the participants accurately reported and weighed all the consumed food and beverages. Moreover, in a previous publication on almost the same participants, we compared this tool to a food frequency questionnaire and demonstrated that the two tools were correlated especially in terms of food groups . The stuClinicalTrials.gov, ref. no. NCT01975155.


Varanus) inhabited Europe at least from the early Miocene to the Pleistocene. Their fossil record is limited to about 40 localities that have provided mostly isolated vertebrae. Due to the poor diagnostic value of these fossils, it was recently claimed that all the European species described prior to the 21st century are not taxonomically valid and a new species, Varanus amnhophilis, was erected on the basis of fragmentary material including cranial elements, from the late Miocene of Samos (Greece). We re-examined the type material of Varanus marathonensis Weithofer, 1888, based on material from the late Miocene of Pikermi (Greece), and concluded that it is a valid, diagnosable species. Previously unpublished Iberian material from the Aragonian (middle Miocene) of Abocador de Can Mata  and the Vallesian (late Miocene) of Batallones (Madrid Basin) is clearly referable to the same species on a morphological basis, further enabling to provide an emended diagnosis for this species. Varanus amnhophilis appears to be a junior subjective synonym of V. marathonensis. On the basis of the most complete fossil Varanus skeleton ever described, it has been possible to further resolve the internal phylogeny of this genus by cladistically analyzing 80 taxa coded for 495 morphological and 5729 molecular characters. Varanus marathonensis was a large-sized species distributed at relatively low latitudes in both southwestern and southeastern Europe from at least MN7+8 to MN12. Our cladistic analysis nests V. marathonensis into an eastern clade of Varanus instead of the African clade comprising Varanus griseus, to which it had been related in the past. At least two different Varanus lineages were present in Europe during the Neogene, represented by Varanus mokrensis (early Miocene) and V. marathonensis (middle to late Miocene), respectively.Monitor lizards (genus  Varanus (Varanidae) originated as early as the late Eocene [Varanus amnhophilis Conrad et al., 2012 , Varanus atticus Nopcsa, 1908 ; Varanus deserticolus Bolkay, 1913 ; Varanus hofmanni Roger, 1898 ; Varanus lungui Zerova & Chkhikvadze, 1986 ; Varanus marathonensis Weithofer, 1888 ; Varanus mokrensis Ivanov et al., 2018 ; Varanus semjonovi Zerova & Chkhikvadze, 1986 ; and Varanus tyrasiensis Lungu et al., 1983 . Except for V. amnhophilis, V. marathonensis and V. mokrensis, all the other nominal species are represented by isolated vertebrae only, or by material which is not clearly referable to Varanus.Monitor lizards have a wide current distribution embracing Africa, Asia, and Australia . The cure Eocene  and thate Eocene –6. The Ee Eocene ,7–9. NevVaranus, based on a combined data set of morphologic and molecular data [Varanus vertebrae are diagnostic to species”. Conrad et al. [Varanus species, but such characters just identify species groups, not species. An example is provided by the only unambiguous morphologic synapomorphy that diagnoses a subclade of Varanus: the “presence of strong precondylar constriction of the presacral vertebrae such that a right or acute angle is formed between the condyle and the centrum just anterior to the posterolateral part of the condyle (state 2 of character 233)”  remarkeVaranus erected based on European materials are not diagnosable (this statement predates the description of V. mokrensis). Based on this assumption, Conrad et al. [V. amnhophilis, from the late Miocene locality Q1 of Samos , which  ~7.1 Ma , such maV. amnhophilis overlooked that V. marathonensis, from the late Miocene (MN12) of Pikermi  was est and the Madrid Basin . As briefly anticipated by Delfino et al. [Varanus skeleton ever described, that the species erected by Weithofer [V. amnhophilis. Furthermore, the phylogenetic relationships of this species with other fossil and extant Varanus are evaluated based on a cladistic analysis including both morphologic and molecular data, and the paleobiogeographic history of Neogene European monitor lizards is discussed.In order to provide a solid ground for the study of the European monitor lizards, here we re-evaluate the morphology of the type material of o et al. ,17, we seithofer  is (1) dVaranus species have been studied as comparative material. A complete list of these specimens is given in The studied material includes varanid remains coming from the Miocene of Greece and the Iberian Peninsula. The Greek material is stored in the Institut für Paläontologie der Universität Wien, in Vienna, whereas the Iberian material is stored in the collections of the Institut Català de Paleontologia Miquel Crusafont in Barcelona  and of the Museo Nacional de Ciencias Naturales in Madrid . Further material from Greece that is stored in the National History Museum of Aegean, Mytiliniii, Samos Island, is mentioned in the discussion, even though it is not studied in detail in this paper. More than 200 skeletons of extant Varanus semiremex, which is better resolved in our analysis. The strict consensus tree presents exactly the same topology as in Conrad et al. [We used the matrix of Conrad et al.  to perfod et al. . Conrad d et al.  did not Varanus mokrensis as taken from Ivanov et al. [Varanus marathonensis, named “Vmarathonensis Vamnhophilis”, mainly based on the information provided by the new skeleton from Batallones, but also including the scorings for a few additional characters as provided by the type of Varanus amnhophilis, here considered a synonym of V. marathonensis (see below), for our main analysis . The skeleton from Batallones is considered representative also for the rest of the material assigned to V. marathonensis , given that their scorings are redundant , the last three characters of the matrix were deactivated. These three characters corresponded to the last one in the matrix provided by Conrad , and two new characters added herein. A variation of the same analyses was performed in order to test the influence of the addition of the new characters. The second set of analyses  comprises the same as above, but with the last two morphological characters of the matrix (added in the present work) activated  coding for the fossil v et al. , except t (sensu ) and allated see .The anatomical terminology follows the one used in Conrad’s works ,11. AnatACM, local stratigraphic series of Abocador de Can Mata ; BAT, Cerro de los Batallones ; C2, C3, C4, C5, different cells from ACM .CM, Carnegie Museum of Natural History ; ICP, Institut Català de Paleontologia Miquel Crusafont, Universitat Autònoma de Barcelona ; IPS, ‘Institut de Paleontologia de Sabadell’, acronym of the collections of the ICP; IPUW, Institut für Paläontologie der Universität Wien ; MNCN, Museo Nacional de Ciencias Naturales–CSIC ; SMF, Senckenberg Museum Frankfurt (Germany); ZFMK, Zoologisches Forschungsmuseum Alexander Koenig .The Vallès-Penedès Basin  is a half-graben that originated as a result of the extensional tectonics that started by the earliest Neogene in the Western Mediterranean, due to the northward movement of the African plate –24. The Megacricetodon crusafonti + Democricetodon crusafonti Interval Subzone of the Vallès-Penedès Basin [The Vallès-Penedès Basin has delivered a rich fossil record of terrestrial vertebrates from the early to the late Miocene ,27. The ès Basin ,36), repVaranus material described in this paper comes from BAT-3, which on the basis of micromammalian remains [Cerro de los Batallones  includes a set (BAT-1 to BAT-10) of exceptionally rich paleontological sites of Vallesian age , right maxilla; IPS50292 (from ACM/C3-A6), right maxilla; IPS57544 (from ACM/C3-A7), tooth-bearing bone; IPS42353 (from ACM/C4-C2), trunk vertebra; IPS42362 (from ACM/C4-C2), trunk vertebra; IPS43719 (from ACM/C4-C2), trunk vertebra; IPS57546 (from ACM/C2-A3), trunk vertebra; IPS42400 (from ACM/C4-C2), caudal vertebra; IPS49408 (from ACM/C2-A3), caudal vertebra; IPS42368 (from ACM/C4-C2), caudal vertebra; IPS57547 (from ACM/C2-A3), caudal vertebra; MNCN BAT-3 1088, right and left maxillae, right prefrontal; MNCN BAT-3 2011–200, premaxilla, right and left maxillae, right and left frontals, left lacrimal, right and left prefontals, right supraorbital, right and left postorbitofrontals, parietal, right and left quadrates, parabasisphenoid, supraoccipital, right and left prootics, right and left otooccipitals, basioccipitas, left palatine, left pterygoid; MNCN BAT-3 2011–252, right and left dentaries, right and left coronoids, right surangular, right prearticular, right articular; MNCN BAT-3 2011–148, right coracoid, left humerus, right and left ilia, right and left femura, right and left tibiae; MNCN BAT-3 2011–2626, six cervical vertebrae (axis included); MNCN BAT-3 2011–2627, 20 trunk vertebrae; MNCN BAT-3 2011–2628, last trunk vertebra, two sacral vertebrae, one cloacal vertebra (plus a fragment of a possible second one), first caudal vertebra; MNCN BAT-3 2011–2629, 51 caudal vertebrae and few chevron bones. All the Batallones material except MNCN BAT-3 1088 was found associated and belongs to a single individual.Type locality and age. Pikermi, near Athens (Greece). Geographic coordinates are 38°01’10”N, 23°59’30”E according to the NOW database [database . Accordidatabase , the latdatabase .Age and distribution. Late Miocene (MN12) of Greece . Middle to late Miocene (MN7+8 to MN10) of Spain .Emended diagnosis.Varanus marathonensis differs from all the extant and other fossil Varanus (for which the maxilla is known) by two maxillary autapomorphies: anterior sloping surface of the facial process characterized by a medially directed, very broad and slightly concave lamina, whose medial edge can be ventrally thickened by a ridge in larger specimens; distinct lateral sulcus developed along the narial margin, anteriorly shallow but more evident posteriorly, where it is delimited by ridges. Moreover, it differs because of the following combination of maxillary characters: crista lateralis of the lateral premaxillary process not developed apically; well-developed, high and laminar crista transversalis on the medial anterior maxillary process. Additional characters: nine to 10 slender, mediolaterally flattened, non-molariform maxillary teeth; anterior edge of the facial process gently sloping ).V. marathonensis: 1) Parietal, transverse posterior margin between the supratemporal processes, absent, no transverse posterior margin between the supratemporal processes; 2) Braincase, occipital condyle, single unit made of basioccipital and otooccipitals; U-shaped; 3) Prootic, facial foramen, single; 4) Prootic, accessory anterostapedial process shape, anteroposteriorly elongate tab that is laterally directed; 5) Prefrontal, anterolateral overlap of the frontal, with strong dorsomedial flange partly constricting the exposed frontal margin; 6) Groove on the lateral surface of the maxilla in the anterior sector of the bony narial opening, present; 7) Medial expansion on the anterior sloping edge of the facial process of the maxilla, present, developed on the ascending branch of the process, and well defined posteriorly .The phylogenetic analysis recovered the following unambiguous apomorphies for Varanus marathonensis was introduced in the literature by Weithofer in 1888 [Varanus? Vertèbre qui ressemble à celles des grands varans de l’Afrique”. Such vertebra is still available in the collections of the Muséum national d'Histoire naturelle  with the accession number “MNHN Pikermi n. 31”. Fejérváry [V. marathonensis [V. marathonensis [V. marathonensis and “treated the partial skull separate from the presumed holotypic vertebra because there is no clear reason to associate them”.The name  in 1888 . He desc in 1888 ) two fos in 1888  and figuejérváry  correctlejérváry ) but othhonensis  or refighonensis . More rehonensis  erroneouIPUW 1888-001-001 is a left incomplete maxilla, 39.80 mm long, preserved on a block of hardened reddish sediment along with a few other unidentified bone fragments . The maxWeithofer  also desVaranus marathonensis as topotypes. The three better-preserved vertebrae  of the maxillae analyzed in this study . The eleThe second maxilla IPS50292  is smallIPS57544 is represented by two tooth-bearing bone fragments. The largest corresponds to two tooth positions, the smallest just to one. None of them preserves a complete tooth, but both show the remnants of labiolingually-compressed teeth with longitudinal basal striations. Due to erosion, such striations are well visible, and one of the two teeth of the largest fragment, broken nearly transversally, clearly shows the internal lamellae typical of the plicidentine.None of the available four trunk and four caudal vertebrae  is complCaudal vertebrae  are charThe two fragmentary maxillae from BAT-3 apparently belong to a single individual. The right maxilla BAT-3 1088a  is betteBAT-3 1088b is represented just by a portion of palatal shelf corresponding to eight tooth positions and a little part of the facial process. Just the third preserved position hosts a tooth. None of the characters described above can be discerned on this element.Two unnumbered isolated teeth and about a dozen bone fragments likely belong to these two maxillae.The right prefrontal BAT-3 1088c is a rather well preserved triradiate element . The maiThe nearly complete skeleton from Batallones-3 is represented by at least 119 skeletal elements, originally found close to each other, corresponding to the following collection numbers MNCN BAT-3 2011–200, –252, –148, –2626, –2627, –2628, and –2629.Premaxilla–The premaxillae . The transverse process is rather thick and tall laterally. Its lateral edge is flattened and develops dorsally in a sort of lamina and ventrally in a rounded expansion. The lateral margin of the transverse process is convex, whereas the medial one, hosting the contact facet with the ectopterygoid, is concave. Both the dorsal and ventral surfaces of the main body of the pterygoid are somewhat concave. The edge of the pterygoid between the transverse and the palatine processes is laminar and concave. The posteromedial edge of the transverse process is thicker than the anterolateral one. A distinct ridge runs along the quadrate process, presumably at the ventromedial edge, and the medial surface is weakly concave dorsal to it.reserved , being rEctopterygoid–BAT-3 2011–200r is a right, partially preserved ectopterygoid .frontals  are wellfrontals . This inPostorbitofrontal–Both the right and left elements preserve their anterior portion, which is characterized by the three evident processes: the anterolateral process, the frontal process and the parietal process . MoreovParietal–This unpaired bone is nearly perfectly preserved  and their preserved tips are 33.80 mm from each other, so that the anterior width of the bone is smaller than the posterior one. The processes are directed posterolaterally in dorsal view and slightly ventrally in lateral view. The posterior angle between the processes is about 90°. Their short axis is ventrolaterally directed. They are somewhat rounded dorsally (but not broad or flat) and rather sharp ventrally. The facets for the contact with the supratemporal extend anteriorly at the level of (on the left) or well beyond (on the right) the anterior limit of the processes, and occupy most of their lateral surface. The contact facets at the distal tip of the supratemporal processes are not preserved or visible with confidence, except for the supratemporal facet that could be present on the left process. The ventral surface of the parietal hosts at its lateral edges, anteriorly to the supratemporal processes, the descensus parietalis , a moderately deleveloped crest nearly anteroposteriorly oriented. The fossa parietalis opens posteriorly and is delimited ventrally by a well-developed ridge, the crista juxtafovealis that gives origin to the crista postfovealis, running along the medial surface of the supratemporal processes.Braincase–The braincase is represented by the isolated parabasisphenoid  is smooth and devoid of any sagittal ridge or recess . The basThe sutures between the supraoccipital and the surrounding elements are well visible . This unV. amnhophilis; [Both the prootics preserve the long, anterodorsally and relatively pointed alar process, each distinctly overhanging the relative inferior process . The fenophilis; ). The prThe tip of the right paroccipital process is not complete but the isolated portion of the left one is perfectly preserved and shows that its dorsal and ventral tips extend equally posterolaterally . The venBoth sphenooccipital tubercles are preserved. They are evident but comparatively small and clearly directed ventrally. They are placed at the anteroventral tip of the tuberal crest. The occipital condyle is proportionally strong and very well defined. It is made ventrally by the basioccipital and laterally by the otooccipitals. The general shape is that of a broad U .The tuberal crests  are lateDentary–The two dentaries are isolated and rather well preserved . The right element  opens oCoronoid–Both coronoids are preserved  and by a strong precondylar constriction. The ratio bewteen the minimum precondylar width of the centrum and the maximum condyle width varies, in the four vertebrae that can be measured, from 70.8% to 75.6% . The centrum length is difficult to measure because most of the vertebrae are preserved in connection. Nevertheless, the length of the longest centrum may reach 15.30 mm.A block of vertebrae cemented by matrix . The distal end of the right diapophysis has the shape of a V laying on one side, with the concavity oriented in posterior direction. The dorsal branch of the V is more robust and longer than the ventral one. The second sacral vertebra is better preserved and exposed than the first one. The estimated length of the centrum could reach approximately 15 mm. The diapophyses are slightly bent downward and their distal tip is simply anteroposteriorly elongated. The maximum width at the level of the diapophyses in the second sacral vertebra is of 37.50 mm. Two short longitudinal (following the main axis of the structure) ridges are located at mid length of each diapophyses, close to its posterodorsal and posteroventral edges. At least one vertebra associated to the sacral ones is interpreted as a cloacal vertebra lacking pedestals for chevron bones and synapophyses, but bearing transverse processes. It also lacks lymphapophyses.Nearly all the tail is preserved on a slab where 51 vertebrae can be counted , it forms a trichotomy with the group formed by V. bengalensis + V. nebulosus + V. dumerilii + V. flavescens and the V. salvator complex + V. rudicollis. The majority rule consensus tree  are recovered as sister taxa, suggesting they might represent the same species. Alternatively, this could be interpreted as indicating a high degree of phylogenetic closeness, but still different species. The evidence reported in the present paper (see V. amnhophilis and V. marathonensis in the same position as V. marathonensis (coded as merged: "Vmarathonensis Vamnhophilis") in analysis 1A. In any case, more than 50% of the trees (as reported by the Majority rule consensus tree) support a position inside the Indo-Asian clade, and, more specifically, again as sister to the group formed by V. bengalensis + V. nebulosus + V. dumerilii. The second set of analyses  yielded trees that are two steps longer, but similar in terms of topology and percentage of trees supported in the majority rule consensus trees. A list of the apomorphies recovered for V. marathonensis and the synapomorphies of the clade containing V. marathonensis and the subgenus Indovaranus as well as those of the Varanus clade are given in the supporting information  and Varanus bengalensis , whose maxillae are briefly described below.The recovery of monitor lizards remains in the late Miocene of Pikermi, close to Athens (Greece), was already mentioned by Gaudry , who pruanus sp. ,59,60. Fanus sp.  carefulleithofer  clearly eithofer ), the Ib species ,61–65. Ocies see  confirmscies see , none ofV. griseus (V. marathonensis) in all studied specimens . The concavity, which hosts a lateral expansion of the septomaxilla, is parallel with the medial concavity and ventral folding of the palatal shelf. In the two disarticulated specimens of V. griseus  examined, it is clear that the dorsal lamina is not confluent with the palatal shelf (as in V. marathonensis IPS50119) and that a foramen opens between the medially expanded lamina and the palatal shelf. However, the medially expanded area (posterior to the concavity) is only partly located on the anterior sloping surface of the facial process and is mostly developed on the horizontal surface, anterior to the facial process itself. This is different from the situation in V. marathonensis, in which it develops on the sloping surface. Such widened surface, significantly smaller than in V. marathonensis, develops nearly horizontally (not inclined as in V. marathonensis) and can be slightly concave (an exception being ZFMK 7848). The surface is delimited anteriorly by a variably developed step (located at the level of the fifth tooth position) and frequently also by a lateral ridge, even in the smallest available specimen . An exceptionally developed ridge is present in SMF 74486. In lateral view, the step corresponds to a small dorsal convexity of the upper profile of the maxilla. In ZFMK 7848, this surface is nearly flat on the left maxilla and irregularly concave on the right maxilla, where the bone clearly shows a healed fracture that probably resulted in the depression.The maxilla of  griseus  is long Varanus bengalensis, in turn, has a very peculiar morphology (V. griseus and V. marathonensis). However, the development of such lamina does not reach the extent seen in V. marathonensis and, in dorsal view, there is only a week medial concavity between the lamina and the crista transversalis.rphology . The criVaranus marathonensis Weithofer, 1888 is a taxonomically valid, diagnosable species. Moreover, thanks to the new Iberian material, it is possible to associate other characters to V. marathonensis (see Diagnosis). It is noteworthy that a lateral sulcus in the anterior sector of the narial opening is present. It is a character unknown in any other fossil Varanus species so far described nor in any of the extant Varanus species directly examined during this study  is shown in Varanus rusingensis Clos, 1995 , the maxillary morphology of which is not known in detail, but that is characterized by the presence of blunt posterior teeth [Finally, all the teeth of identine  and are or teeth .V. marathonensis and V. mokrensis are the only European species so far described on the basis of diagnostic remains. Most of the remaining nominal species are either junior synonyms of V. marathonensis or, being based on isolated vertebrae that are not diagnostic at the species rank, best considered nomina dubia .The question remains as to how many monitor species from the Neogene of Europe can be considered valid from a taxonomic viewpoint. Although other eight nominal species have been erected on the basis of European Neogene materials, it is likely that Varanus amnhophilis Conrad et al., 2012 from Samos was anticipated by Conrad et al. [V. marathonensis, and chronological and geographic proximity of the Q1 locality of Samos and Pikermi , Delfino et al. [V. marathonensis before formal erection. However, Conrad et al. [V. marathonensis from its diagnostic cranial type material  and associated it to Gaudry’s non-diagnostic (at least at species level) vertebra. This opened the way to the erection of the new species V. amnhophilis without comparing it with Weithofer’s material and with the European fossil record of V. marathonensis. The diagnosis of V. amnhophilis is non-differential, but based on a combination of apomorphies that we know now are shared with V. marathonensis . Further support for the synonymization of V. amnhophilis with V. marathonensis is provided by additional, still unpublished material from Samos, hosted in the collections of the Natural History Museum of Aegean, Mytilinii, Samos Island. This material, which will be the subject of a forthcoming publication, comes from another locality of the Mytilinii Formation and comprises the anterior region of a skull  is here considered a junior subjective synonym of V. marathonensis Weithofer, 1888. It is worth mentioning that the size of the Samos remains described by Conrad et al. [V. marathonensis from ACM, at least on the basis of the centrum length  of the  species ).Varanus atticus Nopcsa, 1908 was introduced in the literature just to name the vertebra already described and figured by Gaudry [Varanus sp. Nopcsa [Varanus atticus Nopcsa, 1908 is here considered a junior subjective synonym of Varanus marathonensis Weithofer, 1888, as previously concluded by de Fejérváry [y Gaudry  as Varan. Nopcsa , who did. Nopcsa  had alreejérváry , Hoffsteejérváry , and Ragejérváry . Note thVaranus deserticolus Bolkay, 1913 is rather doubtful. It was erected on the basis of a fragmentary dentary with two teeth .omplete,  and Młynomplete, , it actuomplete, , p. 222)omplete, , it is nm. Estes  and MolnVaranus hofmanni Roger, 1898 is represented by vertebrae characterized by a depression, with an angulate posterior end, developed in the anterior region of the neural arch . Thisee also –76). How[Varanus ,10, it iVaranus lungui Zerova & Chkhikvadze, 1986, Varanus semjonovi Zerova & Chkhikvadze, 1986 and Varanus tyrasiensis Lungu, Zerova & Chkhikvadze, 1983 have been summarized and discussed by Molnar [V. tyrasiensis was originally erected was actually variable in the comparative material that they had later at their disposal.The characteristics of the Eastern European species y Molnar  themselvVaranus mokrensis Ivanov et al., 2018 is based on a large collection of both cranial and postcranial elements and, as such, can easily be compared with V. marathonensis. The single autapomorphy of this species, the acute angle between the parietal and squamosal processes of the postorbitofrontal, is absent in V. marathonensis, the processes of which make in contrast a widely obtuse angle. Based on the figured maxilla and on the descriptions given by Ivanov et al. [V. mokrensis, but the lateral sulcus along the narial margin is distinctly absent. Moreover, V. marathonensis differs from V. mokrensis in other significant features, among which: parietal with narrower anterolateral processes , straight anterior margin (convex in V. mokrensis), and a pineal foramen that is closer to the anterior margin; absence of a distinct crest on the base of the paroccipital process as seen in posterior view; slightly less prominent iliac crest on the ilium. Varanus mokrensis is also distinctly smaller in size [V. marathonensis and V. mokrensis as distinct species.The recently described v et al. , it is n in size . AdmitteVaranus catalaunicus  is a nomen dubium. This species was erected by Hoffstetter [Iberovaranus Hoffstetter, 1969 on the basis of an isolated trunk vertebra. However, Delfino et al. [Varanus. Because of this, they synonymized Iberovaranus with Varanus. The vertebral material described by Hoffstetter [V. catalaunicus as a nomen dubium. Nevertheless, it is interesting to note that the size of the holotypic vertebra of V. catalaunicus is strongly smaller than the largest trunk vertebrae of V. marathonensis (10.60 mm contra 18.36 mm), approaching the vertebral size of a medium-sized monitor lizard like the roughly coeval V. mokrensis from the Czech Republic.fstetter  within to et al.  later defstetter  and Delffstetter  is not sfstetter  view in V. marathonensis and V. mokrensis currently seem to be the only taxonomically valid European species of monitor lizard, the other nominal taxa previously erected from the European Neogene being either junior synonyms  of the former, or nomina dubia. However, the only remains clearly referable to V. marathonensis are those represented at least by maxillae or sharing with V. marathonensis a significant portion of cranial characters, i.e., those from Pikermi (Greece), Abocador de Can Mata , Batallones-3 , and Samos (Greece). The referral to V. marathonensis of very fragmentary cranial elements, isolated vertebrae, or sections of vertebral columns from the early Pliocene of Csarnóta 1 . Identified as V. marathonensis by Morelli [To sum up, Hungary; ) and ÇalHungary; ) should  Morelli , it is c Morelli .Varanus, including the extinct Varanus priscus , the internal phylogeny of the genus is still unclear [Even though there is a general morphology- and molecule-based consensus on the monophyly of  unclear ,58,81,82 unclear , grouped unclear ,64. Comb unclear ).V. griseus, a species with a geographic range that currently approaches Europe, including also the southern and eastern Mediterranean countries [Varanus marathonensis in the same clade as V. griseus, along with another extinct species, Varanus darevskii Levshakova, 1986, from the Pliocene of Tadjiikistan.Such unstable phylogeny seriously hampers deciphering the phylogenetic relationships between European fossil monitor lizards and extant taxa. A priori, it would be expected to find close relationships between the European taxa and the clade of the African forms , which countries ,85. Actuountries  proposedV. amnhophilis in the Indo-Asian A clade and what they considered to be the type of V. marathonensis  nested into the Australasian clade. The cranial material that actually represents the lectotype of V. marathonensis (labeled ‘Varanus’ cf. marathonensis in their tree) fell well outside of crown Varanus (probably related to the large amount of missing data). Based on their phylogenetic results, Conrad et al. [Varanus as a whole and Asian affinities for the European species. These hypotheses seemed to be confirmed by the phylogenetic analysis of Ivanov et al. [V. mokrensis was found as a member of the Indo-Asian A clade but is basal to African varanids, including the extinct V. rusingensis from the early Miocene of Kenya. All these analyses found V. amnhophilis and V. marathonensis  to be phylogenetically well apart.Conrad et al.  recovered et al.  suggestev et al. , in whicV. amnhophilis, and the position of the clade composed by them inside the Indo-Asian A clade is rather stable. More specifically, a sister group relationship with the clade formed by V. dumerilii, V. bengalensis, and V. nebulosus is well supported. Regarding V. mokrensis, it is invariably recovered as the most basal non-African taxon, sister to the group formed by the Indo-Asian B, Indo-Asian A and Indo-Australian groups . This would strongly suggest that European Varanus include at least two different lineages: one would be represented by V. mokrensis; the other one would be represented by, according to our results, V. marathonensis.Problems arising from the inclusion of fragmentary remains in phylogenetic analyses based on large datasets have been already stressed . As expV. mokrensis is different from that recovered by Ivanov et al. [V. mokrensis that were not scored by Ivanov et al. [Varanus mytilini and Varanus amnhophilis, when the former actually was the name for V. amnhophilis in Conrad et al.’s [The position recovered here for v et al. . Howeverv et al. ; and 5) et al.’s  matrix, Varanus is one of the most debated issues concerning the evolution of varanid lizards [Varanus [Varanus taxa in molecular phylogenies [The historical biogeography of  lizards ,87. The [Varanus  could sulogenies ,88. Howelogenies ), as applogenies , 11. Smilogenies  also disVaranus nor the alternative hypothesis of an African origin for the genus. The sister taxon to Varanus recovered in most of the recent phylogenetic analyses, including the one we are presenting here and that performed by Conrad et al. [Saniwa ensidens, from the Eocene of North America. The roughly coeval European Saniwa orsmaelensis was not included in the phylogenetic analysis but Saniwa went extinct in Europe at the end of the Eocene [Varanus appears in the European fossil record only in the early Miocene [Varanus.It has to be noted, however, that our phylogenetic analysis is neither supporting a Eurasian origin for d et al. , is Sanie Eocene , whereas Miocene . The fac Miocene  does notVaranus clade is composed by African taxa. Thus, an African origin of Varanus cannot be discounted. However, the position we recovered for V. mokrensis  is at odds with the ancestral condition inferred by Ivanov et al. [Varanus. Our cladistic analysis recovered V. mokrensis and V. marathonensis as belonging to two different lineages without a direct ancestor-descendant relationship, thus suggesting that a different geographic origin for the two valid European Varanus species may be possible.Moreover, in both our analysis and in Conrad et al.’s , the mosv et al.  for the v et al. , and theVaranus, Rage [Varanus species from the Neogene of Europe  indicate a possible link with an Indo-Asian clade of Varanus. This fits with the hypothesis of a Eurasian origin of the genus. The presence of a Varanus of Asian origin in the European Neogene agrees well with other, well-documented dispersal events of the herpetofauna from Asia into Europe , from the MN7+8  in Spain to the MN12  in Greece, suggests that many of the available European Miocene Varanus remains might belong to this species. Regardless, although Varanus marathonensis was distributed at relatively low latitudes in both Western and Eastern Europe from the MN7+8 to the MN12, it emerges that the genus Varanus displayed a greater chronological and geographic distribution in this continent when all the European record is taken into account.Although, on the basis of available diagnostic material, the presence of Varanus in Central Europe corresponds to the late Miocene, whereas in Southern Europe it survived until the Middle Pleistocene [Varanus material. It would be interesting to test whether the post-Miocene material, especially the Quaternary one, belongs to V. marathonensis, testifying its prolonged permanence in at least the southern part of Europe, or whether it represents a dispersal of other species, more closely related to extant taxa. In the case of the last occurrence of a varanid in Europe , an attrphology .Varanus almost reached the 49th parallel  between MN4 and MN10, i.e. for an extended period of time broadly encompassing the Mid-Miocene Climatic Optimum [Varanus corresponds to an unspecified site in the area of Moreda , wh, Spain; ,108–113.Varanus marathonensis Weithofer, 1888, originally erected on the basis of late Miocene material from Pikermi (Greece), is currently one of the two only European Varanus species that can be considered taxonomically valid. The other is V. mokrensis from the early Miocene of the Czech Republic. The revision of the syntype of V. marathonensis  allowed us to confirm the presence of a character already originally described by Weithofer [Varanus. The description of previously unpublished conspecific materials, including maxillae, from the latest middle Miocene stratigraphic series of Abocador de Can Mata  as well as from the late Miocene of Cerro de los Batallones , confirms the validity of V. marathonensis and implements the diagnosis of this taxon with the inclusion of several new characters. The majority of the remains from Cerro de los Batallones 3 can be referred to a single individual that, being represented by nearly all the skeletal elements, is the most complete Varanus skeleton ever described in the world.eithofer , which hV. marathonensis could be sought in an eastern clade of Varanus instead of the African clade comprising V. griseus, to which it had been related in the past. Regardless of its phylogenetic relationships, our results indicate that V. marathonensis was distributed both in Western and Eastern Europe at least for about 5 Myr, from the middle to the late Miocene, whereas on the whole the genus Varanus inhabited Europe at least from the early Miocene to the late Miocene in Central Europe, further persisting until the Middle Pleistocene in Southern Europe. Due to such a wide geographic and chronological range of V. marathonensis, most of the European fossils of Varanus may belong to this species, at least as far as the Neogene occurrences are concerned. Therefore, comparisons with this taxon are required before erecting additional extinct European species of Varanus in the future. Nevertheless, the presence in Europe of a second valid species, V. mokrensis, in the early Miocene and of remains not clearly attributable to V. marathonensis in the Middle Pleistocene demonstrate that other species were indeed represented in the continent.The phylogenetic relationships of S1 File(PDF)Click here for additional data file.S2 File(PDF)Click here for additional data file.S3 File(NEX)Click here for additional data file.S4 File(PDF)Click here for additional data file.S5 File(PDF)Click here for additional data file.S6 File(PDF)Click here for additional data file.S7 File(PDF)Click here for additional data file.


Background: The Roma population is one of the major marginalized groups in Europe, having higher incidence of all spectrums of disease and a shorter life expectancy. Yet, the reasons for higher morbidity and its exact prevalence were not properly studied. Objectives: The objective of our study was to compare the frequency of metabolic syndrome (MetS) in Roma people to the non-Roma population in Slovakia, and to compare levels of uric acid and its correlation with components of metabolic syndrome. Methods: A group of 452 Roma people aged 18–55 years, was compared to a control group of 403 non-Roma people. The data were obtained by questionnaire, anthropometric measures, and analyzed blood and urine samples Results: The prevalence of MetS was significantly higher among Roma participants  compared with non-Roma participants , p = 0.001. Roma people significantly more often fulfilled obesity and low high-density lipoprotein (HDL) criteria of MetS . There was no difference in the triacylglycerols (TG), glycemia or blood pressure (BP) criteria of MetS. The Roma also presented with greater levels of high sensitivity C-reactive protein (hs-CRP). Baseline levels of uric acid (UA) among the Roma population were significantly lower compared with the majority population (226.54 ± 79.8 vs. 259.11 ± 84.53) (p < 0.001). The levels of UA significantly correlated with fulfilled criteria of MetS. Univariate regression showed that UA is a significant predictor of MetS in the whole cohort (unadjusted odds ratio (OR) 1.005; 95% CI 1.004–1.007; p < 0.0001) also after the adjustment for age, sex, and ethnicity . Conclusions: We were able to show that prevalence of MetS among the Roma is higher than in the majority population. Moreover, the uric acid levels are significantly lower in the Roma group as well as when it comes to a cohort with MetS. Levels of UA, besides others, depend on ethnicity, age, and sex. Because the Roma population is one of the major ethnic minority populations in Europe, its health-related issues should be studied carefully. Mainly because past studies suggest that this marginalized group suffers from an increased prevalence of contagious and non-contagious illnesses in the community, and importantly, a shorter life expectancy than the national averages. The intentions of authorities across Europe to solve these health inequalities have been relatively poor ,2 and, iSerum uric acid is a final enzymatic product of purine metabolism in humans. It is suggested that the increased levels of uric acid are linked with metabolic syndrome (MetS), and they may have a common pathophysiology . In addiObesity, dyslipidemia, hypertension, and insulin resistance are a group of risk factors that define metabolic syndrome . When thThe aim of this study was to determine the prevalence of metabolic syndrome in the Roma population compared with the non-Roma population in the eastern part of Slovakia, and to determine the levels of uric acid and its correlation to metabolic syndrome components and other variables in the same population sample.Data from the cross-sectional population-based HepaMeta study conducted in Slovakia in 2011 were used. The aim of the project was to explore the health, health related behavior, social and economic parameters, and health care accessibility in Roma people in segregated settlements and to compare it to the non-Roma population. All subjects gave their informed consent for inclusion before they participated in the study. The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of the Faculty of Medicine at Šafárik University in Košice (no. 104/2011). Participation in the study was fully voluntary and anonymous.Out of 710 selected non-Roma people, 403 chose to participate (response rate 56.8%). The sample consisted of 452 Roma people  aged 18–55 and 403 non-Roma people  aged 18–55. The Roma in selected settlements were recruited by local Roma community workers. Respondents from the majority population were randomly selected from a list of patients from general practitioners (GP’s). The data were collected via questionnaire, anthropometric measures, and blood sample analyses after an overnight fasting. The samples were collected and modified  at a biochemical laboratory of the Department of Medical and Clinical Biochemistry and LABMED, Faculty of Medicine, P. J. Šafárik University, Košice.Clinical biochemistry tests for determination substrates were as follows: cystatin C (cysC), creatinine, minerals (serum iron level [Fe]), proteins (ferritin and high sensitivity C-reactive protein [hs-CRP] as a risk factor), enzymes , glucose, uric acid (UA), and lipid parameters . All of the biochemical parameters were determined by routine biochemical methods on analyzer ADVIA 2400 or 1650. Ferritin was measured by chemiluminescent immunoassay (CLIA) on analyzer ADVIA Centaur . The methodology is described in detail elsewhere .2) plus any two of the four following factors were present: raised TG ≥1.7 mmol/L (150 mg/dL) or specific treatment for this lipid abnormality; reduced HDL-C <1.03 mmol/L (40 mg/dL) in males and <1.29 mmol/L (50 mg/dL) in females, or specific treatment for these lipid abnormalities; raised systolic blood pressure ≥130 mmHg or diastolic blood pressure ≥85 mmHg, or treatment of previously diagnosed hypertension; raised fasting plasma glucose ≥5.6 mmol/L (100 mg/dL), or previously diagnosed type 2 diabetes. Blood pressure (BP) was taken using the Omron M3 digital automatic blood pressure monitor after 5 min of rest in a sitting position. The mean value of three blood pressure measurements was used in the analysis. The limit for the normal systolic blood pressure was <130 mmHg or normal diastolic blood pressure <85 mmHg.The International Diabetes Federation standard criteria were used for the determination of metabolic syndrome (MetS) . The patThe medical history data were taken from the participants’ records in the GP’s office. The social and economic data were obtained through questionnaires and were self-reported by the participants. The Roma participants answered the questionnaires with the help of research assistants, and the non-Roma people answered the questionnaires individually, but help was provided upon request. The obtained information were as follows: employment (binary), any current smoking (binary), more than six standard drinks of alcohol per month (binary), imprisonment (binary), physical activity more than once per week (binary), education classified into three categories , and poverty (binary), which was an aggregate variable that contained the inability to pay one item of the following: rent, loan payment, healthcare, and energies and other expenses.t-test in the case of two groups, and the ANOVA or Kruskall–Wallis test with post-hoc Tukey HSD in the case of a multiple group comparison, while respecting the tests’ presumptions. The only variables tested as nonparametric were AST, ALT, GGT, and hsCRP.The categorical data are presented as absolute and relative counts. The interval data is presented as mean ± standard error of mean. Additionally, due to the easier visual comparison, non-parametric interval variables are presented as mean and standard errors of means (SEM), because of the sufficient number of participants. The statistical significance of differences between the categorical data was assessed by the chi-square test. The differences in the interval variables were tested by After baseline comparisons, we used the Pearson correlation to evaluate the correlation between UA and other biochemical parameters. The Pearson correlation was used also to evaluate the collinearity of the predictors in the multivariate regression, where we used the correlation coefficient cut-off of 0.7 to flag significant collinearity.Lastly, we performed a multivariate logistic regression with MetS as the dependent variable, to explore the independent predictive value of the potentially significant variables from previous analyses.Since this was an exploratory study, no prior power analysis was performed. The post hoc power analysis for the difference in MetS prevalence between the Roma and non-Roma revealed a power of 91.4%.All of the statistical analyses were performed by SPSS statistical package .p = 0.001. The Roma people significantly more often fulfilled obesity and a low HDL criteria of MetS . There was no difference in the TG, glycemia, or BP criteria of MetS. In this observational study, we examined a total of 442 Roma participants and 399 non-Roma participants (missing data for 10 participants in the Roma and 4 participants from the non-Roma group to categorize the presence of MetS). Prevalence of MetS was significantly higher among the Roma participants  compared with the non-Roma , The Roma population representatives were slightly but significantly older and included less men. Among the basic biochemical characteristics, the Roma people had lower levels of creatinine, UA, and hepatic enzymes activity . Also, the Fe levels were importantly lower in the Roma population. Despite having a significantly greater BMI, the Roma people statistically differed in lower levels of TCH, ApoA, and HDL. On the other hand, they presented with greater levels of hs-CRP. Surprisingly, there was no difference in the baseline glucose, TG, and LDL levels among both of the studied populations. They also did not differ in waist to hip ratio (WHR) and BP. Socioeconomic variables were significantly more prevalent among the Roma population—they reported a higher incidence of poverty, more smoking, and lower incidence of all levels of education. The occupational status was also lower among Roma. Physical activity and imprisonment was importantly more frequent among the Roma.The differences among the four categories  are summarized in The post hoc analysis shows significant differences between the Roma and non-Roma participants in both the MetS positive and negative groups. Glycemia was higher in the participants with MetS, regardless of ethnicity. Uric acid levels were significantly increased in both the Roma and non-Roma participants with MetS, but were overall higher in the non-Roma group. AST activity was higher in the non-Roma group overall, but no difference in the MetS status was observed. ALT activity was higher in MetS group, only in the non-Roma. GMT activity was higher in the MetS group both in the Roma and non-Roma participants. Creatinine was increased in the MetS group, only in the non-Roma participants. The serum level of albumin was decreased only in the non-Roma with MetS, and no difference was observed in the Roma. Both creatinine and cystatin C were higher in the MetS group only in the non-Roma, and no difference was observed among the Roma participants. As expected, all of the lipid parameters were significantly different between the MetS positive and negative patients in both the Roma and non-Roma. High sensitivity CRP levels were significantly increased in the MetS group, both in the Roma and non-Roma, but in the Roma with MetS they were even higher than the non-Roma with MetS. The serum iron levels were decreased, and the ferritin levels were increased in the MetS group both in the Roma and non-Roma.The Roma participants with MetS were older than the non-Roma counterparts, but there was no age difference between the Roma and non-Roma without MetS. Also, no difference in gender was observed between the MetS positive and negative groups. As expected, people with MetS had a higher BMI, and the Roma with MetS had an even higher BMI compared with the non-Roma with MetS. There was no difference in the BMI between the Roma and non-Roma without MetS. However, no difference was observed in the WHR whatsoever. Both the systolic and diastolic blood pressure were increased in all of the people with MetS, but the diastolic blood pressure was also higher in the non-Roma without MetS, compared with their Roma counterparts.There was no difference in employment, alcohol consumption, smoking, or physical activity between the MetS positive and negative Roma, as well as the non-Roma. However, both the Roma and non-Roma who had MetS were more often impoverished. Furthermore, the non-Roma who were less educated had a higher prevalence of MetS, but this was not observed in the Roma participants.p < 0.0001). The Roma ethnicity increased the UA level in multivariate linear regression by 0.163; the female sex decreases the level of UA by 0.438 and age increases level of UA by 0.092. Levels of UA, besides others, depend on ethnicity, age, and sex, which are independent from each other and all together predict 23.5% of the UA variability.The baseline levels of UA among the Roma population were significantly lower compared with the majority population (226.54 ± 79.8 vs. 259.11 ± 84.53) . There was also a weak direct correlation between the UA and age in the Roma but not non-Roma.We observed a significant difference in the UA between the sexes in both the Roma and non-Roma participants  also after the adjustment for age, sex, and ethnicity . The fully adjusted multivariate model . Also, the Fe levels were importantly lower in the Roma population. Despite having a significantly greater BMI, the Roma people failed to reach significant differences in WHR and BP. Moreover, they had lower levels of TCH, ApoA, and HDL, all pointing towards cardiovascular risk factors. Surprisingly, there was no difference in the baseline glucose, TG, and LDL levels among both of the studied populations. On the contrary, the Roma presented with greater levels of hs-CRP. The baseline levels of UA were lower in the Roma representatives. Such a phenomenon may be a result of a genetic background showing a higher frequency of pulation . Physicap < 0.0001). No difference in gender was observed between the MetS positive and negative groups. Glycemia as one of the MetS determinants was higher in participants with MetS (5.4 and 5.16 vs. 4.61 and 4.74), regardless of ethnicity. Uric acid levels were significantly increased in both the Roma and non-Roma participants with MetS (251.61 vs. 303.64) but were overall higher in the non-Roma group. The GMT activity was higher in the MetS group both in the Roma and non-Roma participants. This is probably attributed to non-alcoholic fatty liver disease, as NAFLD is the hepatic manifestation of metabolic syndrome. The serum level of albumin was decreased only in the non-Roma with MetS, and no difference was observed in the Roma. Another potential novel biomarker associated with MetS and obesity are cystatinC and creatinine levels. Both were studied by a group, Ying X et al., who revealed that the CysC was more closely associated with the presence of MetS, as compared with serum creatinine or eGFRCKD-EPI. CysC was positively correlated with BMI, and more strongly and positively correlated with waist circumference and inflammation in their study [Within the population described in this study, the prevalence of MetS was significantly higher among the Roma participants compared with the non-Roma. In the Hungarian environment, a more than 50% incidence of MetS in the Roma population was reported . This reir study . Our datir study . HDL is ir study . In our ir study . High seir study . As expeir study . The preir study .Higher serum uric acid levels are a common laboratory result in patients with metabolic syndrome/obesity, hypertension, kidney disease, and cardiovascular events. Moreover, recent analysis suggests that the high-fructose diet in the United States, as one of the causes of hyperuricemia, may be contributing to the metabolic syndrome/obesity epidemic, diabetes, hypertension, kidney disease, and cardiovascular disorder ,35. Basep < 0.0001; non-Roma males 304 ± 6.2 vs. females 220 ± 4.2 μmol/L; p < 0.0001). There was also a weak direct correlation between UA and age in the Roma, but not the non-Roma. Serum uric acid levels in our study were importantly higher in the subjects with MetS and were significantly correlated with the fulfilled criteria of MetS, except from a HDL level. There was also a significant trend toward the increase of uric acid levels with the number of fulfilled MetS criteria. This finding is in agreement with some other results [Gender differences of UA are well accepted phenomenon. We observed significant difference in the UA between the sexes in both the Roma and non-Roma participants , also after the adjustment for age, sex, and ethnicity . Uric acid remains a significant and independent predictor of MetS in the whole cohort, after excluding the variables defining MetS. The odds of MetS were also increased by age, male sex, elevation of GMT, hsCRP, total cholesterol, and the decrease of ApoA. Poverty was almost a significant predictor of MetS in this model. Interestingly, the Roma ethnicity was not a significant predictor of MetS in this model, along with serum iron and ferritin.Univariate regression showed that UA is a significant predictor of MetS in the whole cohort (unadjusted OR 1.005; 95% CI 1.004–1.007; The strengths of our study are the inclusion of a high number of participants randomly selected from the Roma and non-Roma population, inclusion of marginalized Roma people with high barriers to health care, and a thorough examination of the socio-economic background. Its limitations are the cross-sectional design, which limited us from evaluating the relationship between UA and MetS, its components, and the clinical outcomes longitudinally.Recommendations for practice would be as follows—UA is a routinely available and relatively cheap test that could provide helpful information in the management of patients with metabolic syndrome. However, this test is underused in this indication. Speaking in terms of research—the question remains open if UA is only a marker or a significant causal factor in MetS, therefore further research is needed on the mechanisms connecting the increased levels of UA with MetS and cardiovascular outcomes, and the effects of UA lowering therapy on MetS compensation or cardiovascular outcomes.As the socioeconomic determinants of health have become better understood over the past decade, it is becoming clear that societies with greater inequalities are less healthy overall. We were able to show that the prevalence of MetS with all its consequences among the Roma people in Slovakia is higher than in majority population of the country. Moreover, one of the biochemical determinants of MetS, uric acid levels, are significantly lower in the Roma group, but when it comes to cohort with MetS, its levels are also significantly lower compared with the non-Roma group. The levels of UA, besides others, depend on ethnicity, age, and sex, which are independent from each other. Whether UA is a bystander or a central-role player in the pathogenesis of various diseases should be clarified in future studies.