Aims: Based on important predictors, global functional outcome after traumatic brain injury (TBI) may vary significantly over time. This study sought to: (1) describe changes in the Glasgow Outcome Scale–Extended (GOSE) score in survivors of moderate to severe TBI, (2) examine longitudinal GOSE trajectories up to 10 years after injury, and (3) investigate predictors of these trajectories based on socio-demographic and injury characteristics.Methods: Socio-demographic and injury characteristics of 97 TBI survivors aged 16–55 years were recorded at baseline. GOSE was used as a measure of TBI-related global outcome and assessed at 1-, 2-, 5-, and 10-year follow-ups. Hierarchical linear models were used to examine global outcomes over time and whether those outcomes could be predicted by: time, time*time, sex, age, partner relationship status, education, employment pre-injury, occupation, cause of injury, acute Glasgow Coma Scale score, length of post-traumatic amnesia (PTA), CT findings, and Injury Severity Score (ISS), as well as the interactions between each of the significant predictors and time*time.Results: Between 5- and 10-year follow-ups, 37% had deteriorated, 7% had improved, and 56% showed no change in global outcome. Better GOSE trajectories were predicted by male gender (p = 0.013), younger age (p = 0.012), employment at admission (p = 0.012), white collar occupation (p = 0.014), and shorter PTA length (p = 0.001). The time*time*occupation type interaction effect (p = 0.001) identified different trajectory slopes between survivors in white and blue collar occupations. The time*time*PTA interaction effect (p = 0.023) identified a more marked increase and subsequent decrease in functional level among survivors with longer PTA duration.Conclusion: A larger proportion of survivors experienced deterioration in GOSE scores over time, supporting the concept of TBI as a chronic health condition. Younger age, pre-injury employment, and shorter PTA duration are important prognostic factors for better long-term global outcomes, supporting the existing literature, whereas male gender and white collar occupation are vaguer as prognostic factors. This information suggests that more intensive and tailored rehabilitation programs may be required to counteract a negative global outcome development in survivors with predicted worse outcome and to meet their long-term changing needs. Traumatic brain injury (TBI) remains one of the main causes of life years lost due to disability or death , 2. WorlThe level of disability and global neurological functional outcome following TBI is commonly measured with the Glasgow Outcome Scale (GOS) or its extended version (GOSE) , 6. BothThus far, only a few studies have assessed GOSE trajectories over longer periods after TBI . Corrigan and Hammond  examinedThere is increasing evidence for the factors that predict functional outcome after TBI; age , 18–26, Our research group has published GOSE score trajectories up to 5 years after moderate to severe TBI . The preTo describe GOSE score changes up to 10 years after injury.To assess the trajectories of global functioning in people with moderate to severe TBI at 1, 2, 5, and 10 years post-injury.To investigate whether socio-demographics and injury severity characteristics can predict the trajectories of global functioning.The specific study aims were:Based on results from our previous follow-up studies in the first 5 years  and 10–2The inclusion criteria were: (a) age 16–55 years, (b) admission with ICD-10 diagnosis S06.0-S06.9 within 24 h of injury, (c) moderate to severe TBI, classified by an acute GCS score of 3–12 (The exclusion criteria were: (a) previous neurological disorders/injuries, (b) associated spinal cord injuries, (c) previously diagnosed severe psychiatric or substance abuse disorders, and (d) unknown address or incarceration.The present study is a longitudinal cohort consisting of individuals with TBI who were admitted to the Trauma Referral Centre for the Southeast region of Norway from 2005 to 2007. The participants were assessed in the acute phase (baseline) and followed up at 1, 2, 5, and 10 years after injury.  of 3–12  at admisn = 97), with an attrition rate of 21% from the 1–10-year follow-up. A series of papers on functional outcome and health-related quality of life have previously been published based upon the same longitudinal cohort  or medians with interquartile range (IQR) as appropriate. GOSE score changes over time were also examined with descriptive statistics.n = 97). A conditional (null) model was run first to determine whether there was sufficiently large clustering of GOSE score variance within participants to proceed with HLM. Unconditional growth (linear), quadratic, and cubic models were then run without predictors to determine the most accurate model for linear or polynomial architecture of GOSE scores over time.Hierarchical linear models (HLMs) were used to assess the trajectory of global function and examine baseline predictors of GOSE trajectory architecture across 1, 2, 5, and 10 years after injury. Full information maximum likelihood (FIML) estimation was used for handling missing data at the follow-ups, thus retaining all participants in the model . The first full model used a HLM to determine whether quadratic trajectories of GOSE scores across the four time points could be predicted by the socio-demographic and injury characteristics of time , time*time, sex , age, partner relationship status , education, employment at time of injury , occupation type , GCS score, cause of injury , length of PTA (days), CT severity score, and ISS. A final HLM included the previously significant predictors from the first full model, time, time*time, and the interaction terms between time*time and the previously significant predictors.Once the most accurate curvature model was identified, predictors were entered simultaneously as fixed effects into a HLM after being centered or given a reference point of 0, along with time and timeThe mean age of the 97 participants at the time of injury was 30.3 years (SD = 10.8); 78% of the participants were male. The mean GCS score at hospital admission was 7.2 (SD = 3.2); the mean PTA was 26 days (SD = 30). The mean ISS score was 30.0 (SD = 13.6). Two-thirds of the participants had severe TBI according to GCS score, whereas about half of the participants were classified as having more severe intracranial injury according to the CT head Marshall Score. At time of injury, 83% of the participants were employed and 53% had white collar occupations. n = 28), more than one-third had a dynamic GOSE score change between the time points. When only looking at GOSE score changes between the 1- and 10-year follow-up, 26% of participants had increased one, two, or three GOSE categories in terms of function, 36% showed no change, whereas 38% decreased one to two categories (data not shown).In total, of the 77 participants with GOSE data at both 1- and 10-year follow-up, 77% had changed GOSE scores between follow-ups . Of those with the same GOSE score at 1 and 10 years , and a statistically significant estimated residual variance of 0.83 . The intraclass correlation coefficient was 0.57, indicating that approximately 57% of the total variance of GOSE scores was associated with participant grouping and that the assumption of independence was violated. This suggests there was sufficiently large clustering of GOSE score variance within participants to proceed with a HLM. The unconditional model was then run separately with the successive additions time, quadratic time, and cubic time to determine the shape of the best-fitting curve of the GOSE over time . Younger participants had higher GOSE quadratic trajectories than older participants (p = 0.012). Participants who had been employed at time of injury had higher GOSE quadratic trajectories than those who had been unemployed (p = 0.012). Participants in a white collar profession had higher GOSE quadratic trajectories than those in a blue collar profession (p = 0.014). Finally, participants with a shorter PTA length had higher GOSE quadratic trajectories than those with a longer PTA duration (p = 0.001).The full HLM examined whether socio-demographic and injury characteristics at baseline could predict the quadratic trajectories of GOSE scores over time. an women  , 42% of participants showed no change in GOSE score, whereas 24% improved one or two categories, and 34% deteriorated one or two categories. Compared to the present study, Corrigan and Hammond found a smaller proportion of participants with no change and a higher proportion of participants with improvement. However, similar to our results, a larger proportion of the survivors tended to experience deterioration in GOSE scores over time, supporting the concept of TBI as a chronic health condition , where the GOSE score from 1 year to 12–14 years improved in 34% of survivors, remained the same in 32%, and worsened in 34%. These results are in line with our results from the 1 to 10-year follow-ups. However, they found that 23% of participants improved between the 5–7- and 12–14-year follow-ups, which is a much higher proportion compared to our study (7% from 5 to 10-year follow-up). Methodological differences between the two studies probably contributed to this discrepancy, where the study by McMillan have a high risk of selection bias due to significant drop out over time . In addition, a higher proportion of survivors with positive change can be expected in a study sample that included mild TBI. Andersson et al.  had the largest negative change in GOSE scores from the 1- to 10-year follow-up. Our previous study on self-reported healthcare needs in survivors of moderate to severe TBI  found thBased on our previous studies , 17, we We found that TBI survivors who were male, younger, employed at time of injury, in a white collar occupation and with a shorter PTA duration , had significantly higher global functioning across 1, 2, 5, and 10 years after moderate to severe TBI. Thus, the results are in agreement with our hypothesis.Contrary to previous long-term studies , 19 and The present study has several limitations that should be acknowledged when interpreting the results. The inclusion criteria included survivors of moderate to severe TBI and aged 16–55 years; therefore, the results cannot be readily generalized to individuals with mild TBI or to individuals outside this age range. The participants were recruited through the Trauma Referral Centre and represent a mixed population with regards to the type and extent of inpatient rehabilitation received, and should therefore be representative of a broader range of patients than, for example, those in the TBIMS studies. Previous studies have hypothesized that trajectories of disability in elderly populations (aged >65 years) could differ from that of younger adult survivors of TBI , but we The present study sample is small, and over time there has been an inevitable loss to follow-up. However, the attrition rate of 21% in the 1–10-year follow-up is low compared to that of other studies . The desTo sum up, further research is needed to verify the present study findings, preferentially through international collaboration to establish standardized research methodology and thereby generalizable knowledge on long-term functional outcome following TBI. This can for example be accomplished through multinational clinical TBI trials. Future studies should also incorporate a broader set of variables, such as physical, psychological, and cognitive functioning; personal traits; use of healthcare and rehabilitation services; as well as psychosocial support and lifestyle factors.This study aids understanding of the natural history of recovery following moderate to severe TBI by highlighting the trajectories of global functioning from the 1-year to 10-year follow-up, and examining predictors of better GOSE outcomes. The results suggests that more intensive and tailored rehabilitation programs may be required to counteract a negative global outcome development in survivors of older age, those unemployed at the time of injury and those with a longer PTA duration, as well as to address the long-term changing needs of this population.The dataset for this study will not be made publicly available. The dataset is not anonymous and cannot be shared publicly according to the Norwegian law on research ethics and medical research. The dataset can be reviewed on the grounds of Oslo University Hospital upon request, if considered appropriate and approved by the Regional Committees for Medical and Health Research Ethics (REC).The present study was conducted in accordance with the recommendations of the Norwegian law on research ethics and medical research. The protocol was approved by the Regional Committee for Medical and Health Research Ethics, East Norway, and the Norwegian Data Inspectorate. All subjects gave written informed consent in accordance with the Declaration of Helsinki.MF, CR, SS, and NA contributed to the study design, data acquisition, analysis, interpretation, drafting, and finalizing of the manuscript. PP contributed to the analysis, interpretation, drafting, and finalizing of the manuscript. TH, SB, JL, and JA-L contributed to the data interpretation, drafting, and finalizing of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The study aimed to investigate the mechanism of the effect of Compound Tufuling Granules (CTG) to lower the serum uric acid level in a rat model of hyperuricemia. The rat model was established by administering hypoxanthine through oral gavage and potassium oxonate through intraperitoneal injection. Rats were divided into the normal group, model group, CTG group, and allopurinol group. Serum uric acid, creatinine, urea nitrogen, and inflammatory cytokine levels were determined in each group. In the model group, ultrahigh performance liquid chromatography-mass spectrometry was used to analyze the metabolic profiles and delineate the action mechanism of CTG; in addition, the orthogonal projection method was used to perform latent structure-discrimination analysis to screen the related metabolites. The results indicated significant differences in the metabolic profiles between the model and normal groups. A total of seven related metabolites were identified through screening in the model group, mainly related to the pathways of bile secretion, pyrimidine, purine, and phenylalanine metabolism, pantothenate and CoA biosynthesis, and pentose and glucuronate interconversions; these related pathways were reversed in the CTG group. In the metabolic networks, uracil and acetyl-coenzyme A were the nodal molecules. In addition, the test results of the evaluation of serum biochemical and inflammatory factors confirmed that CTG had significant effect in reducing the levels of serum uric acid and protecting renal function. These results confirmed that CTG primarily regulated the recruitment of nodal molecules to achieve anti-inflammatory effects, reduced uric acid level, and renal protection. Hyperuricemia is characterized by persistent increase in the uric acid level in the circulating blood. Oversaturated uric acid in the body may be due to increased uric acid synthesis or decreased excretion, which is the most important factor in the onset of gout , 2. In aAt present, the uric acid lowering drugs are mainly classified into two major categories: inhibitors of uric acid production and promoters of uric acid excretion. The drugs that inhibit the production of uric acid mainly include allopurinol and febuxostat, and the main drugs that promote its excretion include benzbromarone and probenecid. Due to their serious side effects, such as serious allergic reactions and rashes caused by allopurinol, the drugs that promote excretion have higher requirement for adequate renal function, with exacerbation under combined usage, which limits the use of these drugs, especially in patients with asymptomatic hyperuricemia , 10.Ther Rhizoma Smilacis Glabrae, Rhizoma Dioscoreae Hypoglaucae, Pseudobulbus Cremastrae Seu Pleiones, Radix Achyranthis Bidentatae, and Semen Vaccariae, which has the functions of clearing heat and dampness and activating blood circulation to relieve pain. Previous studies have shown that it lowers the level of uric acid, preventing the recurrence of gout and suppressing the expression of inflammatory factors [As an effective alternative treatment method, traditional Chinese medicine (TCM) has advantages in the treatment of patients with gout and hyperuricemia. Compound Tufuling Granules (CTG) is one of the representative treatments using TCM , 12. It  factors , 14. HowMetabolomics is the study of changes in metabolites produced by biological systems  after they have been stimulated. Small molecules are its target research objective, including their production and metabolism as end result of a series of events; therefore, metabolomics defines the state of biological systems more accurately , 15, 16.α and IL-1β were determined using ELISA method, and for the purpose of serum metabolome study, HPLC-MS was used. The first aim was to elucidate the abnormal metabolic mechanism of hyperuricemia, and the second aim was to identify the relevant specific metabolic markers of uric acid metabolic pathway and other possible metabolic pathways in rats undergoing treatment with CTG, which will enable early diagnosis of patients with hyperuricemia.In this study, oral hypoxanthine and intraperitoneal injection of potassium oxonate were used to establish the hyperuricemia rat model; the rats were divided into the normal group (N), model group (M), CTG group (Fa), and allopurinol group (B) (positive control group). In each group, the serum creatinine (Scr), serum uric acid (SUA), and blood urea nitrogen (BUN) levels were determined using biochemical tests; the levels of inflammatory cytokines TNF-α and IL-1β from Beijing Cheng Lin Biological Technology Co., Ltd ; and methanol, chloroform, formic acid, L-2-chlorobenzene alanine, and acetonitrile from Shanghai Heng Chuang Biological Technology Co., Ltd. In addition, we used the following equipment: ultrasonic cell pulverizer and ultrasonic cleaning machine ; vortex ; high speed refrigerated centrifuge ; and UPLC (ACQUITY UPLC I-Class), High resolution mass spectrometry (VION IMS Q-Tof), and chromatographic column (ACQUITY UPLC BEH C18)  from Voight World Science and Technology Co., Ltd. (Waters) .For the purpose of study, 97% oxonic acid potassium salt and 99% hypoxanthine were purchased from Sigma ; soluble starch from Shanghai Macklin Biochemical Science and Technology Co., Ltd. ; ELISA kits for TNF- Rhizoma Smilacis Glabrae, Rhizoma Dioscoreae Hypoglaucae, Pseudobulbus Cremastrae Seu Pleiones, Radix Achyranthis Bidentatae, and Semen Vaccariae . The blood sample (3 ml) was collected from the abdominal aorta, placed in a red tube (non-anticoagulation tube), allowed to stand at room temperature for 30 minutes, and centrifuged at 3000 rpm for 20 minutes; the obtained serum was sent to the General Hospital of Guangzhou Military Region for laboratory tests including SUA, Scr, and BUN detection. The remaining supernatant was collected for use in ELISA for TNF-μl)  was added to serum (100 μl) and the solution was mixed by vortexing for 10 s; subsequently, methanol-acetonitrile (300 μl)  was added followed by vortexing for 1 min. Extraction was performed in an ice water bath, and the sample was maintained at -20°C for 30 min; centrifugation was performed at 13,000 rpm for 15 min using a 0.22 μm organic phase pinhole filter to obtain filtrate  which was transferred to the liquid chromatography injection vial. The quality control sample (QC) was prepared by mixing equal volume of the extracts of all samples, to obtain the same volume as that of the sample.The internal standard ; solvent, the column was maintained at 45°C and separation was achieved using the following gradient: one to 30% B over 0–1 min, 30–60% B over 1–2.5 min, 60–90% B over 2.5–6.5 min, and 90–100% B over 6.5–8.5 min; the composition was held at 100 % B for 2.2 min, followed by 10.7–10.8 min, 100% to 1% B, and 10.8–13 min holding at 1% B at flow rate of 0.40 ml/min, where B is acetonitrile/methanol 2/3 (v/v)(0.1% (v/v) formic acid) and A is aqueous formic acid (0.1% (v/v) formic acid). Injection volume was 1 μl and the column temperature was set at 45°C.UPLC conditions are as follows: column, ACQUITY BEHC18 column  source operating in either positive or negative ion mode. The capillary voltages, DP, and CE were 2.5 kV, 40 V, and 6 eV, respectively. Source temperature and desolvation temperature were set at 115°C and 450°C, respectively, with desolvation gas flow at 900 l/h. Centroid data was collected from 50 to 1,000 m/z with scan time of 0.2 s and interscan delay of 0.02 s over a 13-min analysis time-period. The QCs were injected at regular intervals (every 10 samples) throughout the analytical run to provide the data set used for repeatability assessment.The acquired UPLC-MS raw data were analyzed using the Progenesis QI software  with the following parameters: precursor tolerance of 5 ppm, fragment tolerance of 10 ppm, and retention time (RT) tolerance of 0.02 min. Internal standard detection parameters were deselected for peak RT alignment, isotopic peaks were excluded from the analysis, noise elimination level was set at 10.00, and minimum intensity was set to 15% of base peak intensity. The excel file with three-dimension data sets was obtained, including m/z, peak RT, and peak intensities; RT–m/z pairs were used as the identifier for each ion. The resulting matrix was further reduced by removing any peaks with missing value (ion intensity=0) in more than 60 % samples. The positive and negative data were combined to obtain a combined data set, which was imported into the SIMCA software . Principal components analysis (PCA) and orthogonal partial least-squares-discriminant analysis (OPLS-DA) were conducted to visualize the metabolic alterations among the experimental groups. Variable importance in the projection (VIP) ranks the overall contribution of each variable to the OPLS-DA model, and those variables with VIP > 1 are considered as relevant for group discrimination. Other data were analyzed using one-way ANOVA followed by the least significant difference (LSD) test. All statistical analyses were performed using SPSS version 20.0 . The results were assumed to be statistically significant at P<0.05.http://www.kegg.jp [The related metabolites were identified as follows: First, potential metabolites were separated in the loading scatter plot of OPLS-DA (the N and M group). Second, the related metabolites were further screened by limiting VIP (VIP > 1) and performing Student's t-test (p<0.05). The information of these metabolites was obtained through searches conducted in the Kyoto encyclopedia of genes and genomes (.kegg.jp ) and HMDα, and IL-1β in the M group were significantly elevated (p<0.05). Compared with the M group, the levels of SUA, Scr, BUN, TNF-α, and IL-1β in the Fa and B groups were lower than those in the M group (p<0.05), without significant difference between the Fa and B groups (p>0.05). These results indicated that the Fa group had reduced level of uric acid, improved renal function, and anti-inflammatory effects.As shown in In all samples, the UPLC-MS method was used to detect the base peak ion current (BPI); the instrument analyses were characterized by strong signal, large peak capacity, and good reproducibility of retention time Figures . In the First, PCA was used to analyze rats in the N and M groups. In the PCA model, there were significant differences between the N and M groups , indicating that the model was reliable . To obta (p<0.05). Compared with the model, CTG reduced the expression level of galactonic acid, pantothenic acid, orotidine, orotic acid, uric acid, and phenylpyruvic acid to varying degree and increased that of chenodeoxycholic acid ( (p <0.05).For purpose of identifying potential drug-treatment target, we established a new PCA model including seven different metabolites. Compared with the model, the B and Fa groups were more similar to the N group , indicatlic acid   is another nodal molecule in the pathways of bile secretion, pantothenate and CoA biosynthesis, and phenylalanine metabolism. In metabolic networks , the corHyperuricemia is closely related to the occurrence of gout, as well as several metabolic diseases such as obesity, diabetes, and hyperlipidemia. Allopurinol inhibits both the synthesis and metabolism of uric acid. By inhibiting xanthine oxidase, it prevents the conversion of hypoxanthine and xanthine to uric acid, thereby reducing the concentration of uric acid in the blood. Previous studies using the rat model of hyperuricemia have shown that CTG inhibited xanthine hydrogenase activity (XO) and xanthine oxidase (XDH) mRNA expression in the liver and anti-inflammation, promoted uric acid excretion by regulating the expression of miR-34a and miR-146a, and inhibited URAT1 and GLUT9 mRNA transcription and protein expression , 26. Howβ, a key cytokine of gout, can act on many cell types to initiate inflammatory responses, whereas TNF-α, a type of macrophage and pro-inflammatory cytokines produced by monocytes, participates in the inflammatory response of gout. Moreover, studies have confirmed that elevated levels of IL-1β and TNF-α can be detected in the blood of rats with gout and those of the hyperuricemia model [ Rhizoma Smilacis Glabrae has the functions of clearing heat and detoxication and promotion of blood flow of the joints and kidney. The main function of Radix Achyranthis Bidentatae is to replenish qi, activate blood circulation, and promote water and uric acid excretion. Rhizoma Dioscoreae Hypoglaucae has the function of dispelling wind and removing dampness and diuresis. Semen Vaccariae has the function of promoting blood circulation and removing blood stasis, promoting metabolism, and improving microcirculation. Colchicine is the active ingredient of Pseudobulbus Cremastrae Seu Pleiones, which significantly reduced the inflammatory reaction [β, and TNF-α were significantly increased in the rat model, while those in the Fa group were significantly lower, indicating that CTG can reduce the level of uric acid through anti-inflammatory action and improving the renal function.Increased synthesis or decreased excretion of uric acid in the body can lead to the occurrence of hyperuricemia. Therefore, currently, animal models of hyperuricemia are established using mainly in vitro xanthine/hypoxanthine infusion and in vivo inhibition of the uricase activity , 19. In ia model , 28. CTGreaction , 25, 26.In clinical studies, the diagnosis of hyperuricemia is based on the SUA level alone, which limits early detection; therefore, identifying significant related metabolites is crucial. In our study, results of screening indicated seven metabolites, mainly related to bile secretion, pyrimidine, purine, and phenylalanine metabolism, pantothenate and CoA biosynthesis, and pentose and glucuronate interconversions.β-glycosylase in the intestine. Galactose for anabolism can be produced from uridine diphosphate glucose (UDPG) in the absence of food substrate. It can be found in dairy products, and plant mucin and bacterial polysaccharides, which is the component of lactose in mammalian milk [In metabolic networks, galactonic acid is the product of pentose and glucuronate interconversion through the oxidation of hydroxy groups in galactose to form shuttle groups. Galactose is a type of monosaccharide that can be catalyzed by ian milk . More imian milk , 31. In Uric acid is the final metabolic product of purine, one of the most important components of DNA and RNA. Purine is decomposed into uric acid through a series of catalytic reactions; in some animals, under the effect of uricase, it is further decomposed to allantoin and urea through association with the pyrimidine metabolism via uracil . PyrimidPhenylpyruvic acid is a dicarbonyl compound, a product of phenylalanine metabolism. Phenylalanine is an essential amino acid, comprising mostly of tyrosine catalyzed by phenylalanine hydroxylase, and is involved in the synthesis of important neurotransmitters and hormones together with tyrosine as part of the body's glucose and lipid metabolism. Under physiological conditions, only a small proportion of phenylalanine is converted to phenylpyruvic acid under the action of aminotransferases. In case of decreased or lost phenylalanine hydroxylase activity, a large amount of phenylpyruvic acid is generated, which may lead to phenylketonuria, affecting brain development, causing mental retardation and nervous system symptoms such as microcephaly and convulsions. Jiang and Liu reported that both hyperuricemia and gout were associated with the phenylalanine metabolism , 16. In Chenodeoxycholic acid (CDCA) is closely related to cholesterol. The combination of CDCA with glycine or taurine in the liver can inhibit the cholesterol synthesis, increase the bile secretion in patients with gallstone disease, and be used to treat cholesterol gallstone disease. Previous studies have shown that CDCA has a wide range of effects on the lipid metabolism; hence, it may be associated with the onset of hyperuricemia and gout . In our β-alanine, which is an acyl transporter and participates in the metabolism process, regulating energy and fat metabolism [In our study, pantothenate and CoA biosynthesis was second core of the hyperuricemia metabolic networks. Pantothenic acid, also known as vitamin B5, is one of the 13 essential vitamins in humans. It consists of pantoic acid and tabolism . Acetyl-tabolism , whereasAmong the metabolic diseases such as hypertension, diabetes, obesity, and hyperlipidemia, hyperuricemia is an independent risk factor for several other metabolic diseases. Studies have demonstrated involvement of other inflammatory factors in their pathogenesis. CTG contains Pseudobulbus Cremastrae Seu Pleiones, whose effective ingredient is colchicine, and can significantly reduce inflammation. It is likely that CTG may regulate the metabolism of carbohydrates, amino acids, lipids, vitamins, purines, and pyrimidines to achieve anti-inflammatory effects, reduced uric acid levels, and renal protection.α and IL-1β were evaluated; the result of serum metabonomics study through UPLC-MS indicated total seven related metabolites including chenodeoxycholic acid, orotic acid, orotidine, uric acid, phenylpyruvic acid, pantothenic acid, and galactonic acid. Hyperuricemia is mainly associated with metabolism of cholesterol, amino acid, lipids, vitamin, and glucose. By regulating the bile secretion, pyrimidine, purine, and phenylalanine metabolism, pantothenate and CoA biosynthesis, and pentose and glucuronate interconversions pathways at various degrees, CTG showed effectiveness to achieve anti-inflammation, lowered level of uric acid in the blood, and protection of the renal function.In this study, the hyperuricemia rat model was successfully prepared by means of oral gavage of hypoxanthine and intraperitoneal injection of oxonic acid potassium for 10 consecutive days. The levels of SUA, Scr, BUN, and inflammatory cytokines such as TNF-


Though several epidemiological surveys of psychiatric disorders have been carried out in China, only a few of them are concerned about the prevalence of psychiatric disorders in central Hunan and reveal the distribution of common psychiatric disorders and their comorbidities.Achenbach’s Child Behavior Checklist (CBCL), the Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID), and Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) were administered to a stratified sample of 17,071 participants aged 6 to 16 years old from two cities in the central part of Hunan province. Twelve-month prevalence rates were calculated.Twelve-month prevalence of the population was 9.74%. The most common psychiatric disorders were attention deficit hyperactivity disorder (ADHD) (4.96%), oppositional defiant disorder (ODD) (2.98%) and generalized anxiety disorder (GAD) (1.77%). Of those with a 12-month prevalence diagnosis, 34.6% had one or more comorbid psychiatric disorders. Most notably, ADHD had comorbidity rates of 25.15% with ODD, 18.18% with CD, 6.38% with GAD, and 3.66% with MDD.Psychiatric disorders are common in Chinese children and adolescents. Being the most prevalent mental disorder, ADHD requires continued focus and support in awareness and education.The online version of this article (10.1186/s12888-018-1823-7) contains supplementary material, which is available to authorized users. Studies focusing on mental disorders of children and adolescents have increased in recent decades . The effHunan province is located in South China, with an area of 21.18 million square kilometers, accounting for 2.2% of China’s land area. It consists of 13 cities and 1 autonomous prefecture, with an overall population of 67.8 million in 2015. Two cities located in the central part of Hunan province, Changsha (population of 7 million) and Yiyang (population of 4.8 million), were selected for the study. The sample size of this study was based on the sample size of the national investigation of psychiatric disorder in China held by Beijing Anding Hospital, which was originally supposed to be 14,000. However, our study included 17,000 participants to ensure that we can obtain an adequate number in case of participation refusal. Thirteen schools, including two urban middle schools, four urban primary schools, three rural middle schools, and four rural primary schools, were selected at random. Approximately 18,778 students were enrolled, of which 17,071 participants (90.9%) gave consent to participate. Of the eligible participants, 782 refused or did not complete their questionnaire, and of those who completed, 522 contained missing data (over 10% incomplete on the questionnaire), and 403 were outside the age range. This was a two-stage study that used Achenbach’s Child Behavior Checklist (CBCL) as a screening tool, the Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID), and the DSM-IV criteria to establish the final diagnosis. Questionnaires were sent to the students, and they brought the scale home for their parents to fill. Of the 17,071 qualified participants who completed the questionnaires, 13,606 participants scored negative to diagnosis, and 3465 scored positive, hinting a potential diagnosis of a disorder. Ten percent of the students with negative scores were selected randomly as controls. All of the 3465 participants with positive scores were given a full diagnostic interview using the MINI-KID  (parent and child versions). For those participants whose parents were unable to perform the diagnostic interview, the teachers were interviewed as alternative informants. Each interview lasted 15–40 min. For any participant with at least one diagnosis or a suspected diagnosis – based on either the parent or the child version of the MINI-KID – a diagnosis would be confirmed using the DSM-IV criteria. Through this procedure, 1663 participants were verified as having a diagnosis of at least one mental health disorder  enrolled students aged 6–16 years; 2) whose parents or guardians have given consent to participate; and 3) who had been living in the investigated sites for at least six months with household municipal registration. Exclusion criteria included the following: 1) informed consent not obtained, 2) students in special schools or not attending school, or 3) students could not be located after at least three attempts to visit at different times. The research protocol was approved by the Ethics Committee of the Second Xiangya Hospital, Central South University, China.The CBCL is a parent−/caregiver-completed questionnaire that assesses behavioral problems, emotional difficulties, and social competencies of a child. This standardized and objective measurement tool has been revised and widely used by child psychiatrists, pediatricians, developmental psychologists, and other mental health professionals for clinical and research purposes . The ChiThe MINI-KID is a guided structured interview that assesses psychiatric disorders based on the DSM-IV and ICD-10 in children and adolescents aged 6 to 17 years in a comprehensive and concise way. Both the parent and child participated in the interview, although it can also be administered solely to the children themselves . The MINχ2) test. All statistical tests were two tailed, with 0.05 as the significance level.Data analyses were performed using SPSS version 18. To estimate the prevalence rate of mental health disorders and comorbidity, frequencies and 95% confidence intervals were calculated. Differences in the prevalence of mental health disorders between different genders and age groups were assessed using the Chi-square  in boys was significantly higher than that (7.55%) in girls (Attention deficit hyperactivity disorder (ADHD) ranked the highest with a prevalence of 4.96%, followed by oppositional defiant disorder (ODD) at 2.98%, generalized anxiety disorder (GAD) at 1.77%, and conduct disorder (CD) at 1.39%. Boys showed a significantly higher prevalence than girls in terms of ADHD, ODD, and CD, whereas girls showed a higher prevalence in terms of GAD and major depressive disorder (MDD). Participants aged ≤11 years showed the highest prevalence in ADHD, CD, and ODD  was within the range of 3.5–40.3% as reported previously 4% was wi. The preThe prevalence of psychiatric disorder was lower than the pooled prevalence of 13.4%. The prevalence of GAD, MDD, and CD was also lower than the pooled prevalence of each kind of disorder reported in a meta-analysis, which indicated a prevalence of 6.5% (anxiety disorder), 2.6% (depressive disorder), and 5.7% (disruptive disorder). By contrast, ADHD was higher than the pooled prevalence of ADHD. One explanation for this perhaps would be that the prevalence rate reported in the meta-analysis study included all types of depressive and anxiety symptoms, whereas our study reported on the prevalence of GAD and MDD. Another reason would be the pressure from public discrimination and stigmatization because Chinese individuals feel ashamed to disclose affective symptoms . FurtherThe prevalence of psychiatric disorders is 9.7% among children and adolescents in our study was lower than the prevalence reported in 2005. There are several reasons contributing to this phenomenon. Firstly, the diagnostic tool is different; in 2005, the diagnostic tool used was Kiddie Schedule for Affective Disorders and Schizophrenia Present and Lifetime Version (K-SADS-PL), and in this study, we used MINI-KID as the diagnostic tool. Secondly, the prevalence of 16.2% reported in 2005 included more psychiatric disorders than this study. In addition to the psychiatric disorders included in MINI-KID, their study also included acute stress disorder, communication disorder , sleep disorders , elimination disorders (including encopresis and enuresis), and elective mutism. This broader spectrum of disorders may have resulted in a higher prevalence. Thirdly, though psychiatric disorders remained prevalent, given the rapid economic growth in China, mental health services were improved , and sevThe current study shows significant gender differences, i.e., prevalence of ADHD, ODD, and CD in boys was higher than that in girls, which is consistent with other studies , 48. VarWe also found that girls tend to suffer from GAD and MDD, which is consistent with previous findings . When coOur study found that ADHD is the most common comorbid disorder, which is consistent with previous findings . Our stu, and a comorbidity rate of 18.8% with CD, which is slightly lower than the rate of 20% reported by Biederman [Disruptive behavior disorders including ODD and CD remain the most common comorbid disorders; our study reported a comorbidity rate of 25.15% with ODD, which lies in the range of 20~ 60% as reported by other studies , 64, andiederman . Reiff aiederman  have proiederman , 67. Seciederman .Our study reported a comorbidity rate of 12.64% in anxiety disorders , which was higher than the rate reported in Denmark , and lieThe strengths of this study included the use of the two-stage method, standardized diagnostic tool, and large sample size. However, this study has several limitations. First, only students enrolled in mainstream schools were included, and children in special schools or who did not go to school were not included. Thus, the findings cannot represent all children and adolescents. Second, we failed to record the number of children with a diagnosis from the MINI-KID but did not meet the criteria of DSM-IV. We considered the diagnosis only made from both the MINI-KID and the DSM-IV criteria. Third, the prevalence of pervasive developmental health disorder was relatively low due to the use of the MINI-KID. The MINI-KID consists of four brief questions on the child’s social skills, repetitive interests, and behaviors. Finally, autism spectrum disorder (ASD) is a significant mental health disorder that we did not examine in this study. Future studies should examine the prevalence and distribution of ASD.Our study revealed that nearly one tenth of Chinese children and adolescents suffer from at least one type of mental health disorder, with a higher prevalence in boys than in girls. Early diagnosis and intervention can help young children when they are most vulnerable to minimize or overcome mental health disorders as they grow older. Over the course of childhood, for those who have a diagnosis, caregivers should be aware of comorbid disorder(s) – either present or potential – and take preventive measures and perform early screening. Doing so can detect underlying or emerging disorders early and help to alleviate a difficult transition into adolescence and adulthood.Additional file 1:Demarcation and total scores for subscales of behavior problem. The Additional file


Background and objectives: This study evaluated the effect of chronic consumption of saccharin on important physiological and biochemical parameters in rats. Materials and Methods: Male Wistar rats were used in this study and were divided into four groups: A control group and three experimental groups  were treated with different doses of saccharin at 2.5, 5, and 10 mg/kg, respectively. Each experimental group received sodium saccharin once per day for 120 days while the control group was treated with distilled water only. In addition to the evaluation of body weight, blood samples  and urine (isoprostane) were collected in zero time, and after 60 and 120 days for biochemical evaluation. Liver  and brain  tissues were collected at time zero and after 120 days. Results: The data showed that saccharin at 5 mg/kg increased body weight of treated rats after 60 (59%) and 120 (67%) days of treatment. Increased concentration of serum glucose was observed after treatment with saccharin at 5 (75% and 62%) and 10 mg/kg (43% and 40%) following 60 and 120 days, respectively. The concentration of albumin decreased after treatment with saccharin at 2.5 (34% and 36%), 5 (39% and 34%), and 10 mg/kg (15% and 21%) after 60 and 120 days of treatment, respectively. The activity of LDH and uric acid increased proportionally with dosage levels and consumption period. There was an increased concentration of creatinine after treatment with saccharin at 2.5 (125% and 68%), 5 (114% and 45%), and 10 mg/kg (26% and 31%) following 60 and 120 days, respectively. Catalase activity and 8-OHdG increased by 51% and 49%, respectively, following 120 days of treatment with saccharin at 2.5 mg/kg. Elevation in the concentration of isoprostane was observed after treatment with saccharin at all doses. Conclusions: The administration of saccharin throughout the treatment period was correlated with impaired kidney and liver function. Both hyperglycemic and obesity-inducing side effects were observed. There was an increased oxidative status of the liver, as well as exposure to increased oxidative stress demonstrated through the increased levels of isoprostane, uric acid, 8-OHdG, and activity of catalase. Therefore, it is suggested that saccharin is unsafe to be included in the diet. The use of non-nutritive artificial sweeteners (NAS) in place of nutritive sweeteners such as sugar is recommended as a way of reducing overall carbohydrate and calorie intake . PatientSaccharin -one-1,1-dioxide) see  is the oSaccharin is a water-soluble acid with a pKa of 1.8. Its absorption is increased in animal species with lower stomach pH, such as rabbits and humans, relative to other mammals with higher stomach pHs such as rats ,7,8. OthSaccharin, in addition to being used as a table-top sweetener, is commonly used in soft drinks, baked foods, jams, canned fruit, candy, dessert toppings, and chewing gum . Since sUnlike glucose and sucrose, saccharin cannot be metabolized by the body . SaccharSince saccharin is not metabolized and does not produce food energy, it has become an important sweetener, especially for diabetics . The affThe Food and Drug Administration (FDA) and the Federal Agency of the United States Department of Health and Human Services (DHHS) consider saccharin to be a safe sweetener .The Joint Food and Agriculture Organization/World Health Organization Expert Committee on Food Additives (JECFA), European Union, US FDA, Japan, France, China, and Taiwan established an acceptable daily intake (ADI) of saccharin at 5 mg/kg body weight .Saccharin and toxicity are arguable. Throughout the 1960s, various studies suggested that saccharin might be an animal carcinogen . Yilmaz A few epidemiological studies also found relationships between saccharin and bladder cancer risk in humans ,18,19,20Saccharin consumption has been associated with adverse effects on most of the biochemical and hematological blood indices in rats . ChronicSaccharin may induce oxidative stress on the liver cells through lowering catalase activity and the total antioxidant concentration (TAC) in plasma . It was Different methodologies have been applied to assess oxidative stress in animal models and humans. DNA bases are highly susceptible to reactive oxygen species (ROS) oxidation. The predominant detectable DNA oxidation product in vivo is 8-hydroxy-2′-deoxyguanosine (8-OHdG). 8-OHdG was established as sensitive marker of DNA damage, becoming a very important biomarker for processes such us carcinogenesis, aging, and degenerative diseases ,31.During the process of lipid peroxidation, a number of compounds are formed including alkanes, malondialdehyde, and isoprostanes, which are used as markers in lipid peroxidation assay . The disDue to the increasing demand for the use of non-nutritive artificial sweeteners as a tool to control the level of blood glucose and body weight, and due to uncertain and little information on the safety of using saccharin as a sweetener, the present study was set to analyze the effect of long-term consumption of saccharin on biochemical parameters when increasingly large doses are administered.60 male Wistar rats (3–4 months), weighing 250–325 g, were housed in the animal house of the College of Veterinary Medicine - University of Duhok. These animals were kept in ventilated cages at a controlled temperature (22 ± 2°C) and were exposed to cycles of light and dark. Food and water were given ad libitum. Rat handling and treatment were according to guidelines for laboratory animal care and use . The stuSodium saccharin was purchased from Alfa Aesar Thermo Fisher Scientific, Germany. Colorimetric assay kits from Biolabo (France) were used to measure the concentration of glucose, total cholesterol (TC), high density lipoprotein , low density lipoprotein , triglycerides (TG), total protein (TP), serum albumin, uric acid, creatinine, activity of the enzymes lactate dehydrogenase (LDH), aspartate transaminase (AST), and alanine aminotransaminase (ALT). The activity of serum catalase was assayed according to Hadwan and Abeds (2016) . UrinaryRats were randomly distributed into four groups, with 15 rats in each group. For the experiment baseline (time zero), five rats from each group were euthanized to remove their brain and liver. The remaining rats (40) were grouped as follows: control group comprised 10 rats and were treated with distilled water. Experimental groups 1, 2, and 3 were of 10 rats each and were treated with sodium saccharine dissolved in water at 2.5, 5, and 10 mg/kg of body weight, respectively. The doses were chosen based on acceptable daily intake (ADI) (5mg/kg). All the treatments were given orally via gavage once a day over 120 days.Blood samples (3 ml) were collected in vivo from the orbital venous plexus  of the tTo evaluate the adverse effects of saccharin on biochemical alterations in blood and tissues, enzymatic methods were applied to measure the serum level of glucose , TC 39]39], and Total protein concentration was determined by the Biuret method . Serum aSerum creatinine level was assayed according to Jaffe’s method using alkaline picrate reagent  and the Finally, for lipid peroxidation, and to detect DNA oxidation in response to toxicity of saccharine, isoprostane and 8-OHDG levels were determined by double-sandwich ELISA method described by Morrow et al. (1990)  and Souzp < 0.05. Values were expressed as mean ± standard error of the mean (SEM) of rats (n = 10) per group.All data were analyzed by one-way analysis of variance (ANOVA). Specific differences between the groups were determined using the Duncan multiple range test . The accTo determine the effect of the saccharin consumption on body weight and blood glucose, different doses of saccharin were given to the rat groups compared to the control. The observed data are shown in The effects of saccharin consumption on lipid profile was detected and the data revealed that TC was decreased after 60 (21% and 22%) and 120 days (22% and 20%) when saccharin was given at 5 and 10 mg/kg, respectively, compared to the control group . SimilarThe effect of saccharin intake at 2.5, 5 and 10 mg/kg from time zero to 60 and 120 days on total protein and albumin levels are shown in The effect of two different doses of saccharin on ALT in treated rats was detected and the observed data revealed a significant increase in the activity of ALT in the treated groups with saccharin at 5 mg/kg  and 10 mg/kg  after 60 days in comparison with the control group (39.3 ± 0.77 IU/L). The activity of ALT returned to normal levels after 120 days of treatment with saccharin at 2.5 and 5 mg/kg. However, after treatment with saccharin at 10 mg/kg, the activity of ALT increased  without returning to normal compared to the control group (41.32 ± 0.76 IU/L) b. The acSerum creatinine, uric acid, LDH, and urinary isoprostane were also investigated in saccharin-treated groups, and the recorded data revealed a significant increase in the level of serum creatinine at 2.5 (125% and 68%), 5 (114% and 45%), and 10 mg/kg (26% and 31%) of saccharin-treated groups after 60 and after 120 days, respectively. The concentration of uric acid also increased after treatment with 2.5 (63% and 119%), 5 (132% and 106%), and 10 mg/kg (183% and 160%) after 60 and 120 days of treatment, respectively. LDH activity increased after treatment with saccharin at 2.5 (344% and 159%), 5 (373% and 263%), and 10 mg/kg (354% and 189%) after 60 and 120 days, respectively. Urinary isoprostane levels increased after treatment with saccharin at 2.5 (647% and 621%), 5 (539% and 1095%), and 10 mg/kg (620% and 675%) after 60 and 120 days, respectively. The uric acid and creatinine data are shown in The activity of liver catalase tested in treated groups and the data revealed increases of liver catalase after 120 days of saccharin at 2.5 mg/kg  treatment compared to the control group (54.05 ± 1.73 kU/g) a. Finally, the recorded concentrations of 8-OHdG are shown in Recently, concerns have been raised about the safety of artificial low-calorie sweeteners that are commonly used as substitutes for sucrose in many diet products. Studies have revealed that the use of artificial sweeteners may present some risks to users like migraines, headaches, skin eruptions, muscle dysfunction, depression, weight gain, liver and kidney toxicity, multiple sclerosis, blurred vision, respiratory problems, cancers, allergies, seizures, and immune system dysfunction ,53.Little was known about the toxicity of the artificial sweeteners, therefore, the present study was designed to give a better understanding about the toxicity of saccharin, particularly the mechanisms leading to dyslipidemia, glucose homeostasis impairment, oxidative stress, hepatotoxicity, and kidney dysfunction. The adverse effects of saccharin on biochemical alterations in blood and tissues of rats treated with different doses of sodium saccharine were analyzed for 120 days.The recorded data found a correlation between the consumption of sodium saccharin and the risk of obesity; administration of 5 mg/kg and 10 mg/kg of sodium saccharin greatly increased body weight after 60 and 120 days. It is believed that the increases within the body weight were due to glucose intolerance in treated groups, where artificial sweeteners including saccharin, sucralose, and aspartame were found to induce microbial communities in the digestive system . Sweetness, when not accompanied by calories, results in ambiguous psychobiological signals that bewilder the body’s regulatory mechanisms, leading to a loss of control over appetite and overeating ,56. As aSwithers and Davidson in their study stated that sweet tastes normally indicate that the body is about to receive a high number of calories, and the digestive system prepares to react accordingly. When sweet tastes are not followed by the expected number of calories, which happens with sweeteners including saccharin, the body becomes conditioned against the expected response to the calories received . The present study recorded increases in blood glucose that were observed in dose-dependent saccharin-treated groups. These data are in line with those described by Prokić et al. (2015). Moreover, it has been reported that sweeteners cause a cephalic phase insulin release that decreases blood glucose levels ,62,63,64The effects of saccharin consumption on lipid profile were also evaluated in this study. The concentrations of TC, TG, and LDL- and HDL-cholesterol were decreased in response to oral treatment with sodium saccharin and were observed after 60 and 120 days of treatment compared to the control group. These findings reflect the conclusion found in previous studies ,64,66.The reductions within the lipid profile could be due to the indirect action of saccharin on the lipid metabolism and on lipid peroxidation, which has been previously observed . It has The hypocholesterolemic and hypolipidemic effect found in the present study could perhaps be attributed to a reduced total cholesterol biosynthesis. Since it is known that saccharin can suppress liver enzymatic activity in vivo, the activity of acetyl-CoA synthetase and citrate lyase could be reduced by the consumption of saccharin. Besides the concentration of mitochondrial citrate, these effects would lead to a reduction of available cytoplasmic acetyl-CoA, a precursor for the synthesis of cholesterol and fatty acids ,70. MoreThe effect of oral consumpation of saccharin at 5 mg/kg and 10 mg/kg on ALT activity was detected and the data found ALT activity increased after 60 days and 120 days of treatment. These findings are in line with ,9 who reLDH activity when compared to other liver function tests (LFTs) stayed elevated at all doses and during the study period, including the acceptable daily intake (ADI). Recently, similar results were obtained when using aspartame as a sweetener instead of saccharin . InteresChronic consumption of saccharin may cause kidney injury, according to the results, which showed a significant elevation in the blood creatinine level at all doses studied when compared to the control group. This result could be due to disturbances in renal functions leading to reduced glomerular filtration rate followed by retention of urea and creatinine in the blood . Similar2O2, and peroxides that could lead to cell damage are produced at a low level by normal aerobic metabolism so that the damage to cells is constantly repaired. However, severe levels of oxidative stress causes ATP depletion, preventing controlled apoptotic cell death which can lead to DNA damage. The oxidative stress induced by high doses of saccharin could be attributed to the inflammation of the liver cells [2O2), in addition to secondary oxidants and DNA-reactive aldehydes [ROS, including free radicals, Her cells . The infldehydes . Increasldehydes .Data obtained using aspartame showed that oxidizing conditions can lead to increased levels of 8-OHdG, a product of deoxyguanosine hydroxylation in DNA . TherefoA positive relationship between oxidative stress and saccharin consumption was found. The lowest dose of saccharin can lead to a release of ROS which could be overcome by the body’s ability to produce antioxidants, such as catalase, as a result of cellular protection against ROS. This mechanism of homeostasis involves an elaborate antioxidant defense system, including several antioxidant enzymes ,85. If t+ as an electron acceptor to induce the formation of superoxide anions and hydrogen peroxide in parallel with uric acid [Purines can be released through tissue injury and hypoxia. It is known that hypoxia is a potent inducer of xanthine oxidase. This enzyme uses molecular oxygen in place of NADric acid ,87. The ric acid .The results obtained in the present study suggest that long-term saccharin consumption increases the risk of obesity and diabetes, as well as liver and renal impairment. The results also suggest an increased risk of brain carcinogenesis.


To investigate the prevalence of malignant and potentially malignant lesions of the lip in an oral pathology service and to compare these data with a literature review.A total of 3173 biopsy reports and histopathological records were analyzed. Cases with a histological diagnosis of actinic cheilitis (AC) with or without epithelial dysplasia, in situ carcinoma, or lip squamous cell carcinoma (LSCC) were included. A comprehensive literature review was conducted to investigate the prevalence of AC and/or LSCC.124 cases (3.91%) were included, 75 (60.5%) had some degree of epithelial dysplasia and 31 (25.0%) were LSCC. Clinically, most of the lesions were diagnosed as AC (50.8%); however, eight cases clinically reported as AC were histologically diagnosed as LSCC. Regarding clinical characteristics, most individuals were fair-skinned male, with mean age of 54.3±12.3 years, and with a history of long-term solar exposure. Furthermore, 18 articles were selected from the literature, showing that the lower lip was predominantly affected and that most individuals were males, fair-skinned, and older than 40 years.Since most of the cases diagnosed clinically as AC presented some degree of epithelial dysplasia, it is important to emphasize the value of biopsy and the histological evaluation of this lesion. Key words:Actinic cheilitis, Precancerous conditions, In situ carcinoma, Oral diagnosis, Mouth neoplasms. Oral cancer is one of the most frequent malignant neoplasia among Brazilian individuals, this malignancy is the fifth more frequent among Brazilian males and the twelfth among Brazilian females . In 2018The main etiological factor associated with these lesions is the long term exposure to ultraviolet (UV) rays without any protection . TherefoIn the state of Santa Catarina/Brazil, approximately 15% of the population lives in rural areas and 84% of the population above 15 years-old is composed of fair-skinned individuals . In addi-Main study (MS)Biopsy reports and histopathological records from March 2007 to February 2018 were analyzed, totalizing 3173 cases. This study was approved by the Ethics Committee of the authors’ institution of affiliation . Firstly, biopsy reports were analyzed and lip lesions were selected (only lesions in the lip vermillion semi-mucosa were considered). Then, cases that were clinically diagnosed as AC, leukoplakia, erythroplakia, erythroleukoplakia, in situ carcinoma, and LSCC were selected. Lastly, histopathological records were evaluated and cases were included in the sample when histologically diagnosed as AC with no epithelial dysplasia (NoED), AC with mild epithelial dysplasia (MiED), AC with moderated epithelial dysplasia (MoED), AC with severe epithelial dysplasia (SED), in situ carcinoma (ISC), and lip squamous cell carcinoma and LSCC. Cases that did not fulfill these criteria were excluded from the sample.From the biopsy reports, information of clinical diagnosis, gender, age and skin color of the patients, lesion location, smoking and/or alcohol consumption habits, and history of chronic solar exposure was collected. Individuals that had outdoor occupations or self-reported periodical outdoor activities with long duration were considered as with “prolonged solar exposure”. All clinical data of patients were collected from biopsy files and, therefore, were reported by the responsible surgeon of each procedure. Furthermore, histological diagnosis was performed following criteria of the WHO  by an or-Literature review (LR)A comprehensive review of the literature was conducted to assess studies that investigated the prevalence of AC and/or LSCC. No time restriction was applied. Retrospective studies and case-series were considered eligible for inclusion. The following exclusion criteria were applied: 1) studies that did not report the histological diagnosis; 2) studies not published in English; and 3) full-text not available.Electronic search strategies were developed and adapted for each of the following bibliographic databases: Embase, PubMed, and Web of Science. In addition, a grey literature search was performed in Google Scholar, ProQuest Dissertations & Thesis, and OpenGrey. The following truncations and word combinations summarize the search strategy:  AND (“actinic cheilitis” OR “actinic cheilosis” OR “actinic elastosis” OR “solar cheilitis” OR “solar cheilosis” OR “solar elastosis” OR “in situ carcinoma” OR “squamous cell carcinoma” OR “epidermoid carcinoma” OR “planocellular carcinoma” OR “squamous carcinoma”) AND . All searches were conducted from the starting coverage date through 26 February 2018. A reference manager  was used to collect references and remove duplicates.A two-phase process was performed in the selection of studies. In phase-1, titles and abstracts of identified references were screened for potentially eligible studies. In phase-2, a full-text read was performed and studies that met eligibility criteria were included. The following data were extracted from the articles included in the LR: author, year of publication, country, sample size, participants’ gender and age, histological diagnosis, and associated factors.-Main study (MS)A total of 3173 cases of the pathology laboratory cases were analyzed; 124 files from 107 patients were selected to comprise the sample . There was an association between smoking habits and histological diagnosis, the LSCC group presented higher rates of smoking habits than the AC group (p=0.03). The majority (80.64%) of AC cases presented some degree of epithelial dysplasia and the majority of LSCC cases were well and moderately differentiated in the histopathological analysis  and in the AC group was 53.7±12.1 years (ranging from 24-79 years). The sex and skin color distribution were similar in both groups, and the concentration of individuals with chronical solar exposure was similar in AC than in LSCC group. 120 (96.8%) lesions were located in the lower lip and 04 (3.2%) in the upper lip. The lesions located in the upper lip were histologically diagnosed as NoED (n=1), AC with MiED (n=2), and LSCC (n=1). There was no statistic difference in regards to age, gender, skin color, solar exposure, and alcohol consumption between LSCC and AC groups  lesions were diagnosed as AC, 19 (15.3%) as leukoplakia, and 20 (16.1%) as LSCC. Considering the histological features of these cases, 31 (25%) were SCC, two (1.6%) consisted of ISC, 77 (62.1%) were AC with some degree of epithelial dysplasia, and 16 (12.9%) were described as AC without epithelial dysplasia. 18 lesions clinically diagnosed as LSCC were squamous cell carcinomas at histological analysis, one was MiED, and one was MoED. In addition, 8 cases were initially described as AC by the surgeon and later diagnosed as LSCC by the oral pathology team .-Literature review (LR)From the main electronic databases searches, 1590 papers were identified, of which 1008 remained after duplicates had been removed. After title and abstract screening, 49 articles were considered eligible for full-text reading, of which 16 met the inclusion criteria and were finally included. Moreover, 2 additional papers were included from the grey literature, resulting in 18 included studies -31  were enrolled in 4 studies investigating AC -16. StudIn regard to LSCC, 12 studies published between 1992-2016 investigated samples from Australia ,18, BrazRegarding populations from the USA in particular, two articles investigating LSSC used national databases and evaluated data from 30733 (18.0% women) Americans . In bothThe reported prevalence of LSCC is variable in the literature, ranging from 1.27 to 5.3 per 100.000 individuals ,32, and The most affected site by LSCC and AC in our sample and in the studies included in the LR was the lower lip, which is frequently related in the literature as the preferential site for LSCC . In our None of the included studies from the LR reported data from both lesions (AC and LSCC), therefore, demographic profiles’ differences between the MS results and the LR, considering both lesions simultaneously, was not possible to be performed. Data from our survey showed that the most prevalent profile of the patients, for both AC and LSCC, was fair-skinned males, older than 40 years of age, and exposed to solar UV radiation due to labor or leisure activities. Overall, these results were similar to findings of LR; however, in regards to LSSC, few studies presented data of the ethnicity of the individuals ,28,30,31Only five of the fourteen papers investigating LSCC reported data in regards to solar exposure of the individuals -21,25,27Fair-skinned people are naturally more susceptive to UV related disorders, such as skin cancer ,6. This It should be mentioned that the consumption of smoking tobacco was significantly higher in individuals with LSCC than in individuals with AC in the MS sample. The rates of smoking tobacco in the MS LSCC sample were similar to other studies included in the LR ,25,27. SIn regards to histopathological diagnosis, 10% of cases of LSCC in the MS were poorly differentiated, which is higher than most of the included studies from the LR. Overall, most studies reported less than 6% of LSCC as poorly differentiated and only two studies reported higher rates of poorly differentiated LSCC than MS ,28. In aThis study may present limitations concerning its methodology; because of the retrospective design, it was not possible to follow the patients’ clinical course. Therefore, it was not feasible to measure survival rates and evolution of AC to LSCC. LSCC survival rates vary in the literature, patients affected by this disorder seem to present better survival rates when compared to intraoral carcinomas. LSCC survival rates range between 62 and 81% ,38 withiIn conclusion, most cases of AC and LSCC in the MS were in fair-skinned individuals with solar exposure, and these data were similar to findings from the LR. It should be emphasized that most of the lesions clinically diagnosed as AC had some kind of epithelial dysplasia or, in some cases, the presence of LSCC after histopathological evaluation. Patients with a history of chronic and cumulative UV exposure should be carefully evaluated and, when lip alterations are present, biopsy and histopathological evaluation should be considered. Additionally, community-based prevention campaigns might have a marked importance in tropical countries populations, especially in the ones with a high concentration of outdoor labor occupations.


Phania matricarioides (Spreng.) Griseb. is a traditionally used plant with various pharmacological properties. However, there are only scarce reports about the phytochemistry and biological activity of this plant. In this work, P. matricarioides was collected from three different localities of Cuba: PmB , PmC , and PmI , extracted with aqueous ethanol, and analyzed macroscopically and microscopically. The extracts were screened for phytochemical contents, analyzed by TLC and HPLC, and screened for antioxidant activity using the FRAP and DPPH assays. Macroscopic analysis showed similar results for all samples; however, microscopic, physicochemical and phytochemical studies showed appreciable differences. In particular, the total solid of PmC extract was higher (1.94 ± 0.03%) than the other samples. In HPLC profiles, quercetin was identified in the three samples and a greater similarity between samples PmB and PmI was observed. All samples demonstrated radical-scavenging antioxidant activity by the DPPH assay, which PmC also demonstrated the smaller (p < 0.05) value (IC50 = 27.4 ± 0.1 µg/mL), but was statistically superior (p < 0.05) to vitamin C (IC50 = 23.7 ± 0 µg/mL). Also, in the FRAP assay, a higher vitamin C equivalent of PmC was significantly superior (p < 0.05) to the other extracts at the evaluated concentrations, which is likely due to a higher concentration of quercetin. In conclusion, P. matricarioides could constitute a potential resource in the field of phytotherapeutic products, and the results obtained can contribute to the development of the quality control norms for this species. Asteraceae or Compositae is a very large and widespread family of flowering plants, with approximately 2000 genera . Many mePhania matricarioides (Spreng.) Griseb., the accepted name of Hymenopappus matricarioides Spreng, is a very branched plant that has white corollas  and dermatological lesions [Among species of this family, corollas . It is t lesions ,9.P. matricarioides. In addition, the antidiarrheal, analgesic and anti-inflammatory effects have been demonstrated [In Cuba, the plant is also found throughout the island, cultivated in gardens and commonly known as chamomile, garden chamomile or chamomile of the earth . As partnstrated .P. matricarioides collected in different localities of Cuba, which could be applicable in quality control assessment and therapeutic utility of this and other plants in the development of natural products.Herein, we have carried out a comparative analysis relating pharmacognosy, chemical profile and antioxidant activity of extracts from p > 0.05) were found between the samples , short petiole, oblong-oval contour, dentate–lobulate, rounded apex, truncated-subacorazonate base, sometimes obtuse or somewhat acute. Although the leaf dimensions of sample PhI appear to be higher, no statistical differences  were observed among samples collected in different geographical localities. However, appreciated differences (p < 0.05) in total solids were observed among extracts.The physicochemical parameters of p < 0.05) among samples  and color characteristics displayed . The PmCThe profile obtained by HPLC showed qualitative and quantitative differences A. A totap < 0.05) to other extracts at evaluated concentrations . In addition, as summarized in p < 0.05) than the PmB and PmI, and higher (p < 0.05) than vitamin C.In this study, two different methods, ferric reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays, were performed in order to quantify the antioxidant capacity and compare among three extracts. In the FRAP assay , the vitPhania matricarioides constitutes a species with medicinal properties and has been used in traditional herbal medicine. However, there is currently little information available about the plant, chemical composition remains unidentified and therapeutic value has not been scientifically demonstrated. From the above context, this study was designed to describe pharmacognostic characteristics, obtain the chemical profile and evaluate the antioxidant activity of three extracts from P. matricarioides collected from different localities in Cuba.Medicinal plants have been used for centuries by humanity in the prevention and treatment of various diseases. However, the chemical constituents and biological properties of a wide variety of endemic plants used by people have been poorly studied and uncharacterized . Phania The macroscopic and microscopic characteristics of any plant to be used in the pharmaceutical industry should be considered as preliminary steps to establish their quality control profile. As per the guidelines of the World Health Organization (WHO) , pharmacThe microscopic analysis of the leaves and stems of the plants from the three collection sites displayed the possible structural differences that could accompany this plant as functions of the environmental conditions in which it is developed. In addition, accurate data on the climatological data of each region could also be a direct influence. The three zones or areas selected in general are subject to the same macroclimatic conditions; however, the conditions of habitat or ecological niche differ from one another, and are aspects that can cause some variations in the internal morphology of the plant.The highest yield of soluble extractives was obtained for the 50% hydroalcoholic mixture, being higher in the PmC sample. In studies carried out by Cabrera et al., similar behavior was observed . In the No differences were observed in the chemical composition determined by phytochemical screening in the evaluated samples. However, differences in the color intensity of some trials were observed, which could be related to different concentrations of functional groups. The results of the preliminary phytochemical screening are also in correspondence with those obtained by Cabrera et al. , demonstAmong the evaluated phytochemical parameters, differences in total solids were observed, which could bring relative information about quantities of metabolites or non-volatile constituents in the extracts. The PmC extracts displayed higher quantity of total solids, which could be in correspondence with the ecosystem of plant cultivation such as soil characteristics .We then performed comparative analysis of the three extracts by HPLC, which is a versatile and very rapid tool that could be useful for chemotaxonomy, identification of the plant material, and to set up chemical fingerprints of studied extracts ,23. In aP. matricarioides independent of locality of cultivation, (ii) it can be used as marker component in different collections, and (iii) it is a metabolite with known medicinal value [P. matricarioides-derived products. However, the metabolite maps of the extracts showed the accumulation patterns of quercetin to be different, also suggesting the need for further bioactivity screening. In addition, a peak with RT of 4.87 min was observed in the three studied samples. The UV spectrum is characteristic of chlorogenic acid or a derivative. This compound exhibited peaks at 325, 300 (shoulder) and 250 nm [In the studied extracts, the presence of quercetin was confirmed, which reflects three important findings: (i) it could be a common compound present in al value ,25,26,27d 250 nm ,29,30,31P. matricarioides extracts, higher antioxidant activity was observed in the PmC extract, which also displayed the higher concentration of quercetin according to the chemical profile as shown in the quantitative map. Thus, it is likely that better antioxidant capacity may depend on quercetin concentration and locality collection area.In recent years, natural antioxidants have gained importance for their prophylactic and therapeutic potential for many diseases, during which the search for medicinal plants with antioxidant properties has intensified in recent years ,33. NatuPhania matricarioides in the vegetative state was collected in March 2013, from three geographical localities: (i) Bauta , labeled as sample PmB, Artemisa Province, Cuba, which is characterized by a ferralitic soil, compact red clay, saturated in calcium, very plastic in the wet state and very hard or compact in the dry state; (ii) Cangrejeras , labeled as PmC, also from Artemisa Province and presents a typical red ferralitic soil, with high calcium content, good superficial and internal drainage; and (iii) gardens of the Faculty of Pharmacy and Food (IFAL) in La Lisa , labeled as PmI, Havana Province, Cuba, which is characterized by a red ferralitic soil, hydrated with humidity and frequent drainage. Plants were authenticated by Professor Dr. Jorge Gutiérrez Amaro and identified at the herbarium of National Botany Garden of Havana, Cuba, where the voucher specimen has been deposited under the number HFC 88669.Vegetable material (leaves and stems) was washed with copious running water and immediately treated with 1% sodium hypochlorite solution for 5 min and then rinsed with copious running water. Fresh leaves and stems were used for macromorphology and micromorphology analyses. Another portion of sample (leaves and stems) was dried in a digital temperature controller VLD-6000  with controlled temperature, at 35 °C ± 2 °C, over 7 days. The powdered sample (2 mm) was used for extract preparation, phytochemical analysis and phytochemical screening.P. matricarioides collected in the different localities belonging to the three collections were elaborated using a 50% hydroalcoholic mixture as solvent. Briefly, previously powdered sample was extracted by the maceration method, during a period of 7 days, at a temperature of 30 °C ± 2 °C according to the procedure described in the Cuban Standard Norm of Public Health (NRSP) 312 [Hydroalcoholic extracts from vegetable material (leaves and stems) of RSP) 312  and MartRSP) 312 .To carry out the pharmacognostic studies, 20 samples of plant material  were collected from each geographical area. For macroscopic analysis, 100 leaves were included and size, shape, petiole, color, odor and extra features of leaves and stems from collected samples were studied ,19. For v/v) utilizing maceration method, total ash content, water-soluble ash and acid-insoluble ash were tested. Extracts were also characterized according to the Cuban standard NRSP 312 [The physicochemical analysis was carried out on the powdered sample (leaves and stems) following standard methods ,19,44. INRSP 312 , includiTotal contents of phenols and flavonoids were determined. In the first case, total phenol content was calculated determined by the Folin–Ciocalteu method , using gIn addition, preliminary phytochemical screening for secondary metabolites was carried out. The powdered materials were extracted with solvents like petroleum ether, ethanol, and water. The extracts were tested for fats or oil, volatile oil, reducing sugars, resins, saponins, sterols, triterpenes, phenols/tannins, flavonoids, anthocyanins, free amino acids or amines, alkaloids, coumarins and quinones .P. matricarioides from different localities, a profile by thin-layer chromatography (TLC) was also performed. Aluminum-backed silica gel TLC plates F 254 nm from Merck  were used and quercetin  was used as a standard. The chromatography was carried out using as mobile phase: n-butanol:acetic acid:water . The TLC plates were then sprayed with 5% H2SO4 in ethanol and heated to approximately 105 °C until the appearance of spots or modification of the appearance of existing ones. In another system, TLC was revealed with aluminum chloride  at 5% in methanol. Finally, TLC plates were visualized under UV light at 254/365 nm.In order to corroborate qualitative chemical composition of the hydroalcoholic extracts of v/v), oven temperature of 25 °C, detector by diode array at 370 nm (200–400), flow at 0.9 mL/min., pressure of 14.1 μPa, injection volume of 20 μL, column of Uptisphere 5 0DB 708965 (RP-18). Relative abundance was determined according to area under curve (AUC). Finally, chemical compositions of each sample were subjected to the heat map for qualitative and quantitative comparison. Finally, average of retention time (Rt) for peaks was performed and integrations were used to carry out the hierarchical clustering analysis using the XLSTAT software, version 2018.5.53172. Pearson correlation was selected as a measure of similarity, and the unweighted pair-group method with arithmetic average.The samples were filtered through a Teflon membrane 0.2 µm and introduced directly into the equipment. A Shimadzu liquid chromatograph  was used for the study. The chromatographic working conditions were: mobile phase acetonitrile and phosphate buffer pH 2.4  to ferrous (Fe2+). The determinations were carried out in a spectrophotometer Rayleigh UV-1601 (China) at 593 nm and concentration of FRAP was calculated from a linear equation obtained from a curve of vitamin C  concentration vs absorbance. Different extract concentrations (ranging 25–40 μg/mL) were tested and equivalents μmol of vitamin C according to the standard curve of ascorbic acid  were calculated. The experiment was carried out in triplicate and the results are expressed as vitamin C equivalents.The ferric reducing antioxidant power (FRAP) assay was measured as described previously by Benzie and Strain , which d50), obtained from dose-response curves in Graphprism 5.0 Statistical Program of three replicates.In parallel, the reduction of 2,2-diphenyl-1-picrylhydrazyl  radical to 2,2-diphenyl-1-picryl hydrazine was used for the radical-scavenging action of compounds containing –OH groups that decolorize the DPPH reagent . ExtractP. matricarioides collected in different localities, an analysis of variance was carried out, followed by the Dunnett or Tukey test. To antioxidant activity, data were analyzed by ANOVA test, followed by Duncan test. The analysis were carried out through the Statgraphics®Plus program, version 5.0, considering statistical differences as p < 0.05.To compare the macroscopic characteristics, physicochemical parameters and antioxidant activity among the samples of P. matricarioides as an herbal product, which has been used for centuries by the Cuban population.The pharmacognostic study performed for this plant species has established the micromorphologic features of leaves and stems, together with some physical–chemical parameters of plant material and extracts, which are essential for correct identification of plants and contribute to the development of the norms for quality control of the species. In addition, the identified compound (quercetin) constitutes a flavonoid with a broad spectrum of biological activities and could be used as a chemical marker of extracts. Finally, the antioxidant activity of these extracts could suggest pharmacological use of this plant and contribute to scientific validation of P. matricarioides could constitute a potential resource in the field of phytotherapeutic products, expanding the chemical–pharmacognostic knowledge of the rich Cuban flora. Further experiments could investigate the antioxidant activity and other biological activities more deeply and examine this plant species for improvements of the pathologic status of patients with chronic diseases such as cancer and infections.In conclusion,


The objective of this study was to evaluate the dentoalveolar effects and the changes of buccal cortical bone in the posterior area after expansion obtained with TMA auxiliary expansion arch in adult patients.A retrospective analysis of CT scans of 13 patients  treated at a private clinic, taken immediately before and after the use of an auxiliary expansion archwire, was performed. Mean age at installation of TMA auxiliary expansion arch was 29.23 years (s.d.=9.13) and the mean age when the auxiliary arch was removed was 29.52 years (s.d.=9.16). Mean time of the use of the TMA auxiliary expansion arch was 0.29 years (s.d.=0.09). The patients used fixed appliances and after leveling and alignment, a TMA auxiliary expansion arch was installed, combined with the primary 0.017x0.025-inch thermoactivated Ni-Ti archwire. CBCT scans were taken at T1 and T2. Linear and angular measurements regarding the positioning of maxillary molar, premolars and canines were performed. Intragroup comparison of the variables at T1 and T2 was performed with dependent t tests.There was statistically significant transverse increase and buccal inclination of all teeth. The cortical bone showed adaptability and displacement in the same direction of tooth movement, but in smaller amounts.The auxiliary expansion arch proved to be effective to correct dentoalveolar constriction in adult patients, by increasing the buccal dental inclination with larger displacements than the bone crest adaptation and with significant transverse gains. Key words:Cone-Beam Computed Tomography, Maxillary Expansion, Adult treatment. Maxillary atresia is a common malocclusion in children, adolescents and adults -3. The tWhen maxillary atresia is maintained until adulthood and therefore, without the possibility of orthopedic intervention, slow expansion of the maxilla or dentoalveolar expansion become treatment options ,6. In thAnother method of dentoalveolar expansion described in the literature is the auxiliary expansion arch, which is a 0.6mm stainless steel wire inserted into the orthodontic accessory tube of the first maxillary molars and tied with steel ligatures between the central incisors. The purpose of this arch is to correct the posterior crossbite of the patients and expand the maxillary arch .The TMA auxiliary expansion arch  is a proposal to achieve the same dentoalveolar effects of the abovementioned devices, with the advantage of presenting less discomfort to adult patients, as it is in the same position of the orthodontic leveling, as an over-arch. The choice of TMA material was due to the physical characteristics of this alloy, due to its formability and modulus of elasticity, with a more gradual release of force than steel -12. AnotFor the evaluation of dental movement in the presence of orthopedic transverse forces, there is a large literature demonstrating methodologies and results ,14,18,19Dentoalveolar expansion in adults is a widely used mechanics in cases of maxillary atresia and in cases of Class III orthodontic compensation. The technique with TMA auxiliary expansion arch has been used in clinical practice, since it is a viable option and without discomfort to the patient. However, the use of this mechanics does not present evident results in the literature. This way, the objective of this study was to evaluate the dentoalveolar effects and the changes of buccal cortical bone in the posterior area after expansion obtained with a TMA auxiliary expansion arch in adult patients.MaterialThis study was approved by the Ethics in Research Committee of Bauru Dental School, University of São Paulo, Bauru, SP, Brazil. All patients read and signed informed consent forms.The sample size calculation was based on an alpha significance level of 5% and a beta of 20% to achieve 80% test power to detect a minimum difference of 2.1° with a standard deviation of 2.47 for the maxillary first molar angulation , with a mean age at T1  of 29.23 years . The mean age when the auxiliary arch was removed (T2) was 29.52 years . Mean usage time of the TMA auxiliary expansion arch (T2-T1) was 0.29 years . A computed based tomography was taken at T1 and T2 for each patient.All patients were treated by the same orthodontist, in the same private clinic, and all CBCTs were performed at the same orthodontic record center.-Orthodontic treatmentPatients were treated with pre-adjusted, Roth prescription, self-ligating brackets , with the same wire sequence for leveling and alignment: 0.014, 0.018, 0.016x0.022 and 0.017x0.025-inch thermoactivated NiTi archwires. At this stage of leveling, a CBCT of the maxilla was performed, previously to installation of the expansion arch.The TMA auxiliary expansion arch was made with 0.8mm round titanium molybdenum alloy wire. Helicoids were made at 90 degrees, mesially to the first molars tubes. Thus, the main leveling wire (0.017x0.025-inch thermoactivated NiTi) would pass through these helicoids and enter the tubes of the maxillary first molars, bilaterally. In addition to these points of attachment, a 0.010-inch stainless-steel wire was also used to attach the auxiliary arch to the main leveling arch, in the region between the premolars bilaterally and between the maxillary central incisors , and the voxel size used was 0.25mm. Exams were saved in DICOM format, and measurements were made in OsiriX Lite software (version v.7.0.3 32-bit). The software allows multiplanar image visualization. Since only the maxilla was evaluated in CBCT, the palatal plane was used as the horizontal reference . Perpendicular to this plane, passing through the incisive foramen, the median vertical plane was used as a vertical reference. In coronal sectioning, for head position standardization, the palatal contour at the second molar region was used as reference, adjusting the image to be parallel to the palatal plane established in the axial section.Measurements were performed through the coronal sections, marking selected points and measuring them up to the median vertical plane (MVP). Some filters were used for contrast, such as the flow and perfusion contrast. Following the orthodontic mechanics used in this study, the reference points to obtain these plans were not altered, increasing the reliability of the measurements obtained. For this research, the linear measurements were thus divided, following a previously described methodology :Linear measurements Fig. :External measurements:- Mesial and buccal cusps of the maxillary first molar to MVP (BCUSP 6)- Buccal cusp of maxillary second premolar to MVP (BCUSP 5)- Buccal cusp of maxillary first premolar to MVP (BCUSP 4)- Buccal cusp of maxillary canine to MVP (BCUSP 3)- Mesial and buccal root apex of maxillary first molar to MVP (BROOT 6)- Buccal root apex of maxillary second premolar to MVP (BROOT 5)- Buccal root apex of maxillary first premolar to MVP (BROOT 4)- Buccal root apex of maxillary canine to MVP (BROOT 3)- Buccal alveolar crest to MVP (BAC)- Buccal alveolar crest to palatal plane vertical (BAC-PPV)Internal measurements:- Palatal alveolar crest to MVP (PAC)- Palatal alveolar crest to palatal plane vertical (PAC-PPV)To evaluate changes in buccal inclination, angular measurements were obtained :Angular measurements Fig. :- Mesial and buccal cusps of maxillary first molar to mesial root apex to MVP (ANG 6)- Mesial cusp of maxillary second premolar to root apex to MVP (ANG 5)- Buccal cusp of maxillary first premolar to root apex to MVP (ANG 4)- Buccal cusp of maxillary canine to root apex to MVP (ANG 3)Other linear measurements performed were interdental widths: intercanine, inter-first premolar, inter-second premolar and intermolar. The reference point for these measurements was the area of union of the bracket or tube to the tooth.-Error studyMeasurements were performed twice by the same operator, with interval of at least one month, in 4 subjects of the sample. Random and systematic errors were calculated by Dahlberg’s formula and dependent t tests, respectively.-Statistical analysisNormality of data was verified by the Kolmogorov-Smirnov test. As data presented normal distribution, parametric tests were used.P<0.05.Intragroup comparison of T1 and T2 was performed by dependent t tests. Tests were performed with Statistica software  and were considered significant at There were significant systematic errors in 3 variables . The random errors varied from 0.04mm (BAC-PPV 5) to 0.25mm (I1PM) and from 0.29º (ANG 4) to 0.40º (ANG 5).For the maxillary first molar, there was significant increase in distances BCUSP, BAC and BAC-PPV and for ANG (Table 1). For the second premolar, significant increase was observed in the variables BCUSP, BROOT, ANG and BAC . Regardi-MethodologyA number of studies are currently using CT scans, especially cone-beam, in order to complete and elucidate changes during craniofacial growth -24, the et al. (The present study used the methodology used by Baka et al.  since th-Treatment effectsThe use of TMA auxiliary expansion arch in adult patients showed significant increase of the measures of cusp tips to the MVP, in all teeth evaluated, being more expressive from first premolar to molar, although for the canines it was also statistically significant , Table 2et al. (In the posterior teeth, the increases in cusp tips measurements to MVP were more expressive, 1.33mm for first molars, 1.35mm for second premolars and 1.13mm for first premolars, respectively. Movement of root apices to MVP were -0.20mm, -0.37mm and 0.21mm, respectively, but statistically significant only for the second premolars . These iet al. (Variation from T1 to T2 in canine teeth was on average 0.65mm at cusp level and -0.35 measured at the root apex, numerically small but yet statistically significant . This inet al. , in whicThe greater values for cusp tip measurements than for root apices are explained by the greater increase in angulation values, indicating buccal inclination. Angulation increases were of 4.16º, 5.27º and 3.73º for first molars and first and second premolars, respectively, and all were statistically significant , Table 2There was significant increase in the distance from the buccal alveolar crest to MVP only for first molars and second premolars, of 0.65mm and 0.31mm, on average . VerticaAnalyzing the transversal widths, the measurements of intermolar, inter-first and inter-second premolars and intercanine distances showed mean increase of 2.40mm, 2.49mm, 2.12mm and 0.71mm, respectively . These iTherefore, the effects of the use of TMA auxiliary expansion arch are limited to dentoalveolar compensation, with dental inclinations, minor movements within the alveolar bone and slight remodeling of alveolar bone crest, primarily in the buccal region.• The effects of TMA auxiliary expansion arch are limited to dentoalveolar compensation, with dental inclinations, minor movements within the alveolar bone and slight remodeling of the bone crest, primarily in the buccal region.• There was statistically significant transverse increase and buccal inclination of all teeth from maxillary first molar to canine. The cortical bone showed adaptability and displacement in the same direction of tooth movement, but in smaller amounts.