Sacroiliitis in inflammatory bowel disease on abdominal computed tomography: prevalence, misses, and associated factors.

OBJECTIVE: To evaluate the prevalence and rate of a missed diagnosis of sacroiliitis on abdominal computed tomography (CT) in patients with inflammatory bowel disease (IBD). Factors associated with sacroiliitis were also assessed. METHOD: This retrospective study included 210 patients with IBD (mean age 31.1 years) who underwent abdominal CT. Based on a validated abdominal CT scoring tool, bilateral sacroiliac (SI) joints on abdominal CT in the whole study population were retrospectively reviewed. Subsequently, patients were classified into the 'patients with sacroiliitis' group and the 'patients without sacroiliitis' group. Univariate and multivariate regression analyses were used to clarify the factors associated with sacroiliitis. RESULTS: Sacroiliitis was identified in 26 out of 210 patients (12.4%). However, sacroiliitis was recognized on the primary reading in only five of these 26 patients (19.2%) and was missed on the initial report in the remaining 21 patients (80.8%). Among the 21 patients, 20 (95.2%) were finally diagnosed with axial spondyloarthritis (axSpA). There was a higher prevalence of female sex (p = 0.04), upper gastrointestinal involvement (p = 0.04), and back pain (p < 0.01) in patients with sacroiliitis than in those without sacroiliitis. However, on multivariate analysis, back pain was the only factor associated with sacroiliitis (p = 0.01). CONCLUSION: Physicians should carefully evaluate SI joints on abdominal CT in patients with IBD to enable early detection of sacroiliitis, potentially leading to an early diagnosis of axSpA. In addition, if patients with IBD present with back pain, the possibility of sacroiliitis should be considered.

Position paper on olfactory dysfunction: 2023

BACKGROUND: Since publication of the original Position Paper on Olfactory Dysfunction in 2017 (PPOD-17), the personal and societal burden of olfactory disorders has come sharply into focus through the lens of the COVID-19 pandemic. Clinicians, scientists and the public are now more aware of the importance of olfaction, and the impact of its dysfunction on quality of life, nutrition, social relationships and mental health. Accordingly, new basic, translational and clinical research has resulted in significant progress since the PPOD-17. In this updated document, we present and discuss currently available evidence for the diagnosis and management of olfactory dysfunction. Major updates to the current version include, amongst others: new recommendations on olfactory related terminology; new imaging recommendations; new sections on qualitative OD and COVID-19 OD; updated management section. Recommendations were agreed by all co-authors using a modified Delphi process. CONCLUSIONS: We have provided an overview of current evidence and expert-agreed recommendations for the definition, investigation, and management of OD. As for our original Position Paper, we hope that this updated document will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency, and generalisability of work in this field.

Resection of the femoral neck: a new technique for the treatment of mallory type I intraoperative femoral fracture during total hip arthroplasty.

Intraoperative femoral fracture is a common complication during cementless total hip arthroplasty (THA). Cerclage wiring has been used for this type of fractures to attain intraoperative stability of the femoral stem. We designed a new technique to treat Mallory type 1 intraoperative femoral fractures. We excised fractured femoral neck fragment and without additional fixation and lightly tapped down the femoral stem to obtain a tight contact to the femoral cortex at the subtrochanteric level. In this case series, we described this technique and reported its outcomes. From January 2015 to December 2017, 600 cementless THAs (557 patients) were done with use of a proximally coated tapered stem design at our department. Among the 600 THAs, Mallory type 1 intraoperative femoral fracture occurred in 8 hips (8 patients), and all of them were treated with the excision of the fractured femoral neck. Mean age of the 8 patients was 58.1 years (range, 30.4 to 81.3 years) at the time of surgery. We report the results of this new technique at postoperative 2 to 5 years (mean, 3.4 years). All stems were placed in the neutral position. There was no revision and no stem showed any evidence of subsidence or loosening during the follow-up. The mean Harris hip score was 85.9 points at the latest follow-up. We recommend to use the femoral neck excision technique for the treatment of Mallory type 1 intraoperative femoral fractures.

The role of endometrial staining for CD138 as a marker of chronic endometritis in predicting live birth.

PURPOSE: Chronic endometritis (CE) is diagnosed via endometrial biopsy and staining for plasma cells. A threshold plasma cell count that identifies CE and predicts pregnancy outcomes has not been established, and the prevalence of plasma cells in the general infertile population is unknown. The purpose of this study was to determine the prevalence of plasma cells in the general infertile population and whether a threshold exists which predicts live birth. METHODS: Endometrial samples were obtained prospectively from 80 women undergoing IVF, embedded in paraffin, and stained for plasma cells using mouse mono-clonal antibody for CD138. Slides were reviewed at 20× magnification and 10 random images captured. Three reviewers graded each image for plasma cells. Participants underwent single, euploid, and frozen blastocyst transfer. RESULTS: Forty-nine percent of samples had ≥1 plasma cell across 10 HPFs, 11% had ≥5 cells across 10 HPFs, and 4% had ≥10 cells across 10 HPFs. There was no difference in prevalence between those who did and did not achieve live birth. Using thresholds of 1, 5, and 10 plasma cells per 10 HPFs, there were no differences in implantation, clinical pregnancy, clinical pregnancy loss, or live birth rates between patients with and without CE. CONCLUSION: Endometrial plasma cells are present in half the general infertile population and do not predict implantation, clinical pregnancy, clinical pregnancy loss, or live birth rates at low levels.

Radiomics-based model for predicting pathological complete response to neoadjuvant chemotherapy in muscle-invasive bladder cancer.

AIM: To develop and validate a radiomics-based model for predicting response to neoadjuvant chemotherapy (NAC) using baseline computed tomography (CT) images in patients with muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: A radiomics signature for predicting pathological complete response (pCR) was developed using radiomics features selected by a random forest classifier on baseline CT images, and imaging predictors were identified in the training set (87 patients). By incorporating imaging predictors and radiomics signature, an imaging-based model was constructed using multivariate logistic regression analysis and validated in an independent validation set consisting of 48 patients with CT from outside institutions. The performance and clinical usefulness of the imaging-based model for predicting pCR were evaluated using area under the receiver operating characteristic curve (AUC) and decision curve analysis. Using a cut-off determined in the training set, the positive likelihood ratios of the imaging-based model were calculated and compared with imaging and histological predictors. RESULTS: The radiomics signature was developed based on six stable radiomics features. An imaging-based model incorporating radiomics signature, tumour shape, tumour size, and clinical stage showed good performance for predicting pCR in both the training (AUC, 0.85; 95% confidence interval [CI], 0.78-0.93) and validation (AUC, 0.75; 95% CI, 0.60-0.86) sets, providing a larger net benefit in decision curve analysis. The imaging-based model showed a higher positive likelihood ratio (1.91) for pCR than imaging and histological predictors (1.33-1.63). CONCLUSIONS: The radiomics-based model using baseline CT images may predict the response of patients with MIBC to NAC.

Viral stimulation modulates endotype-related ACE2 expression in eosinophilic chronic rhinosinusitis.

BACKGROUND: Angiotensin-converting enzyme 2 (ACE2), a receptor targeted by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is highly expressed in the nasal mucosa. Chronic rhinosinusitis (CRS) shows diverse endotypes and is aggravated by viral infection. Whether viral stimulation and CRS endotype influence ACE2 expression remains unclear. We investigated the expression of ACE2 and the transmembrane protease, serine 2 (TMPRSS2), which mediate the entry of SARS-CoV-2 into cells, and assessed polyinosinic:polycytidylic acid (poly[I:C])-induced changes based on CRS endotype. METHODOLOGY: ACE2 and TMPRSS2 expression was evaluated based on CRS phenotype, endotype, and tissue type. Correlations between ACE2/TMPRSS2 expression and inflammatory mediators in nasal polyps (NP) were examined. Air-liquid interface culture experiments were performed to assess the effects of major cytokines or poly(I:C) stimulation on ACE2/TMPRSS2 expression in primary epithelial cells from healthy nasal mucosa, eosinophilic NP (ENP), and non-eosinophilic NP (NENP). RESULTS: In primary nasal epithelial cells, interleukin (IL)-13 decreased ACE2 expression but increased TMPRSS2. Eosinophilic CRS showed lower ACE2 expression than non-eosinophilic CRS, regardless of CRS phenotype. CRS endotype was an independent factor associated with ACE2/TMPRSS2 expression in NP. Serum and tissue eosinophilic marker levels were inversely correlated with ACE2 expression, whereas tissue neutrophilic marker levels and ACE2 expression were positively correlated in NP. ACE2 expression was suppressed in ENP tissues; however, a combination of poly(I:C) and IL-13 induced ACE2/TMPRSS2 upregulation in ENP. CONCLUSIONS: ENP tissues have lower ACE2 expression than NENP; however, viral stimulation promotes ACE2/TMPRSS2 upregulation in ENP.

Subepithelial neutrophil infiltration as a predictor of the surgical outcome of chronic rhinosinusitis with nasal polyps.

BACKGROUND: Neutrophils present as major inflammatory cells in refractory chronic rhinosinusitis with nasal polyps (CRSwNP), regardless of the endotype. However, their role in the pathophysiology of CRSwNP remains poorly understood. We investigated factors predicting the surgical outcomes of CRSwNP patients with focus on neutrophilic localization. METHODS: We employed machine-learning methods such as the decision tree and random forest models to predict the surgical outcomes of CRSwNP. Immunofluorescence analysis was conducted to detect human neutrophil elastase (HNE), Bcl-2, and Ki-67 in NP tissues. We counted the immunofluorescence-positive cells and divided them into three groups based on the infiltrated area, namely, epithelial, subepithelial, and perivascular groups. RESULTS: On machine learning, the decision tree algorithm demonstrated that the number of subepithelial HNE-positive cells, Lund-Mackay (LM) scores, and endotype (eosinophilic or non-eosinophilic) were the most important predictors of surgical outcomes in CRSwNP patients. Additionally, the random forest algorithm showed that, after ranking the mean decrease in the Gini index or the accuracy of each factor, the top three ranking factors associated with surgical outcomes were the LM score, age, and number of subepithelial HNE-positive cells. In terms of cellular proliferation, immunofluorescence analysis revealed that Ki-67/HNE-double positive and Bcl-2/HNE-double positive cells were significantly increased in the subepithelial area in refractory CRSwNP. CONCLUSION: Our machine-learning approach and immunofluorescence analysis demonstrated that subepithelial neutrophils in NP tissues had a high expression of Ki-67 and could serve as a cellular biomarker for predicting surgical outcomes in CRSwNP patients.

The organ-specific differential roles of rice DXS and DXR, the first two enzymes of the MEP pathway, in carotenoid metabolism in Oryza sativa leaves and seeds.

BACKGROUND: Deoxyxylulose 5-phosphate synthase (DXS) and deoxyxylulose 5-phosphate reductoisomerase (DXR) are the enzymes that catalyze the first two enzyme steps of the methylerythritol 4-phosphate (MEP) pathway to supply the isoprene building-blocks of carotenoids. Plant DXR and DXS enzymes have been reported to function differently depending on the plant species. In this study, the differential roles of rice DXS and DXR genes in carotenoid metabolism were investigated. RESULTS: The accumulation of carotenoids in rice seeds co-expressing OsDXS2 and stPAC was largely enhanced by 3.4-fold relative to the stPAC seeds and 315.3-fold relative to non-transgenic (NT) seeds, while the overexpression of each OsDXS2 or OsDXR caused no positive effect on the accumulation of either carotenoids or chlorophylls in leaves and seeds, suggesting that OsDXS2 functions as a rate-limiting enzyme supplying IPP/DMAPPs to seed carotenoid metabolism, but OsDXR doesn't in either leaves or seeds. The expressions of OsDXS1, OsPSY1, OsPSY2, and OsBCH2 genes were upregulated regardless of the reductions of chlorophylls and carotenoids in leaves; however, there was no significant change in the expression of most carotenogenic genes, even though there was a 315.3-fold increase in the amount of carotenoid in rice seeds. These non-proportional expression patterns in leaves and seeds suggest that those metabolic changes of carotenoids were associated with overexpression of the OsDXS2, OsDXR and stPAC transgenes, and the capacities of the intermediate biosynthetic enzymes might be much more important for those metabolic alterations than the transcript levels of intermediate biosynthetic genes are. Taken together, we propose a 'Three Faucets and Cisterns Model' about the relationship among the rate-limiting enzymes OsDXSs, OsPSYs, and OsBCHs as a "Faucet", the biosynthetic capacity of intermediate metabolites as a "Cistern", and the carotenoid accumulations as the content of "Cistern". CONCLUSION: Our study suggests that OsDXS2 plays an important role as a rate-limiting enzyme supplying IPP/DMAPPs to the seed-carotenoid accumulation, and rice seed carotenoid metabolism could be largely enhanced without any significant transcriptional alteration of carotenogenic genes. Finally, the "Three Faucets and Cisterns model" presents the extenuating circumstance to elucidate rice seed carotenoid metabolism.

Montel mirror based collimating analyzer system for high-pressure resonant inelastic X-ray scattering experiments.

Resonant inelastic X-ray scattering (RIXS) is increasingly playing a significant role in studying highly correlated systems, especially since it was proven capable of measuring low-energy magnetic excitations. However, despite high expectations for experimental evidence of novel magnetic phases at high pressure, unequivocal low-energy spectral signatures remain obscured by extrinsic scattering from material surrounding the sample in a diamond anvil cell (DAC): pressure media, Be gasket and the diamond anvils themselves. A scattered X-ray collimation based medium-energy resolution (∼100 meV) analyzer system for a RIXS spectrometer at the Ir L3-absorption edge has been designed and built to remediate these difficulties. Due to the confocal nature of the analyzer system, the majority of extrinsic scattering is rejected, yielding a clean low-energy excitation spectrum of an iridate Sr2IrO4 sample in a DAC cell. Furthermore, the energy resolution of different configurations of the collimating and analyzing optics are discussed.

Deficient autophagy in microglia impairs synaptic pruning and causes social behavioral defects.

Autism spectrum disorders (ASDs) are neurodevelopmental disorders caused by various genetic and environmental factors that result in synaptic abnormalities. ASD development is suggested to involve microglia, which have a role in synaptic refinement during development. Autophagy and related pathways are also suggested to be involved in ASDs. However, the precise roles of microglial autophagy in synapses and ASDs are unknown. Here, we show that microglial autophagy is involved in synaptic refinement and neurobehavior regulation. We found that deletion of atg7, which is vital for autophagy, from myeloid cell-specific lysozyme M-Cre mice resulted in social behavioral defects and repetitive behaviors, characteristic features of ASDs. These mice also had increases in dendritic spines and synaptic markers and altered connectivity between brain regions, indicating defects in synaptic refinement. Synaptosome degradation was impaired in atg7-deficient microglia and immature dendritic filopodia were increased in neurons co-cultured with atg7-deficient microglia. To our knowledge, our results are the first to show the role of microglial autophagy in the regulation of the synapse and neurobehaviors. We anticipate our results to be a starting point for more comprehensive studies of microglial autophagy in ASDs and the development of putative therapeutics.

Salivary gland ultrasonography findings are associated with clinical, histological, and serologic features of Sjögren's syndrome.

OBJECTIVE: Salivary gland ultrasonography (SGUS) has been applied in the diagnosis of Sjögren's syndrome (SS). The aim of this study is to investigate the association of SGUS findings with clinical, histological, and serologic features of SS. METHODS: A total of 104 patients with suspected SS underwent SGUS for evaluation of salivary gland involvement. Patients with primary SS were determined according to the classification criteria for SS. The parenchymal inhomogeneity of bilateral parotid and submandibular glands was graded from 0 (homogeneity) to 4 (gross inhomogeneity). Receiver operating characteristic curve analysis was performed to compare the diagnostic performance of different SGUS scoring methods. Clinical and serologic features were compared between groups classified by SGUS score. The association between SGUS and these features of SS was explored by multivariable linear regression analysis. RESULTS: Study participants were predominantly women (96.2%) and had a mean age of 54.1 years. Eighty-seven patients and 88 patients with primary SS were identified based on AECG criteria and ACR/EULAR classification criteria for SS, respectively. Among the different scoring methods, the sum of the grades of four salivary glands (range 0-16) had the best diagnostic performance, with sensitivity of 77.3% and specificity of 87.5% (cutoff value, 7) for distinguishing primary SS from sicca non-SS. SGUS score was associated with focus score in labial salivary gland biopsy (ß = 0.240, p = 0.033) and anti-Ro/SSA serology (ß = 0.283, p = 0.016) and inversely associated with unstimulated whole salivary flow (ß = -0.298, p = 0.011). CONCLUSION: Ultrasonography of major salivary glands is associated with histopathology of minor salivary glands, serology of SS, and salivary gland function.

Diabetes mellitus exacerbates the clinical and electrophysiological features of Guillain-Barré syndrome.

BACKGROUND AND PURPOSE: It is known that underlying diabetes mellitus (DM) can affect the clinical and electrophysiological pattern of coexisting peripheral neuropathies of other etiologies. The aim of this study was to identify the effect of underlying DM on the clinical and electrophysiological features of Guillain-Barré syndrome (GBS) and on the prognosis of GBS with regard to functional outcome. METHODS: This study prospectively included 27 GBS patients with DM (GBS-DM+) and 58 GBS patients without DM (GBS-DM-) from two university-based hospitals. The clinical and electrophysiological findings were compared between the two groups. The functional outcomes were quantified by measuring the Hughes grade, whose values were compared between the groups at 3 months after symptom onset. RESULTS: All three sudden deaths that occurred during the acute stage of GBS were GBS-DM+ patients. GBS-DM+ patients had a tendency toward more frequent sensory involvement, and specific electrophysiological patterns and calculated indices disclosed a distal accentuation of conduction abnormalities in these patients. In addition, multivariate analysis identified history of mechanical ventilation (odds ratio 10.057, 95% confidence interval 2.057-49.164, P = 0.04) and DM (odds ratio 9.049, 95% confidence interval 2.152-38.044, P = 0.003) as independent factors for poor functional outcome at 3 months. CONCLUSIONS: The findings of this study suggest that DM exacerbates the clinical and electrophysiological features of GBS and influences long-term disability. Both chronic inflammation and nerve ischaemia in DM may intervene in the disease course of GBS, which is a prototype of acute inflammatory neuropathy.

Prevalence and prognosis of hypoglycaemia in patients receiving maintenance dialysis.

BACKGROUND: End-stage renal disease is a common predisposing condition for the development of hypoglycaemia. AIM: To determine the effect of hypoglycaemia on the mortality of patients undergoing maintenance dialysis. METHODS: Retrospective and descriptive analyses were performed in five dialysis centres in the Republic of Korea between June 2002 and August 2008. We enrolled 1685 patients who had undergone dialysis for at least 1 month. RESULTS: We identified 453 episodes of hypoglycaemia in 256 of 1685 patients (15.2%); 189 patients (73.8%) had diabetes, whereas the other patients did not. The occurrence of hypoglycaemia in patients receiving dialysis appeared to be a life-threatening complication because 27.0% of patients died within two days of the onset of a hypoglycaemic episode. Older age, low serum albumin levels and infections were independent risk factors for total mortality in these patients. Furthermore, the absence of diabetes, age and serum glucose levels were independent factors associated with early mortality within two days of the development of hypoglycaemia. CONCLUSION: Although several factors were associated with mortality, the degree of hypoglycaemia, absence of diabetes and old age were associated with early mortality. Elderly hypoglycaemic patients, especially those without diabetes, should be closely monitored.

Characterization of microRNAs and their target genes associated with transcriptomic changes in gamma-irradiated Arabidopsis.

MicroRNAs (miRNAs) regulate gene expression in response to biotic and abiotic stress in plants. We investigated gamma-ray-responsive miRNAs in Arabidopsis wild-type and cmt3-11t mutant plants using miRNA microarray analysis. miRNA expression was differentiated between the wild-type and cmt3-11t mutants. miR164a, miR169d, miR169h, miR172b*, and miR403 were identified as repressible in the wild-type and/or cmt3-11t mutant in response to gamma irradiation, while miR827, miR840, and miR850 were strongly inducible. These eight miRNA genes contain UV-B-responsive cis-elements, including G-box, I-box core, ARE, and/or MBS in the putative promoter regions. Moreover, Box 4, MBS, TCA-element, and Unnamed_4, as well as CAAT- and TATA-box, were identified in these eight miRNA genes. However, a positive correlation between the transcriptions of miRNAs and their putative target genes was only observed between miR169d and At1g30560 in the wild-type, and between miR827 and At1g70700 in the cmt3-11t mutant. Quantitative RT-PCR analysis confirmed that the transcription of miR164a, miR169d, miR169h, miR172b*, miR403, and miR827 differed after gamma irradiation depending on the genotype (wild-type, cmt3-11t, drm2, drd1-6, and ddm1-2) and developmental stage (14 or 28 days after sowing). In contrast, high transcriptional induction of miR840 and miR850 was observed in these six genotypes regardless of the developmental stage. Although the actual target genes and functions of miR840 and miR850 remain to be determined, our results indicate that these two miRNAs may be strongly induced and reproducible genetic markers in Arabidopsis plants exposed to gamma rays.

Genetic diversity and population structure of Hyporhamphus sajori (Beloniformes: Hemiramphidae) inferred from mtDNA control region and msDNA markers.

This paper presents preliminary data on the genetic diversity and population structure of Hyporhamphus sajori by analysing a 510 bp sequence in the mitochondrial DNA (mtDNA) control region and eight polymorphic microsatellite DNA loci. The H. sajori individuals from different locations were indistinguishable from one another based on mtDNA variation, as demonstrated with a neighbour-joining tree and minimum spanning network analysis. Low level of genetic diversity and the absence of population structure in H. sajori from the north-west Pacific Ocean, combined with negative indices for neutral evolution in these populations, suggest that H. sajori underwent a population expansion after a recent bottleneck. The Structure analysis, discriminant analysis of principal components (DAPC) and the pair-wise ΦST values after Bonferroni correction using eight microsatellite loci provided no clear inference on the genetic differentiation and thus no evidence of population structure of H. sajori. The genetic connectivity among locations might be due to fairly high gene flow via transport of eggs and larvae by the Kuroshio and Tsushima warm current. This study revealed low levels of genetic diversity and suggested high level of contemporary gene flow among populations of H. sajori in the East (Japan) Sea and the Pacific Ocean.

Factors affecting long-term outcome of transoral surgery for submandibular stones: a follow-up study of 125 patients.

OBJECTIVE: To investigate the long-term results of transoral surgery for submandibular stones and assess factors that may affect the long-term outcomes. STUDY DESIGN: A follow-up study including retrospective review of medical records and prospective telephone survey. SETTING: Tertiary Hospital. PARTICIPANTS: A total of 125 patients who had undergone transoral surgery for submandibular stones and responded to telephone survey. MAIN OUTCOME MEASURES: Recurrent obstructive symptoms, tongue paraesthesia. RESULTS: The period between transoral surgery and telephone survey was mean 54.8 months. Eighteen (14.4%) of 125 patients had recurrent obstructive symptoms, and 7 (5.6%) patients showed tongue paraesthesia. Proximal stones (P = 0.041) and partially removed stones (P = 0.003) had significant impact on the development of recurrent obstructive symptoms via multivariate analysis. No significant factors for increased risk of tongue paraesthesia were identified. Recurred symptoms could be managed by subsequent transoral surgeries or conservative management. CONCLUSIONS: Complete removal of proximal stones and gland-preserving management of recurred symptoms are the essential elements to achieve good long-term outcome of transoral surgery for the submandibular stones.

Comparison of two preventive interventions on dental caries among children in Democratic People's Republic of Korea.

OBJECTIVES: The aim was to compare the change in dental caries status in two different intervention groups of the Children's Oral Health Promotion Programme (COHPP). METHODS: A longitudinal study among 500 children who had participated into the COHPP for 6 years was conducted in Pyongyang, Democratic People's Republic of Korea (DPRK). Children in Group I received intensified school-based intervention and were clinically examined at the age of 7 years in 2007 (n = 250), 10 years in 2010 (n = 250) and 13 years in 2013 (n = 242). Children in Group II (n = 250) joined the programme at the age of 4 years in kindergarten in 2007, were provided with early preschool-based intervention and were clinically examined at the age of 7 years in 2010 and 10 years in 2013. RESULTS: Both the prevalence and the mean number of dt + DT decreased significantly in both groups during the follow-up. This was due to decrease in the number of dt, whereas the number of DT remained relatively constant. Poisson regression showed that the association between the group status and the change in the number of dt + DT was statistically significant when adjusted for gender but disappeared when the school was included in the analysis. CONCLUSIONS: The decrease in dental caries may be partly due to the exfoliation of deciduous teeth and dental treatment received. However, the study gave some reference emphasizing the early starting of the prevention.