Utility of long-read sequencing for All of Us.

The All of Us (AoU) initiative aims to sequence the genomes of over one million Americans from diverse ethnic backgrounds to improve personalized medical care. In a recent technical pilot, we compare the performance of traditional short-read sequencing with long-read sequencing in a small cohort of samples from the HapMap project and two AoU control samples representing eight datasets. Our analysis reveals substantial differences in the ability of these technologies to accurately sequence complex medically relevant genes, particularly in terms of gene coverage and pathogenic variant identification. We also consider the advantages and challenges of using low coverage sequencing to increase sample numbers in large cohort analysis. Our results show that HiFi reads produce the most accurate results for both small and large variants. Further, we present a cloud-based pipeline to optimize SNV, indel and SV calling at scale for long-reads analysis. These results lead to widespread improvements across AoU.

A proposal for an oral health educational programme for the first 1000 days of life: from pregnancy to childhood.

AIM: The aim of this paper is to highlight the need to consider oral health during the first 1000 days of a child's life with a view to developing appropriate educational programmes. CONTEXT: The first 1000 days of life represent a window of opportunity for prevention in children. This concept is built on a consideration of the overall health of mother and child, taking into account social inequalities in health. It is now established that the oral health of the mother determines the oral health of her child. Furthermore, parents' knowledge and behaviour have a direct influence on their child's health. CONCLUSION: The majority of the population does not have the necessary skills to adopt behaviours that promote oral health. The need for oral health education begins in the first 1000 days of life. Following the model of family health education, these programmes would involve providing pregnant women and, therefore, families with the skills they need to manage their own oral health and that of their future child as early as possible.

Predicting Dental Caries in Young Children in Primary Health Care Settings.

Young children need increased access to dental prevention and care. Targeting high caries risk children first helps meet this need. The objective of this study was to develop a parent-completed, easy-to-score, short, accurate caries risk tool for screening in primary health care settings to identify children at increased risk for cavities. A longitudinal, prospective, multisite, cohort study enrolled (primarily through primary health care settings) and followed 985 (out of 1,326) 1-y-old children and their primary caregivers (PCGs) until age 4. The PCG completed a 52-item self-administered questionnaire, and children were examined using the International Caries Detection and Assessment Criteria (ICDAS) at 12 ± 3 mo (baseline), 30 ± 3 mo (80% retention), and 48 ± 3 mo of age (74% retention). Cavitated caries lesion (dmfs = decayed, missing, and filled surfaces; d = ICDAS ≥3) experience at 4 y of age was assessed and tested for associations with questionnaire items using generalized estimating equation models applied to logistic regression. Multivariable analysis used backward model selection, with a limit of 10 items. At age 4, 24% of children had cavitated-level caries experience; 49% were female; 14% were Hispanic, 41% were White, 33% were Black, 2% were other, and 10% were multiracial; 58% enrolled in Medicaid; and 95% lived in urban communities. The age 4 multivariable prediction model, using age 1 responses (area under the receiver operating characteristic curve = 0.73), included the following significant (P < 0.001) variables (odds ratios): child participating in public assistance programs such as Medicaid (1.74), being non-White (1.80-1.96), born premature (1.48), not born by caesarean section (1.28), snacking on sugary snacks (3 or more/d, 2.22; 1-2/d or weekly, 1.55), PCG cleaning the pacifier with juice/soda/honey or sweet drink (2.17), PCG daily sharing/tasting food with child using same spoon/fork/glass (1.32), PCG brushing their teeth less than daily (2.72), PCG's gums bleeding daily when brushing or PCG having no teeth (1.83-2.00), and PCG having cavities/fillings/extractions in past 2 y (1.55). A 10-item caries risk tool at age 1 shows good agreement with cavitated-level caries experience by age 4.

Microbial Indicators of Dental Health, Dysbiosis, and Early Childhood Caries.

Dental caries lesions are a clinical manifestation of disease, preceded by microbial dysbiosis, which is poorly characterized and thought to be associated with saccharolytic taxa. Here, we assessed the associations between the oral microbiome of children and various caries risk factors such as demographics and behavioral and clinical data across early childhood and characterized over time the salivary and dental plaque microbiome of children before clinical diagnosis of caries lesions. Children (N = 266) were examined clinically at ~1, 2.5, 4, and 6.5 y of age. The microbiome samples were collected at 1, 2.5, and 4 y. Caries groups consisted of children who remained caries free (International Caries Detection and Assessment System [ICDAS] = 0) at all time points (CFAT) (n = 50); children diagnosed with caries (ICDAS ≥ 1) at 6.5 y (C6.5), 4 y (C4), or 2.5 y of age (C2.5); and children with early caries or advanced caries lesions at specific time points. Microbial community analyses were performed on zero-radius operational taxonomic units (zOTUs) obtained from V4 of 16S ribosomal RNA gene amplicon sequences. The oral microbiome of the children was affected by various factors, including antibiotic use, demographics, and dietary habits of the children and their caregivers. At all time points, various risk factors explained more of the variation in the dental plaque microbiome than in saliva. At 1 y, composition of saliva of the C4 group differed from that of the CFAT group, while at 2.5 y, this difference was observed only in plaque. At 4 y, multiple salivary and plaque zOTUs of genera Prevotella and Leptotrichia were significantly higher in samples of the C6.5 group than those of the CFAT group. In conclusion, up to 3 y prior to clinical caries detection, the oral microbial communities were already in a state of dysbiosis that was dominated by proteolytic taxa. Plaque discriminated dysbiotic oral ecosystems from healthy ones better than saliva.

Immunologic Heterogeneity in 2 Cartilage-Hair Hypoplasia Patients With a Distinct Clinical Course.

BACKGROUND AND OBJECTIVE: Cartilage-hair hypoplasia (CHH) syndrome is a rare autosomal recessive syndrome associated with skeletal dysplasia, varying degrees of combined immunodeficiency (CID), short stature, hair hypoplasia, macrocytic anemia, increased risk of malignancies, and Hirschsprung disease. To provide clinical and immunological insights obtained from 2 unrelated patients who displayed clinical characteristics of CHH. METHODS: Two patients with suspected CHH syndrome due to skeletal dysplasia and immunodeficiency underwent an immunological and genetic work-up using flow cytometry, next-generation sequencing (NGS) of the immune repertoire, and Sanger sequencing to identify the underlying defects. RESULTS: Patient 1 presented with low birth weight and skeletal dysplasia. Newborn screening was suggestive of T-cell immunodeficiency, as T-cell receptor excision circle levels were undetectable. Both the T-cell receptor (TCR) Vß and TCR-g (TRG) repertoires were restricted, with evidence of clonal expansion. Genetic analysis identified compound heterozygous RMRP variants inherited from both parents. Patient 2 presented with recurrent lung and gastrointestinal infections, skeletal dysplasia, failure to thrive, and hepatomegaly. The polyclonal pattern of the TCRß repertoire was normal, with only slight overexpression of TCR-ßV20 and restricted expression of Vßs. TRG expressed a normal diverse repertoire, similar to that of the healthy control sample. Genetic analysis identified biallelic novel regulatory variants in RMRP. Both parents are carriers of this mutation. CONCLUSION: Our findings demonstrate how the immunological work-up, supported by genetic findings, can dramatically change treatment and future outcome in patients with the same clinical syndrome.

Impact of Fluoride on Associations between Free Sugars Intake and Dental Caries in US Children.

OBJECTIVE: Dental caries is the most prevalent chronic disease in US children, with the highest burden among Black and Hispanic youth. Sugars are a primary risk factor, but few studies have specifically measured intakes of free sugars and related this to dental caries or explored the extent to which water fluoride mitigates the cariogenicity of free sugars. Furthermore, the cariogenicity of certain free sugars sources, such as extruded fruit and vegetable products, is unclear. METHODS: Using cross-sectional data on 4,906 children aged 2 to 19 y in the US National Health and Nutrition Examination Survey 2013-2016, we examined associations of free sugars intake with counts of decayed or filled primary tooth surfaces (dfs) and decayed, missing, or filled permanent surfaces (DMFS) in negative binomial regressions. Stratified models examined these associations in children with home water fluoride above or below the Centers for Disease Control and Prevention (CDC)-recommended level of 0.7 ppm. RESULTS: Free sugars accounted for 16.4% of energy, primarily contributed by added sugars. In adjusted models, a doubling in the percentage of energy from free sugars was associated with 22% (95% confidence interval [CI], 1%-47%) greater dfs among children aged 2 to 8. A doubling in energy from added sugars was associated with 20% (95% CI, 1%-42%) greater dfs and 10% (95% CI, 2%-20%) greater DMFS in children aged 6 to 19 y. Beverages were the most important source of added sugars associated with increased caries. Other free sugars were not associated with dfs or DMFS. Associations between free sugars and caries were diminished among children with home water fluoride of 0.7 ppm or greater. CONCLUSIONS: Free sugars intake, especially in the form of added sugars and specifically in sweetened beverages, was associated with higher dental caries. Water fluoride exposures modify these associations, reducing caries risk in the primary dentition of children whose home water meets recommended fluoride levels. KNOWLEDGE TRANSFER STATEMENT: Intake of free sugars, especially in the form of added sugars and specifically in beverages, was associated with higher dental caries in US children in this study. Water fluoride exposure at CDC-recommended levels protected against caries, especially in the primary dentition. These findings suggest that household water fluoridation at CDC-recommended levels protects against the cariogenic potential of free and added sugars during childhood.

RLSuite: An Integrative R-Loop Bioinformatics Framework.

We recently described the development of a database of 810 R-loop mapping datasets and used this data to conduct a meta-analysis of R-loops. R-loops are three-stranded nucleic acid structures containing RNA:DNA hybrids and we were able to verify that 30% of expressed genes have an associated R-loop in a location conserved manner.. Moreover, intergenic R-loops map to enhancers, super enhancers and with TAD domain boundaries. This work demonstrated that R-loop mapping via high-throughput sequencing can reveal novel insight into R-loop biology, however the analysis and quality control of these data is a non-trivial task for which few bioinformatic tools exist. Herein we describe RLSuite, an integrative R-loop bioinformatics framework for pre-processing, quality control, and downstream analysis of R-loop mapping data. RLSuite enables users to compare their data to hundreds of public datasets and generate a user-friendly analysis report for sharing with non-bioinformatician colleagues. Taken together, RLSuite is a novel analysis framework that should greatly benefit the emerging R-loop bioinformatics community in a rapidly expanding aspect of epigenetic control that is still poorly understood.

Immunologic Heterogeneity in 2 Cartilage-Hair Hypoplasia Patients With a Distinct Clinical Course

Introduction: Cartilage-hair hypoplasia (CHH) syndrome is a rare autosomal recessive syndrome associated with skeletal dysplasia, varying degrees of combined immunodeficiency (CID), short stature, hair hypoplasia, macrocytic anemia, increased risk of malignancies, and Hirschsprung disease. Purpose: To provide clinical and immunological insights obtained from 2 unrelated patients who displayed clinical characteristics of CHH. Methods: Two patients with suspected CHH syndrome due to skeletal dysplasia and immunodeficiency underwent an immunological and genetic work-up using flow cytometry, next-generation sequencing (NGS) of the immune repertoire, and Sanger sequencing to identify the underlying defects. Results: Patient 1 presented with low birth weight and skeletal dysplasia. Newborn screening was suggestive of T-cell immunodeficiency, as T-cell receptor excision circle levels were undetectable. Both the T-cell receptor (TCR) Vß and TCR-g (TRG) repertoires were restricted, with evidence of clonal expansion. Genetic analysis identified compound heterozygous RMRP variants inherited from both parents. Patient 2 presented with recurrent lung and gastrointestinal infections, skeletal dysplasia, failure to thrive, and hepatomegaly. The polyclonal pattern of the TCRß repertoire was normal, with only slight overexpression of TCR-ßV20 and restricted expression of Vßs. TRG expressed a normal diverse repertoire, similar to that of the healthy control sample. Genetic analysis identified biallelic novel regulatory variants in RMRP. Both parents are carriers of this mutation. Conclusion: Our findings demonstrate how the immunological work-up, supported by genetic findings, can dramatically change treatment and future outcome in patients with the same clinical syndrome (AU)

Phenotype Harmonization in the GLIDE2 Oral Health Genomics Consortium.

Genetic risk factors play important roles in the etiology of oral, dental, and craniofacial diseases. Identifying the relevant risk loci and understanding their molecular biology could highlight new prevention and management avenues. Our current understanding of oral health genomics suggests that dental caries and periodontitis are polygenic diseases, and very large sample sizes and informative phenotypic measures are required to discover signals and adequately map associations across the human genome. In this article, we introduce the second wave of the Gene-Lifestyle Interactions and Dental Endpoints consortium (GLIDE2) and discuss relevant data analytics challenges, opportunities, and applications. In this phase, the consortium comprises a diverse, multiethnic sample of over 700,000 participants from 21 studies contributing clinical data on dental caries experience and periodontitis. We outline the methodological challenges of combining data from heterogeneous populations, as well as the data reduction problem in resolving detailed clinical examination records into tractable phenotypes, and describe a strategy that addresses this. Specifically, we propose a 3-tiered phenotyping approach aimed at leveraging both the large sample size in the consortium and the detailed clinical information available in some studies, wherein binary, severity-encompassing, and "precision," data-driven clinical traits are employed. As an illustration of the use of data-driven traits across multiple cohorts, we present an application of dental caries experience data harmonization in 8 participating studies (N = 55,143) using previously developed permanent dentition tooth surface-level dental caries pattern traits. We demonstrate that these clinical patterns are transferable across multiple cohorts, have similar relative contributions within each study, and thus are prime targets for genetic interrogation in the expanded and diverse multiethnic sample of GLIDE2. We anticipate that results from GLIDE2 will decisively advance the knowledge base of mechanisms at play in oral, dental, and craniofacial health and disease and further catalyze international collaboration and data and resource sharing in genomics research.

Concurrent validity of the short-form Family Impact Scale (FIS-8) in 4-year-old US children.

BACKGROUND: US data on the validity and reliability of the short-form Family Impact Scale (FIS-8; a scale for measuring the impact of a child's oral condition on his/her family) are lacking. METHODS: Cross-sectional analysis of data on four-year-old US children taking part in a multi-center cohort study. For child-caregiver dyads recruited at child age 12 months, the impact of the child's oral condition on the family was assessed at age 48 months using the FIS-8, with a subsample of 422 caregivers (from 686 who were approached). Internal consistency reliability was assessed using Cronbach's α, with concurrent validity assessed against a global family impact item ("How much are your family's daily lives affected by your child's teeth, lips, jaws or mouth?") and a global oral health item ("How would you describe the health of your child's teeth and mouth?"). RESULTS: Cronbach's alpha was 0.83. Although gradients in mean scores across ordinal response categories of the global family impact item were inconsistent, there were marked, consistent gradients across the ordinal categories of the global item on the child's oral health, with scores highest for those rating their child's oral health as 'Poor'. CONCLUSIONS: While the findings provide some evidence for the utility of the FIS in a US child sample, the study's replication in samples of preschoolers with greater disease experience would be useful.

[Factors associated with intrahospital mortality in older patients with COVID-19 in Belgium : The COVID-AgeBru study]. / Face à la COVID-19. Mortalité intra-hospitalière chez les patients âgés de plus de 70 ans avec COVID-19 dans un hôpital universitaire en Belgique :l'étude COVID-AgeBru.

OBJECTIVE: We aimed at assessing the association between demographical and clinical data and the intrahospital mortality in older patients with COVID-19 in Belgium. METHODS: Descriptive, retrospective study of consecutive patients admitted to Brugmann university hospital, Brussels (Belgium) due to COVID-19 (Mars-September-2020). INCLUSION CRITERIA: Patients aged ≥ 70 years admitted to acute care with a positive PCR-RT test, or a highly indicative computed tomography scan. EXCLUSION CRITERIA: Patients transferred to another institution during hospitalization. OUTCOME MEASURE: All-cause intrahospital mortality. Demographic, clinical data, presence of comordibidties and comprehensive geriatric assessment were collected. Adjusted and unadjusted logistic regression were performed. RESULTS: From the 226 eligible patients, 160 (82.7 ± 6.5-year-old; 57.5 % females) met inclusion criteria, from which 67 (42 %) died during hospital stay. The adjusted logistic regression showed an association between intrahospital mortality and increasing age [OR = 1.09 per every year increase (95 % CI 1.02-1.16); p <0.001], type 2 diabetes [OR = 2.75 ( 1.17-6.46); p = 0.021], and acute respiratory distress syndrome (ARDS) [OR = 8.67 ( 3.48-21.61); p < 0.01]. CONCLUSIONS: A higher positive association between intrahospital mortality and increasing age, type 2 diabetes, and ARDS was found. The prognosis value of the comprehensive geriatric assessment in older people with COVID-19 in Belgium requires further studies.

INTRODUCTION: Les études sur l'impact de la pandémie en Belgique sont rares. L'objectif est d'évaluer l'association de l'âge et des comorbidités à la mortalité intra-hospitalière de toutes causes chez les patients âgés ? 70 ans avec COVID-19 dans un hôpital universitaire à Bruxelles, Belgique. Méthodes : Etude rétrospective descriptive des patients admis au CHU Brugmann pour cause de maladie COVID-19 (mars-septembre 2020). Critères d'inclusion : âge ≥ 70 ans admis avec PCR-RT positif ou haute probabilité d'infection au CT-scan thoracique. Critères d'exclusion : transfert dans un autre hôpital. Critère de jugement : toute cause de mortalité intra-hospitalière. Variables collectées : démographiques, cliniques et gériatriques [Katz, Lawton, MMSE, MNA, MNA-SF]. Une régression logistique non ajustée et ajustée a été réalisée. Résultats : Parmi les 226 patients éligibles, 160 (82,7 ± 6,5 ans; 57,5 % femmes) ont rempli les critères d'inclusion. Au total, 67 (42 %) sont décédés durant l'hospitalisation. La régression logistique a montré une association augmentée entre la mortalité et l'âge [odds ratio ou OR = 1,09/année en plus (IC 95 % 1,02-1,16) ; p< 0,001], le diabète de type 2 [OR = 2,75 (1,17-6,46); p = 0,021], l'ARDS [OR = 8,67 (3,48-21,61); p < 0,01]. CONCLUSION: L'âge, le diabète de type 2 et le syndrome de détresse respiratoire aiguë (ARDS) sont associés à une augmentation de la mortalité chez les patients âgés hospitalisés avec COVID-19 en Belgique.

Characterization of the public transit air microbiome and resistome reveals geographical specificity.

BACKGROUND: The public transit is a built environment with high occupant density across the globe, and identifying factors shaping public transit air microbiomes will help design strategies to minimize the transmission of pathogens. However, the majority of microbiome works dedicated to the public transit air are limited to amplicon sequencing, and our knowledge regarding the functional potentials and the repertoire of resistance genes (i.e. resistome) is limited. Furthermore, current air microbiome investigations on public transit systems are focused on single cities, and a multi-city assessment of the public transit air microbiome will allow a greater understanding of whether and how broad environmental, building, and anthropogenic factors shape the public transit air microbiome in an international scale. Therefore, in this study, the public transit air microbiomes and resistomes of six cities across three continents (Denver, Hong Kong, London, New York City, Oslo, Stockholm) were characterized. RESULTS: City was the sole factor associated with public transit air microbiome differences, with diverse taxa identified as drivers for geography-associated functional potentials, concomitant with geographical differences in species- and strain-level inferred growth profiles. Related bacterial strains differed among cities in genes encoding resistance, transposase, and other functions. Sourcetracking estimated that human skin, soil, and wastewater were major presumptive resistome sources of public transit air, and adjacent public transit surfaces may also be considered presumptive sources. Large proportions of detected resistance genes were co-located with mobile genetic elements including plasmids. Biosynthetic gene clusters and city-unique coding sequences were found in the metagenome-assembled genomes. CONCLUSIONS: Overall, geographical specificity transcends multiple aspects of the public transit air microbiome, and future efforts on a global scale are warranted to increase our understanding of factors shaping the microbiome of this unique built environment.

T1 Mapping for Microstructural Assessment of the Cervical Spinal Cord in the Evaluation of Patients with Degenerative Cervical Myelopathy.

BACKGROUND AND PURPOSE: Although current radiologic evaluation of degenerative cervical myelopathy by conventional MR imaging accurately demonstrates spondylosis or degenerative disc disease causing spinal cord dysfunction, conventional MR imaging still fails to provide satisfactory anatomic and clinical correlations. In this context, we assessed the potential value of quantitative cervical spinal cord T1 mapping regarding the evaluation of patients with degenerative cervical myelopathy. MATERIALS AND METHODS: Twenty patients diagnosed with mild and moderate-to-severe degenerative cervical myelopathy and 10 healthy subjects were enrolled in a multiparametric MR imaging protocol. Cervical spinal cord T1 mapping was performed with the MP2RAGE sequence procedure. Retrieved data were processed and analyzed regarding the global spinal cord and white and anterior gray matter on the basis of the clinical severity and the spinal canal stenosis grading. RESULTS: Noncompressed levels in healthy controls demonstrated significantly lower T1 values than noncompressed, mild, moderate, and severe stenotic levels in patients. Concerning the entire spinal cord T1 mapping, patients with moderate-to-severe degenerative cervical myelopathy had higher T1 values compared with healthy controls. Regarding the specific levels, patients with moderate-to-severe degenerative cervical myelopathy demonstrated a T1 value increase at C1, C7, and the level of maximal compression compared with healthy controls. Patients with mild degenerative cervical myelopathy had lower T1 values than those with moderate-to-severe degenerative cervical myelopathy at the level of maximal compression. Analyses of white and anterior gray matter confirmed similar results. Strong negative correlations between individual modified Japanese Orthopaedic Association scores and T1 values were also observed. CONCLUSIONS: In this preliminary study, 3D-MP2RAGE T1 mapping demonstrated increased T1 values in the pathology tissue samples, with diffuse medullary alterations in all patients with degenerative cervical myelopathy, especially relevant at C1 (nonstenotic level) and at the maximal compression level. Encouraging correlations observed with the modified Japanese Orthopaedic Association score make this novel approach a potential quantitative biomarker related to clinical severity in degenerative cervical myelopathy. Nevertheless, patients with mild degenerative cervical myelopathy demonstrated nonsignificant results compared with healthy controls and should now be studied in multicenter studies with larger patient populations.

Metabolic and Renal Effects of Mammalian Target of Rapamycin Inhibitors Treatment After Liver Transplantation: Real-Life Single-Center Experience.

BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitors following liver transplantation (LT) are used to minimize calcineurin inhibitor (CNI)-related nephrotoxicity. Data about metabolic effects of mTOR inhibitors are still limited. AIM: This study aims to determine the renal and metabolic effects of different mTOR inhibitor-based protocols in real-life LT patients. METHODS: This is a retrospective cohort study of patients treated with mTOR inhibitors after LT. Demographics, treatment protocols, glomerular filtration rate (GFR), and metabolic parameters were collected over a period of 4 years. Initiation of blood pressure (BP), diabetes mellitus, and lipid medications was also noted. RESULTS: Fifty-two LT recipients received mTOR inhibitors. GFR improved significantly (by 1.96 mL/min/year), with greater improvement in patients with baseline renal dysfunction (+13.3 mL/min vs +4.5 mL/min at 3 years). Conversion to an mTOR inhibitor during the first post-transplant year resulted in a more durable improvement in GFR (for 4 years vs only 1 year for later conversion).No significant weight gain or new-onset diabetes mellitus was observed. However, there was some increase in total cholesterol (+7 mg/dL) and blood pressure (+2 mm Hg during the third year and +8 mm Hg in the fourth years), followed by initiation of lipid-lowering and BP medications in 25% and 13% of patients, respectively. CONCLUSIONS: Treatment with an mTOR inhibitor following LT resulted in improved kidney functions without significant negative metabolic effects such as weight gain or new-onset diabetes mellitus. This makes mTOR inhibitors a valuable immunosuppressive option in the face of the growing incidence of nonalcoholic steatohepatitis as a leading cause for LT.

[Social inequalities in oral health and early childhood caries: How can they be effectively prevented? A scoping review of disease predictors]. / Inégalités sociales de santé orale et caries précoces de l'enfant : comment prévenir efficacement ? Une revue de portée des prédicteurs de la maladie.

BACKGROUND: Early childhood caries represent a major public health problem. In addition to their individual impact, the massive social inequalities in oral health that are at the roots and result from the disease have largely underestimated consequences for the child, his family and the community. In response to the question of "how and where to act?", this scoping review identifies the individual characteristics associated with the disease on which it would be possible to act, using appropriate prevention strategies. METHODS: This scoping review is aimed at describing and analyzing available data in the literature on the different factors associated with early childhood caries. RESULTS: The predictors of early childhood caries are represented by mediating (knowledge, attitudes and parents' oral health practices) and moderating (psychosocial parameters, parental health literacy and alcohol consumption) factors. Twenty-eight articles fulfilled the selection criteria, twenty of which studied mediators related to early childhood caries, and fourteen of which dealt with moderators. The lower the parents' level of knowledge and literacy in oral health, the higher a child's dmft index. Additional studies are needed to assess the role of psychosocial parameters. CONCLUSION: Parents' knowledge and oral health literacy are the key predictors to be preferentially targeted in view of reducing social inequalities in health through actions undertaken on a local scale. The prevention of early childhood caries necessitates a combination of generic and targeted interventions.

Decline in Dental Fluorosis Severity during Adolescence: A Cohort Study.

Dental fluorosis occurs from overingestion of fluoride during tooth formation. However, there is little evidence in the literature on whether or how fluorosis prevalence and severity change over time after tooth eruption. Permanent dentition dental examinations were conducted at ages 9, 13, 17, and 23 as part of the Iowa Fluoride Study, which has followed a cohort from birth. Fluorosis was assessed using the Fluorosis Risk Index (FRI) and Russell's criteria for differential diagnosis. Measures of fluorosis severity at the person and tooth level were calculated: second highest FRI score at the person level (the maximum FRI score for each tooth was determined and the tooth with the second highest maximum FRI score was used) and highest FRI score at the tooth level. At both the person and tooth levels, a decline in mild to moderate fluorosis severity was observed across adolescence and young adulthood. Across each pair of adjacent examinations at the person level, for participants with a baseline second highest FRI of 0, most participants stayed at 0 (82% to 91%). Many participants with a baseline second highest FRI of 1 had a follow-up score of 0 (47% to 54%), while about a third had a follow-up score of 1 (34% to 38%), and a lower percentage had an increase to a score of 2 (9% to 15%). For participants with baseline second highest FRI score of 2, between 25% and 44% of participants had follow-up FRI scores each of 0, 1, and 2. Similar patterns were observed at the tooth level. These results were consistent with most of the existing, limited literature. Overall, fluorosis severity, which was initially mild to moderate, tended to decline during adolescence and young adulthood. Additional study of how this trend affects esthetic perceptions of fluorosis is warranted.

[Lack of medical or dental care: Impact on health expenditures for people with chronic disease]. / L'effet du non-recours aux soins médicaux et dentaires sur les dépenses de santé des personnes ayant une maladie chronique.

BACKGROUND: People with chronic disease often have dental (especially periodontal) disorders. Nevertheless, people with chronic disease seek dental care less often than others. We wanted to know if there is a relationship between the consumption of medical care and the consumption of dental care, and if so if the relationship is especially strong for people with chronic disease. METHODS: We conducted a longitudinal study that combined two data-sets: consumption data from the French National Health Insurance Fund and health and socioeconomic welfare data collected with a dedicated national survey. We studied healthcare expenditure and analyzed the association between healthcare consumption, health status and healthcare expenditure over a four-year period (2010-2013). RESULTS: People who did not seek medical or dental care in 2010 exhibited irregular consumer behavior thereafter. This pattern was particularly evident among those with chronic disease whose healthcare expenditures did not stabilize during the study period compared with the rest of the study population. Among people who did not seek medical care in 2010, variation in average dental care expenditure was 91% in people with chronic disease versus 42% for those without chronic disease. Lack of medical care during the first year of the study was also associated with greater expenditure-delay in people with chronic disease (77%) compared with 15% in people without chronic disease. CONCLUSION: The lack of medical or dental care in 2010 for people with chronic disease did not lead to an increase in medical and dental consumption in the following years. The catch-up delay was longer than four years. This highlights a problem of monitoring and identifies a marginalized population within the healthcare system.

Potential tick vectors for Theileria equi in Israel.

Theileria equi Mehlhorn and Schein, 1998 (Piroplasmida: Babesiidae) is an important tick-borne pathogen of horses that is highly endemic in many parts of the world, including Israel. The present study evaluated the potential roles of five hard tick species [Hyalomma excavatum Koch, 1844; Hyalomma marginatum Koch, 1844; Rhipicephalus turanicus Pomerantsev 1936; Rhipicephalus annulatus Say, 1821; Haemaphysalis parva (Neumann, 1897) (all: Ixodida: Ixodidae)], previously found to infest horses in Israel, in acting as vectors for piroplasmosis. For this, DNA was extracted from whole ticks and, when possible, from the salivary glands in each species (n = 10-59). Polymerase chain reaction amplification and sequencing of the 18S rRNA gene were used to detect T. equi in 48 of the 127 ticks (37.8%) and in 21 of the 90 extracted salivary glands (23.3%) in all five species. All but two sequences were classified as T. equi genotype A; the remaining two were classified as genotype D. The findings of this study point to Ha. parva and R. annulatus as potential novel vectors of T. equi, and suggest that parasite genotype selection occurs within the tick vector.

[Children's consultations for dental emergency. Retrospective study in Île-de-France]. / Consultations pour urgence bucco-dentaire chez les enfants : étude rétrospective en Île-de-France.

BACKGROUND: In France, the children oral health status has improved but the use of care remains insufficient. The complexity of the acts, the access to care difficulties and the programs of prevention and care for children lack of knowledge contribute to late care and often, in emergency. This study aims to describe the young patients' characteristics consulting in dental emergency and analyse the modalities of recourse. METHODS: A retrospective study was conducted on medical records. An extraction of data was carried out concerning all children under the age of 16, admitted to the Dental Emergency Functional Unit of the Pitié-Salpêtrière Hospital Group in 2015. Several variables of interest were analysed: socio-demographic characteristics, the time of the visit and the diagnostic category (tooth pathologies, facial trauma, infections, periodontal diseases and other emergencies). Descriptive and bivariate analyses were conducted. RESULTS: On the 62,500 dental emergency consultations in 2015, 5359 were for patients under 16 years of age (8%). Data were available for 5044 children. Among these, children aged 6 to 11 accounted most of consultations (43.9%). There were more boys (57.2%). The most frequent emergency diagnoses were related to a tooth pathology (42.9%) and traumatic event (38.4%). Consultations were more held on the evening schedule on weekdays and the day on weekends. Patients aged 0 to 5 years consulted more at night (P<10-3) and were, proportionally, the most affected by traumatic events (39.2%). Children aged 6 to 11 and 12 to 16 years consulted more often during the day (P<10-3), for emergencies related to a carious event (43.9% and 43.6%). Patients residing in Seine-Saint-Denis accounted for 22.6% of total visits and those living in Paris accounted for 20.8%. CONCLUSION: A large proportion of children presenting for dental emergencies, have most of the time, only the need for usual care. An offer of dental care, adapted to the territory needs, is necessary for the children dental health management. Preventive measures from an early age and early recourse would be favourable.

Maturation of the Oral Microbiome in Caries-Free Toddlers: A Longitudinal Study.

Understanding the development of the oral microbiota in healthy children is of great importance to oral and general health. However, limited data exist on a healthy maturation of the oral microbial ecosystem in children. Moreover, the data are biased by mislabeling "caries-free" populations. Therefore, we aimed to characterize the healthy salivary and dental plaque microbiome in young children. Caries-free (ICDAS [International Caries Detection and Assessment System] score 0) children (n = 119) and their primary caregivers were followed from 1 until 4 y of child age. Salivary and dental plaque samples were collected from the children at 3 time points (T1, ~1 y old; T2, ~2.5 y old; and T3, ~4 y old). Only saliva samples were collected from the caregivers. Bacterial V4 16S ribosomal DNA amplicons were sequenced using Illumina MiSeq. The reads were denoised and mapped to the zero-radius operational taxonomic units (zOTUs). Taxonomy was assigned using HOMD. The microbial profiles of children showed significant differences (P = 0.0001) over time. Various taxa increased, including Fusobacterium, Actinomyces, and Corynebacterium, while others showed significant decreases (e.g., Alloprevotella and Capnocytophaga) in their relative abundances over time. Microbial diversity and child-caregiver similarity increased most between 1 and 2.5 y of age while still not reaching the complexity of the caregivers at 4 y of age. The microbiome at 1 y of age differed the most from those at later time points. A single zOTU (Streptococcus) was present in all samples (n = 925) of the study. A large variation in the proportion of shared zOTUs was observed within an individual child over time (2% to 42% of zOTUs in saliva; 2.5% to 38% in dental plaque). These findings indicate that the oral ecosystem of caries-free toddlers is highly heterogeneous and dynamic with substantial changes in microbial composition over time and only few taxa persisting across the 3 y of the study. The salivary microbiome of 4-y-old children is still distinct from that of their caregivers.