A systematic review and meta-analysis on early-childhood-caries global data.

OBJECTIVES: The present study systematically reviewed and provided a meta-analysis on early childhood caries (ECC) global prevalence and its association with socioeconomic indicators, both geographical and regarding unemployment rate, national income as well as income inequalities. METHODS: Only cross-sectional or cohort studies covering ECC prevalence and experience in children younger than 71 months, reporting sample size, diagnostic criteria and conducted in urban and rural communities were considered. No language restriction was selected. Studies published from 2011 to 2022 available in PubMed, Web of Science, Embase and Open Grey literature were retrieved by ad hoc prepared search strings. The meta-analyses were conducted for both overall ECC prevalence and experience stratified by country of publication as well as measures of socioeconomic indicators using a random effects model using STATA 18®. RESULTS: One hundred publications reporting ECC data from 49 countries (published from 2011 to 2022) were included and summarized by meta-analysis. The lowest prevalence was reported in Japan (20.6%) and Greece (19.3%). The global estimated random-effect pooled prevalence of ECC was 49% (95%CI: 0.44-0.55). The random-effect pooled caries prevalence (ECC) was 34% (95%CI: 02.20-0.48) (Central/South America), 36% (95%CI: 0.25-0.47) (Europe), 42% (95%CI: 0.32-0.53) (Africa), 52% (95%CI: 0.45-0.60) (Asia-Oceania), 57% (95%CI: 0.36-0.77) (North America) and 72% (95%CI: 0.58-0.85) (Middle East). When stratified by gross national income (GNI) the ECC prevalence ranged from 30% ($20,000-$39,999) to 57% in countries with the lowest GNI (<$5000). Stratification by inequality index (Gini index) resulted in an ECC prevalence range of 39% (low inequality) to 62% (no inequality), while for life expectancy the ECC prevalence ranged from 28% in countries with the highest life expectancy (< 80 years) to 62% in countries with 71-75 years life expectancy. DISCUSSION: Within the limitations of this study (lack of certainty about the results as many countries are not represented and lack of uniformity in prevalence and experience data represented), results from 49 different countries reported a wide range of ECC prevalence. These reports indicated persisting high worldwide distribution of the disease. Both ECC prevalence and experience were associated with geographical areas and GNI. REGISTRATION: PROSPERO: CRD-42,022,290,418.

Global prevalence of edentulism and dental caries in middle-aged and elderly persons: A systematic review and meta-analysis.

OBJECTIVE: The aim of the study was to analyze data collected from studies worldwide on the prevalence of edentulism and dental caries, in community-dwellers aged ≥ 45 years. DATA: Inclusion criteria; participants aged ≥ 45 years, community-dwellers. Exclusion criteria; participants aged < 45 years, in nursing homes, data obtained from dental clinics or pre-2005. The quality assessment tool by The National Heart, Lung and Blood Institute for Observational Cohort and Cross-sectional studies was used. Meta-analysis using the random-effects model (95% confidence interval) was done with data on participants who were edentulous and/or had active dental caries and stratified by regions of the world, age and Gross National Income per capita. Limitations in the data arose from several factors such as design of the studies included differences in socioeconomic status and access to health care among different countries. SOURCES: Embase, MEDLINE via Pubmed and Scopus, manual searches, from January 2016, restricted to English. Experts from different countries were contacted to identify National oral health surveys (NOHS) conducted from 2010 onwards. STUDY SELECTION: Eighty-six papers and seventeen NOHS were selected for data extraction. Majority of the studies (n = 69) were cross-sectional and of fair quality. 1.1%-70%, 4.9% - 98% prevalence of edentulism and dental caries, respectively. 22%, 45% estimated random-effects pooled prevalence of edentulism and dental caries, respectively. CONCLUSIONS: Within the limitations of this study, the findings indicate that untreated dental caries and tooth loss are prevalent on a global level with wide variations among different countries, age groups and socioeconomic status. CLINICAL SIGNIFICANCE: The findings demonstrate the reality of the new cohort of older adults, with higher tooth retention implying more dental caries incidence and the need for different care strategies to ensure better oral health. Large variations and difficulty in making comparisons among different countries highlight the need for more standardized, regular research.

Functionally distinct roles for different miR-155 expression levels through contrasting effects on gene expression, in acute myeloid leukaemia.

Enforced expression of microRNA-155 (miR-155) in myeloid cells has been shown to have both oncogenic or tumour-suppressor functions in acute myeloid leukaemia (AML). We sought to resolve these contrasting effects of miR-155 overexpression using murine models of AML and human paediatric AML data sets. We show that the highest miR-155 expression levels inhibited proliferation in murine AML models. Over time, enforced miR-155 expression in AML in vitro and in vivo, however, favours selection of intermediate miR-155 expression levels that results in increased tumour burden in mice, without accelerating the onset of disease. Strikingly, we show that intermediate and high miR-155 expression also regulate very different subsets of miR-155 targets and have contrasting downstream effects on the transcriptional environments of AML cells, including genes involved in haematopoiesis and leukaemia. Furthermore, we show that elevated miR-155 expression detected in paediatric AML correlates with intermediate and not high miR-155 expression identified in our experimental models. These findings collectively describe a novel dose-dependent role for miR-155 in the regulation of AML, which may have important therapeutic implications.

Acetabular component navigation in lateral decubitus based on EOS imaging: A preliminary study of 13 cases.

INTRODUCTION: Acetabular component navigation classically requires palpation of the bone landmarks defining the anterior pelvic plane (APP) (anterior superior iliac spine [ASIS] and pubis), the recording of which is not very reliable when performed in lateral decubitus. The objectives of the current experimental study were: (1) to assess the clinical feasibility of NAVEOS navigation (based on EOS imaging) in lateral decubitus; and (2) to compare precision versus classical APP-based navigation (NAVAPP). HYPOTHESIS: Iliac plane navigation using EOS is as reliable as APP navigation. PATIENTS AND METHODS: A continuous prospective series of 13 total hip replacements were implanted in lateral decubitus under APP-guided navigation (NAVAPP). Planning used preoperative EOS measurement. The ASIS, pubis and ipsilateral posterior superior iliac spine (PSIS) were located and exported to the navigator. Intra-operatively, NAVEOS landmarks (acetabular center, ASIS and PSIS on the operated side) were palpated. Postoperatively, cup inclination and anteversion with respect to the APP were measured on EOS imaging (SterEOS3D software). The SterEOS3D measurements were compared to those of the performed NAVAPP and simulated NAVEOS navigations. RESULTS: Three patients were excluded for technical reasons. In the remaining 10, inclination on NAVAPP and SterEOS3D differed by a median 4° (range, 0-12°), and on NAVEOS versus SteEOS3D by 5° (range, 2-10°); anteversion on NAVAPP and SterEOS3D differed by a median 4.5° (range, 0-12°), and on NAVEOS versus SteEOS3D by 4° (range, 0-14°). CONCLUSION: Precision was comparable between NAVEOS and classical navigation. NAVEOS simplifies cup navigation in lateral decubitus on initial acquisition. These results require validation on a larger sample.

Bak apoptotic function is not directly regulated by phosphorylation.

During apoptosis, Bak and Bax permeabilize the mitochondrial outer membrane by undergoing major conformational change and oligomerization. This activation process in Bak is reported to require dephosphorylation of tyrosine-108 close to an activation trigger site. To investigate how dephosphorylation of Bak contributes to its activation and conformational change, one-dimensional isoelectric focusing (1D-IEF) and mutagenesis was used to monitor Bak phosphorylation. On 1D-IEF, Bak extracted from a range of cell types migrated as a single band near the predicted isoelectric point of 5.6 both before and after phosphatase treatment, indicating that Bak is not significantly phosphorylated at any residue. In contrast, three engineered 'phosphotagged' Bak variants showed a second band at lower pI, indicating phosphorylation. Apoptosis induced by several stimuli failed to alter Bak pI, indicating little change in phosphorylation status. In addition, alanine substitution of tyrosine-108 and other putative phosphorylation sites failed to enhance Bak activation or pro-apoptotic function. In summary, Bak is not significantly phosphorylated at any residue, and Bak activation during apoptosis does not require dephosphorylation.

Molecular and functional characterization of the cystic fibrosis transmembrane conductance regulator from the Australian common brushtail possum, Trichosurus vulpecula.

Unlike eutherian mammals, the colon of the Australian common brushtail possum, Trichosurus vulpecula, a metatherian mammal, is incapable of electrogenic Cl(-) secretion and has elevated levels of electrogenic Na(+) absorption, while the ileum secretes HCO (3) (-) rather than Cl(-). In eutherian mammals, the cystic fibrosis transmembrane conductance regulator (CFTR) is essential for both Cl(-) and HCO (3) (-) secretion and the regulation of Na(+) absorption. Therefore, we have sequenced possum (p)CFTR, described its distribution and characterized the properties of cloned pCFTR expressed in Fischer rat thyroid (FRT) cells. pCFTR (GenBank accession No. AY916796) has a 1,478 amino acid open reading frame, which has >90% identity with CFTR from other marsupials and >80% identity with non-rodent eutherian mammals. In pCFTR, there is a high level of conservation of the transmembrane and nucleotide binding domains although, with the exception of other marsupials, there is considerable divergence from other species in the R domain. FRT cells transfected with pCFTR express mature CFTR protein which functions as a small Cl(-) channel activated by cAMP-dependent phosphorylation. In whole-cell recordings it has a linear, time and voltage-independent conductance, with a selectivity sequence P(Br) > P(Cl) > P(I) > P(HCO)(3) >> P(Gluconate). pCFTR transcript is present in a range of epithelia, including the ileum and the colon. The presence of pCFTR in the ileum and its measured HCO (3) (-) permeability suggest that it may be involved in ileal HCO (3) (-) secretion. Why the possum colon does not secrete Cl(-) and has elevated electrogenic Na(+) absorption, despite the apparent expression of CFTR, remains to be determined.

Oxcarbazepine and atypical evolution of benign idiopathic focal epilepsy of childhood.

Patients that have benign epilepsy with centrotemporal spikes (BECTS) may occasionally experience an atypical development in their course when treated with drugs such as carbamazepine. Three patients with electroclinical patterns consistent with BECTS showed seizure exacerbation during oxacarbazepine (OXC) therapy. Two manifested atypical absences, neuropsychological disturbances, and generalized spike-and-wave discharges in their electroencephalograms (EEGs) that became continuous during sleep. The third patient showed, during OXC therapy, more frequent partial motor seizures which ended with ictal vomiting and post-ictal obnubilation. EEGs recorded during sleep showed discontinuous paroxysmal activity in the right centrotemporal area. Symptoms were reversed following discontinuation of the OXC therapy. Although electroclinical findings were consistent with a BECTS diagnosis, all patients had some atypical features. Our observations show that BECTS patients, in particular those presenting with atypical findings, might be at risk for developing paradoxical reactions to OXC therapy. We suggest that OXC should be included in the list of drugs that may cause electroclinical deterioration in these patients.

Occipital intermittent rhythmic delta activity only following eye closure in atypical CNS Salmonellosis.

OBJECTIVE: A statement recently published on the base of a large retrospective analysis, report that the occipital intermittent rhythmic delta activity (OIRDA) "is associated with epilepsy but not acute encephalopathy" [Gullapalli and Fountain. J Clin Neurophysiol 2003;20:35-41]. Our aim is to report, the exception from a child with an intermittent fever, in which the finding of an occipital intermittent rhythmic delta activity (OIRDA) following the eye closure in the EEG recording was the first clinical sign addressing to a CNS involvement. METHODS: To review the record from a five-year-old girl with a normal basal electroencephalogram and OIRDA that only appeared following eye closure. RESULTS: We found OIRDA associated with atypical CNS Salmonellosis. Brain MRI and CSF examination confirmed an acute encephalopathy, which was due to Salmonella infection. The only symptoms of the infection were episodes of nightly fever that had lasted for four weeks, sometimes associated with headache and vomiting. Both OIRDA only induced by eye closing and other symptoms disappeared after starting antimicrobial therapy. CONCLUSIONS: OIRDA only following eye closure is a non-specific abnormality and the present findings, based on a single case, merely indicate that intracranial infection is among the possible causes. SIGNIFICANCE: The new clinical association is certainly worth recording, as the presence of this electrophysiological sign may provoke clinicians to then delve further into a diagnostic work up.

Efficacy and safety of topiramate in infants according to epilepsy syndromes.

Studies of the efficacy of topiramate (TPM) in infants and young children are few. Here we report an open, prospective, and pragmatic study of effectiveness of TPM in terms of epilepsy syndromes, in children aged less than 2 years. The median follow-up period was 11 months. We enrolled 59 children in the study: 22 affected by localization-related epilepsy (LRE), 23 by generalized epilepsy, six by Dravet's syndrome, and eight with unclassifiable epilepsy. TPM was effective (responders showed a decrease of more than 50% in seizure frequency) in 47% of patients, including 13% who were seizure-free at the last visit. TPM was more effective in localization-related epilepsy (48% of responders) than in generalized epilepsy (32% of responders). In the latter group, 19 patients suffered from infantile spasms. Four of six patients with cryptogenic infantile spasms became seizure-free. Of the 13 patients with symptomatic infantile spasms, only one was seizure-free. Results were poor for patients with Dravet's syndrome. In general, TPM was well tolerated. The most frequently reported adverse effects were drowsiness, irritability, hyperthermia, and anorexia. The present study concludes that TPM is effective for a broad range of seizures in infants and young children and represents a valid therapeutic option in this population.

Chromosome 18 aberrations and epilepsy: a review.

Epilepsy is commonly observed in patients with chromosomal aberrations. We evaluated epilepsy and electroencephalographic (EEG) features in a group of patients carrying aberrations of chromosome 18. Fourteen patients were recruited: five with an 18p deletion syndrome (18pDS); six with an 18q deletion syndrome (18qDS); two with trisomy 18p syndrome; and one with a 45,XY,t(17-18) (cen-q11.2) karyotype. Patients with 18pDS had neither epilepsy nor EEG anomalies; four patients with 18qDS had epilepsy with partial seizures occurring during infancy or early childhood. Partial seizures were also present in both patients with trisomy 18p. By contrast, mixed seizures were observed in the patient carrying a translocation between chromosomes 17 and 18. Our data and a re-evaluation of the literature suggest that epilepsy is infrequent in patients with 18pDS. Conversely, partial seizures and focal EEG anomalies may be observed in those with patients with 18qDS. Our observations suggest that the haplo-insufficiency of genes located on the long arm of chromosome 18 is more likely to be associated with epilepsy, than is haplo-insufficiency of genes located on the short arm. While further EEG/clinical investigations are needed to validate these observations, this study indicates a possible relationship between chromosome 18 genes and epilepsy.

Contrasting effects of Cd2+ and Co2+ on the blocking/unblocking of human Cav3 channels.

Inorganic ions have been used widely to investigate biophysical properties of high voltage-activated calcium channels (HVA: Ca(v)1 and Ca(v)2 families). In contrast, such information regarding low voltage-activated calcium channels (LVA: Ca(v)3 family) is less documented. We have studied the blocking effect of Cd2+, Co2+ and Ni2+ on T-currents expressed by human Ca(v)3 channels: Ca(v)3.1, Ca(v)3.2, and Ca(v)3.3. With the use of the whole-cell configuration of the patch-clamp technique, we have recorded Ca2+ (2 mM: ) currents from HEK-293 cells stably expressing recombinant T-type channels. Cd2+ and Co2+ block was 2- to 3-fold more potent for Ca(v)3.2 channels (EC50 = 65 and 122 microM, respectively) than for the other two LVA channel family members. Current-voltage relationships indicate that Co2+ and Ni2+ shift the voltage dependence of Ca(v)3.1 and Ca(v)3.3 channels activation to more positive potentials. Interestingly, block of those two Ca(v)3 channels by Co2+ and Ni2+ was drastically increased at extreme negative voltages; in contrast, block due to Cd2+ was significantly decreased. This unblocking effect was slightly voltage-dependent. Tail-current analysis reveals a differential effect of Cd2+ on Ca(v)3.3 channels, which can not close while the pore is occupied with this metal cation. The results suggest that metal cations affect differentially T-type channel activity by a mechanism involving the ionic radii of inorganic ions and structural characteristics of the channels pore.

Atypical BECTS and homocystinuria.

Reported is an association of atypical benign childhood epilepsy with centrotemporal spikes (BECTS) and homocystinuria in three apparently healthy children with borderline intelligence, two of whom had difficult-to-control seizures. In all three, EEG were suggestive of BECTS, although the clinical features were not. Homocystinuria could not be diagnosed for several years, pending metabolic evaluation.

Development of bacterial resistance to several biocides and effects on antibiotic susceptibility.

The aims of this study were to investigate the development of bacterial resistance to eugenol, thymol, trichlorocarbanalide (TCC), didecyldimethylammonium chloride (DDDMAC) and C10-16-alkyldimethyl, N-oxides (ADMAO) and subsequent effects on antibiotic susceptibility. An agar minimum inhibitory concentration (MIC) method was used to assess the activity of the biocides against standard bacterial strains and laboratory mutants. A range of techniques including disk diffusion and gradient plate experiments were used to attempt to develop bacterial 'resistance' or tolerance to the biocides. The mutants produced were examined for cross-resistance to the other biocides and to antibiotics via disk diffusion and gradient plate MIC methods. Outer membrane proteins of the mutants were extracted and examined using sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Escherichia coli triclosan-resistant mutants were not cross-resistant to eugenol, thymol, TCC, DDDMAC and ADMAO. Mutants with elevated MICs to DDDMAC (E. coli and Pseudomonas aeruginosa), thymol (E. coli) and eugenol (E. coli) were isolated, but all remained sensitive to higher concentrations of the agents. Bacteria with elevated MICs to TCC and ADMAO were not obtained. Some low-level cross-resistance between DDDMAC, eugenol and thymol was observed with the E. coli gradient plate mutants, as well as reduced susceptibility to antibiotics, most notably chloramphenicol. The lack of cross-resistance of the triclosan mutants suggested that the mode of action of triclosan is not shared with the other biocides studied. SDS-PAGE results indicated that the DDDMAC P. aeruginosa mutant had a reduced amount (or absence) of one outer membrane protein in comparison with the standard strain. In conclusion, under laboratory conditions, bacterial exposure to thymol, eugenol and DDDMAC can lead to reduced susceptibility between selected biocidal agents and antibiotics, more specifically, chloramphenicol. However, further studies are required to determine if this is of clinical significance.

Growth and molecular characterization of dental plaque microcosms.

AIMS: (i) To compare the effects of feeding protocols upon the composition and stability of dental plaque microcosms formed in constant-depth film fermenters (CDFF). (ii) To evaluate the utility of denaturing gradient gel electrophoresis (DGGE) and culture methodologies for the investigation of such models. METHODS AND RESULTS: Microcosms were established anaerobically in the CDFFs from freshly collected saliva. These were fed either with artificial saliva alone (famine) or combined with discontinuous feeding (feast-famine). Culture and 16s rDNA sequencing indicated that supplemental feeding gave ca. 2 log increases in Lactobacillus rhamnosus and Prevotella buccae. Feast-famine microcosms were then further characterized by DGGE using primers specific for the V2-V3 region of eubacterial rDNA. These gave single major bands with pure cultures (eight species) and resolved all strains apart from Lact. rhamnosus and Actinomyces naeslundii. Whilst culture with selective media indicated a degree of stability and reproducibility between replicate microcosms, DGGE showed a considerable degree of variability that related to several putatively uncultured bacteria. CONCLUSIONS: Feast-famine regimes altered community composition. DGGE analyses identified putatively unculturable species and demonstrated variability between replicate fermenters. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrates the utility of DGGE for the analysis of dental plaque, especially with respect to unculturable bacteria. Results question the assumptions of reproducibility of plaque microcosms established in non-replicated CDFFs made on the basis of selective media. Feeding regimes, particularly those involving complex nutrients, will dramatically affect population dynamics.

Activity and mechanisms of action of selected biocidal agents on Gram-positive and -negative bacteria.

AIMS: This study investigates the antimicrobial activity and mode of action of two natural products, eugenol and thymol, a commonly utilized biostatic agent, triclocarban (TCC), and two surfactants, didecyldimethylammonium chloride (DDDMAC) and C10-C16 alkyldimethyl amine N-oxides (ADMAO). METHODS AND RESULTS: Methods used included: determination of minimum inhibitory concentrations (MICs), lethal effect studies with suspension tests and the investigation of sub-MIC concentrations on growth of E. coli, Staph. aureus and Ps. aeruginosa using a Bioscreen microbiological analyser. Leakage of intracellular constituents and the effects of potentiating agents were also investigated. Only DDDMAC was bactericidal against all of the organisms tested. Eugenol, thymol and ADMAO showed bacteriostatic and bactericidal activity, but not against Ps. aeruginosa. TCC was only bacteristatic against Staph. aureus, but like the other agents, it did affect the growth of the other organisms in the Bioscreen experiments. All of the antimicrobial agents tested were potentiated by the permeabilizers to some extent and leakage of potassium was seen with all of the agents except TCC. CONCLUSIONS: DDDMAC was bactericidal against all organisms tested and all compounds had some bacteriostatic action. Low level static effects on bacterial growth were seen with sub-MIC concentrations. Membrane damage may account for at least part of the mode of action of thymol, eugenol, DDDMAC and ADMAO. SIGNIFICANCE AND IMPACT OF THE STUDY: The ingredients evaluated demonstrated a range of bactericidal and bacteriostatic properties against the Gram-negative and -positive organisms evaluated and the membrane (leakage of intracellular components) was implicated in the mode of action for most (except TCC). Sub-MIC levels of all ingredients did induce subtle effects on the organisms which impacted bacterial growth, even for those which had no true inhibitory effects.

18q-syndrome and ectodermal dysplasia syndrome: description of a child and his family.

The 18q- syndrome [MIM #601808] is a terminal deletion of the long arm of chromosome 18. The most common deletion extends from region q21 to qter. We report here a nine-year-old boy possessing a simple 18q- deletion who had abnormalities of the brain, skull, face, tooth, hair, bone, and skin, plus joint laxity, tongue palsy, subtle sensoneural deafness, mental and speech delay, attention deficit hyperactivity disorder (ADHD), tic, and restless legs syndromes. His karyotype was 46, XY, del (18)(q21.31-qter). The size of the deletion was approximately 45 cM. Most of these abnormalities were not explained by the 18q- deletion. The family pedigree suggested the presence of a subtle involvement of ectodermal and/or mesodermal structures. Karyotypes of the other family members were normal.