Clinical manifestations of tooth eruption in the first year of life and related risk factors in three regions of Brazil: multicenter birth cohort study.

PURPOSE: Estimate the incidence of teething symptoms and investigate risk factors at three centers in different regions of Brazil. METHODS: A prospective cohort study enrolled children at birth in the cities of Manaus (northern region), Porto Alegre (southern region) and Salvador (northeast region). Sociodemographic and anthropometric variables were collected at baseline and 6 months. At 12 months, data were collected on the child's health through structured interviews and dental examinations, including the primary outcome: occurrence of signs and symptoms of tooth eruption reported by parents. Statistical analysis involved Poisson regression with robust variance, with calculation of relative risks (RR). RESULTS: The incidence of teething symptoms was 82.4% (238/289). The multivariate analysis revealed a higher occurrence of the outcome in the city of Salvador (RR = 1.39; 95% CI 1.23-1.58), when mother's education was more than 11 years (RR = 1.31; 95% CI 1.04-1.65), when a larger number of individuals resided in the home (RR = 1.15; 95% CI 1.02-1.29), when a smoker resided in the home (RR = 1.16; 95% CI 1.03-1.31) and when the child presented flu or cold in the first year of life (RR = 1.23; 95% CI 1.09-1.38). The most reported symptoms were fever (50.5%), irritability (42.6%), itching (40.8%) and diarrhea (35.3%). Most parents (82%) took some action to alleviate symptoms, including unprescribed systemic medication, such as analgesic, anti-inflammatory and anti-diarrheic agents. CONCLUSION: Reports of teething symptoms were associated with the city investigated, socioeconomic factors of the families and characteristics of the child's health. A high rate of administering unprescribed medication was also found.

Model-based comparison of organ at risk protection between VMAT and robustly optimised IMPT plans.

The comparison between intensity-modulated proton therapy (IMPT) and volume-modulated arc therapy (VMAT) plans, based on models of normal tissue complication probabilities (NTCP), can support the choice of radiation modality. IMPT irradiation plans for 50 patients with head and neck tumours originally treated with photon therapy have been robustly optimised against density and setup uncertainties. The dose distribution has been calculated with a Monte Carlo (MC) algorithm. The comparison of the plans was based on dose-volume parameters in organs at risk (OARs) and NTCP-calculations for xerostomia, sticky saliva, dysphagia and tube feeding using Langendijk's model-based approach. While the dose distribution in the target volumes is similar, the IMPT plans show better protection of OARs. Therefore, it is not the high dose confirmation that constitutes the advantage of protons, but it is the reduction of the mid-to-low dose levels compared to photons. This work investigates to what extent the advantages of proton radiation are beneficial for the patient's post-therapeutic quality of life (QoL). As a result, approximately one third of the patients examined benefit significantly from proton therapy with regard to possible late side effects. Clinical data is needed to confirm the model-based calculations.

Dental behaviour management problems and associated factors in Brazilian children.

AIM: To identify factors associated with negative child behaviour in the dental setting. MATERIALS AND METHODS: A cross-sectional study was conducted with a sample of 324 mother-child pairs (children aged 3 to 12 years) seen at a university clinic in Canoas, southern Brazil. Mother's anxiety was measured using the Beck Anxiety Inventory. Oral examinations were performed to determine caries experience (dmft/DMFT index) in the mothers and children. Child behaviour was evaluated at six moments of the dental visit using the Frankl scale. Statistical analysis involved Poisson regression with robust variance. RESULTS: The prevalence of negative child behaviour was 9.3%, with a greater frequency among younger children, those with no previous use of dental services and those whose mothers exhibited a moderate to severe level of anxiety. The multivariable analysis demonstrated that the probability of negative behaviour was 2.4-fold greater among children who had not previous dental services attendance (PR = 2.37, 95% CI:1.13-4.95; p=0.022) and 3.1-fold greater among those whose mothers had a moderate to severe level of anxiety (PR = 3.08, 95% CI:1.64-5.75; p<0.001). CONCLUSION: Mother's anxiety, younger age and no previous history of visiting a dentist are associated with negative behaviour during a dental appointment and therefore merit special attention.

Developmental defects of enamel in primary teeth: highly prevalent, unevenly distributed in the oral cavity and not associated with birth weight.

AIM: Estimate the prevalence of developmental defects of enamel (DDE) in the primary dentition, describe the distribution among tooth groups and investigate the association with birth weight. METHODS: A cross-sectional study was conducted with a sample of 827 children aged 2-5 years representative of the city of Canela in southern Brazil. Demographic characteristics (gender and age) and birth weight were collected from vaccination cards. The diagnosis of DDE was performed by six trained examiners following the criteria of the Federation Dentaire International. DDE were described both jointly and separately as opacity and hypoplasia. Statistical analysis involved the Chi square test, Mann-Whitney test and Poisson regression with robust variance. RESULTS: The prevalence of DDE was 55.1% (95% CI 51.6-58.5%), with a mean of 3.0 ± 2.2 teeth affected. Opacity was the more frequent defect (50.4%), followed by hypoplasia (15.5%). Distribution of the defects was uneven, with opacity predominant on second molars and hypoplasia predominant on canines and second molars. Children with a low birth weight did not have a greater probability of opacity (PR: 1.13; 95% CI 0.91-1.41), hypoplasia (PR: 1.33; 95% CI 0.80-2.22) or DDE (PR: 1.11; 95% CI 0.91-1.37). CONCLUSION: The prevalence of DDE was high, predominant on second molars and not associated with birth weight. These findings indicate directions for future examination/diagnosis protocols and specific orientations.

Proton Therapy for Craniopharyngioma - An Early Report from a Single European Centre.

AIMS: Proton beam therapy (PBT) is being increasingly used for craniopharyngioma. We describe our early outcome of patients treated with PBT. MATERIALS AND METHODS: Between August 2013 and July 2016, 18 patients with craniopharyngiomas were treated with 54 Cobalt Gray Equivalent (CGE) in 30 fractions over 6 weeks at our centre. The early outcome of 16 patients included in a registry study was analysed. Radiological response was assessed by RECIST criteria and the disease- and treatment-related toxicities were scored according to the CTCAE 4.0. RESULTS: All patients are alive at a median follow-up of 32.6 months (range 9.2-70.6 months) from initial diagnosis. The median age at PBT was 10.2 years (range 5.4-46.9 years). One patient progressed 8.7 months after PBT and subsequently had complete resection of the tumour. At a median follow-up of 18.4 months after PBT, five patients remained in complete remission, four in partial remission and seven with stable disease. The most common adverse effects during PBT were grade 1 (cutaneous in seven patients and fatigue in six patients). There were no treatment-related grade 3 toxicities. CONCLUSIONS: Our early results are encouraging and comparable with the limited literature on PBT for craniopharyngioma.

Comprehensive clinical commissioning and validation of the RayStation treatment planning system for proton therapy with active scanning and passive treatment techniques.

PURPOSE: To commission the treatment planning system (TPS) RayStation for proton therapy including beam models for spot scanning and for uniform scanning. METHODS: Tests consist of procedures from ESTRO booklet number 7, the German DIN for constancy checks of TPSs, and extra tests checking the dose perturbation function. The dose distributions within patients were verified in silico by a comparison of 65 clinical treatment plans with the TPS XiO. Dose-volume parameters, dose differences, and three-dimensional gamma-indices serve as measures of similarity. The monthly constancy checks of Raystation have been automatized with a script. RESULTS: The basic functionality of the software complies with ESTRO booklet number 7. For a few features minor enhancements are suggested. The dose distribution in RayStation agrees with the calculation in XiO. This is supported by a gamma-index (3mm/3%) pass rate of >98.9% (median over 59 plans) for the volume within the 20% isodose line and a difference of <0.3% of V95 of the PTV (median over 59 plans). If spot scanning is used together with a range shifter, the dose level calculated by RayStation can be off by a few percent. CONCLUSIONS: RayStation can be used for the creation of clinical proton treatment plans. Compared to XiO RayStation has an improved modelling of the lateral dose fall-off in passively delivered fields. For spot scanning fields with range shifter blocks an empirical adjustment of monitor units is required. The computation of perturbed doses also allows the evaluation of the robustness of a treatment plan.

Mobile demersal megafauna at common offshore wind turbine foundations in the German Bight (North Sea) two years after deployment - increased production rate of Cancer pagurus.

Within the next decades the construction of thousands of different types of large wind turbine foundations in the North Sea will substantially increase the amount of habitat available to reef fauna. To gain first insights which effect these substantial changes in habitat structure and diversity might have on faunal stocks settling on hard substrata, we compared the mobile demersal megafauna associated with the common types of wind turbine foundations ('jacket', 'tripod' and 'monopile with scour protections of natural rock') in the southern German Bight, North Sea. Monopiles with scour protection were mostly colonized by typical reef fauna. They were inhabited by an average of about 5000 edible crabs Cancer pagurus (per foundation), which is more than twice as much as found at the foundation types without scour protection. Strong evidence was found that all three foundation types not only function as aggregation sites, but also as nursery grounds for C. pagurus. Assuming equal shares of the three foundation types in future wind farms, we project that about 27% of the local stock of C. pagurus might be produced on site. When, for example, comparing the existing fauna at 1000 ship wrecks and on the autochthonous soft substrate with those which probably will establish at the foundations of 5000 hypothetically realized wind turbines, it becomes clear that the German Bight in the future will provide new artificial reef habitats for another 320% crabs (C. pagurus) and 50% wrasse (Ctenolabrus rupestris) representing substrata-limited mobile demersal hard bottom species. Further research is urgently required in order to evaluate this overspill as it would be an important ecological effect of the recent offshore wind power development.

Neighbourhood Determinants of Caries Experience in Preschool Children: A Multilevel Study.

OBJECTIVES: To investigate the association between neighbourhood factors and decayed, missing, and filled teeth (dmft) index among preschool children. METHODS: The sample of this cross-sectional study comprised 1,110 children (0-5 years old) clustered in 16 official neighbourhoods of Canoas city, southern Brazil. Multilevel binomial models were used to estimate the association of contextual variables at neighbourhood level (Human Development Index, average income, and public primary health care units) with two oral health outcomes: decayed teeth (dt) and missing or filled teeth (mft), after adjusting for individual variables (gender, age, maternal education, equivalent household income logarithm, household, and point of care). RESULTS: Overall, 24.9% of the sample had dental caries experience (dmft >0), and 92.3% of the dmft was untreated caries. There was no statistical significant association (p > 0.05) of contextual characteristics with the decay component. The teeth of children living in richer areas had 2.87 (95% CI: 1.05-7.86) times more chances of being treated (mft component). Variance attributed to neighbourhood level was estimated as 5.9% (p < 0.01) and 4.1% (p = 0.17) for dt and mft, respectively, in adjusted models. CONCLUSIONS: Intra-urban areas seem homogeneous, with small variability between neighbourhoods, having no contextual effect on untreated dental caries (dt). Contextual variables may influence treatment access (mft) through the use of dental services in preschool children.

Presence of inclusions positive for polyglycine containing protein, FMRpolyG, indicates that repeat-associated non-AUG translation plays a role in fragile X-associated primary ovarian insufficiency.

STUDY QUESTION: Does repeat-associated non-AUG (RAN) translation play a role in fragile X-associated primary ovarian insufficiency (FXPOI), leading to the presence of polyglycine containing protein (FMRpolyG)-positive inclusions in ovarian tissue? SUMMARY ANSWER: Ovaries of a woman with FXPOI and of an Fmr1 premutation (PM) mouse model (exCGG-KI) contain intranuclear inclusions that stain positive for both FMRpolyG and ubiquitin. WHAT IS KNOWN ALREADY: Women who carry the FMR1 PM are at 20-fold increased risk to develop primary ovarian insufficiency (FXPOI). A toxic RNA gain-of-function has been suggested as the underlying mechanism since the PM results in increased levels of mRNA containing an expanded repeat, but reduced protein levels of fragile X mental retardation protein (FMRP). Recently, RAN translation has been shown to occur from FMR1 mRNA that contains PM repeat expansions, leading to FMRpolyG inclusions in brain and non-CNS tissues of fragile X-associated tremor/ataxia syndrome (FXTAS) patients. STUDY DESIGN, SIZE, DURATION: Ovaries of a woman with FXPOI and women without PM (controls), and ovaries from wild-type and exCGG-KI mice were analyzed by immunohistochemistry for the presence of inclusions that stained for ubiquitin and FMRpolyG . The ovaries from wild-type and exCGG-KI mice were further characterized for the number of follicles, Fmr1 mRNA levels and FMRP protein expression. The presence of inclusions was also analyzed in pituitaries of a man with FXTAS and the exCGG-KI mice. PARTICIPANTS/MATERIALS, SETTING, METHODS: Human ovaries from a woman with FXPOI and two control subjects and pituitaries from a man with FXTAS and a control subjects were fixed in 4% formalin. Ovaries and pituitaries of wild-type and exCGG mice were fixed in Bouin's fluid or 4% paraformaldehyde. Immunohistochemistry was performed on the human and mouse samples using FMRpolyG, ubiquitin and Fmrp antibodies. Fmr1 mRNA and protein expression were determined in mouse ovaries by quantitative RT-PCR and Western blot analysis. Follicle numbers in mouse ovaries were determined in serial sections by microscopy. MAIN RESULTS AND THE ROLE OF CHANCE: FMRpolyG-positive inclusions were present in ovarian stromal cells of a woman with FXPOI but not in the ovaries of control subjects. The FMRpolyG-positive inclusions colocalized with ubiquitin-positive inclusions. Similar inclusions were also observed in the pituitary of a man with FXTAS but not in control subjects. Similarly, ovaries of 40-week-old exCGG-KI mice, but not wild-type mice, contained numerous inclusions in the stromal cells that stained for both FMRpolyG- and ubiquitin, while the ovaries of 20-week-old exCGG-KI contained fewer inclusions. At 40 weeks ovarian Fmr1 mRNA expression was increased by 5-fold in exCGG-KI mice compared with wild-type mice, while Fmrp expression was reduced by 2-fold. With respect to ovarian function in exCGG-KI mice: (i) although the number of healthy growing follicles did not differ between wild-type and exCGG-KI mice, the number of atretic large antral follicles was increased by nearly 9-fold in 40-week old exCGG-KI mice (P < 0.001); (ii) at 40 weeks of age only 50% of exCGG-KI mice had recent ovulations compared with 89% in wild-type mice (P = 0.07) and (iii) those exCGG-KI mice with recent ovulations tended to have a reduced number of fresh corpora lutea (4.8 ± 1.74 versus 8.50 ± 0.98, exCGG-KI versus wild-type mice, respectively, P = 0.07). LIMITATIONS, REASONS FOR CAUTION: Although FMRpolyG-positive inclusions were detected in ovaries of both a woman with FXPOI and a mouse model of the FMR1 PM, we only analyzed one ovary from a FXPOI subject. Caution is needed to extrapolate these results to all women with the FMR1 PM. Furthermore, the functional consequence of FMRpolyG-positive inclusions in the ovaries for reproduction remains to be determined. WIDER IMPLICATIONS OF THE FINDINGS: Our results suggest that a dysfunctional hypothalamic-pituitary-gonadal-axis may contribute to FXPOI in FMR1 PM carriers. STUDY FUNDING/COMPETING INTERESTS: This study was supported by grants from NFXF, ZonMW, the Netherlands Brain Foundation and NIH. The authors have no conflict of interest to declare.

Adult-onset congenital thrombotic thrombocytopenic purpura caused by a novel compound heterozygous mutation of the ADAMTS13 gene.

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease, characterized by microangiopathic hemolytic anaemia and thrombocytopenia, resulting in neurologic and/or renal abnormalities. We report a 49-year-old patient with a history of thrombotic events, renal failure, and thrombocytopenia. Blood analysis demonstrated no ADAMTS13 activity in the absence of antibodies against ADAMTS13. The complete ADAMTS13 gene was sequenced, and two mutations were identified: one mutation on exon 24 (Arg1060Asp), which had previously been described, and a mutation on exon 27 (Met1260IlefsX34), which has not been reported. For these mutations, compound heterozygosity appears to be necessary to cause TTP, as family members of the patient display only one of the mutations and all displayed normal ADAMTS13 activity.

Infusion of Gabrα6 siRNA into the trigeminal ganglia increased the myogenic orofacial nociceptive response of ovariectomized rats treated with 17ß-estradiol.

High levels of 17ß-estradiol (E2) have been found to reduce inflammatory temporomandibular joint (TMJ) pain. A search for genes effected by a high concentration of estradiol showed an increase in GABAA receptor subunit alpha 6 (Gabrα6) in the trigeminal ganglia (TG). Blockade of Gabrα6 expression in the TG increases masseter muscle nociception in male rats, but the relationship between estradiol's effect on nociception and Gabrα6 expression remains unclear in females. To address this knowledge gap we hypothesized that reducing Gabrα6 expression in the TG will increase the orofacial nociceptive response of ovariectomized female rats treated with estradiol. To administer hormone osmotic pumps were placed in rats that dispensed a low diestrus plasma concentration of 17ß-estradiol, in addition, 17ß-estradiol was injected to produce a high proestrus plasma concentration of estradiol. A ligature was then placed around the masseter tendon to induce a nociceptive response; a model for TMJ muscle pain. Gabrα6 small interfering RNA (siRNA) was later infused into the TG and the nociceptive response was measured using von Frey filaments and a meal duration assay. GABAA receptor expression was measured in the TG and trigeminal nucleus caudalis and upper cervical region (Vc-C1). Ligature significantly increased the nociceptive response but a high proestrus concentration of 17ß-estradiol attenuated this response. Gabrα6 siRNA infusion decreased Gabrα6 expression in the TG and Vc-C1 but increased the nociceptive response after 17ß-estradiol treatment. The results suggest estradiol decreased the orofacial nociceptive response, in part, by causing an increase in Gabrα6 expression.

Comparison of vertebral and intervertebral disc lesions in aging humans and rhesus monkeys.

OBJECTIVE: To compare gross and histologic patterns of age-related degeneration within the intervertebral disc and adjacent vertebra between rhesus monkeys and humans. MATERIALS AND METHODS: We examined age-related patterns of disc degeneration from mid-sagittal sections of the intervertebral disc and adjacent vertebral bodies (VB) among six rhesus monkey thoracolumbar and seven human lumbar spines. Gross morphology and histopathology were assessed via the Thompson grading scheme and other degenerative features of the disc and adjacent bone. RESULTS: Thompson grades ranged from 3 through 5 for rhesus monkey discs (T9-L1) and 2 through 5 for the human discs (T12-S1). In both rhesus monkey and human discs, presence of distinct lesions was positively associated with Thompson grade of the overall segment. Degenerative patterns differed for radial tears, which were more prevalent with advanced disc degeneration in humans only. Additionally, compared to the more uniform anteroposterior disc degeneration patterns of humans, rhesus monkeys showed more severe osteophytosis and degeneration on the anterior border of the vertebral column. CONCLUSIONS: Rhesus monkey spines evaluated in the present study appear to develop age-related patterns of disc degeneration similar to humans. One exception is the absence of an association between radial tears and disc degeneration, which could reflect species-specific differences in posture and spinal curvature. Considering rhesus monkeys demonstrate similar patterns of disc degeneration, and age at a faster rate than humans, these findings suggest longitudinal studies of rhesus monkeys may be a valuable model for better understanding the progression of human age-related spinal osteoarthritis (OA) and disc degeneration.

Reduced GABAA receptor α6 expression in the trigeminal ganglion enhanced myofascial nociceptive response.

Activation of the GABAA receptor results in inhibition of neuronal activity. One subunit of this multi-subunit receptor termed alpha 6 (Gabrα6) contributed to inflammatory temporomandibular joint (TMJ) nociception but TMJ disorders often include myofascial pain. To address Gabrα6 role in myofascial pain we hypothesized that Gabrα6 has an inhibitory role in myofascial nociceptive responses similar to inflammatory TMJ arthritis. To test this hypothesis a, myofascial nociceptive response was induced by placing a ligature bilaterally on the tendon attachment of the anterior superficial part of a male rat's masseter muscle. Four days after ligature placement Gabrα6 expression was reduced by infusing the trigeminal ganglia (TG) with small interfering RNA (siRNA) having homology to either the Gabrα6 gene (Gabrα6 siRNA) or no known gene (control siRNA). After siRNA infusion nociceptive behavioral responses were measured, i.e., feeding behavior and head withdrawal after pressing upon the region above the ligature with von Frey filaments. Neuronal activity in the TG and trigeminal nucleus caudalis and upper cervical region (Vc-C1) was measured by quantitating the amount of phosphorylated extracellular signal-regulated kinase (p-ERK). Total Gabrα6 and GABAA receptor contents in the TG and Vc-C1 were determined. Gabrα6 siRNA infusion reduced Gabrα6 and GABAA receptor expression and significantly increased the nociceptive response in both nociceptive assays. Gabrα6 siRNA infusion also significantly increased TG p-ERK expression of the ligated rats. From these results we conclude GABAA receptors consisting of the Gabrα6 subunit inhibit TG nociceptive sensory afferents in the trigeminal pathway and have an important role in the regulation of myofascial nociception.

Modulation of temporomandibular joint nociception and inflammation in male rats after administering a physiological concentration of 17ß-oestradiol.

BACKGROUND: Previous studies have shown 17ß-estradiol will reduce temporomandibular joint (TMJ) inflammation and hypersensitivity in female rats. Although male rats contain significant amounts of oestradiol, it was unknown whether a physiological concentration of 17ß-estradiol would attenuate male TMJ inflammation and nociception. METHODS: Intact and castrated rats were given a physiological concentration of oestradiol to examine first, if oestradiol will affect male TMJ nociception/inflammation and, second, if administration of oestradiol would act synergistically with endogenous male hormones to attenuate TMJ nociception. The hormonally treated rats were given TMJ injections of complete Freund's adjuvant (CFA) and then nociception was measured using a validated method in which a lengthening in meal duration is directly correlated to the intensity of deep TMJ nociception. Inflammation was assayed by quantitating pro-inflammatory gene expression. RESULTS: Meal duration was significantly lengthened after TMJ CFA injection and this lengthening was significantly attenuated in the castrated but not intact males after administering a physiological concentration of oestradiol. A physiological concentration of 17ß-estradiol also significantly increased IL-6 expression in the inflamed TMJ of castrated males while 17ß-estradiol did not alter IL-1ß, CXCL2 and CCL20 expression. Castration increased pro-inflammatory mediators IL-6, IL-1ß and CXCL2 suggesting male sex hormones were anti-inflammatory. Calcitonin gene-related peptide in the trigeminal ganglia was unchanged. CONCLUSIONS: Similar to females, male rats with TMJ inflammation showed a reduced nociceptive response after treatment with a physiological concentration of oestradiol suggesting the effects of oestradiol treatment were not constrained by organizational processes in the males.

A non-invasive model for measuring nociception after tooth pulp exposure.

Temporomandibular arthritis will lengthen a rodent's meal duration. We hypothesized that meal duration would also lengthen after tooth pulp exposure, suggesting that this behavior could be used to measure tooth nociception. To test this hypothesis, we placed rats in feeding units and subjected 4 anterior mandibular molars to pulp exposure, with and without pre-treatment with the analgesic buprenorphine-HCl. In the first study, male Sprague-Dawley rats were placed in computerized sound-attenuated feeding modules, the pulp of 4 molars on the mandible were exposed, and meal duration was measured for 13 days. In a second study, rats were injected with either the analgesic buprenorphine-HCl or saline every 12 hrs; injections were started one day before pulp exposure. Meal duration was determined before and after treatment. In the first study, pulp exposure significantly increased daily meal duration for 8 days. In the second study, pulp exposure lengthened daily meal duration, but the group that was treated with buprenorphine-HCl showed no significant difference compared with control rats without pulp exposure. Evidence supports that a lengthening in meal duration is a response to tooth nociception and that this nociception can be measured for over a week.

Reduced GABA(A) receptor α6 expression in the trigeminal ganglion alters inflammatory TMJ hypersensitivity.

Trigeminal ganglia neurons express the GABA(A) receptor subunit alpha 6 (Gabrα6) but the role of this particular subunit in orofacial hypersensitivity is unknown. In this report the function of Gabrα6 was tested by reducing its expression in the trigeminal ganglia and measuring the effect of this reduction on inflammatory temporomandibular joint (TMJ) hypersensitivity. Gabrα6 expression was reduced by infusing the trigeminal ganglia of male Sprague Dawley rats with small interfering RNA (siRNA) having homology to either the Gabrα6 gene (Gabrα6 siRNA) or no known gene (control siRNA). Sixty hours after siRNA infusion the rats received a bilateral TMJ injection of complete Freund's adjuvant to induce an inflammatory response. Hypersensitivity was then quantitated by measuring meal duration, which lengthens when hypersensitivity increases. Neuronal activity in the trigeminal ganglia was also measured by quantitating the amount of phosphorylated ERK. Rats in a different group that did not have TMJ inflammation had an electrode placed in the spinal cord at the level of C1 sixty hours after siRNA infusion to record extracellular electrical activity of neurons that responded to TMJ stimulation. Our results show that Gabrα6 was expressed in both neurons and satellite glia of the trigeminal ganglia and that Gabrα6 positive neurons within the trigeminal ganglia have afferents in the TMJ. Gabrα6 siRNA infusion reduced Gabrα6 gene expression by 30% and significantly lengthened meal duration in rats with TMJ inflammation. Gabrα6 siRNA infusion also significantly increased p-ERK expression in the trigeminal ganglia of rats with TMJ inflammation and increased electrical activity in the spinal cord of rats without TMJ inflammation. These results suggest that maintaining Gabrα6 expression was necessary to inhibit primary sensory afferents in the trigeminal pathway and reduce inflammatory orofacial nociception.

Maternal education is an independent determinant of cariogenic feeding practices in the first year of life.

AIM: To identify risk factors for cariogenic feeding practices in the first year of life. STUDY DESIGN: Cohort study. METHODS: 500 children born within the public health care system in São Leopoldo, Brazil, were recruited in a follow-up program. Anthropometric and demographic data were collected soon after birth; data on feeding practices were assessed at 12 months of age using a standardised questionnaire; clinical examination at 4 years of age allowed identification of cariogenic feeding practices in the first year of life and to quantify their relative risks. In the present study, the attributable risks of each child were summed, and the outcome was assessed for the upper quartile of scores for cariogenic feeding practices. STATISTICS: Adjusted relative risks for the outcome were estimated using robust Poisson regression models. RESULTS: A total of 327 children comprised the final study sample, i.e. were followed from birth to 4 years of age. Multivariate analysis showed that the risk of cariogenic feeding practices doubled in children from mothers with less than 5 years of education (RR 2.19, 95%CI 1.26-3.82) and was 70% higher in children from mothers with 5-8 years of education when compared with maternal education >8 years. The other independent variables were not associated with the outcome. CONCLUSIONS: Low maternal education is a risk factor for cariogenic feeding practices, independently of other factors. Mothers with low educational levels should be the focus of child health promotion interventions, especially those aimed at controlling dental caries.

Implementation of flow cytometry in the diagnostic work-up of myelodysplastic syndromes in a multicenter approach: report from the Dutch Working Party on Flow Cytometry in MDS.

Flow cytometry (FC) is recognized as an important tool in the diagnosis of myelodysplastic syndromes (MDS) especially when standard criteria fail. A working group within the Dutch Society of Cytometry aimed to implement FC in the diagnostic work-up of MDS. Hereto, guidelines for data acquisition, analysis and interpretation were formulated. Based on discussions on analyses of list mode data files and fresh MDS bone marrow samples and recent literature, the guidelines were modified. Over the years (2005-2011), the concordance between the participating centers increased indicating that the proposed guidelines contributed to a more objective, standardized FC analysis, thereby ratifying the implementation of FC in MDS.

Local kinetic interpretation of entropy production through reversed diffusion.

The time reversal of stochastic diffusion processes is revisited with emphasis on the physical meaning of the time-reversed drift and the noise prescription in the case of multiplicative noise. The local kinematics and mechanics of free diffusion are linked to the hydrodynamic description. These properties also provide an interpretation of the Pope-Ching formula for the steady-state probability density function along with a geometric interpretation of the fluctuation-dissipation relation. Finally, the statistics of the local entropy production rate of diffusion are discussed in the light of local diffusion properties, and a stochastic differential equation for entropy production is obtained using the Girsanov theorem for reversed diffusion. The results are illustrated for the Ornstein-Uhlenbeck process.

Critical evaluation of key evidence on the human health hazards of exposure to bisphenol A.

Despite the fact that more than 5000 safety-related studies have been published on bisphenol A (BPA), there seems to be no resolution of the apparently deadlocked controversy as to whether exposure of the general population to BPA causes adverse effects due to its estrogenicity. Therefore, the Advisory Committee of the German Society of Toxicology reviewed the background and cutting-edge topics of this BPA controversy. The current tolerable daily intake value (TDI) of 0.05 mg/kg body weight [bw]/day, derived by the European Food Safety Authority (EFSA), is mainly based on body weight changes in two- and three-generation studies in mice and rats. Recently, these studies and the derivation of the TDI have been criticized. After having carefully considered all arguments, the Committee had to conclude that the criticism was scientifically not justified; moreover, recently published additional data further support the reliability of the two- and three-generation studies demonstrating a lack of estrogen-dependent effects at and below doses on which the current TDI is based. A frequently discussed topic is whether doses below 5 mg/kg bw/day may cause adverse health effects in laboratory animals. Meanwhile, it has become clear that positive results from some explorative studies have not been confirmed in subsequent studies with higher numbers of animals or a priori defined hypotheses. Particularly relevant are some recent studies with negative outcomes that addressed effects of BPA on the brain, behavior, and the prostate in rodents for extrapolation to the human situation. The Committee came to the conclusion that rodent data can well be used as a basis for human risk evaluation. Currently published conjectures that rats are insensitive to estrogens compared to humans can be refuted. Data from toxicokinetics studies show that the half-life of BPA in adult human subjects is less than 2 hours and BPA is completely recovered in urine as BPA-conjugates. Tissue deconjugation of BPA-glucuronide and -sulfate may occur. Because of the extremely low quantities, it is only of minor relevance for BPA toxicity. Biomonitoring studies have been used to estimate human BPA exposure and show that the daily intake of BPA is far below the TDI for the general population. Further topics addressed in this article include reasons why some studies on BPA are not reproducible; the relevance of oral versus non-oral exposure routes; the degree to which newborns are at higher systemic BPA exposure; increased BPA exposure by infusions in intensive care units; mechanisms of action other than estrogen receptor activation; and the current regulatory status in Europe, as well as in the USA, Canada, Japan, New Zealand, and Australia. Overall, the Committee concluded that the current TDI for BPA is adequately justified and that the available evidence indicates that BPA exposure represents no noteworthy risk to the health of the human population, including newborns and babies.