Prenatal and postnatal exposures to endocrine disrupting chemicals and timing of pubertal onset in girls and boys: a systematic review and meta-analysis.

BACKGROUND: Globally, the ages at pubertal onset for girls and boys have been decreasing during recent decades, partly attributed to excess body fat accumulation. However, a growing body of literature has recognized that endocrine disrupting chemicals (EDCs) may play an important role in this global trend, but the association has not yet been fully established. OBJECTIVE AND RATIONALE: EDCs can interfere with normal hormone function and metabolism and play a role in pubertal onset. We aimed to systematically identify and evaluate the current evidence on the timing of pubertal onset in girls and boys following prenatal or postnatal exposures to xenobiotic EDCs. SEARCH METHODS: Following PRISMA guidelines, we performed a systematic literature search of original peer-reviewed publications in the PubMed database through a block search approach using a combination of index MeSH and free text search terms. Publications were considered if they covered biomarkers of prenatal or postnatal exposures to xenobiotic EDCs (European Commission's list of category 1 EDCs) measured in maternal or child biospecimen and pubertal onset defined by the progression of the following milestones (and assessed in terms of the following measures): menarche (age), thelarche (Tanner staging) and pubarche (Tanner staging), in girls, and genital stage (Tanner staging), testicular volume (ml) and pubarche (Tanner staging), in boys. OUTCOMES: The literature search resulted in 703 references, of which we identified 52 publications fulfilling the eligibility criteria for the qualitative trend synthesis and 23 publications for the meta-analysis. The qualitative trend synthesis provided data on 103 combinations of associations between prenatal or postnatal exposure to EDC compounds groups and puberty outcomes and the meta-analysis enabled 18 summary risk estimates of meta-associations. WIDER IMPLICATIONS: Statistically significant associations in the qualitative trend synthesis suggested that postnatal exposure to phthalates may be associated with earlier thelarche and later pubarche. However, we did not find consistent evidence in the meta-analysis for associations between timing of pubertal onset in girls and boys and exposures to any of the studied xenobiotic EDCs. We were not able to identify specific pre- or postnatal windows of exposure as particularly critical and susceptible for effects of EDCs. Current evidence is subject to several methodological challenges and inconsistencies and evidence on specific exposure-outcome associations remains too scarce to firmly confirm EDC exposure as a risk factor for changes in age of pubertal onset in the general child population. To create a more uniform foundation for future comparison of evidence and to strengthen pooled studies, we recommend the use of more standardized approaches in the choice of statistical analyses, with exposure transformations, and in the definitions and assessments of puberty outcomes. The impact of mixtures of EDC exposures on the association also remains unestablished and would be valuable to elucidate for prenatal and postnatal windows of exposure. Future large, longitudinal epidemiological studies are needed to clarify the overall association.

The possible correlation between the chronic esophageal achalasia and periodontal disease - a pilot study.

OBJECTIVE: Achalasia is a very rare disease characterized by the lack of motor coordination in various phases of contraction-relaxation of esophageal muscles. The aim of the study is to determine the correlation between esophageal achalasia and oral diseases. PATIENTS AND METHODS: Thirteen esophageal achalasia patients were assessed for the presence of any potential oral symptoms through a questionnaire. 5 volunteered to be included in the study. The oral health status of these 5 patients was assessed by a clinical oral examination. The oral health status of the included cases was compared to the oral health status data from a published observational study on healthy individuals belonging to the same (Italian) population. RESULTS: Our results show that the number of periodontal pockets with Probing Pocket Dept > 4 mm is significantly increased, compared to the average of the Italian population; the Bleeding On Probing (BOP) is not related to the Plaque Control Record (PCR); so we can say that the value of periodontal index is not correlated with the value of oral hygiene index. CONCLUSIONS: Considering the limitations of a research based on small numbers, it nevertheless seems advisable to assert that there is a correlation between esophageal achalasia and periodontal disease.

Prenatal exposure to maternal stressful life events and earlier age at menarche: the Raine Study.

STUDY QUESTION: Is there an association between prenatal exposure to stressful life events and age at menarche, and does childhood BMI mediate this association? SUMMARY ANSWER: Girls exposed to prenatal stress had a slightly earlier age at menarche, but this association did not show a dose-response effect and was not mediated by childhood offspring BMI. WHAT IS ALREADY KNOWN: Prenatal stress may impact on reproductive function in females including age at menarche, but human data are very limited. High childhood BMI is known to be associated with earlier age at menarche. Only one small study has measured the association between maternal stress and age at menarche and reported that childhood BMI mediated the association between maternal stress and earlier age at menarche. However, neither maternal stress nor age at menarche was prospectively recorded and the study was limited to 31 mother-daughter pairs. STUDY DESIGN, SIZE, DURATION: The Raine Study is a large prospective population-based pregnancy cohort study (n = 1414 mother-daughter pairs) continuously followed from prenatal life through to adolescence. In the present study, we examined the association between exposure to maternal stressful life events during early, late and total gestation and age at menarche in offspring using 753 mother-daughter pairs with complete case information. PARTICIPANTS/MATERIALS, SETTING, METHODS: Mothers prospectively reported stressful life events during pregnancy at 18 and 34 weeks using a standardized 10-point questionnaire. Exact date of menarche was assessed using a purpose-designed questionnaire at 8, 10, 14 and 17 years of age. Complete information on exposure, outcome and confounding variables was obtained from 753 mothers-daughter pairs. Multivariate linear regression complete case analysis was used to examine associations between maternal stressful life event exposure and age at menarche. Potential selection bias was evaluated using multiple imputations (50 datasets). The mediating effects of offspring childhood BMI (ages 5, 8, or 10 years) on these associations were measured in separate sub-analyses. MAIN RESULTS AND ROLE OF CHANCE: Most (580/753, 77%) daughters were exposed to at least one prenatal stressful life event. Exposure to maternal stressful life events during the entire pregnancy was associated with a non-linear earlier age at menarche. Exposure to one event and two or more psychological stressful events was associated with a 3.5 and 1.7-month earlier onset of puberty, respectively when compared to the reference group with no exposure maternal stressful life events. The estimates from multiple imputation with 50 datasets were comparable with complete case analysis confirming the existence of an underlying effect. No separate significant effects were observed for exposure during early or late gestation. The association between prenatal stressful events and age at menarche was not mediated by childhood BMI in the offspring. LIMITATIONS, REASONS FOR CAUTION: Stressful life events may have affected pregnant women in different ways and self-perceived maternal stress severity may have provided a more precise estimate of gestational psychological stress. The observed non-linear U-shape of the association between maternal psychological stress and age at menarche did not reflect a dose-response. This suggests that the first exposure to prenatal stress exerts a greater effect on fetal reproductive development. A potential mechanism is via dramatic initial activation of the hypothalamic-pituitary-adrenal (HPA) axis following the first stressful life event which is greater than that observed following subsequent exposure to two or more maternal stressful life events. Whilst we adjusted for a priori chosen confounders, we cannot exclude residual confounding or confounding by factors we did not include. Maternal age at menarche was not available so the effects of familial history/genetics could not be assessed. There was a large loss due to the number of girls with no information on date of menarche and missing confounder information implying risk of selection bias and multiple imputation analyses did not fully exclude this risk (similar direction but slightly weaker estimate magnitude). WIDER IMPLICATIONS OF THE FINDINGS: Menarche is a sentinel reproductive event and earlier age at menarche carries implications for psychological, social and reproductive health and for long-term risk of common non-communicable diseases. Understanding the factors regulating age at menarche has extensive health implications. This is the first population-based cohort study in humans to demonstrate that prenatal psychological stress might directly modify age at menarche. STUDY FUNDING/COMPETING INTEREST(S): Dr. Bräuner and Trine Koch's salaries were supported by Doctor Sofus Carl Emil Friis and spouse Olga Doris Friis foundation, The Danish Cancer Society (Kræftens Bekæmpelse, RP15468, R204-A12636, Denmark) and The Danish Health Foundation (Helsefonden, F-22181-23, Denmark). Martha Hickey was funded by NHMRC Practitioner Fellowships. The funding bodies played no role in the design, collection, analysis, or interpretation of data; in the writing of the manuscript; or in the decision to submit the manuscript for publication. Dr. Hart has received personal fees in his function as the Medical Director of Fertility Specialists of Western Australia and received educational sponsorship grants from MSD, Merck-Serono and from Ferring Pharmaceuticals. Dr Hart has also received personal fees from Shareholders in Western IVF outside the submitted work. TRIAL REGISTRATION NUMBER: NA.

The association between in utero exposure to maternal psychological stress and female reproductive function in adolescence: A prospective cohort study.

Background: Experimental studies suggest that prenatal stress affects reproductive function in female offspring, but human evidence is sparse and inconsistent. In this present study, we aim to investigate whether maternal psychological stress, quantified as stressful life events during pregnancy, affect reproductive function in the female offspring. Method: In a large population-based pregnancy cohort study (The Raine Study) continuously followed from prenatal life through to adolescence we examined the association between the number of maternal stressful life events in both early and late gestation and subsequent ovarian and uterine function in 228 female adolescent offspring. Mothers prospectively reported stressful life events during pregnancy at 18 and 34 weeks using a standardized 10-point questionnaire. Female offspring (n â€‹= â€‹228) age 14-16 years underwent gynecological examination including transabdominal abdominal ultrasound (TAUS) to measure uterine volume and ovarian AFC. Plasma samples on day 2-6 of the spontaneous menstrual cycle measured circulating AMH and inhibin B. Multivariate linear regression analysis was used to examine the associations between maternal stressful life events and reproductive function in female offspring. Adolescents taking hormonal contraception were excluded. Results: Most adolescents (145/228, 64%) were exposed to at least one stressful life event in early gestation and around half (125/228, 55%) were exposed to at least one in later gestation. Exposure to one or more maternal stressful life events in late gestation was associated with a greater uterine volume (ߠ​= â€‹0.13, 95% CI 0.04; 0.23) and higher ovarian AFC (ߠ​= â€‹0.19, 95% CI 0.02; 0.35) at age 14-16 years. No associations between maternal stressful events in late gestation and reproductive function were identified. No associations between stressful life events in early or late gestation and circulating AMH or Inhibin B were observed. Conclusion: Maternal psychological stress in late, but not early gestation was associated with a significantly greater uterine volume and ovarian antral follicle count (AFC) in adolescent offspring but did not affect ovarian production of antimullerian hormone (AMH) or Inhibin B. These findings suggest that female reproductive function is influenced by prenatal exposure to stress.

In utero exposure to maternal stressful life events and risk of polycystic ovary syndrome in the offspring: The Raine Study.

BACKGROUND: PCOS is the most common endocrine disorder in reproductive age women. The origins of PCOS are unknown but experimental and limited human evidence suggests that greater prenatal exposure to androgens may predispose to PCOS. Experimental evidence suggests that maternal stressors may affect reproductive function in the offspring via changes in prenatal androgen exposure. In this present study, we aim to investigate whether maternal stressful life events during pregnancy are associated with polycystic ovary morphology (PCOM) or polycystic ovary syndrome (PCOS) in adolescent offspring. METHOD: In a large population-based pregnancy cohort study (The Raine Study) continuously followed from prenatal life through to adolescence we examined the association between maternal stressful life events during pregnancy in both early and late gestation, and subsequent circulating concentrations of ovarian and adrenal androgens, PCOM and PCOS in the normal menstrual cycle of offspring age 14-16 years. Maternal stressful life events were prospectively recorded during pregnancy at 18 and 34 weeks using a 10-point questionnaire. Female offspring (n = 223) completed a questionnaire about their menstrual cycles, underwent a clinical examination for hirsutism (Ferriman-Gallwey score) and transabdominal pelvic ultrasound examination to determine ovarian morphology according to standardized criteria for classification of PCOM. Plasma samples were obtained at day 2-6 of the normal menstrual cycle for measurement of androgens. PCOM was defined according to the international consensus definition, 2003 and the evidence-based guideline for the assessment and management of PCOS, 2018. PCOS was diagnosed according to Rotterdam criteria and National Institute of Health (NIH) criteria. Multivariate linear and logistic regression analyses were used to examine the associations between maternal stressful life event exposure and ovarian morphology (PCOM), circulating ovarian and adrenal androgens (clinical and biochemical hyperandrogenism (hirsutism)) and presence of PCOS. RESULTS: Of 223 recruited adolescent girls, 78 (35.9%) and 68 (31.3%) had PCOM by the 2003 and 2018 criteria respectively, while 66 (29.6%) and 37 (16.6%) had PCOS, using Rotterdam and NIH criteria, respectively. Most girls (141/223, 63.2%) were exposed to at least one stressful life event in early gestation and around half (121/223, 54.3%) were exposed to at least one stressful life event in late gestation. Maternal stressful life events in early gestation were associated with a statistically significant lower prevalence of PCOM when applying the 2003 criteria [adjusted odds ratio [aOR] and 95% confidence intervals (CI): 0.74 (95% CI: 0.55; 0.99)], and a similar association was detected when applying the 2018 PCOM criteria (aOR, 0.69, 95% CI: 0.50; 0.95)]. Maternal stressful life events in early gestation were also associated with lower circulating concentrations of testosterone (ß = -0.05, 95% CI: -0.09; -0.004) and androstenedione (ß = -0.05, 95% CI: -0.10; -0.002) in the offspring. No similar effects for PCOM or circulating androgens were detected in late gestation. No statistically significant associations between maternal stressful life events in early or late gestation with PCOS (neither Rotterdam nor NIH criteria) in adolescence were detected. The prospective collection of maternal stressful life events during both early and late gestation and direct measurement of PCOM, PCOS and circulating androgens in adolescence and key co-variates implies minimal possibility of recall, information bias and selection bias. CONCLUSION: Maternal exposure to stressful life events in early gestation is associated with significantly reduced circulating ovarian and adrenal androgen concentrations in adolescence (testosterone and androstenedione), and an indication of fewer cases of polycystic ovary morphology (PCOM) defined by the 2003 international consensus definition and by the 2018 international evidence-based guideline, but has no effect on polycystic ovary syndrome (PCOS), diagnosed using either Rotterdam or NIH criteria.

Flexural strength and elastic modulus evaluation of structures made by conventional PMMA and PMMA reinforced with graphene.

OBJECTIVE: The aim of this study was to compare both the elastic modulus (EM) and the flexural strength (FS) of two materials used in dental prosthesis, namely polymethylmethacrylate (PMMA) and polymethylmethacrylate reinforced with graphene (G-PMMA). MATERIALS AND METHODS: Twenty rectangular samples were manufactured by a milling machine and divided into two groups (n= 10/group): Group 1, PMMA; Group 2, G-PMMA. The specimens were subjected to a three-point bending test conducted in the elastic range to evaluate EM. A similar test was protracted until fracture to evaluate FS. Data on EM and FS were statistically analyzed with independent-samples t-test in order to compare the two groups. A scanning electron microscope (SEM) (5.00 kx and 1.00 kx magnification) was used to evaluate the morphology of sample's fracture. RESULTS: Compared to PMMA samples, each G-PMMA sample showed significantly higher values of FS (p <0.001) and EM (p <0.001). SEM images analysis showed an inhomogeneous fracture morphology in G-PMMA samples. CONCLUSIONS: The results show that G-PMMA is a promising material to be used for prosthetic purposes. This is demonstrated by a significant increase in both peak load and bending stiffness, resulting from the bending test performed on G-PMMA samples. Furthermore, the latter exhibit greater homogeneity in their mechanical behavior, supporting the potential value of this material in dental prosthesis.

Implant placement in oral squamous cells carcinoma patients treated with chemoradiotherapy: "Sapienza Head and Neck Unit" clinical recommendations.

OBJECTIVE: To date, the treatment of patients affected by head and neck squamous cell carcinoma (HNSCC) is highly challenging for clinicians. Possible therapies are surgical resection of the tumor mass, radiotherapy, chemotherapy or, more often, a combined treatment that inevitably affects both normal and tumor cells. Consequently, patients' anatomy and functions become reduced or altered. Nowadays the functional restoration is significantly improved thanks to the innovation in prosthetic rehabilitation and in radiotherapy. The current IMRT (Intensity Modulated Radiation Therapy) allows planning adequate treatments evaluating different tissues' involvement and radiation dosage. It is possible to define the most suitable sites for implant insertion, using data provided by dose-volume histogram (DVH). This study aims to illustrate the idea of obtaining a unique CT image by blending radiation-planning CT and Cone Beam CT. PATIENTS AND METHODS: Five patients among 54 candidates were selected for this study. Selection criteria were: good general health (PS0-1), age between 18 and 72 years, absence of metastatic disease or local recurrence, disease-free interval of at least 18 months. Radiation planning CT scan and maxillo-facial CT Cone Beam of every patient were overlapped and merged. Only one CT for every evaluated patient was obtained in order to plan the most suitable areas for implant placement. RESULTS: The placement of 10 implants in 5 patients was programmed using the explained method. Patients (all male) were aged between 48 and 72 years old, with a median age of 64.4 years. In every case of this study, a modification of the initial program of implant placement was necessary. The new imaging method we are proposing was able to provide information about radiation isodoses received in the planned osseointegrated implants' positions. CONCLUSIONS: This new method allows operators to correct their own therapy plans and choices, customizing the treatment plan on the actual condition of the patient. Moreover, it makes all the rehabilitation process safer and can reduce the risk of failure, side effects and inconveniences for the patients.

Implant-Supported Rehabilitation Using GBR Combined with Bone Graft on a Reconstructed Maxilla with the Fibula Free Flap.

Alveolar ridge augmentation procedures allow restoring jaw defects due to teeth extractions, periodontal diseases, trauma, or outcomes from a previous surgery. This case report describes a patient suffering from Fibrous Dysplasia of the right upper maxilla surgically reconstructed by fibula free flap. In 2003, four dental implants were placed in the 1.2, 1.3, 1.5, and 1.6 areas. Twelve years later, the onset of peri-implantitis led to the failure of osseointegration with consequent thinning of the fibula flap. To avoid the risk of fracture and to restore the bone volumes necessary for a new implant-prosthetic rehabilitation, we used heterologous biomaterials in combination with a non-reabsorbable membrane, according to the Guided Bone Regeneration (GBR) technique. GBR was performed using the Equimatrix® natural bone mineral matrix, Cytoplast™ Ti-150, a non-reabsorbable titanium-reinforced membrane, and four fastening screws to pin the membrane. After six months, the membrane was removed and two Zimmer® implants 3.7 × 13 mm were placed in the 1.1 and 1.2 areas. A fixed implant-supported prosthesis with a custom-milled titanium bar screwed to the implants was made. Computed tomography (CT) six months after GBR showed a good bone regeneration of 1.5 cm mesiodistal (MD), 1.8 cm buccopalatal (BP), and 2.8 cm in height. The main difficulty of this clinical case concerns the low predictability of success of GBR on a maxillary reconstructed area with a free fibula flap: there is no previous evidence in the literature. Clinical and radiographic exams nowadays show that there is no macroscopic bone reabsorption; however, further research is needed to obtain more information.

Timing for implant placement in patients treated with radiotherapy of head and neck.

BACKGROUND: Aim of this retrospective study was to evaluate the most appropriate timing for the implant placement in oral cancer patients treated with radiation therapy. MATERIALS AND METHODS: We collected data for 17 subjects (10 females, 7 males; mean age: 51 ± 19) with malignant oral tumors who had been treated with ablative surgery and radiation therapy of head and neck. The radiotherapy was set in accordance with the NCCN guidelines. Every patient received dental implant rehabilitation between 2014 and 2016. A total of 84 titanium implants were placed, at a minimum interval of 12 months, in irradiated residual bone. Every patient underwent a minimum follow-up of 12 months. RESULT: Implant loss was dependent on the position and location of the implants (P = 0.05-0.1). Moreover, implant survival was dependent on the total dose of radiation and, mostly, on the timing of implant insertion after the end of the radiation therapy. This result was highly statistically significant (P < 0.01). Whether the implant was loaded is another highly significant (P < 0.01) factor determining survival. We observed significantly better outcomes when the implant was placed at least after 14 months and not loaded until at least 6 months after placement. CONCLUSION: Although the retrospective design of this study could be affected by selection and information biases, we conclude that a delayed implant placement after the end of the radiation therapy and a delayed loading protocol will give the best chance of implant osseointegration, stability and, ultimately, effective dental rehabilitation.

The association between in-utero exposure to stressful life events during pregnancy and male reproductive function in a cohort of 20-year-old offspring: The Raine Study.

STUDY QUESTION: Is exposure to gestational stress in the critical time window for the normal differentiation and growth of male reproductive tissue associated with male reproductive function in offspring in later life? SUMMARY ANSWER: Exposure to stressful life events (SLEs) in early, but not late gestation, are associated with reduced adult male reproductive function, consistent with the hypothesis that events during early prenatal life programme adult male reproductive function. WHAT IS ALREADY KNOWN: Animal studies suggest that gestational stress may impact on the reproductive function of male offspring, but human evidence is sparse. STUDY DESIGN, SIZE, DURATION: Using a prospective longitudinal cohort, we examined the association between number and type of maternal stressors during pregnancy in both early and late gestation and reproductive function in 643 male Generation 2 (offspring) at age 20 years. Mothers and their male Generation 2 (offspring) from The Raine Study participated. Mothers prospectively reported SLEs during pregnancy recorded at gestational weeks 18 and 34 using a standardized 10-point questionnaire. PARTICIPANTS/MATERIALS, SETTING, METHODS: The 643 male Generation 2 (offspring) underwent testicular ultrasound examination and semen analysis and provided serum for reproductive hormone analysis. Multivariate linear regression analysis was used to examine associations. MAIN RESULTS AND ROLE OF CHANCE: Of 643 recruited males, 407 (63%) were exposed to at least one SLE in early gestation. Fewer SLEs were reported in late gestation (n = 343, 53%). Maternal SLE exposure in early gestation was negatively associated with total sperm count (ß = -0.31, 95% CI -0.58; -0.03), number of progressive motile sperm (ß = -0.15, 95% CI -0.31; 0.00) and morning serum testosterone concentration (ß = -0.04, 95% CI -0.09; -0.00). No similar effects of maternal SLE exposure in late pregnancy were detected. The large sample size and an objective detailed direct assessment of adult male reproductive function with strict external quality control for sperm quality, as well as detailed prospectively collected information on prenatal SLEs in two distinct time windows of pregnancy reported by the women in early and late gestation along with other risk factors, imply minimal possibility of recall, information bias and selection bias. When assessing our results, we adjusted for a priori chosen confounders, but residual confounding or confounding by factors unbeknown to us cannot be ruled out. LIMITATIONS, REASONS FOR CAUTION: It is not possible to measure how SLEs impacted differently on the mother's experience or perception of stress. Resilience (coping) gradients may alter cortisol levels and thus modify the associations we observed and the mothers' own perception of stress severity may have provided a more precise estimate of her exposure. WIDER IMPLICATIONS OF THE FINDINGS: Our findings suggest that exposure to SLEs in early, but not late gestation, are associated with reduced adult male reproductive function. Improved support for women with exposure to SLEs during pregnancy, particularly during the first trimester, may improve the reproductive health of their male offspring in later life. Intervention studies of improved pregnancy support could provide more insight into this association and more information is needed about the potential specific epigenetic mechanisms underlying this association. STUDY FUNDING/COMPETING INTEREST(S): The male fertility sub-study was funded by NHMRC Grant 634 457. The core management of the Raine Study is funded by University of Western Australia, Curtin University, Telethon Kids Institute, Women and Infants Research Foundation, Edith Cowan University, Murdoch University, The University of Notre Dame Australia and Raine Medical Research foundation. Dr Bräuner's salary was supported by Læge Sofus Carl Emil Friis og Hustru Olga Doris Friis foundation in Denmark. All authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Crestal bone loss around dental implants placed in head and neck cancer patients treated with different radiotherapy techniques: a prospective cohort study.

The aim of this prospective cohort study was to evaluate how the radiation technique can affect crestal bone loss and the implant survival rate in head and neck cancer patients treated with radiotherapy. In this study, the type of radiotherapy treatment, i.e. three-dimensional conformal radiotherapy (3D-CRT) or intensity modulated radiation therapy (IMRT), was the predictor variable. The primary outcome variable was crestal bone loss, recorded at implant placement and after 3, 6, 12, and 24 months. A descriptive analysis and ANOVA test were performed; significance was set at P<0.05. Thirty-two patients were enrolled and a total of 113 dental implants placed in irradiated residual bone. There was no statistically significant difference in crestal bone loss levels between the groups at any of the intervals (P>0.05), except after 6 months (P=0.028). The cumulative dental implant survival rate was 94.7%. After 24 months, the mean marginal bone loss was 0.83±0.12mm in the 3D-CRT group and 0.74±0.15mm in the IMRT group (P=0.179). The data suggest that the different radiation techniques did not affect the outcomes of implant-supported prosthetic rehabilitation, as related to crestal bone loss and implant survival. However, long-term follow-up studies are necessary to evaluate the real influence of the radiotherapy technique on dental implants.

Histological and immunohistochemical evaluation of mandibular bone tissue regeneration.

The purpose of the study was to perform an immunohistochemical and histological evaluation of samples taken from different bone regeneration procedures in atrophic human mandible. 30 patients (15 men and 15 women, age range of 35-60 years), non-smokers, with good general and oral health were recruited in this study and divided into three groups. The first group included patients who were treated with blood Concentration Growth Factors (bCGF), the second group included patients who were treated with a mixture of bCGF and autologous bone, while the third group of patients was treated with bCGF and tricalcium phosphate/hydroxyapatite (TCP-HA). Six months after the regenerative procedures, all patients undergone implant surgery, and a bone biopsy was carried out in the site of implant insertion. Each sample was histologically and immunohistochemically examined. Histological evaluation showed a complete bone formation for group II, partial ossification for group I, and moderate ossification for group III. Immunohistochemical analysis demonstrated a statistically significant difference between the three groups, and the best clinical result was obtained with a mixture of bCGF and autologous bone.

Aesthetic satisfaction in lip and palate clefts: a comparative study between secondary and tertiary bone grafting.

Lip and palate cleft represent one of the most frequently occurring congenital deformity, which includes dental anomalies, such as variation in tooth number and position. In case of hypodontia implant-prosthetic rehabilitation offers significant advantages in terms of function, aesthetics and quality of life and bone graft is usually needed. Secondary bone grafting, generally performed in the mixed dentition phase (years 8-11) seems to be the most successful method to allow for rehabilitation. It's often necessary to perform a tertiary bone grafting in adult age in order to achieve better bone quantity and quality before implant placement. Aim of this retrospective study was to evaluate the aesthetic perception that patients had of themselves comparing dental implants placed in tertiary grafted alveolar cleft sites with a previous secondary grafting to only secondary grafting. Between 2009 and 2012, fourteen alveolar cleft were treated with implant rehabilitation and eleven of them received tertiary bone grafting six months prior to implant placement. All patients were questioned to give a score from 1 to 10 their aesthetic satisfaction of their smile before and after implant rehabilitation and during pre-surgery provisional rehabilitation. At the end of their prosthesis rehabilitation patients who received tertiary bone grafting resulted more satisfied than those who had secondary bone grafting only (9.5 vs 8).

Prosthetic rehabilitation involving the use of implants following a fibula free flap reconstruction in the treatment of Osteosarcoma of the maxilla: a case report.

INTRODUCTION: Osteosarcoma is an aggressive primary bone tumor composed of connective tissue cells directly producing osteoid and bone. Prosthetic rehabilitations in post-oncological patients after bone reconstruction are not substantially different than those of patients affected by severe atrophy of upper or lower jaw after bone reconstruction. The treatment for patients with a malignant neoplasia of the oral cavity requires multidisciplinary approach by a team of different specialists that follow the patient through the phases of diagnosis, therapy and oral rehabilitation. Reconstructive surgery of jaws using vascularized free flap allows a significant gain of tissues that enables a successful final prosthetic rehabilitation. In fact main prosthetics difficulties result from lack of hard and soft tissues in affected area. Reconstructed patients have a greater ease of care management. CASE PRESENTATION: A 25-year-old Caucasian male was diagnosed with chondroblastic osteosarcoma of the pre-maxilla. The patient initially noticed the displacement of his maxillary incisors with progression into a definite swelling of the pre-maxillary a month later. Computerized Tomographic Scan and Radionuclide Bone Scan revealed the absence of both distant metastasis and regional nodal involvement. A biopsy and subsequent histopathology examination confirmed the lesion as being a chondroblastic type of osteosarcoma. The case study directed us to rehabilitate the patient by implant supported prosthesis consisting 3 different components: a titanium base screwed on implants, a titanium structure (primary structure) assembled on the base and a composite coatedstructure (secondary structure) that reproduced teeth and gum. At surgery, we proceeded placing 6 dental implants in 1.4, 1.3 1.2, 2.1, 2.2 and 2.4 positions. Contextually was performed a bone graft using particulate bone and collagen membranes. CONCLUSIONS: Prosthetic rehabilitation in Maxillofacial Osteosarcoma treatment is an hard challenge for prosthodontist due to anatomic conditions of this kind of patients. Dental implants play a crucialrole in the therapy of patients affected by malignancies in the head-and-neck region. The goal of implant rehabilitationis to improve the quality of life of these patients by allowing proper retention of removable prostheses and a reduction in the load placed on vulnerable soft tissues. Today prosthetically guided rehabilitation represents the main rehabilitation protocol in prosthodontics, especially in those oncological patients with relevant lost of tissues and modified anatomy.

Monolithic zirconia and digital impression: case report.

AIMS: The aim of this study is to present a clinical case of a full arch prosthetic rehabilitation on natural teeth, combining both digital work-flow and monolithic zirconia. PATIENTS AND METHODS: Digital impression was taken with an intraoral optical scanner (CS3500, Carestream Dental, Atlanta, GA, USA). A prosthetic rehabilitation was realized on natural teeth using monolithic zirconia from 1.6 to 1.4 and from 2.7 to 2.4 frameworks, while in the aesthetic area (from 2.3 to 1.3), technicians left on the structure a 0.8 mm vestibular space for ceramic layering. DISCUSSION: The combination of digital impression technology and the use of the monolithic zirconia had demonstrated the delivery of the final prosthetic device in a quick time without the need to remodel functional or aesthetic areas. The digital work-flow combines intraoral optical impression techniques and CAD/CAM technology, in order to achieve a fully digital and successful way to deliver prosthetic restorations to patients, providing aesthetics and function in shorter intervals of time. The clinical outcome of this study was satisfactory but a long-term evaluation is needed.

Pleomorphic adenoma rehabilitative treatment in growing up patient: a 20-years follow-up.

OBJECTIVE: Although tumors of minor salivary glands are rare, the pleomorphic adenoma is the most common pathology among the benign neoplasm and can be found with high prevalence in the junction between hard palate and soft palate. Most of the maxillary tumors are surgically treated through either a total or partial maxillectomy. However, surgical defects lead to both clinical and psychologic disorders for the patient. A postoperative obturator prosthesis is a good option in patients who underwent maxillectomy. It allows to restore both masticatory and speaking functions, as well as aesthetic appearance. When reconstruction of the surgical site is possible, an implant-supported prosthesis can be considered to guarantee a better function and aesthetic's rehabilitation. CASE REPORT: This clinical report presents the prosthetic rehabilitation of a patient who underwent maxillectomy because of a pleomorphic adenoma of hard palate minor salivary glands. The patient was treated with a palatal obturator prosthesis first and with an implant-supported prosthesis after surgical site's reconstruction and complete healing. CONCLUSIONS: The rehabilitation of the patient after maxillectomy through both these devices was an excellent option and provided clinical benefits, improving the patient's quality of life, allowing the patient's reinsertion into society.

Ventilation in day care centers and sick leave among nursery children.

Several studies have reported poor indoor air quality (IAQ) in day care centers (DCCs), and other studies have shown that children attending them have an increased risk of respiratory and gastrointestinal infections. The aim of this study was to investigate whether there is an association between ventilation in DCCs and sick leave among nursery children. Data on child sick leave within an 11-week period were obtained for 635 children attending 20 DCCs. Ventilation measurements included three proxies of ventilation: air exchange rate (ACR) measured with the decay method, ACR measured by the perfluorocarbon tracer gas (PFT) method, and CO2 concentration measured over a 1-week period. All but two DCCs had balanced mechanical ventilation system, which could explain the low CO2 levels measured. The mean concentration of CO2 was 643 ppm, exceeding 1000 ppm in only one DCC. A statistically significant inverse relationship between the number of sick days and ACR measured with the decay method was found for crude and adjusted analysis, with a 12% decrease in number of sick days per hour increase in ACR measured with the decay method. This study suggests a relationship between sick leave among nursery children and ventilation in DCCs, as measured with the decay method.

Variation in residential radon levels in new Danish homes.

Radon-222 gas arises from the radioactive decay of radium-226 and has a half-life of 3.8 days. This gas percolates up through soil into buildings, and if it is not evacuated, there can be much higher exposure levels indoors than outdoors, which is where human exposure occurs. Radon exposure is classified as a human carcinogen, and new Danish homes must be constructed to ensure indoor radon levels below 100 Bq/m(3). Our purpose was to assess how well 200 newly constructed single detached homes perform according to building regulations pertaining to radon and identify the association between indoor radon in these homes and municipality, home age, floor area, floor level, basement, and outer wall and roof construction. Median (5-95 percentile) indoor radon levels were 36.8 (9.0-118) Bq/m(3) , but indoor radon exceeded 100 Bq/m(3) in 14 of these new homes. The investigated variables explained nine percent of the variation in indoor radon levels, and although associations were positive, none of these were statistically significant. In this study, radon levels were generally low, but we found that 14 (7%) of the 200 new homes had indoor radon levels over 100 Bq/m(3). More work is needed to determine the determinants of indoor radon.

Two clinical cases of prosthetical rehabilitation after a tumor of the upper maxilla.

The most frequent type of treatment for patients diagnosed with a malignant neoplasia of the oral cavity is surgical removal of the tumor. As a result of the resection performed, it is difficult to obtain satisfactory results in the oral rehabilitation of these patients. When possible, fixed prostheses are the best option, because they guarantee stability, but they should be made so that the operator can remove them periodically to check the health of the oral tissues underneath and to intercept any relapse of the tumor. This study analyses two cases of patients surgically treated for a tumor of the upper maxilla at the Oral and Maxillo-Facial Surgery of Sapienza University, in Rome. In the first case the surgical site was covered with local flaps, and the patient was rehabilitated with an implant-supported removable prosthesis. In the second case the maxilla was reconstructed with a fibula vascularized free flap, and the patient was rehabilitated with an implant-supported prosthesis screwed to a titanium bar solidarizing the implants. Therefore, this prosthesis was fixed, but could be removed by the dentist. The different approach to these two cases was influenced by the different anatomic situations after the reconstruction. It is important for the dentist to approach these patients knowing the kind of surgery they received because this aspect will influence rehabilitative choices. Rehabilitation should be planned, when possible, before surgical treatment, in order to cooperate with the maxillo-facial surgeon in choosing the most appropriate restorative treatment.

Treatment of facial vascular malformations with embolisation and surgical resection.

INTRODUCTION: Facial arteriovenous malformations (AVMs) are quite rare morbid conditions that clinically present themselves mainly as a massive bleeding or a significant aesthetic defect. Vascular malformations do not regress spontaneously; this is the reason why their resection is necessary. The successful treatment of these vascular anomalies is often compromised, since a high incidence of recurrence could be expected if the lesion is not managed properly. A multidisciplinary approach is needed for the assessment and treatment of these lesions. The therapeutic management involves a preoperative superselective embolisation, a surgical resection of the lesion within the following 24 hours and finally an aesthetic reconstruction. PATIENTS AND METHODS: The study was carried out on a total of 62 patients with facial AVMs; all the patients underwent surgical procedures from 2000 to 2010. RESULTS: The case series consisted of 8 patients with haemangiomas and 54 patients with AVMs; in 31 cases of the latter group the vascular malformations showed a low blood flow, whereas the remaining 23 cases had a high blood flow. The lips were the most common localization. All 54 patients with AVMs underwent a surgical resection. Among the 23 patients with facial high-blood flow AVM, 21.7% were classified as stage I Schobinger, 47.9% as stage II, and 30.4% as stage III. The treatment consisting of associated embolisation and resection was performed in 14 arteriovenous malformations (stage II, III) with high blood flow; 5 of them required a flap reconstruction. CONCLUSION: Recent advances in microsurgery and interventional angioradiology have improved the prognosis of treatment for these malformations. Combining embolisation and resection with aesthetic flap reconstruction represents the therapy of choice for facial arteriovenous malformations, as it prevents their recurrence.