Unequal Impact of COL1A1 and COL1A2 Variants on Dentinogenesis Imperfecta.

Dentinogenesis imperfecta (DI) is the main orodental manifestation of osteogenesis imperfecta (OI) caused by COL1A1 or COL1A2 heterozygous pathogenic variants. Its prevalence varies according to the studied population. Here, we report the molecular analysis of 81 patients with OI followed at reference centers in Brazil and France presenting COL1A1 or COL1A2 variants. Patients were submitted to clinical and radiographic dental examinations to diagnose the presence of DI. In addition, a systematic literature search and a descriptive statistical analysis were performed to investigate OI/DI phenotype-genotype correlation in a worldwide sample. In our cohort, 50 patients had COL1A1 pathogenic variants, and 31 patients had COL1A2 variants. A total of 25 novel variants were identified. Overall, data from a total of 906 individuals with OI were assessed. Results show that DI was more frequent in severe and moderate OI cases. DI prevalence was also more often associated with COL1A2 (67.6%) than with COL1A1 variants (45.4%) because COL1A2 variants mainly lead to qualitative defects that predispose to DI more than quantitative defects. For the first time, 4 DI hotspots were identified. In addition, we showed that 1) glycine substitution by branched and charged amino acids in the α2(I) chain and 2) substitutions occurring in major ligand binding regions-MLRB2 in α1(I) and MLBR 3 in α2(I)-could significantly predict DI (P < 0.05). The accumulated variant data analysis in this study provides a further basis for increasing our comprehension to better predict the occurrence and severity of DI and appropriate OI patient management.

Hypertension and frailty in older adults.

The association between hypertension and frailty syndrome in older adults remains unclear. There is scarce information about the prevalence of hypertension among frail elderly patients or on its relationship with frailty. Up to one quarter of frail elderly patients present without comorbidity or disability, yet frailty is a leading cause of death. The knowledge and better control of frailty risk factors could influence prognosis. The present study evaluated: (1) the prevalence of hypertension in robust, prefrail, and frail elderly; and (2) factors that might be associated with frailty including hypertension. A cross-sectional study was conducted in 619 older adults at a university-based outpatient center. Study protocol included sociodemographic data, measures of blood pressure and body mass index, frailty screening according to the internationally validated FRAIL (fatigue, resistance, ambulation, illnesses, and loss of weight) scale, number of comorbidities, drug use assessment, physical activity, cognitive status, and activities of daily living. Ordinal logistic regression was used to evaluate factors associated with frailty. Prevalence of hypertension and frailty was 67.3% and 14.8%, respectively, in the total sample. Hypertension was more prevalent in the prefrail (72.5%) and frail (83%) groups than among controls (51.7%). Hypertension, physical activity, number of prescribed drugs, and cognitive performance were significantly associated with frailty status. Hypertension presented an odds ratio of 1.77 towards frailty (95% confidence interval, 1.21-2.60; P = .002). Hypertension was more prevalent in frail elderly patients and was significantly associated with frailty. Intensive control of hypertension could influence the trajectory of frailty, and this hypothesis should be explored in future prospective clinical trials.

Partial caries removal in deep caries lesions: a 5-year multicenter randomized controlled trial.

OBJECTIVE: This multicenter randomized controlled clinical trial aimed to compare the outcomes of stepwise excavation (SW) and partial caries removal (PCR) regarding the maintenance of pulp vitality in deep caries lesions over 5 years. METHODS: At baseline, 299 permanent molars with deep caries lesions were randomly assigned to control or test groups. The control group received the stepwise excavation treatment (SW), while the test group received partial caries removal from the pulpal wall followed by restoration in a single session (PCR). Treatments were conducted in two centers located in the cities of Porto Alegre (South Brazil) and Brasília (Midwest Brazil). Survival analysis was performed to compare PCR and SW over time (Weibull regression models). The primary outcome of this study was pulp vitality, determined by the combination of the following characteristics: positive response to cold test, negative response to percussion, absence of spontaneous pain, and absence of periapical lesion (radiographic examination). RESULTS: This 5-year study includes data pertaining to 229 teeth: 121 teeth actually examined at the 5-year appointment, and 108 teeth contributed with data collected in previous follow-ups (18 months or 3 years). Survival analysis showed success rates of 80% in PCR group and 56% in SW group (p < 0.001). Failure was significantly associated with treatment [PCR, HR=0.38; 95%CI=0.23-0.63)] and region [South, HR=2.22; 95%CI=1.21-4.08]. CONCLUSION: PCR significantly reduced the occurrence of pulp necrosis when compared with SW. CLINICAL RELEVANCE: This study supports the PCR as a single-visit technique to manage deep caries lesions in permanent teeth.

Nonannual tree rings in a climate-sensitive Prioria copaifera chronology in the Atrato River, Colombia.

In temperate climates, tree growth dormancy usually ensures the annual nature of tree rings, but in tropical environments, determination of annual periodicity can be more complex. The purposes of the work are as follows: (1) to generate a reliable tree-ring width chronology for Prioria copaifera Griseb. (Leguminoceae), a tropical tree species dwelling in the Atrato River floodplains, Colombia; (2) to assess the climate signal recorded by the tree-ring records; and (3) to validate the annual periodicity of the tree rings using independent methods. We used standard dendrochronological procedures to generate the P. copaifera tree-ring chronology. We used Pearson correlations to evaluate the relationship of the chronology with the meteorological records, climate regional indices, and gridded precipitation/sea surface temperature products. We also evaluated 24 high-precision 14C measurements spread over a range of preselected tree rings, with assigned calendar years by dendrochronological techniques, before and after the bomb spike in order to validate the annual nature of the tree rings. The tree-ring width chronology was statistically reliable, and it correlated significantly with local records of annual and October-December (OND) streamflow and precipitation across the upper river watershed (positive), and OND temperature (negative). It was also significantly related to the Oceanic Niño Index, Pacific Decadal Oscillation, and the Southern Oscillation Index, as well as sea surface temperatures over the Caribbean and the Pacific region. However, 14C high-precision measurements over the tree rings demonstrated offsets of up to 40 years that indicate that P. copaifera can produce more than one ring in certain years. Results derived from the strongest climate-growth relationship during the most recent years of the record suggest that the climatic signal reported may be due to the presence of annual rings in some of those trees in recent years. Our study alerts about the risk of applying dendrochronology in species with challenging anatomical features defining tree rings, commonly found in the tropics, without an independent validation of annual periodicity of tree rings. High-precision 14C measurements in multiple trees are a useful method to validate the identification of annual tree rings.

Pamidronate affects the mandibular cortex of children with osteogenesis imperfecta.

We hypothesized that mandibular cortical width (MCW) is smaller in children with osteogenesis imperfecta (OI) than in healthy children and that pamidronate can improve the cortical mandibular thickness. The aim of this study was to assess changes in the MCW on dental panoramic radiographs (DPRs) of children with normal bone mineral density (BMD) and with OI. We also compared the MCW of children with different types of OI regarding the number of pamidronate cycles and age at the beginning of treatment. MCW measurements were retrospectively obtained from 197 DPRs of 66 children with OI types I, III, and IV who were in treatment with a comparable dosage of cyclical intravenous pamidronate between 2007 and 2013. The control group had 92 DPRs from normal BMD children. Factorial analysis of variance was used to compare MCW measurements among different age groups and between sexes and also to compare MCW measurements of children with different types of OI among different pamidronate cycles and age at the beginning of treatment. No significant differences in results were found between male and female subjects in both OI and healthy children, so they were evaluated altogether (P > 0.05). There was an increase of MCW values related to aging in all normal BMD and OI children but on a smaller scale in children with OI types I and III. Children with OI presented lower mean MCW values than did children with normal BMD at the beginning of treatment (P < 0.05). A linear model estimated the number of pamidronate cycles necessary to achieve mean MCW values equivalent to those of healthy children. The thinning of the mandibular cortex depended on the number of pamidronate cycles, the type of OI, and the age at the beginning of treatment. DPRs could thus provide a way to identify cyclic pamidronate treatment outcomes in patients with OI.

Apoptosis-associated genes related to photodynamic therapy in breast carcinomas.

The aim of this study was to find the apoptosis molecular markers involved in the cell death that might be related to photodynamic therapy (PDT) mechanisms in breast cancer. The mammary tumors were induced in 25 Sprague-Dawley female rats by a single, oral gavage of 7,12-dimethylbenz(a)anthracene (DMBA; 70 mg/kg body weight). Animals were divided into four groups: G1 (normal, without DMBA), G2 (control, without PDT treatment), G3 (euthanized 48 h after PDT), and G4 (euthanized 24 h after PDT). For PDT experiments, the photosensitizer used was Photodithazine, and 100 J/cm of light at a fluence rate of 100 mW/cm was delivered to treat lesions. A sample of each animal was investigated by quantitative real-time PCR using Rat Apoptosis RT2 Profiler™ PCR Array platform. The results showed 20 genes with differential expression between PDT and control groups. A significant upregulation was observed for pro-apoptotic genes CASP4, CASP12, CIDEA, GADD45A, and FAS and downregulation of anti-apoptotic genes MAPK8IP1, TNFRSF11B, and NAIP2 in PDT-treated tumors. These results indicate that these genes are more directly involved in cell apoptosis induced by PDT.

Dental anomalies in primary dentition and their corresponding permanent teeth.

OBJECTIVES: The objectives of this paper are to estimate the prevalence of dental anomalies in primary dentition in a sample of 2- to 5-year-old Brazilian preschool children, determine their distribution, and investigate their occurrence in the succedaneous teeth of the sample compared with a control group of children with no dental anomalies in the primary dentition. MATERIALS AND METHODS: The one-stage sample comprised 1,718 two to five-year-old children with fully erupted primary dentition clinically examined for dental anomalies. All children presenting dental anomalies underwent panoramic radiographs. Descriptive statistics were performed for the studied variables. A control group matched by sex and age was studied to compare the prevalence ratio for dental anomalies in the permanent dentition. RESULTS: The prevalence of dental anomalies in the primary dentition was 1.8 %, with no significant statistical difference between sexes. Double teeth were the most frequently observed. Dental anomalies on the succedaneous permanent teeth were diagnosed in 54.8 % of the children with affected primary dentition. The prevalence ratio (PR) for dental anomalies in the succedaneous permanent teeth was 17.1 (confidence interval (CI) 5.33-54.12) higher compared with the control group, higher in children with bilateral anomalies (PR = 31.2, CI 10.18-94.36). CONCLUSIONS: An association between anomalies of the permanent dentition and the presence of dental anomalies in primary teeth was observed, especially when they occur bilaterally. CLINICAL RELEVANCE: The results in the present study have a clinical relevance in the diagnosis of children with dental anomalies in primary dentition. Early identification of these anomalies can aid the dentist in planning dental treatment at the appropriate time.

Partial removal of carious dentine: a multicenter randomized controlled trial and 18-month follow-up results.

AIM: The aim of this study was to evaluate the effectiveness of partial removal of carious dentine and restoration in a single session (PDR) and stepwise excavation (SW), both of which are treatments for deep carious lesions, in Public Health Services in Brazil. INCLUSION CRITERIA: patients ≥6 years old, permanent molars with deep caries lesions (having a radiolucency halfway or more into dentine) and pulp vitality but absence of spontaneous pain, positive percussion test, and periapical alterations. The subjects received either PDR (test group) or SW (control group). The radiological and clinical exams were performed after a mean time of 18 months. OUTCOMES: success was defined as pulp sensitivity to cold test and absence of periapical alterations. RESULTS: Of the 299 treatments performed, 146 were SW and 153 were PDR; 122 were amalgam restorations and 168 resin-composite restorations. There were no differences between the groups regarding the baseline characteristics (i.e. age, gender and family income). After 18 months, 212 evaluations were performed, which indicated 99 and 86% success rates in the PDR and SW groups, respectively (p = 0.016). Reasons for failure were: PDR - 1 pulpitis; SW - 8 pulpitis; 1 osteitis; 4 necrosis; 1 endodontic treatment. None of the baseline variables were significantly associated with the outcomes. CONCLUSION: The retention of carious dentine does not interfere in pulp vitality. Data from this 18-month study suggest that the procedure of reopening the cavity to remove the residual infected dentine is not necessary.

Randomized trial of partial vs. stepwise caries removal: 3-year follow-up.

This randomized, multicenter clinical trial evaluated the effectiveness of 2 treatments for deep caries lesions - partial caries removal (PCR) and stepwise excavation (SW) - with respect to the primary outcome of pulp vitality for a 3-year follow-up period. Inclusion criteria were as follows: patients with permanent molars presenting deep caries lesions (lesion affecting ≥ 1/2 of the dentin on radiographic examination), positive response to a cold test, absence of spontaneous pain, negative sensitivity to percussion, and absence of periapical lesions (radiographic examination). Teeth randomly assigned to PCR (test) received incomplete caries removal and filling in a single session. Outcome success was evaluated by assessment of pulp vitality, determined by pulp sensitivity to a cold test and the absence of periapical lesions. Data were analyzed by a Weibull regression model with shared frailty term (survival analysis). At baseline, 299 treatments were executed: PCR, 152 and SW, 147. By the end of the 3-year follow-up period, 213 teeth had been evaluated. Adjusted survival rates were 91% for PCR and 69% for SW (p = 0.004). These results suggest that there is no need to re-open a cavity and perform a second excavation for pulp vitality to be preserved (Clinical trials registration NCT00887952).

Autosomal-dominant ankyloglossia and tooth number anomalies.

Ankyloglossia is a congenital oral anomaly characterized by the presence of a hypertrophic lingual frenulum. It frequently accompanies X-linked cleft palate and is sometimes seen alone due to mutations in the gene encoding the transcription factor TBX22, while knockout of Lgr5 in the mouse results in ankyloglossia. The aim of the present study was to characterize the phenotype and to verify sequence variations in the LGR5 gene in a Brazilian family with ankyloglossia associated with tooth number anomalies. Twelve individuals of three generations were submitted to physical, oral, and radiographic examinations and molecular analysis. Eight had ankyloglossia with various degrees of severity. Six also had hypodontia in the lower incisor region; one had a supernumerary tooth in this region, and another had a supernumerary tooth in the lower premolar region. The characterization of this family determined an autosomal-dominant inheritance and excluded the LGR5 gene mutations as being involved in the pathogenesis of this condition.

Phenotype characterization and DSPP mutational analysis of three Brazilian dentinogenesis imperfecta type II families.

The aim of this study was to perform phenotype analysis and dentin sialophosphoprotein (DSPP) mutational analysis on 3 Brazilian families diagnosed with dentinogenesis imperfecta type II (DGI-II) attending the Dental Anomalies Clinic in Brasilia, Brazil. Physical and oral examinations, as well as radiographic and histopathological analyses, were performed on 28 affected and unaffected individuals. Clinical, radiographic and histopathological analyses confirmed the diagnosis of DGI-II in 19 individuals. Pulp stones were observed in ground sections of several teeth in 2 families, suggesting that obliteration of pulp chambers and root canals results from the growth of these nodular structures. Mutational DSPP gene analysis of representative affected family members revealed 7 various non-disease-causing alterations in exons 1-4 within the dentin sialoprotein domain. Further longitudinal studies are necessary to elucidate the progression of pulpal obliteration in the DGI-II patients studied as well as the molecular basis of their disease.

Case report of a rare syndrome associating amelogenesis imperfecta and nephrocalcinosis in a consanguineous family.

A rare syndrome associating amelogenesis imperfecta (AI) with nephrocalcinosis has been reported. The purpose of this study is to characterise the phenotype of a consanguineous family presenting amelogenesis imperfecta, delayed permanent teeth eruption and nephrocalcinosis. Six family members were examined. Ground sections of the case index deciduous teeth and biopsies of enlarged dental follicles were analysed. The patients's parents were first cousins. The case index had yellow discoloration and altered teeth shapes, retention of deciduous teeth, and delayed eruption. Panoramic radiographs revealed multiple enlarged pericoronal follicles in unerupted teeth and generalised intrapulpal calcifications. Renal ultrasound showed the presence of nephrocalcinosis. No other family members presented enamel defects or nephrocalcinosis. Histologically, the enamel appeared hypoplastic, and dental follicles indicated pericoronal hamartoma. The consanguineous marriage suggests an autosomal recessive mode of inheritance. Further studies are necessary to clarify the genetic defect behind this syndrome that associates AI, nephrocalcinosis and impaired tooth eruption.

Assessment of thromboembolism after the Cox-Maze procedure for chronic atrial fibrillation secondary to mitral valve lesion.

OBJECTIVE: To assess the occurrence of late thromboembolism after surgical repair of chronic atrial fibrillation (AF) simultaneously with repair of mitral valve using the Cox-Maze procedure. METHODS: 69 patients underwent Cox 3 procedure, with no cryoablation simultaneously with mitral valvuloplasty or prosthesis. Mean age was 49.9+/-13.2 years. Mean follow-up was of 31.7+/-19 months. Types of lesion were as follows: 33 (48%) stenoses, 23 (33%) insufficiencies, and 13 (19%) double lesions. Procedures were: 64 (93%) valvuloplasties, 3 (4%) biological and 2 (3%) mechanical prosthesis placement. There were 9 (13%) patients with previous systemic embolism and 2 (3%) had left atrial thrombi. RESULTS: Early mortality was 7% and late 1%. 2 patients (3%) were reoperated for mitral placement. At last evaluation, 10 patients (15%), were in AF. The remaining 59 (85%) were either in sinus / atrial rythm (74%) or under pacing (12%). There were no occurrence of early or late, systemic or pulmonary embolism. Permanent anticoagulation was employed in 16 cases, 10 in regular rythm and 6 in AF. The remaining 47 (75%), 2 in AF and 45 in regular rythm, did not receive anticoagulants. CONCLUSIONS: These results are in accordance with others series, where the occurrence of embolism was rare after maze procedure. Permanent systemic anticoagulation seems to be unnecessary in those cases.

Avaliação de tromboembolismo em pós-operatório da cirurgia do labirinto (Cox-Maze) para fibrilação atrial crônica secundária a lesão mitral / Assessment of thromboembolism after the Cox-Maze procedure for chronic atrial fibrillation secondary to mitral valve lesion

OBJECTIVE: To assess the occurrence of late thromboembolism after surgical repair of chronic atrial fibrillation (AF) simultaneously with repair of mitral valve using the Cox-Maze procedure. METHODS: 69 patients underwent Cox 3 procedure, with no cryoablation simultaneously with mitral valvuloplasty or prosthesis. Mean age was 49.9±13.2 years. Mean follow-up was of 31.7±19 months. Types of lesion were as follows: 33 (48 percent) stenoses, 23 (33 percent) insufficiencies, and 13 (19 percent) double lesions. Procedures were: 64 (93 percent) valvuloplasties, 3 (4 percent) biological and 2 (3 percent) mechanical prosthesis placement. There were 9 (13 percent) patients with previous systemic embolism and 2 (3 percent) had left atrial thrombi. RESULTS: Early mortality was 7 percent and late 1 percent. 2 patients (3 percent) were reoperated for mitral placement. At last evaluation, 10 patients (15 percent), were in AF. The remaining 59 (85 percent) were either in sinus / atrial rythm (74 percent) or under pacing (12 percent). There were no occurrence of early or late, systemic or pulmonary embolism. Permanent anticoagulation was employed in 16 cases, 10 in regular rythm and 6 in AF. The remaining 47 (75 percent), 2 in AF and 45 in regular rythm, did not receive anticoagulants. CONCLUSIONS: These results are in accordance with others series, where the occurrence of embolism was rare after maze procedure. Permanent systemic anticoagulation seems to be unnecessary in those cases