The Frailty Index in centenarians and their offspring.

Frailty has been indicated as a way for capturing biological aging of the individual and Frailty Index (FI) may serve for this purpose. This study designed the FI in a cohort of centenarians, their offspring and control subjects sex- and age-matched with offspring. The FI mean value was 0.47 (SD 0.13) in centenarians, 0.15 (SD 0.12) in their offspring, and 0.22 (SD 0.14) in controls (p < 0.001). The difference between offspring and controls was statistically significant (p = 0.003). The correlation between FI and age was significant in offspring (r = 0.46, p < 0.001), close to significance in controls (r = 0.25, p = 0.08) and not significant in centenarians. Our study confirms that FI is a marker of biological age useful to discriminate different degrees of frailty even at extremely advanced age.

Increased expression of TREM2 in peripheral cells from mild cognitive impairment patients who progress into Alzheimer's disease.

BACKGROUND AND PURPOSE: Neuroinflammation plays a role in the aetiopathogenesis of Alzheimer's disease (AD). Triggering receptor expressed on myeloid cells 2 (TREM2), a cell surface receptor of the immunoglobulin superfamily, seems to have protective anti-inflammatory activity in AD. METHODS: Triggering receptor expressed on myeloid cells 2 expression was analysed in peripheral blood mononuclear cells from healthy subjects (CT) and from patients with either AD or mild cognitive impairment (MCI). MCI patients were re-evaluated at a 2-year follow-up to investigate their progression to AD (MCI-AD) or lack thereof (MCI-MCI). RESULTS: Triggering receptor expressed on myeloid cells 2 gene expression was higher in AD than CT patients, but was highest in MCI. At recruitment TREM2 levels were higher in MCI-AD than in MCI-MCI, and in MCI-AD were higher initially than at follow-up. TREM2 displayed a moderate degree of sensitivity and specificity for identifying MCI-AD in all MCI patients. Our data showed higher TREM2 levels in allele ε4 of apolipoprotein E (ApoE ε4) carriers than non-carriers in MCI and particularly in MCI-AD. CONCLUSIONS: These data seem to confirm the protective role of TREM2 in the pre-clinical stage of AD. Upregulation of TREM2 in MCI-AD could be a mechanism to counteract the activation of neuroinflammatory processes. It is possible that TREM2 and ApoE ε4 interact synergistically in the pre-clinical stage of AD. Therefore, TREM2 may be useful as an early peripheral biomarker for the development of AD.

Systemic treatment with resveratrol and/or curcumin reduces the progression of experimental periodontitis in rats.

BACKGROUND AND OBJECTIVE: Periodontitis is a chronic inflammatory disease of periodontal tissues that leads to the destruction of bone and other connective tissues. Resveratrol and curcumin are plant-derived substances with biological properties that may have immunomodulatory properties. This study investigated the effect of continuous administration of resveratrol and curcumin and the association of resveratrol and curcumin on the progression of experimental periodontitis in rats. MATERIAL AND METHODS: Forty Wistar rats were assigned randomly to the following groups: group 1, experimental periodontitis + placebo (PL) (n = 10); group 2, experimental periodontitis + resveratrol (RSV) (n = 10); group 3, experimental periodontitis + curcumin (C) (n = 10); and group 4, experimental periodontitis + resveratrol + curcumin (COMBI) (n = 10). Periodontitis was induced in rats by tying a silk suture, as a ligature, around one of the first molars. Daily administration of the placebo solution, 10 mg/kg of resveratrol, 100 mg/kg of curcumin or 10 mg/kg of resveratrol plus 100 mg/kg of curcumin was carried out from day 0 to day 30. At the end of the relevant experimental periods, rats were killed and the specimens obtained were processed for morphometric analysis of bone loss. Gingival tissues surrounding the first molar were collected for quantification of interleukin (IL)-1ß, IL-4, interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) using a Luminex/MAGPIX assay. RESULTS: Intergroup comparisons of the morphometric outcomes revealed higher bone-loss values in the PL group (p < 0.05) when compared with RSV, C and COMBI groups. There was no difference in bone-loss values among RSV, C and COMBI groups (p > 0.05). The immunoenzymatic assay of the gingival tissue showed a lower concentration of IL-1ß in the COMBI group in comparison with the PL group (p < 0.05). Higher values of IL-4 were demonstrated in groups RSV, C and COMBI in comparison with the PL group (p < 0.05). Only RSV caused a reduction in the levels of IFN-γ (p < 0.05). There was no difference in the concentration of TNF-α amongst the four groups (p > 0.05). CONCLUSION: Resveratrol and curcumin are capable of reducing alveolar bone loss in an animal model of periodontitis. This occurred when these agents were added singly or in combination with one another, but there did not appear to be either synergistic or additive effects.

Impact of smoking on experimental gingivitis. A clinical, microbiological and immunological prospective study.

OBJECTIVE: The present study assessed the effect of smoking on clinical, microbiological and immunological parameters in an experimental gingivitis model. MATERIAL AND METHODS: Twenty-four healthy dental students were divided into two groups: smokers (n = 10); and nonsmokers (n = 14). Stents were used to prevent biofilm removal during brushing. Visible plaque index (VPI) and gingival bleeding index (GBI) were determined 5- on day -7 (running phase), baseline, 21 d (experimental gingivitis) and 28 d (resolution phase). Supragingival biofilm and gingival crevicular fluid were collected and assayed by checkerboard DNA-DNA hybridization and a multiplex analysis, respectively. Intragroup comparison was performed by Friedman and Dunn's multiple comparison tests, whereas the Mann-Whitney U-test was applied for intergroup analyses. RESULTS: Cessation of oral hygiene resulted in a significant increase in VPI, GBI and gingival crevicular fluid volume in both groups, which returned to baseline levels 7 d after oral hygiene was resumed. Smokers presented lower GBI than did nonsmokers (p < 0.05) at day 21. Smokers had higher total bacterial counts and higher proportions of red- and orange complex bacteria, as well as lower proportions of Actinomyces spp., and of purple- and yellow-complex bacteria (p < 0.05). Furthermore, the levels of key immune-regulatory cytokines, including interleukin (IL)-8, IL-17 and interferon-γ, were higher in smokers than in nonsmokers (p < 0.05). CONCLUSION: Smokers and nonsmokers developed gingival inflammation after supragingival biofilm accumulation, but smokers had less bleeding, higher proportions of periodontal pathogens and distinct host-response patterns during the course of experimental gingivitis.

Alcohol intake may impair bone density and new cementum formation after enamel matrix derivative treatment: histometric study in rats.

BACKGROUND AND OBJECTIVE: Alcohol intake may interfere with bone metabolism; however, there is a lack of information about the outcomes of regenerative approaches in the presence of alcohol intake. Enamel matrix derivative (EMD) has been used in periodontal regenerative procedures resulting in improvement of clinical parameters. Thus, the aim of this histomorphometric study is to evaluate the healing of periodontal defects after treatment with EMD under the influence of alcohol intake. MATERIAL AND METHODS: Twenty Wistar rats were randomly assigned to two groups: G1 = alcohol intake (n = 10) and G2 = non-exposed to alcohol intake (n = 10). Thirty days after initiation of alcohol intake, fenestration defects were created at the buccal aspect of the first mandibular molar of all animals from both groups. After the surgeries, the defects of each animal were randomly assigned to two subgroups: non-treated control and treated with EMD. The animals were killed 21 d later. RESULTS: G1 showed less defect fill for non-treated controls. Bone density (BD) and new cementum formation were lower for G1 when compared to G2, for EMD-treated and non-treated sites. EMD treatment resulted in greater BD and new cementum formation in both groups and defect fill was not significantly different between groups in the EMD-treated sites. The number of tartrate-resistant acid phosphatase-positive osteoclasts was significantly higher in G1 when compared to G2 and in EMD-treated sites of both groups. CONCLUSION: Alcohol intake may produce a significant detrimental effect on BD and new cementum formation, even in sites treated with EMD. A limited positive effect may be expected after EMD treatment under this condition.

Cigarette smoke inhalation increases the alveolar bone loss caused by primary occlusal trauma in a rat model.

BACKGROUND AND OBJECTIVE: Occlusal trauma (OT) and smoking are both factors that alter alveolar bone metabolism and therefore could synergistically act on alveolar bone loss. The aim of this experimental study was to evaluate the influence of short-term cigarette smoke inhalation (CSI) on inter-radicular alveolar bone loss promoted by primary OT in a rat model. MATERIAL AND METHODS: Forty-eight animals were randomly assigned to one of three groups based on treatment type: OT + CSI (n = 16), animals were exposed to CSI three times per day, for 8 min per exposure, and they concomitantly received unilateral vertical augmentation creating an occlusal interference inducing experimental OT; OT (n = 16), animals received only unilateral vertical augmentation; negative control (NC; n = 16), animals maintained for equal periods to achieve periodontal baseline values of periodontal ligament dimension. Each group was divided into two subgroups (n = 8) based on treatment length: 7 or 14 d. RESULTS: After 7 d, the OT + CSI group exhibited significantly higher bone loss compared to the NC group (p = 0.0022). After 14 d, the OT (p < 0.0001) and OT + CSI (p < 0.0001) groups presented significantly higher bone loss compared to the NC group, and OT + CSI resulted in significantly higher bone loss than OT alone (p = 0.0241). The number of tartrate-resistant acid phosphatase-positive cells on the linear surface of the bone crest after 7 d was significantly higher in the OT + CSI group as compared to the NC and OT groups (p < 0.0001 and p = 0.0045, respectively) and remained significantly higher in the OT + CSI group after 14 d, compared to the OT group (p < 0.0001). CONCLUSION: Short-term CSI increases early bone loss in association with OT after 7 d, and this worsens in severity after 14 d of exposure.

Perinatal periodontal disease reduces social behavior in male offspring.

OBJECTIVE: Our objective was to verify whether prenatal maternal periodontitis is a risk factor for the development of central nervous system disorders in rats. METHODS: Periodontitis was induced by placing a ligature around the upper and lower first molars in 9 female Wistar rats (experimental group); 9 rats were left unligated (control group). The maternal general activity in an open field was observed on gestational day (GD) 0, GD 4, and GD 14, and the maternal performance was assessed on the second day after birth. The pups' play behavior was assessed on postnatal day 30. The relative level of reelin was measured in the frontal cortex by real-time PCR analysis. RESULTS: The results showed that, compared with the control group, (1) the general activity in female rats with periodontitis was decreased, (2) the maternal performance of these rats was not modified by periodontitis, (3) the play behavior of pups from dams with periodontitis was decreased, and (4) there were no differences in the frontal cortex reelin levels of pups from dams with periodontitis. CONCLUSIONS: We conclude that pre- and postnatal periodontitis induces maternal sickness behavior and reduces the pups' play behavior without interference with frontal cortex reelin expression.

Subgingival biodiversity in subjects with uncontrolled type-2 diabetes and chronic periodontitis.

BACKGROUND AND OBJECTIVE: There is a bidirectional relationship between periodontal disease and type-2 diabetes mellitus (DM). Inflammatory mediators may negatively affect glycemic control, and increased glucose levels and resultant glycation end-products may alter the host response against bacterial infection. However, no agreement has been reached regarding the effect of DM on periodontal subgingival microbiota. Therefore, the purpose of the present study was to compare the subgingival biodiversity in deep periodontal pockets of subjects with chronic periodontitis and either uncontrolled type-2 diabetes or no diabetes using 16S rRNA gene cloning and sequencing. MATERIAL AND METHODS: Twelve subjects with uncontrolled type-2 diabetes (glycated hemoglobin > 8%) and eleven nondiabetic subjects presenting severe and generalized chronic periodontitis were selected. Subgingival biofilm from periodontal pockets > 5 mm were assessed using the 16S rRNA gene cloning and sequencing technique. RESULTS: Significant differences were observed in subgingival microbiota between diabetic and nondiabetic subjects. Diabetic subjects presented higher percentages of total clones of TM7, Aggregatibacter, Neisseria, Gemella, Eikenella, Selenomonas, Actinomyces, Capnocytophaga, Fusobacterium, Veillonella and Streptococcus genera, and lower percentages of Porphyromonas, Filifactor, Eubacterium, Synergistetes, Tannerella and Treponema genera than nondiabetic individuals (p < 0.05). Moreover, some phylotypes, such as Fusobacterium nucleatum, Veillonella parvula, V. dispar and Eikenella corrodens were detected significantly more often in diabetic subjects than in nondiabetic subjects (p < 0.05). CONCLUSION: Subjects with uncontrolled type-2 diabetes and chronic periodontitis presented significant dissimilarities in subgingival biodiversity compared with nondiabetic subjects.

A semi-automatic planning technique for whole breast irradiation with tangential IMRT fields.

PURPOSE: To implement a semi-automatic planning technique for whole breast irradiation with two tangential IMRT fields and to test the produced dose distribution against clinical 3DCRT plans, for introducing the technique in clinical practice. METHODS: The Auto-Planning module of the Pinnacle3 (Philips) treatment planning system was used for generating a Treatment Technique on left-sided breast cancer patients treated in free breathing or in deep inspiration breath hold (DIBH) and to right-sided breast cancer patients. The technique was evaluated against 3DCRT clinical plans in terms of dosimetric plan parameters. Plan robustness toward patient displacements was assessed on a subset of patients by inducing shifts to the isocenter. RESULTS: A statistically significant improvement in target coverage and dose homogeneity was observed for autoIMRT. No statistically significant differences were observed for ipsilateral organs, except for the ipsilateral lung in left DIBH, where slightly lower Dmean and V18% are registered for autoIMRT. Slightly higher Dmean doses (although far below the constraints) to contralateral organs were observed for autoIMRT plans. AutoIMRT plans were shown to be as robust as 3DCRT plans toward isocenter shifts, with a maximum decrease in CTV coverage of -2.2% and -2.1% for autoIMRT and 3DCRT, respectively. Average planning times were 40 min for 3DCRT and 6 min for IMRT plans. CONCLUSIONS: The developed autoIMRT technique was proven to be advantageous for target coverage and homogeneity and sufficiently robust towards isocenter displacements. The use of automated planning consistently reduces the planning workload with improvements in plan quality.

Impact of smoking on inflammation: overview of molecular mechanisms.

BACKGROUND: Inflammation is a critical component of normal tissue repair, as well as being fundamental to the body's defense against infection. Environmental factors, such as smoking, have been reported to modify the host response and hence modify inflammation progression, severity and outcome. Therefore, a comprehensive understanding of the molecular mechanisms by which smoking affects inflammation is vital for preventive and therapeutic strategies on a clinical level. AIM: The purpose of the present article is to review the potential biological mechanisms by which smoking affects inflammation, emphasizing recent developments. RESULTS: Smoking is reported to effect a number of biological mediators of inflammation through its effect on immune-inflammatory cells, leading to an immunosuppressant state. Recent evidence strongly suggests that the molecular mechanisms behind the modulation of inflammation by smoking mainly involve the nuclear factor-kappa B (NF-kB) family, through the activation of both an inhibitor of IkB kinase (IKK)-dependent and -independent pathway. In addition to NF-kB activation, a number of transcriptional factors including GATA, PAX5 and Smad 3/4, have also been implicated. CONCLUSION: Multiple mechanisms may be responsible for the association of smoking and inflammation, and the identification of potential therapeutic targets should guide future research.

Impact of Porphyromonas gingivalis inoculation on ligature-induced alveolar bone loss. A pilot study in rats.

BACKGROUND AND OBJECTIVE: Periodontitis is a polymicrobial infection characterized by the loss of connective tissue attachment, periodontal ligament and alveolar bone. The aim of this study was to evaluate the impact of Porphyromonas gingivalis inoculation on the ligature-induced alveolar bone loss (ABL) model in rats. MATERIAL AND METHODS: Forty male Wistar rats were randomly assigned to the following groups: G1, control (n = 10); G2, ligature-induced ABL (n = 15); and G3, ligature-induced ABL + P. gingivalis inoculation (n = 15). Rats in G2 and G3 were killed 15, 21 and 30 d after ligature placement, and the following parameters were assessed: microbiological load; ABL; and interleukin (IL)-1ß (Il1beta)/Il1ra, Il6/Il10 and Rankl/osteoprotegerin (Opg) mRNA ratios in the gingival tissues, as determined by quantitative PCR. RESULTS: Microbiological analyses demonstrated that rats in G1, G2 and G3 were positive for the presence of bacteria (determined using PCR amplification of the 16S gene), but that only the treatment sites of rats in G3 were positive for P. gingivalis at all time-points investigated. Histometrically, significant bone loss (p<0.001) was observed for both ligated groups (G2 and G3) compared with the nonligated group (G1), with higher ABL observed for G2 at all the experimental time-points. Furthermore, gene-expression analysis demonstrated that the presence of P. gingivalis in the dentogingival area significantly decreased the Il1ß/Il1ra, Il6/Il10 and Rankl/Opg mRNA ratios compared with ligature alone. CONCLUSION: Within the limits of this pilot study, it was concluded that inoculation of P. gingivalis affected the ligature-induced ABL model by the induction of an anti-inflammatory and antiresorptive host response.

Automatic VMAT technique to treat glioblastoma: A two years' experience.

PURPOSE: The present work aims to guide the physicist in order to start automated planning for the VMAT treatment of glioblastoma multiforme (GBM) by giving a recipe that was set up and tested during a long-term (two years) evaluation. METHODS: An automatic technique in AutoPlanning module of the Pinnacle3 (Philips Medical Systems, Fitchburg, WI) treatment planning system was created and validated by comparing dose distributions of automatic plans (APs) and manual plans (MPs) and by performing a blind AP-MP comparison on a cohort of 20 patients. Automatic technique was then applied to 145 patients and failures were recorded i.e. the number of times for which dose distributions produced by the automatic module were not suitable for treatment. RESULTS: Each of the 20 APs considered in the validation step was clinically acceptable and proved to be better (15 cases) or equal (5 cases) respect to MPs. A statistically significant improvement in brain stem, optic pathways, cochleae, pituitary gland and scalp sparing was observed for APs, while no statistically significant differences were recorded in target coverage or plan parameters. For only 5 cases out of the 145 plans the operator intervention was needed in order to obtain a clinical acceptable plan, while for the remaining 140 plans the automatic created solution was suitable. CONCLUSIONS: A straightforward automatic procedure has been created and tested in our clinic. The AutoPlanning technique proposed represents a reliable tool to improve treatment planning efficiency and the recipe, here presented, could be simply imported to every radiotherapy center.

In phantom evaluation of targeting accuracy in MRI-based brain radiosurgery.

PURPOSE: To determine the targeting accuracy of brain radiosurgery when planning procedures employing different MRI and MRI + CT combinations are adopted. MATERIALS AND METHOD: A new phantom, the BrainTool, has been designed and realized to test image co-registration and targeting accuracy in a realistic anatomical situation. The phantom was created with a 3D printer and materials that mimic realistic brain MRI and CT contrast using a model extracted from a synthetic MRI study of a human brain. Eight markers distributed within the BrainTool provide for assessment of the accuracy of image registrations while two cavities that host an ionization chamber are used to perform targeting accuracy measurements with an iterative cross-scan method. Two procedures employing 1.5 T MRI-only or a combination of MRI (taken with 1.5 T or 3 T scanners) and CT to carry out Gamma Knife treatments were investigated. As distortions can impact targeting accuracy, MR images were preliminary evaluated to assess image deformation extent using GammaTool phantom. RESULTS: MR images taken with both scanners showed average and maximum distortion of 0.3 mm and 1 mm respectively. The marker distances in co-registered images resulted below 0.5 mm for both MRI scans. The targeting mismatches obtained were 0.8 mm, 1.0 mm and 1.2 mm for MRI-only and MRI + CT (1,5T and 3 T), respectively. CONCLUSIONS: Procedures using a combination of MR and CT images provide targeting accuracies comparable to those of MRI-only procedures. The BrainTool proved to be a suitable tool for carrying out co-registration and targeting accuracy of Gamma Knife brain radiosurgery treatments.

Could implant position influence the peri-implant parameters in edentulous mandibles of diabetics rehabilitated with overdentures? A split-mouth randomized study.

This randomized controlled trial assessed the impact of crestal level position of implants installed in type 2 diabetes mellitus (T2DM) patients rehabilitated with overdentures. Twenty-two mandibular edentulous T2DM patients were submitted to implant placement for retention of an overdenture. By means of a split-mouth design, two implants were installed: one at supracrestal level (SL) and one at crestal level (CL). Clinical, immunoenzymatic and tomographic analyses were performed at prosthesis placement (baseline) and after 6, 12 and 24 months following implant loading. Increased peri-implant probing depths were detected in CL implants when compared with SL implants at all time-points (baseline P=0.047; 6 months P=0.014; 12 months P=0.027; 24 months P=0.036). Indeed, augmented clinical attachment levels were also detected in CL implants when compared with SL implants at all time-points (baseline P=003; 6 months P=0.045; 12 months P=0.029; 24 months P=0.026). CL implants demonstrated increased amounts of interleukin-6 (IL-6) at 6 months (P=0.043) and higher IL-17 (P=0.021), IL-21 (P=0.034) and tumour necrosis factor alpha (TNF-α) concentrations (P=0.030) at 24 months in comparison with SL implants. CL group revealed enhanced bone loss from baseline to 6 (P=0.032), 12 (P=0.043) and 24 months (P=0.028) when compared with SL. In conclusion, this study showed that implants placed supracrestally in T2DM patients rehabilitated with overdentures demonstrated lower bone loss and better clinical parameters with beneficial modulation of peri-implant immunoinflammatory biomarkers when compared with implants positioned at crestal level.

Levels of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, inflammatory cytokines and species-specific immunoglobulin G in generalized aggressive and chronic periodontitis.

BACKGROUND AND OBJECTIVE: Aggressive periodontitis pathogenesis still is not completely understood in the literature regarding the relationship between microbial and inflammatory aspects. So this study aimed to compare microbial and inflammatory patterns in the gingival crevicular fluid of generalized aggressive and chronic periodontitis patients. MATERIAL AND METHODS: Forty aggressive and 28 chronic periodontitis patients were selected. Biofilm and gingival crevicular fluid were collected from a deep pocket (periodontal probing depth >7 mm) and a moderate pocket (periodontal probing depth = 5 mm) of each patient, and microbiological and immunoenzymatic assays were performed. Real-time PCR was used to determine quantities of Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis. Enzyme-linked immunosorbent assay (ELISA) was employed to determine gingival crevicular fluid levels of interleukin-1beta, interferon-gamma, prostaglandin E(2) and interleukin-10. In addition, immunoglobulin G (IgG) levels against A. actinomycetemcomitans and P. gingivalis lipopolysaccharide were also determined by ELISA. Analysis of variance/Tukey test, Mann-Whitney U-test and the Pearson correlation test were used to determine differences and correlations between variables analysed (alpha = 5%). RESULTS: Patients suffering from generalized aggressive periodontitis had their mouth colonized by higher amounts of A. actinomycetemcomitans and P. gingivalis than chronic periodontitis patients. Conversely, the gingival crevicular fluid levels of IgG against both pathogens were statistically inferior in aggressive periodontitis patients (p < 0.05). With regard to gingival crevicular fluid levels of cytokines, aggressive periodontitis patients presented reduced levels of interleukin-10 (p < 0.05). CONCLUSION: In comparison to chronic periodontitis, generalized aggressive periodontitis patients have an imbalance in the host response, with reduced levels of interleukin-10 and IgG, and increased periodontal pathogens.

Subgingival Host-Microbial Interactions in Hyperglycemic Individuals.

Type 2 diabetes mellitus (T2DM) is an established risk factor for periodontitis, yet its contribution to creating host-bacterial disequilibrium in the subgingival crevice is poorly understood. The present investigation aimed to quantify the impact of hyperglycemia on host-bacterial interactions in established periodontitis and to map shifts in these dynamics following mechanical nonsurgical therapy. Seventeen T2DM and 17 non-T2DM subjects with generalized severe chronic periodontitis were recruited along with 20 periodontally healthy individuals. Subjects with periodontitis were treated with scaling and root planing (SRP). Samples of subgingival biofilm and gingival crevicular fluid were collected at baseline and at 1-, 3-, and 6 mo postoperatively. Correlations were generated between 13.7 million 16S ribosomal DNA sequences and 8 immune mediators. Intermicrobial and host-microbial interactions were modeled using differential network analysis. Periodontal health was characterized by a sparse interbacterial and highly connected cytokine-bacterial network, while both normoglycemics and T2DM subjects with periodontitis demonstrated robust congeneric and intergeneric hubs but significantly fewer cytokine-bacterial connections. Following SRP, the cytokine-bacterial edges demonstrated a 2-fold increase 1 mo postoperatively and a 10-fold increase at 6 mo in normoglycemics. In hyperglycemics, there was a doubling at 1 mo but no further changes thereafter. These shifts accompanied an increasingly sparse interbacterial network. In normoglycemics, the nodes anchored by interleukin (IL)-4, IL-6, and IL-10 demonstrated greatest rewiring, while in hyperglycemics, IL-1ß, IL-6, INF-γ, and IL-17 exhibited progressive rewiring. Thus, the present investigation points to a breakdown in host-bacterial mutualism in periodontitis, with interbacterial interactions rather than host-bacterial interactions primarily determining community assembly. Hyperglycemia further exacerbates this uncoupled mutualism. Our data also demonstrate that while nonsurgical therapy might not consistently alter microbial abundances or lower proinflammatory molecules, it "reboots" the interaction between the immunoinflammatory system and the newly colonizing microbiome, restoring a role for the immune system in determining bacterial colonization. However, this outcome is lower and delayed in hyperglycemics.

The influence of thyroid hormones on periodontitis-related bone loss and tooth-supporting alveolar bone: a histological study in rats.

BACKGROUND AND OBJECTIVE: Recent studies have pointed to potentially periodontal risk indicators, however no information is available on the impact of changes in thyroid hormone levels on the progression of periodontitis and on the quality of alveolar bone. Thus, the aim of the present study was to evaluate histologically, in rats, the influence of thyroid hormones on the rate of periodontal bone loss resulting from ligature placement and on the quality of tooth-supporting alveolar bone. MATERIAL AND METHODS: Thirty-six male Wistar rats were randomly assigned to the following groups: healthy (control, n = 12), hypothyroidism (n = 12) and hyperthyroidism (n = 12). Once alterations were confirmed by total serum levels of triiodothyronine and thyroxine, ligatures were randomly placed around one of the first mandibular molars. Thirty days later, the animals were killed and specimens routinely processed for serial decalcified sections. The parameters assessed were periodontitis-related bone loss, quality of tooth-supporting alveolar bone and the number of cells positive for tartrate-resistant acid phosphatase (TRAP), a marker of bone resorption. RESULTS: At the ligated sites, intergroup analysis revealed that hypothyroidism significantly increased the bone loss resulting from ligature-induced periodontitis (p = 0.02) and the number of TRAP-positive cells on the linear surface of bone crest (p = 0.01). In addition, no significant differences were detected regarding the quality of the bone (p = 0.24) or the number of TRAP-positive cells in the area of the interradicular bone for ligated teeth among the groups (p = 0.17). CONCLUSION: It may be concluded that decreased serum levels of thyroid hormones may enhance periodontitis-related bone loss, as a function of an increased number of resorbing cells, whereas the tooth-supporting alveolar bone seems to be less sensitive to alterations in hormone levels.

The Triggering Receptor Expressed on Myeloid Cells-2 (TREM-2) as Expression of the Relationship between Microglia and Alzheimer's Disease: A Novel Marker for a Promising Pathway to Explore.

Alzheimer's disease (AD) is a common neurodegenerative disorder, strongly related with age. It has been reported that genetic variants of the Triggering Receptor Expressed on Myeloid Cells-2 (TREM2), a cell-surface receptor expressed in microglial cells, greatly increase the risk of AD, thus suggesting an involvement of the microglia in the AD pathogenesis. The aim of this report is to provide an overview of the TREM2 and of its possible implication in the pathogenesis of AD.

Short implants versus bone augmentation in combination with standard-length implants in posterior atrophic partially edentulous mandibles: systematic review and meta-analysis with the Bayesian approach.

The use of short implants as an alternative to bone reconstruction techniques for the placement of standard-length dental implants is a debated topic. The aim of this study was to perform a systematic review and meta-analysis in order to assist in the clinical decision making about the most appropriate approach for the fixed rehabilitation of the posterior atrophic partially edentulous lower jaws. Only randomized trials with at least 1-year follow-up were included. Of the 1024 studies initially retrieved, 14 articles were selected and independently evaluated by two reviewers. Finally, four studies were included, and underwent data extraction and meta-analysis with the Bayesian approach. Both treatment approaches provide high implant survival rate after 1year of function. However, the probability of survival rate of short implants being greater than standard length implants is 84%, and the probability of complications using short implants being greater than standard-length implants is 15.7%. In spite of similar survival rates when the residual bone is sufficient for placement of short implants, the latter should be preferred to augmentation techniques and standard-length implants due to fewer complications, lower morbidity and greater comfort for patients.

Apolipoprotein E gene in physiological and pathological aging.

INTRODUCTION: The genetic background plays a role on longevity. The distribution of the apolipoprotein E gene (APOE) variants (ε2, ε3, ε4) may differ across age groups, especially in the oldest old and despite geographical and ethnic specificities. Since the ε4 variant is associated with Alzheimer's disease (AD), it might represent an opportunity for exploring the relationship of APOE with physiological and pathological aging. AIM: To explore the role played by APOE genotype/alleles on physiological and pathological brain aging. MATERIALS AND METHODS: The study was conducted in a cohort of centenarians (n = 106), and two cohorts of octogenarians (without cognitive decline, n = 351 controls; and with AD, n = 294). RESULTS: No significant differences in genotype/allele distributions were observed comparing controls to centenarians. The prevalence of ε2/ε3, ε3/ε3, ε3/ε4 and ε4/ε4 genotypes were significantly different in centenarians compared to AD. The prevalence of ε2 and ε3 alleles were significantly higher in centenarians, whereas the ε4 was less frequent. The ε4 allele was positively associated with AD, whereas a negative association was found for ε2 and ε3 alleles. CONCLUSIONS: Our study indicates that ε4 allele is strongly associated with AD. APOE significantly affects AD risk, but apparently not longevity.