Universal DNA methylation age across mammalian tissues.

Aging, often considered a result of random cellular damage, can be accurately estimated using DNA methylation profiles, the foundation of pan-tissue epigenetic clocks. Here, we demonstrate the development of universal pan-mammalian clocks, using 11,754 methylation arrays from our Mammalian Methylation Consortium, which encompass 59 tissue types across 185 mammalian species. These predictive models estimate mammalian tissue age with high accuracy (r > 0.96). Age deviations correlate with human mortality risk, mouse somatotropic axis mutations and caloric restriction. We identified specific cytosines with methylation levels that change with age across numerous species. These sites, highly enriched in polycomb repressive complex 2-binding locations, are near genes implicated in mammalian development, cancer, obesity and longevity. Our findings offer new evidence suggesting that aging is evolutionarily conserved and intertwined with developmental processes across all mammals.

Effect on osseointegration of two implant macro-designs:A histomorphometric analysis of bicortically installed implants in different topographic sites of rabbit's tibiae.

BACKGROUND: To evaluate the effect of two different implant macro-designs on the sequential osseointegration at bicortically installed implants in the rabbit tibia. A further aim is to compare the osseointegration at different topographic zones. MATERIAL AND METHODS: 27 New Zealand rabbits were implemented. Two implants, one for each macro-design (Ticare Inhex® or Ticare Quattro®, Mozo-Grau, Valladolid, Spain), were randomly implanted in the diaphysis or metaphysis of each tibia. The flaps were sutured to allow a submerged healing. The animals were sacrificed after 2, 4 or 8 weeks. Ground sections were prepared and analyzed. RESULTS: No statistically significant differences were found between the two groups for newly formed bone in contact with the implant surface, being about 16%, 19% and 33% in both groups, after 2, 4, and 8 weeks of healing. Bone apposition was slightly higher in the diaphysis, reaching values of 36.4% in the diaphysis, and 29.3% in the metaphysis at 8 weeks of healing. It was observed that the implant position showed a statistical significance regarding BIC values at 4 and 8 weeks (p<0.05). Multivariate analysis fails to detect statistical significant differences for the interaction between implant designs and topographic site. Ticare Quattro® design had a slight better BIC values at diaphysis sites across healing stages, but without reaching a statistical significance. CONCLUSIONS: The both implant macro-designs provided similar degrees of osseointegration. Bone morphometry and density may affect bone apposition onto the implant surface. The apposition rates were slightly better in diaphysis compared to metaphysis.

Relation between the distance from the cementoenamel junction to the bone crest and the thickness of the facial bone in anterior maxillary teeth: A cross-sectional tomographic study.

BACKGROUND: The purpose of this cross-sectional study was to evaluate radiologically, the relation between the distance from the cementoenamel junction (CEJ) to the facial bone crest (FBC), and the facial alveolar bone (FAB) width at maxillary anterior teeth. A further aim was to assess if the CEJ-FBC distance had an impact in the prevalence to find a FAB thickness greater than one mm. STUDY DESIGN: CBCT images were retrospectively obtained from the database of the Oral Surgery Unit of the University of Valencia. The teeth were divided in 3 groups according to the CEJ-FBC distance: Shorter (≤3mm), Middle (>3 ≤4.5 mm) and Larger (>4.5 mm). FAB thickness was measured by two different examiners at 1, 2 and 3 mm apical to the FBC. Normality of means were evaluated by Kolmogorov-Smirnov test and an ANOVA-type linear model was performed. RESULTS: 82 patients were included in the study, with 156 central incisors, 149 lateral incisors and 152 canines analyzed. A significant greater FAB thickness in Shorter (≤3mm CEJ-FBC) than Middle and Larger group was observed in all distances measured apical to the FBC. There was a significant inverse relation between the distance CEJ-FBC and FAB thickness at all distances measured. The prevalence of a FAB thickness equal or greater than one mm was 35.9% of all teeth analyzed from Shorter, 17.4% of Middle and 8.9% of Larger group at 1 mm apical to the FBC. CONCLUSIONS: When the distance from the CEJ to the FBC is augmented, thinner FAB thickness has to be expected in all teeth of the anterior maxilla. The prevalence to find a FAB thicker than one mm decreases as the distance from the FBC to the CEJ increases.

Retrospective study of foreign body-associated pathology in stranded cetaceans, Canary Islands (2000-2015).

Marine pollution, overrepresented by plastic, is a growing concern worldwide. However, there is little knowledge on occurrence and detrimental impacts of marine debris in cetaceans. To partially fill in this gap of knowledge, we aimed to investigate the occurrence and pathologies associated with foreign bodies (FBs) in a large cohort of cetaceans (n = 465) stranded in the Canary Islands. The Canary Islands shelter the greatest cetacean biodiversity in Europe, with up to 30 different species, of which nine are regularly present year around. We found at least one ingested FB in 36 out of 465 (7.74%) studied cetaceans, involving 15 different species, including eight out of the nine (80%) cetacean species present year-round in the Canary Islands. Risso's dolphin was the species most affected, followed by sperm whale, beaked whale and mysticetes. Plastic FB were the most common item found (80.56%). FB was directly associated with death in 13/36 (36.11%) animals. Poor body condition and deep diving behavior were found to be risk factors for FB ingestion, whereas the adult age was a protective factor. To the authors knowledge this is the first study that use statistical analysis to investigate risk and protective factors for FB ingestion. This study also provides insights of the potential impact caused by ingested FBs on the animal's health and mortality. This knowledge is critical to better understand and assess the impact of FB in cetaceans setting the scientific basis for prospective impact monitoring and future conservation policies.

Clinical parameters of implants placed in healed sites using flapped and flapless techniques: A systematic review.

BACKGROUND: Dental implant placement using flapless surgery is a minimally invasive technique that improves blood supply compared with flapped surgery. However, the flapless technique does not provide access to allow bone regeneration. OBJECTIVE: The aim of this systematic review was to evaluate the clinical parameters following implant surgery in healed sites, using two procedures: flapped vs. flapless surgery. MATERIALS AND METHODS: A detailed electronic search was carried out in the PubMed/Medline, Embase and Cochrane Library databases. The focused question was, "How do flapped and flapless surgical techniques affect the clinical parameters of dental implants placed in healed sites?". All the studies included with a prospective controlled design were considered separately, depending on whether they had been conducted on animals or humans. The following data were recorded in all the included studies: number of implants, failures, location (maxilla, mandible), type of rehabilitation (partial or single), follow-up and flap design. The variables selected for comparison in the animal studies were the following: flap design, gingival index, mucosal height, recession and probing pocket depth. In humans studies the variables were as follows: flap design, plaque index, gingival index, recession, probing pocket depth, papilla index and keratinized gingiva. RESULTS: Ten studies were included, six were experimental studies and four were clinical studies. Studies in animals showed better results using the flapless technique in the parameters analyzed. There is no consensus in the clinical parameters analyzed in human studies, but there is a trend to better results using flapless approach. CONCLUSION: The animal studies included in the present review show that implants placed in healed sites with a flapless approach have better clinical parameters than the flapped procedure in a short-term follow-up. In human studies, there is no consensus about which technique offer better results in terms of clinical parameters. Therefore, more research in humans is required in order to overcome the limitations and contrast these results.

Influence of different types of pulp treatment during isolation in the obtention of human dental pulp stem cells.

BACKGROUND: Different methods have been used in order to isolate dental pulp stem cells. The aim of this study was to study the effect of different types of pulp treatment during isolation, under 3% O2 conditions, in the time needed and the efficacy for obtaining dental pulp stem cells. MATERIAL AND METHODS: One hundred and twenty dental pulps were used to isolate dental pulp stem cells treating the pulp tissue during isolation using 9 different methods, using digestive, disgregation, or mechanical agents, or combining them. The cells were positive for CD133, Oct4, Nestin, Stro-1, CD34 markers, and negative for the hematopoietic cell marker CD-45, thus confirming the presence of mesenchymal stem cells. The efficacy of dental pulp stem cells obtention and the minimum time needed to obtain such cells comparing the 9 different methods was analyzed. RESULTS: Dental pulp stem cells were obtained from 97 of the 120 pulps used in the study, i.e. 80.8% of the cases. They were obtained with all the methods used except with mechanical fragmentation of the pulp, where no enzymatic digestion was performed. The minimum time needed to isolate dental pulp stem cells was 8 hours, digesting with 2mg/ml EDTA for 10 minutes, 4mg/ml of type I collagenase, 4mg/ml of type II dispase for 40 minutes, 13ng/ml of thermolysine for 40 minutes and sonicating the culture for one minute. CONCLUSIONS: Dental pulp stem cells were obtained in 97 cases from a series of 120 pulps. The time for obtaining dental pulp stem cells was reduced maximally, without compromising the obtention of the cells, by combining digestive, disgregation, and mechanical agents.

Calcium phosphate neuron-like structures: a rare case or a common structure?

Underneath the unique and beautiful structures of biominerals there is always the presence of organic molecules that tightly interact with the developing inorganic nuclei/crystal directing its growth and assembly towards the final structure. This close interdigitation between organic and inorganic matter renders biominerals not only unique in their appearance but also with exceptional properties. A notable case of such combination is observed when combining double hydrophilic block copolymers (DHBCs) with different ions. In the particular case of calcium phosphate systems, the incorporation of DHBCs was found to induce the formation of unique and delicate neuron-like structures. The present article highlights that such structures are more common than probably expected and they can be created using much simpler organic molecules of a wider nature such as non-ionic surfactants (Tween 80 or Span 20), anionic polymers (sodium polyacrylate) and cationic polymers (polydiallyldimethylammonium chloride). The reaction conditions are however crucial in the stabilization of the structures.