Neurobiology and Changing Ecosystems: Mechanisms Underlying Responses to Human-Generated Environmental Impacts.

Human generated environmental change profoundly affects organisms that reside across diverse ecosystems. Although nervous systems evolved to flexibly sense, respond, and adapt to environmental change, it is unclear whether the rapid rate of environmental change outpaces the adaptive capacity of complex nervous systems. Here, we explore neural systems mediating responses to, or impacted by, changing environments, such as those induced by global heating, sensory pollution, and changing habitation zones. We focus on rising temperature and accelerated changes in environments that impact sensory experience as examples of perturbations that directly or indirectly impact neural function, respectively. We also explore a mechanism involved in cross-species interactions that arises from changing habitation zones. We demonstrate that anthropogenic influences on neurons, circuits, and behaviors are widespread across taxa and require further scientific investigation to understand principles underlying neural resilience to accelerating environmental change.SIGNIFICANCE STATEMENT Neural systems evolved over hundreds of millions of years to allow organisms to sense and respond to their environments - to be receptive and responsive, yet flexible. Recent rapid, human-generated environmental changes are testing the limits of the adaptive capacity of neural systems. This presents an opportunity and an urgency to understand how neurobiological processes, including molecular, cellular, and circuit-level mechanisms, are vulnerable or resilient to changing environmental conditions. We showcase examples that range from molecular to circuit to behavioral levels of analysis across several model species, framing a broad neuroscientific approach to explore topics of neural adaptation, plasticity, and resilience. We believe this emerging scientific area is of great societal and scientific importance and will provide a unique opportunity to reexamine our understanding of neural adaptation and the mechanisms underlying neural resilience.

Socio-ecological drivers of multiple zoonotic hazards in highly urbanized cities.

The ongoing COVID-19 pandemic is a stark reminder of the devastating consequences of pathogen spillover from wildlife to human hosts, particularly in densely populated urban centers. Prevention of future zoonotic disease is contingent on informed surveillance for known and novel threats across diverse human-wildlife interfaces. Cities are a key venue for potential spillover events because of the presence of zoonotic pathogens transmitted by hosts and vectors living in close proximity to dense human settlements. Effectively identifying and managing zoonotic hazards requires understanding the socio-ecological processes driving hazard distribution and pathogen prevalence in dynamic and heterogeneous urban landscapes. Despite increasing awareness of the human health impacts of zoonotic hazards, the integration of an eco-epidemiological perspective into public health management plans remains limited. Here we discuss how landscape patterns, abiotic conditions, and biotic interactions influence zoonotic hazards across highly urbanized cities (HUCs) in temperate climates to promote their efficient and effective management by a multi-sectoral coalition of public health stakeholders. We describe how to interpret both direct and indirect ecological processes, incorporate spatial scale, and evaluate networks of connectivity specific to different zoonotic hazards to promote biologically-informed and targeted decision-making. Using New York City, USA as a case study, we identify major zoonotic threats, apply knowledge of relevant ecological factors, and highlight opportunities and challenges for research and intervention. We aim to broaden the toolbox of urban public health stakeholders by providing ecologically-informed, practical guidance for the evaluation and management of zoonotic hazards.

Proposal of 'Candidatus Frankia alpina', the uncultured symbiont of Alnus alnobetula and A. incana that forms spore-containing nitrogen-fixing root nodules.

The members of the genus Frankia are, with a few exceptions, a group of nitrogen-fixing symbiotic actinobacteria that nodulate mostly woody dicotyledonous plants belonging to three orders, eight families and 23 genera of pioneer dicots. These bacteria have been characterized phylogenetically and grouped into four molecular clusters. One of the clusters, cluster 1 contains strains that induce nodules on Alnus spp. (Betulaceae), Myrica spp., Morella spp. and Comptonia spp. (Myricaceae) that have global distributions. Some of these strains produce not only hyphae and vesicles, as other cluster 1 strains do, but also numerous sporangia in their host symbiotic tissues, hence their phenotype being described as spore-positive (Sp+). While Sp+ strains have resisted repeated attempts at cultivation, their genomes have recently been characterized and found to be different from those of all described species, being markedly smaller than their phylogenetic neighbours. We thus hereby propose to create a 'Candidatus Frankia alpina' species for some strains present in nodules of Alnus alnobetula and A. incana that grow in alpine environments at high altitudes or in subarctic environments at high latitudes.

Solitary Fibrous Tumor of the Orbit: A Case Series With Clinicopathologic Correlation and Evaluation of STAT6 as a Diagnostic Marker.

PURPOSE: To retrospectively describe the clinical characteristics, management, and outcomes of a series of patients with solitary fibrous tumor (SFT) of the orbit and to evaluate signal transducer and activator of transcription 6 (STAT6) as a diagnostic marker. METHODS: Review of a retrospective, noncomparative, consecutive series of patients treated at a single institution with a histopathologic diagnosis of SFT. Demographic, clinical, and imaging data were collected, and paraffin-embedded tissue sections were stained to evaluate for the presence of STAT6 and other pertinent markers. RESULTS: Twenty-one patients were identified. Most presented with painless progressive proptosis or eyelid swelling for less than 6 months. Imaging revealed well-circumscribed, firm, variably vascular contrast-enhancing lesions with low to medium reflectivity on ultrasound. Four tumors were histopathologically malignant. All tumors were primarily excised, and 1 patient required exenteration. Two patients were treated with adjuvant radiation therapy. Six patients had recurrent disease of which 3 underwent repeat excision, and 2 were observed. No metastatic disease or attributable deaths were observed. All lesions with available tissue stained positively for both CD34 and STAT6. CONCLUSION: This is the largest single institution case series of orbital SFT with clinicopathologic correlation and the largest series to confirm the presence of STAT6 in orbital lesions. The management of SFT remains challenging due to unpredictable tumor behavior, and complete excision is the generally recommended treatment. It remains unclear whether a subset of asymptomatic patients with histopathologically benign disease can be durably observed without negative sequelae.

Distribution, Host-Seeking Phenology, and Host and Habitat Associations of Haemaphysalis longicornis Ticks, Staten Island, New York, USA.

Haemaphysalis longicornis, an invasive Ixodid tick, was recently reported in the eastern United States. The emergence of these ticks represents a potential threat for livestock, wildlife, and human health. We describe the distribution, host-seeking phenology, and host and habitat associations of these ticks on Staten Island, New York, a borough of New York City.

Correlation between age and corneal edema in pediatric patients with Peters anomaly.

PURPOSE: To evaluate corneal edema in different-aged pediatric patients with Peters anomaly and to correlate in vivo with ex vivo histopathologic findings. METHODS: A retrospective cross-sectional study was performed. The medical records of patients diagnosed with Peters anomaly who underwent examination under anesthesia (EUA) between 2011 and 2015 were reviewed. Eyes in which central corneal thickness (CCT) measurements were taken were included. The thickest point in the CCT pachymetric map was used to objectively quantify corneal edema. Correlation between CCT and age was calculated. Additionally, a retrospective review of histopathologic studies of excised corneal buttons from pediatric eyes with Peters anomaly between 2011 and 2015 was performed. RESULTS: Eighteen eyes of 12 children were included. Mean age was 14 ± 15 months, and mean CCT was 842 ± 304 µm. A significant inverse correlation was noted between the CCT and the age of the patients, with lower CCT values in older children (r = 0.6; P = 0.01). Seven excised corneal buttons that underwent penetrating keratoplasty were reviewed. All corneal buttons showed absence of Descemet membrane and localized absence of endothelium. However, three specimens showed presence of corneal endothelium in areas of absent or attenuated Descemet membrane. CONCLUSIONS: In Peters anomaly, the CCT decreases with age, possibly due to a decrease in corneal edema. Histopathologic studies show cases of endothelial expansion in areas of absent or attenuated Descemet membrane. This may contribute to improved endothelial function and decreased edema with age.

Patterns of diversity, endemism and specialization in the root symbiont communities of alder species on the island of Corsica.

We investigated whether the diversity, endemicity and specificity of alder symbionts could be changed by isolation in a Mediterranean glacial refugium. We studied both ectomycorrhizal (EM) fungi and nitrogen-fixing actinobacteria associated with alders, and compared their communities in Corsica and on the European continent. Nodules and root tips were sampled on the three alder species present in Corsica and continental France and Italy. Phylogenies based on internal transcribed spacer (ITS) and a multilocus sequence analysis approach were used to characterize fungal and Frankia species, respectively. Patterns of diversity, endemism and specialization were compared between hosts and regions for each symbiont community. In Corsica, communities were not generally richer than on the mainland. The species richness per site depended mainly on host identity: Alnus glutinosa and Alnus cordata hosted richer Frankia and EM communities, respectively. Half of the Frankia species were endemic to Corsica against only 4% of EM species. Corsica is not a hotspot of diversity for all alder symbionts but sustains an increased frequency of poor-dispersers such as hypogeous fungi. Generalist EM fungi and host-dependent profusely sporulating (Sp+) Frankia were abundantly associated with Corsican A. cordata, a pattern related to a more thermophilic and xerophylic climate and to the co-occurrence with other host trees.

Blue Nevi of the Ocular Surface: Clinical Characteristics, Pathologic Features, and Clinical Course.

PURPOSE: Blue nevus is a melanocytic tumor that is commonly found in the skin. Extracutaneous presentations, including the ocular surface, are rare. As such, the purpose of this study was to characterize the clinical features and clinical course of congenital melanocytic tumor (blue nevus) of the conjunctiva. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: Twenty-one patients with 23 blue nevi of the ocular surface that were excised surgically between 2000 and 2016. METHODS: Chart review of patients identified from a database search of the Florida Lions Ocular Pathology Laboratory records. Pathologic diagnoses were confirmed by 2 pathologists (S.R.D. and G.E.). All specimens were bleached and, tissue permitting, stained using SOX10 (MilliporeSigma, Darmstadt, Germany) and CD68 (Leica Biosystems, Nussloch, Germany). MAIN OUTCOME MEASURES: Clinical characteristics, pathologic features, and clinical course. RESULTS: Mean age of the population was 55±15 years; 71.4% (n = 15) were white and 57.1% (n = 12) were men. One patient had 3 lesions, for a total of 23 lesions examined. Clinically, 13 lesions were on the bulbar conjunctiva, 3 were on the tarsal conjunctiva, 3 were in the fornix, 2 were caruncular, 1 was episcleral, and 1 was at the limbus. Before excision, 8 patients were thought to have primary acquired melanosis, 4 with concern for primary conjunctival melanoma, and 1 thought to have metastatic disease from a plantar melanoma. Five lesions were thought to be benign, and in 8 patients, the lesions were identified incidentally after other ocular surgeries, with no diagnosis of the lesions before excision. Pathologic features were consistent with simple blue nevi in 21 lesions and cellular blue nevus in 2 lesions. No malignant transformations were noted in any patient over the mean 20.2-month follow-up period (range, 2 weeks-103 months). CONCLUSIONS: Blue nevus is a rare deeply pigmented congenital melanocytic lesion with a benign clinical course that can appear clinically similar to primary acquired melanosis or melanoma.

Frankia canadensis sp. nov., isolated from root nodules of Alnus incana subspecies rugosa.

Strain ARgP5T, an actinobacterium isolated from a root nodule present on an Alnus incana subspecies rugosa shrub growing in Quebec City, Canada, was the subject of polyphasic taxonomic studies to clarify its status within the genus Frankia. 16S rRNA gene sequence similarities and ANI values between ARgP5T and type strains of species of the genus Frankiawith validly published names were 98.8 and 82 % or less, respectively. The in silico DNA G+C content was 72.4 mol%. ARgP5T is characterised by the presence of meso-A2pm, galactose, glucose, mannose, rhamnose (trace), ribose and xylose as whole-organism hydrolysates; MK-9(H8) as predominant menaquinone; diphosphatidylglycerol, phosphatidylinositol and phosphatidylglycerol as polar lipids and iso-C16 : 0 and C17 : 1ω8c as major fatty acids. The proteomic results confirmed the distinct position of ARgP5T from its closest neighbours in Frankiacluster 1. ARgP5T was found to be infective on two alder (Alnus glutinosa and Alnusalnobetula subsp. crispa) and on one bayberry (Morella pensylvanica) species and to fix nitrogen in symbiosis and in pure culture. On the basis of phylogenetic (16S rRNA gene sequence), genomic, proteomic and phenotypic results, strain ARgP5T (=DSM 45898=CECT 9033) is considered to represent a novel species within the genus Frankia for which the name Frankia canadensis sp. nov., is proposed.

A comparative evaluation between aluminium and titanium dioxide microparticles for blasting the surface titanium dental implants: an experimental study in rabbits.

OBJECTIVE: The aim of this study was to compare, through biomechanical and histological analysis, the aluminium (AlO2) and titanium dioxide (TiO2) microparticles for blasting during the sandblasting acid surface treatment in titanium dental implants using a rabbit tibia model. MATERIALS AND METHODS: Forty-eight commercially available titanium dental implants were divided into two test groups (n = 24 per group): implants with surface treated by AlO2 followed by acid etching as control group (Con group) and implants with surface treated by TiO2 followed by acid etching as test group (Test group). The implants were randomly installed in both tibias of eight rabbits and block samples were removed 4 and 8 weeks after implantation. Resonance Frequency Analyses were performed immediately after the implantation and at 8 weeks. Twelve implants of each group were removed to measure the reverse torque. The remaining implants were used for histological analysis. The data were compared using statistical tests (α = 0.05). RESULTS: In comparing the implant stability quotient at the two time points, no significant statistical differences were found (P > 0.05), as well as in the removal torque test at 8 weeks after implant placement, no found significant difference between the two groups was tested. Histomorphometric analysis showed a high degree of bone organization in all samples with no significant difference between groups in the bone-to-implant contact (P > 0.05). CONCLUSION: Within the limitations of this study, the results indicate that the media of surface blasting (AlO2 or TiO2 microparticles) did not show significant differences in the tested parameters for assessing the osseointegration of the implants.

Proposal of 'Candidatus Frankia californiensis', the uncultured symbiont in nitrogen-fixing root nodules of a phylogenetically broad group of hosts endemic to western North America.

The genus Frankia comprises a group of nitrogen-fixing actinobacteria that form root-nodule symbioses with perennial dicotyledonous plants in the nitrogen-fixing clade. These bacteria have been characterized phylogenetically and grouped into four clusters (clusters 1-4). Cluster 2 contains mostly uncultured strains that induce nodules on species of the genera Datisca (Datiscaceae), Coriaria (Coriariaceae), Ceanothus (Rhamnaceae) and several genera in the family Rosaceae (Cercocarpus, Chamaebatia, Dryas, Purshia), all of which except members of the genus Coriaria are present within the California Floristic Province (CFP) or neighbouring areas of western North America. Those strains occurring in western North America are genetically very closely related to one another, and genetically distinct from strains characterized from other locales. We hereby propose to create a 'Candidatus Frankia californiensis' species for those cluster 2 strains of the genus Frankia with both high genetic similarity and a geographical distribution in or near the CFP.

Proposal of a type strain for Frankia alni (Woronin 1866) Von Tubeuf 1895, emended description of Frankia alni, and recognition of Frankia casuarinae sp. nov. and Frankia elaeagni sp. nov.

Before the establishment of pure cultures, the species Frankia alni, 'Frankia casuarinae' and 'Frankia elaeagni' were proposed to encompass all causal agents of the nitrogen-fixing root nodules of dicotyledonous plants from the genera Alnus, Casuarina or Elaeagnus. The sole Frankia species with a validly published name, the type species F. alni, was described by Woronin (1866) as present in the root of alder. Until now no type strain has been designated for F. alni, even though the absence of a type strain has seriously inhibited the application of modern taxonomic methods to the genus Frankia. Thus, we propose that strain ACN14aT, isolated in pure culture from Alnus viridis ssp. crispa with morphological properties matching the original description of F. alni, be recognized as the type strain of this species according to Rule 18f of the International Code of Nomenclature of Bacteria. We compared ACN14aT to two strains, CcI3T and BMG5.12T, isolated from Casuarina cunninghamiana and Elaeagnus angustifolia, respectively, based on chemotaxonomy, phenotype microarray data and molecular data retrieved from genome sequences. All three tested strains grew as branched hyphae, produced vesicles and multilocular sporangia containing non-motile spores and metabolized short fatty acids, TCA-cycle intermediates and carbohydrates. Chemotaxonomically, the three strains were indistinguishable with respect to phospholipids (phosphatidylinositol, diphosphatidylglycerol, glycophospholipids and phosphatidylglycerol) and cell-sugar composition (glucose, mannose, ribose, rhamnose, galactose and xylose, with the latter two being diagnostic for the genus). The major fatty acids identified in all three strains were iso-C16 : 0, C17 : 1ω8c, C15 : 0, C17 : 0 and C16 : 0. ACN14aT and BMG5.12T also shared C15 : 1ω6c, while C18 : 1ω9c was found to be unique to BMG5.12T. The major menaquinones identified in all three novel type strains were MK-9(H8), MK-9(H6) and MK-9(H4). MK-9(H2) was shared by ACN14aT and BMG5.12T, while MK-10(H4) and MK-8(H4) were only found in BMG5.12T. Analysis of 16S rRNA gene sequences showed 98.1-98.9 % identity between strains ACN14aT, CcI3T and BMG5.12T. Digital DNA-DNA hybridization values between the three type strains were well below 70 %. These results confirm the separation of the strains into three distinct species, Frankia alni, Frankia casuarinae sp. nov. and Frankia elaeagni sp. nov. Thus, we propose ACN14aT (=DSM 45986T=CECT 9034T), CcI3T (=DSM 45818T=CECT 9043T) and BMG5.12T (=DSM 46783T=CECT 9031T) as the respective type strains.

Topical applications of vitamin D on implant surface for bone-to-implant contact enhance: a pilot study in dogs part II.

OBJECTIVE: The aim of this study was to evaluate the effect of topical application of vitamin D over implant surface, placed immediately to the extraction, throughout histological and histomorphometric analysis of peri-implant tissue. MATERIAL AND METHODS: Six American foxhound dogs were used in the study. Mandibular premolar distal roots were extracted. Twenty-four immediate conical C1 implants (MIS, Barlev, Israel) were randomly assigned to the distal site on each site of the mandible in three groups: (Group CI) 12 titanium implants alone; (Test Group DI) 12 titanium implants supplemented with vitamin D. Prior to implanting, test implants (DI) were submerged in vitamin D 10% solution. No treatment was applied at control implants (CI). After 12 weeks, animals were sacrificed. Block sections were obtained and processed for mineralized ground sectioning. Bone-to-implant contact (Total BIC and BIC%), new bone formation (NBF), interthread bone (ITB), and histological linear measurements (HLM) were analyzed. RESULTS: At 12 weeks, all implants were clinically stable and histologically osseointegrated. BIC evaluation showed Total BIC mean and SD values for DI (48.96 ± 2.14), CI (44.56 ± 1.75) (P < 0.05), BIC% DI (43.59 ± 0.98), and CI (42.67 ± 9.26) (P > 0.05). For interthread bone formation, values were as follows: DI (15.21 ± 3.87), CI (14.79 ± 1.45) (P > 0.05), no statistically differences. Regarding peri-implant new bone formation, no statistically differences could be found between the two groups DI (31.87 ± 1.23), CI (27.18 ± 2.38) (P > 0.05). For linear measurements, test group (DI) showed statistically significant less buccal crestal bone loss (CBL) DI (0.37 ± 0.12)*, CI (1.26 ± 0.8) (P < 0.05), and vitamin D implants showed less lingual junctional epithelium DI (1.58 ± 0.43)*, CI (2.18 ± 0.48) (P < 0.05). No differences were observed in the buccal mucosa. CONCLUSION: With the limitation of animal studies, topical application of vitamin D on dental implants could reduce crestal bone loss and increase 10% more bone-to-implant contact at 12-week follow-up period.

Bone response to collagenized xenografts of porcine origin (mp3(®) ) and a bovine bone mineral grafting (4BONE(™) XBM) grafts in tibia defects: experimental study in rabbits.

OBJECTIVES: This study aimed to carry out the evaluation of bone response of new bone formation to two different xenografts (bovine and porcine) biomaterials inserted in rabbit tibiae. MATERIALS AND METHODS: The study used a total of 20 male New Zealand albino rabbits. They received a total of 40 grafts in the proximal metaphyseal areas of both tibiae. Two biomaterials were evaluated: 20 porcine xenografts, as a bone granulate (OsteoBiol(®) MP3(®) ; Tecnoss srl, Giaveno, Italy), were placed in the proximal metaphyseal area of the right tibia, 20 anorganic bovine bone mineral grafting (4BONE(™) XBM, MIS Implants Inc., BARLEV, Israel) were placed in the left tibia. Following graft insertion, the animals were sacrificed in two groups of 10 animals, after 1 and 4 months, respectively. For each group, biomaterials were analyzed: newly formed bone, residual graft materials and the connective tissue. Histomorphometric, EDX analysis and element mapping were performed at 1 and 4 months after graft insertion. RESULTS: At 4 months after treatment, the bone defects displayed radiological images that showed complete repair of osseous defects. Histomorphometric evaluation showed that for the porcine xenograft, the study averages for newly formed bone represented 84.23 ± 2.9%, while bovine matrix was 79.34 ± 2.1%. For residual graft material, the porcine biomaterial had 11.23 ± 1.7% and the bovine graft 31.56 ± 2.3%. Finally, the connective tissue for MP3 was 10.33 ± 1.8%, while for the 4BONE(™) XBM we obtained 14.34 ± 2.9%. Element analysis revealed higher percentages of Ca (54 ± 9%) and P (35 ± 6%) in the group B than group A and control group (P < 0.05). CONCLUSIONS: Defects of a critical size in a rabbit tibia model can be sealed using a bovine porous biphasic calcium phosphate and MP3 material; this supports new bone formation, creates a bridge between borders, and facilitates bone ingrowth in both biomaterials. Furthermore, this study observed partial dissolution of the mineral phase of four bone graft and complete resorption of porcine MP3 biomaterial and its incorporation into the surrounding bone. Depending on clinical needs, each biomaterial could be useful in daily clinical practice.

In-planta sporulation phenotype: a major life history trait to understand the evolution of Alnus-infective Frankia strains.

Two major types of Frankia strains are usually recognized, based on the ability to sporulate in-planta: spore-positive (Sp+) and spore-negative (Sp-). We carried out a study of Sp+ and Sp- Frankia strains based on nodules collected on Alnus glutinosa, Alnus incana and Alnus viridis. The nodules were phenotyped using improved histology methods, and endophytic Frankia strain genotype was determined using a multilocus sequence analysis approach. An additional sampling was done to assess the relation between Sp+ phenotype frequency and genetic diversity of Frankia strains at the alder stand scale. Our results revealed that (i) Sp+ and Sp- Alnus-infective Frankia strains are genetically different even when sampled from the same alder stand and the same host-plant species; (ii) there are at least two distinct phylogenetic lineages of Sp+ Frankia that cluster according to the host-plant species and without regard of geographic distance and (iii) genetic diversity of Sp+ strains is very low at the alder stand scale compared with Sp- strains. Difference in evolutionary history and genetic diversity between Sp+ and Sp- Frankia allows us to discuss the possible ecological role of in-planta sporulation.

Rethinking aromaticity in H-bonded systems. Caveats for transition structures involving hydrogen transfer and π-delocalization.

Monoaza- and diaza-derivatives of malondialdehydes, in short aminoacroleins and vinamidines, are prototypical examples of open-chain structures prone to π-electron delocalization, for which intramolecular hydrogen bonding enhances (or diminishes) their pseudoaromaticity depending on the substitution pattern. This interplay is illustrated herein by DFT-based calculations of aromaticity indices in the gas phase and polar solvents. Elucidation of transition structures involved in tautomeric conversions helps to solve how the intramolecular hydrogen transfer occurs. While TSs exhibit a high degree of aromaticity, the dichotomy between forward and backward pathways points to a complex trajectory. Addition of thermal corrections to the electronic energy decreases both the enthalpy and free energy leading to negative ΔH(‡) and ΔG(‡) values. This variational effect accounts for the otherwise elusive distinction between transition structures and saddle points (usually overlooked for high electronic barriers). Also, this rationale fits well within the framework of Marcus' theory.

Bone neo-formation and mineral degradation of 4Bone.(®) Part I: material characterization and SEM study in critical size defects in rabbits.

OBJECTIVE: This study reports the characterization process and in vivo application of a new high-porosity biphasic calcium phosphate (4Bone(®) - HA 60%/ß-TCP 40%) inserted into the critical size defect of a rabbit tibiae. MATERIAL AND METHODS: Two critical size defects of 6 mm diameter were created in each tibia of 15 New Zealand rabbits, and a total of 60 defects were divided into a test group filled with 4Bone(®) (n = 30) and a control group (n = 30). The material and the implants were characterized by scanning electron microscope (SEM) fitted with energy-dispersive X-ray spectroscopy (EDX). RESULTS: The biomaterial's grain size decreased progressively with the graft integration process over the 60-day study period. Element analysis revealed increased percentages of Ca/P (2.86 ± 0.32 vs. 1.97 ± 0.59) in new bone and at the interface (P < 0.05). Element mapping showed that Ca and P were concentrated in the medullary and cortical zones in the test group but were concentrated only in cortical zones in the control group. CONCLUSIONS: Critical size defects in a rabbit tibia model can be sealed using this highly porous biphasic calcium phosphate; it supports new bone formation, creates a bridge between defect borders, and facilitates bone in growth.

Biphasic ß-TCP mixed with silicon increases bone formation in critical site defects in rabbit calvaria.

OBJECTIVE: The aim of this study was to assess the bone regeneration of critical size defects in rabbit calvarias filled with ß-TCP doped with silicon. MATERIALS AND METHODS: Twenty-one New Zealand rabbits were used in this study. Two critical size defects were created in the parietal bones. Three experimental groups were evaluated: Test A (HA/ß-TCP granules alone), Test B (HA/ß-TCP granules plus 3% silicon), Control (empty defect). The animals were sacrificed at 8 and 12 weeks. Evaluation was performed by µCT analysis and histomorphometry. RESULTS: µCT evaluation showed higher volume reduction in Test A group compared with Test B (P < 0.05). The Test B group showed the highest values for cortical closure and bone formation around the particles, followed by Test A and controls (P < 0.05). CONCLUSIONS: Within the limitations of this animal study, it can be concluded that HA/ß-TCP plus 3% silicon increases bone formation in critical size defects in rabbit calvarias, and the incorporation of 3% silicon reduces the resorption rate of the HA/ß-TCP granules.

Enhanced bone regeneration with a novel synthetic bone substitute in combination with a new natural cross-linked collagen membrane: radiographic and histomorphometric study.

OBJECTIVES: 4Bone is a fully synthetic bioactive bone substitute composed of 60% hydroxyapatite (HA) and 40% beta-tricalcium phosphate (ß-TCP). This study aimed to investigate the effect of resorbable collagen membranes (RCM) on critical size defects in rabbit tibiae filled with this novel biphasic calcium phosphate at 15, 30, 45, and 60 days by radiological and histomorphometric analysis. MATERIAL AND METHODS: Three critical size defects of 6 mm diameter were created in both tibiae of 20 New Zealand rabbits and divided into three groups according to the filling material: Group A (4Bone), Group B (4Bone plus RCM), and Group C (unfilled control group). At each of the four study periods, five rabbits were sacrificed. Anteroposterior and lateral radiographs were taken. Samples were processed for observation under light microscopy. RESULTS: At the end of treatment, radiological analysis found that cortical defect closure was greater in Group B than Group A, and radiopacity was clearly lower and more heterogeneous in Group A cortical defects than in Group B. There was no cortical defect closure in Group C. Histomorphometric evaluation showed significant differences in newly formed bone and cortical closure in Group B compared with Groups A and C, with the presence of higher density newly formed bone in cortical and medullar zones. CONCLUSIONS: Biphasic calcium phosphate functioned well as a scaffolding material allowing bone ingrowth and mineralization. The addition of absorbable collagen membranes enhanced bone gain compared with non-membrane-treated sites. This rabbit study provides radiological and histological evidence confirming the suitability of this new material for guided tissue regeneration of critical defects.

Pseudo-cyclic structures of mono- and di-azaderivatives of malondialdehydes. Synthesis and conformational disentanglement by computational analyses.

Mono- and diaza-derivatives of malondialdehydes, namely 3-alkyl(aryl)amino-2-arylacroleins and 1,5-dialkyl(aryl)-3-arylvinamidines are open-chain systems in which extended electron delocalization and pseudoaromaticity can be envisaged. A set of diversely functionalized compounds has been synthesized and characterized by spectroscopic data and X-ray diffractometry. Quantum-chemical calculations were performed for all possible neutral tautomers and conformers in the gas phase and compared to those in polar solvents (CHCl3, DMSO, and EtOH) at the M06-2X/6-311++G(d,p) level. Tautomeric equilibria and conformational preferences can be rationalized in terms of structural factors, which can be roughly estimated as summation or subtractions of intramolecular interactions. As expected, a key role is played by intramolecular hydrogen bonds whose strength varies from the gas phase to polar ethanol. This issue also delves into the concept of resonance-assisted H-bond, where the donor and acceptor atoms are connected by a π-conjugated system. The most stable conformers (structures a and c) possess a high degree of pseudoaromaticity as inferred from HOMA indexes and other delocalization parameters.