Electrolytic Surface Decontamination in the Reconstructive Therapy of Peri-Implantitis: Single-Center Outcomes of a Randomized Controlled Trial.

Surface decontamination in the reconstructive therapy of peri-implantitis is of paramount importance to achieve favorable outcomes. The objective of this single-center study derived from a large multicenter clinical trial was to compare the electrolytic method (EM) used as an adjunct to mechanical decontamination, to hydrogen peroxide (HP) also used as an adjunct to mechanical decontamination, in the reconstructive therapy of peri-implantitis. At 12-month (T2) follow-up, 19 patients (Nimplants= 23) completed the study. None of the tested modalities demonstrated superiority in terms of the assessed clinical parameters. Only mucosal recession showed higher stability in the EM group. Alike, radiographic marginal bone level gain and defect angle changes at T2 did not differ between the evaluated strategies. Notably, disease resolution was ∼16% higher in the EM; however, differences did not reach statistical significance. Additionally, it was demonstrated that pocket depth and intra-bony component depth at baseline were predictors of disease resolution. In conclusion, the EM combined with mechanical instrumentation results in a safe and effective surface decontamination modality in the reconstructive therapy of peri-implantitis. This strategy resulted in ∼91% disease resolution rate.

Peri-implantitis and maxillary sinus membrane thickening: A retrospective cohort study.

OBJECTIVE: The objective of this study is to investigate the association of peri-implantitis (PI) and sinus membrane thickening and to assess the resolution of membrane thickening following intervention (implant removal or peri-implantitis treatment) aimed at arresting PI. MATERIALS AND METHODS: Forty-five patients with 61 implants in the posterior maxillary region were retrospectively included in the study. Twenty-four patients were diagnosed with peri-implantitis (PI) and 21 had peri-implant health (PH). Cone-beam computed tomography (CBCT) scans were evaluated to assess maxillary sinus characteristics, including membrane thickening, sinus occupancy and ostium patency. The CBCT scans taken 6 months after intervention aimed at arresting disease (implant removal or treatment of PI) in the PI group were also appraised and compared to baseline scans. RESULTS: At baseline, all parameters evaluating membrane thickness disorders yielded significant differences between groups (p < .001). Patients with posterior maxillary implants diagnosed with PI were 7× more likely to present membrane thickening compatible with pathology when compared to patients with healthy implants (OR = 7.14; p = .005). Furthermore, the likelihood was 6x greater in implants diagnosed with PI to exhibit moderate membrane thickening (OR = 6.75, p = .001). The patients receiving interventions aimed at arresting PI experienced significant enhancement in all radiographic parameters related to the sinus cavity at the 6-month follow-up (p < .001), though these variations were similarly independent of whether treatment consisted of PI treatment or implant removal. CONCLUSIONS: Maxillary sinus membrane thickening and the permeability/obstruction of the ostium are frequently associated with the presence of PI in posterior implants. Interventions targeting disease resolution effectively reduce membrane thickness to levels compatible with maxillary sinus health.

A Nano-Based Approach to Deliver Satureja thymbra Essential Oil to the Skin: Formulation and Characterization.

Essential oils are well known for their biological properties, making them useful for the treatment of various diseases. However, because of their poor stability and high volatility, their potential cannot be fully exploited. The use of nanoformulations to deliver essential oils can solve these critical issues and amplify their biological activities. We characterized an essential oil from Satureja thymbra via GC-MS and HPLC-DAD to provide qualitative and quantitative data. The essential oil was formulated in phospholipid vesicles which were characterized for size, surface charge, and storage stability. The entrapment efficiency was evaluated as the quantification of the major monoterpenoid phenols via HPLC-DAD. The morphological characterization of the vesicles was carried out via cryo-TEM and SAXS analyses. The essential oil's antioxidant potential was assayed via two colorimetric tests (DPPH• and FRAP) and its cytocompatibility was evaluated in HaCaT skin cell cultures. The results showed that the nanoformulations developed for the loading of S. thymbra essential oil were below 100 nm in size, predominantly unilamellar, stable in storage, and had high entrapment efficiencies. The vesicles also displayed antioxidant properties and high cytocompatibility. These promising findings pave the way for further investigation of the therapeutic potential of S. thymbra nanoformulations upon skin application.

Tailored Design of a Water-Based Nanoreactor Technology for Producing Processable Sub-40 Nm 3D COF Nanoparticles at Atmospheric Conditions.

Covalent organic frameworks (COFs) are crystalline materials with intrinsic porosity that offer a wide range of potential applications spanning diverse fields. Yet, the main goal in the COF research area is to achieve the most stable thermodynamic product while simultaneously targeting the desired size and structure crucial for enabling specific functions. While significant progress is made in the synthesis and processing of 2D COFs, the development of processable 3D COF nanocrystals remains challenging. Here, a water-based nanoreactor technology for producing processable sub-40 nm 3D COF nanoparticles at ambient conditions is presented. Significantly, this technology not only improves the processability of the synthesized 3D COF, but also unveils exciting possibilities for their utilization in previously unexplored domains, such as nano/microrobotics and biomedicine, which are limited by larger crystallites.

Proximal Periodontal Support Adjacent to Untreated Peri-implantitis Lesions: A Cross-Sectional Analysis.

PURPOSE: To assess site-related features of peri-implantitis occurring adjacent to teeth and its association with the proximal periodontal bone level. MATERIALS AND METHODS: Periapical radiographs were collected from partially edentulous patients exhibiting peri-implantitis adjacent to teeth. The following variables were quantified: intrabony defect width (DW), implant marginal bone loss (MBLi), tooth marginal bone loss (MBLt), implant-tooth distance (ITd), intrabony defect angulation (DA), adjacent periodontal bone peak height (ABPh), and implant-tooth angulation (ITa). A correlation matrix using the Spearman correlation coefficient was created to explore the dependence of these variables. Univariate linear regression analysis was carried out by means of generalized estimating equations (GEE), using MBLt as dependent variable. RESULTS: Overall, 61 patients and 84 implants were included in this study, consisting of a total of 105 implant sites facing adjacent teeth. This resulted in 515 linear and 194 angular measurements. A total of 11 different statistically significant associations were demonstrated between the different variables analyzed. Moreover, the univariate regression analysis revealed significant positive associations between MBLt and MBLi (P = .013) and between MBLt and periodontitis (PD) (P = .014). These associations were confirmed in the multivariate model. CONCLUSIONS: Teeth adjacent to untreated peri-implantitis lesions are associated with proximal loss of periodontal support. This finding is more remarkable in scenarios that display short implant-tooth distance.

Selecting biomaterials in the reconstructive therapy of peri-implantitis.

Peri-implantitis is a pathogenic inflammatory condition characterized by progressive bone loss and clinical inflammation that may compromise the stability of dental implants. Therapeutic modalities have been advocated to arrest the disorder and to establish peri-implant health. Reconstructive therapy is indicated for bone defects exhibiting contained/angular components. This therapeutic modality is based upon the application of the biological and technical principles of periodontal regeneration. Nonetheless, the comparative efficacy of reconstructive therapy and nonreconstructive modalities remains unclear. Therefore, the aim of this narrative review is to address major clinical concerns regarding the efficacy, effectiveness, and feasibility of using biomaterials in peri-implantitis therapy. In particular, the use of bone grafting materials, barrier membranes, and biologics is comprehensively explored.

Phenylalanine and Tryptophan-Based Surfactants as New Antibacterial Agents: Characterization, Self-Aggregation Properties, and DPPC/Surfactants Vesicles Formulation.

Cationic surfactants based on phenylalanine (CnPC3NH3Cl) and tryptophan (CnTC3NH3Cl) were synthesized using renewable raw materials as starting compounds and a green synthetic procedure. The synthesis, acid-base equilibrium, aggregation properties, and antibacterial activity were investigated. Conductivity and fluorescence were used to establish critical micelle concentrations. Micellization of CnPC3NH3Cl and CnTC3NH3Cl occurred in the ranges of 0.42-16.2 mM and 0.29-4.6 mM, respectively. Since those surfactants have some acidic character, the apparent pKa was determined through titrations, observing increasing acidity with increasing chain length and being slightly more acidic with the phenylalanine than the tryptophan derivatives. Both families showed promising antibacterial efficacy against eight different bacterial strains. Molecular docking studies against the enzyme peptidoglycan glycosyltransferase (PDB ID:2OQO) were used to investigate the potential binding mechanism of target surfactant molecules. According to small angle X-ray scattering (SAXS) results, the surfactants incorporate into DPPC (Dipalmitoyl Phosphatidyl Choline) bilayers without strong perturbation up to high surfactant concentration. Some of the C12TC3NH3Cl/DPPC formulations (40%/60% and 20%/80% molar ratios) exhibited good antibacterial activity, while the others were not effective against the tested bacteria. The strong affinity between DPPC and surfactant molecules, as determined by the DFT (density functional theory) method, could be one of the reasons for the loss of antibacterial activity of these cationic surfactants when they are incorporated in vesicles.

Defect angle as prognostic indicator in the reconstructive therapy of peri-implantitis.

OBJECTIVE: To analyze the influence of the characteristics of bone defects caused by peri-implantitis on the clinical resolution and radiographic bone gain following reconstructive surgery. METHODS: This is a secondary analysis of a randomized clinical trial. Periapical x-rays of bone defects, caused by peri-implantitis exhibiting intrabony component, were analyzed at baseline and 12-month follow-up after reconstructive surgery. Therapy consisted of anti-infective therapy along with a mixture of allografts with or without a collagen barrier membrane. The association of defect configuration, defect angle (DA), defect width (DW), and baseline marginal bone level (MBL) with clinical resolution (based on a prior defined composite criteria) and radiographic bone gain was correlated by means of generalized estimating equations. RESULTS: Overall, 33 patients with a total of 48 implants exhibiting peri-implantitis were included. None of the evaluated variables yielded statistical significance with disease resolution. Defect configuration demonstrated statistical significance when compared to class 1B and 3B, favoring radiographic bone gain for the former (p = 0.005). DW and MBL did not demonstrate statistical significance with radiographic bone gain. On the contrary, DA exhibited strong statistical significance with bone gain (p < 0.001) in the simple and multiple logistic regression analyses. Mean DA reported in this study was 40°, and this resulted in 1.85 mm radiographic bone gain. To achieve ≥1 mm of bone gain, DA must be <57°, while to attain ≥2 mm of bone gain, DA must be <30°. CONCLUSION: Baseline DA of peri-implantitis intrabony components predicts radiographic bone gain in reconstructive therapy (NCT05282667-this clinical trial was not registered prior to participant recruitment and randomization).

Ceratonia siliqua L. Pod Extract: From Phytochemical Characterization to Liposomal Formulation and Evaluation of Behaviour in Cells.

The formulation of plant extracts in phospholipid vesicles is a promising strategy to exploit their biological properties while solving problems related to poor solubility in water, high instability, and low skin permeation and retention time. In this study, Ceratonia siliqua ripe pods were used for the preparation of a hydro-ethanolic extract, which showed antioxidant properties owing to the presence of biologically active compounds identified by liquid chromatography-mass spectrometry (e.g., hydroxybenzoic acid and flavonoid derivatives). To improve the applicability of the extract in therapy, a topical formulation based on liposomes was explored. The vesicles were characterized by small size (around 100 nm), negative charge (-13 mV), and high entrapment efficiency (>90%). Furthermore, they displayed both spherical and elongated shapes, with oligolamellar structure. Their biocompatibility was demonstrated in cells, including erythrocytes and representative skin cell lines. The antioxidant activity of the extract was proved by the scavenging of free radicals, the reduction of ferric ions, and the protection of skin cells from oxidative damage.

Influence of immediate postoperative gingival thickness and gingival margin position on the outcomes of root coverage therapy: A 6 months prospective case series study using 3D digital measuring methods.

BACKGROUND: To assess linear and volumetric changes following the treatment of gingival recessions (GRs) by means of a modified coronally advanced tunnel technique combined with acellular dermal matrix (MTUN + ADM). MATERIALS AND METHODS: Patients presenting GR type 1 (RT1) GRs underwent root coverage surgery consisting of MTUN + ADM. Clinical measurements were made, and intraoral scans were obtained at baseline, postoperatively, and 6 weeks, 3 and 6 months after surgery, to evaluate changes in probing depth (PD), keratinized tissue width (KTW), recession depth (RD), recession area (RA), marginal gingival thickness (MGT), and mucosal volume (MV). The impact of patient-level and surgical-site variables upon percentage root coverage (% RC) and the likelihood of achieving complete root coverage (CRC) were explored. RESULTS: A total of 20 patients (n = 47 teeth) were treated. After 6 months, RD and RA decreased, while KTW, MGT, and MV increased. The mean % RC was 93% at 6 months and CRC was found on 72.3% of the sites at 6 months. The postoperative MGT changes at 1.5 and 3 mm were significantly correlated to % RC and CRC at 6 months. Each additional mm of postoperative gain of gingival thickness resulted in a 4-fold increase in the probability of achieving CRC. Additionally, gingival margin positioned ≥0.5 mm coronal to the cementoenamel junction immediately after surgery was a strong predictor of CRC. CONCLUSIONS: The MGT gain at 1.5 and 3 mm achieved in the immediate postoperative period is a significant predictor of CRC at 6 months when treating multiple GRs via MTUN + ADM. CLINICAL SIGNIFICANCE: The Scientific rationale for the study relies on the lack of 3D digital measuring tools in the assessment of soft tissue healing dynamics after root coverage therapy. The principal findings of this study can be summarized as follows: tooth type, tooth position, and post-operative gingival margin position and gingival thickness and volume changes are predictors of CRC. Therefore, the practical implications are that the more thickness and more coronal advancement achieved immediately after root coverage surgery, the higher chance of achieving CRC.

Phenolic Fingerprint, Bioactivity and Nanoformulation of Prunus spinosa L. Fruit Extract for Skin Delivery.

The nanoformulation of plant extracts in phospholipid vesicles is a promising strategy to exploit the biological properties of natural bioactive substances and overcome drawbacks such as poor aqueous solubility, chemical instability, low skin permeation and retention time, which strongly limit their topical application. In this study, Prunus spinosa berries were used for the preparation of a hydro-ethanolic extract, which showed antioxidant and antibacterial properties owing to the presence of phenolic compounds. Two types of phospholipid vesicles were developed to improve the applicability as topical formulations. Liposomes and Penetration Enhancer-containing Vesicles were characterized for mean diameter, polydispersity, surface charge, shape, lamellarity, and entrapment efficiency. Additionally, their safety was assayed with different cell models, including erythrocytes and representative skin cell lines.

Outcome indicators of non-surgical therapy of peri-implantitis: a prospective case series analysis.

OBJECTIVES: This study aims to identify patient and implant indicators influencing the non-surgical therapeutic outcomes of peri-implantitis at 6 months of follow-up. METHODS: This case series involved patients with at least one implant diagnosed with peri-implantitis according to the 2017 World Workshop criteria. Non-surgical therapy consisted of mechanical debridement of the peri-implant pockets combined with metronidazole 500 mg 3 times a day for 7 days. At baseline and at 6 months, clinical and radiographic variables were collected to calculate treatment success (probing pocket depth reduction to 5 mm without bleeding on probing or < 5 mm irrespective of bleeding on probing at all implant sites, and lack of bone loss progression). The primary outcome was treatment success (%) at 6 months. The influence of the patient and implant/prosthetic variables upon disease resolution was assessed through simple and multiple logistic regression analyses at patient and implant level, using generalized estimation equations models. RESULTS: A total of 74 patients and 107 implants were analyzed at 6 months. Disease resolution was established in 25.7% of the patients and 24.1% of the implants. Patients with stage IV and grade C periodontitis, inadequate oral hygiene at baseline, and wide diameter (≥ 4.5 mm) presented significantly greater treatment failure, whereas smokers and former smokers demonstrated a tendency toward failure. At 6 months, there was a significant decrease in probing pocket depth and bleeding on probing of 1.08 ± 1.06 mm and 14%, respectively. Radiographically, a significant gain in marginal bone level of 0.43 ± 0.56 mm was observed. CONCLUSION: Disease resolution after non-surgical treatment of peri-implantitis is negatively influenced by the loss of support of the adjacent periodontium, poor baseline oral hygiene, and wide diameter implants (≥ 4.5 mm). CLINICAL RELEVANCE: This study helps to discriminate the clinical situations in which non-surgical treatment is less likely to achieve treatment success at short term.

Significance of barrier membrane on the reconstructive therapy of peri-implantitis: A randomized controlled trial.

BACKGROUND: The objective of this trial was to investigate the clinical and radiographic significance of using a mixture of mineralized and demineralized allografts in combination (M) or not (NM) with a resorbable cross-linked barrier membrane in the reconstructive therapy of peri-implantitis defects. METHODS: A two-arm randomized clinical trial was performed in patients diagnosed with peri-implantitis that exhibited contained defects. Clinical parameters were recorded at baseline (T0 ), 6 months (T1 ), and 12 months (T2 ). Radiographic parameters were recorded at T0 and T2 . A composite criterion for disease resolution was defined a priori. A generalized linear model of repeated measures with generalized estimation equation statistical methods was used. RESULTS: Overall, 33 patients (nimplants  = 48) completed the study. At T2 , mean disease resolution was 77.1%. The use of a barrier membrane did not enhance the probability of disease resolution at T2 (odds ratio [OR] = 1.55, p = 0.737). Conversely, the odds of disease resolution were statistically associated with the modified plaque index recorded at T0 (OR = 0.13, p = 0.006) and keratinized mucosa width (OR = 2.10, p = 0.035). Moreover, women exhibited greater odds to show disease resolution (OR = 5.56, p = 0.02). CONCLUSION: Reconstructive therapy by means of a mixture of mineralized and demineralized allografts is effective in clinically resolving peri-implantitis and in gaining radiographic marginal bone level. The addition of a barrier membrane to reconstructive therapy of peri-implantitis does not seem to enhance the outcomes of contained bone defects (NCT05282667).

High Performance Computing PP-Distance Algorithms to Generate X-ray Spectra from 3D Models.

X-ray crystallography is a powerful method that has significantly contributed to our understanding of the biological function of proteins and other molecules. This method relies on the production of crystals that, however, are usually a bottleneck in the process. For some molecules, no crystallization has been achieved or insufficient crystals were obtained. Some other systems do not crystallize at all, such as nanoparticles which, because of their dimensions, cannot be treated by the usual crystallographic methods. To solve this, whole pair distribution function has been proposed to bridge the gap between Bragg and Debye scattering theories. To execute a fitting, the spectra of several different constructs, composed of millions of particles each, should be computed using a particle-pair or particle-particle (pp) distance algorithm. Using this computation as a test bench for current field-programmable gate array (FPGA) technology, we evaluate how the parallel computation capability of FPGAs can be exploited to reduce the computation time. We present two different solutions to the problem using two state-of-the-art FPGA technologies. In the first one, the main C program uses OmpSs (a high-level programming model developed at the Barcelona Supercomputing Center, that enables task offload to different high-performance computing devices) for task invocation, and kernels are built with OpenCL using reduced data sizes to save transmission time. The second approach uses task and data parallelism to operate on data locally and update data globally in a decoupled task. Benchmarks have been evaluated over an Intel D5005 Programmable Acceleration Card, computing a model of 2 million particles in 81.57 s - 24.5 billion atom pairs per second (bapps)- and over a ZU102 in 115.31 s. In our last test, over an up-to-date Alveo U200 board, the computation lasted for 34.68 s (57.67 bapps). In this study, we analyze the results in relation to the classic terms of speed-up and efficiency and give hints for future improvements focused on reducing the global job time.

Strategies for implant surface decontamination in peri-implantitis therapy.

Peri-implantitis is an infectious disease that leads to progressive bone loss. Surgical therapy has been advocated as a way of halting its progression and re-establishing peri-implant health. One of the most challenging but crucial tasks in the management of peri-implantitis is biofilm removal to achieve reosseointegration and promote the reduction of peri-implant pockets. A wide variety of strategies have been used for implant surface decontamination. Mechanical means have been demonstrated to be effective in eliminating calculus deposits and residual debris; however, the presence of undercuts and the grooves and porosities along the roughened implant surface make it difficult to achieve an aseptic surface. In conjunction with mechanical measures, use of chemical adjuncts has been advocated to dilute bacterial concentrations, destroy the bacteria's organic components and eliminate endotoxins. Pharmacological adjuncts have also been recommended to diminish the bacterial load. Other strategies, such as use of lasers, implantoplasty and electrolysis, have been suggested for implant surface decontamination to promote predictable clinical and radiographic outcomes.

The mGlu5 Receptor Protomer-Mediated Dopamine D2 Receptor Trans-Inhibition Is Dependent on the Adenosine A2A Receptor Protomer: Implications for Parkinson's Disease.

The adenosine A2A receptor (A2AR), dopamine D2 receptor (D2R) and metabotropic glutamate receptor type 5 (mGluR5) form A2AR-D2R-mGluR5 heteroreceptor complexes in living cells and in rat striatal neurons. In the current study, we present experimental data supporting the view that the A2AR protomer plays a major role in the inhibitory modulation of the density and the allosteric receptor-receptor interaction within the D2R-mGluR5 heteromeric component of the A2AR-D2R-mGluR5 complex in vitro and in vivo. The A2AR and mGluR5 protomers interact and modulate D2R protomer recognition and signalling upon forming a trimeric complex from these receptors. Expression of A2AR in HEK293T cells co-expressing D2R and mGluR5 resulted in a significant and marked increase in the formation of the D2R-mGluR5 heteromeric component in both bioluminescence resonance energy transfer and proximity ligation assays. A highly significant increase of the the high-affinity component of D2R (D2RKi High) values was found upon cotreatment with the mGluR5 and A2AR agonists in the cells expressing A2AR, D2R and mGluR5 with a significant effect observed also with the mGluR5 agonist alone compared to cells expressing only D2R and mGluR5. In cells co-expressing A2AR, D2R and mGluR5, stimulation of the cells with an mGluR5 agonist like or D2R antagonist fully counteracted the D2R agonist-induced inhibition of the cAMP levels which was not true in cells only expressing mGluR5 and D2R. In agreement, the mGluR5-negative allosteric modulator raseglurant significantly reduced the haloperidol-induced catalepsy in mice, and in A2AR knockout mice, the haloperidol action had almost disappeared, supporting a functional role for mGluR5 and A2AR in enhancing D2R blockade resulting in catalepsy. The results represent a relevant example of integrative activity within higher-order heteroreceptor complexes.

Resolution of peri-implantitis by means of implantoplasty as adjunct to surgical therapy: A retrospective study.

BACKGROUND: There is a paucity of data on the effectiveness of implantoplasty as adjunct to the surgical management of peri-implantitis. The purpose of this study was to evaluate the resolution of peri-implantitis by means of implantoplasty as adjunct to surgical resective (RES) and reconstructive (REC) therapies and supportive maintenance. METHODS: Patients that underwent surgical therapy to manage peri-implantitis with a follow-up of ≥12 months and enrolled in a regular peri-implant supportive care were recruited. RES group consisted of two interventions that included osseous recontouring and apically position flap (APF) and soft tissue conditioning (STC). REC was performed in the infra-osseous compartment of combined defects. Implant survival rate was recorded. Clinical and radiographic parameters were evaluated to define a "dogmatic" (case definition #1) and a "flexible" (case definition #2) therapeutic success. Univariate and multivariate multilevel backward logistic regression were applied for statistical analysis. RESULTS: Overall, 43 patients (nimplants  = 135) were retrospectively assessed. Mean observational period was ∼24 months. Implant survival rate was 97.8%, being significantly higher for APF, STC, and APF + STC (RES) when compared with REC (P = 0.01) therapy, in particular for advanced lesions (>50% of bone loss). The overall therapeutic success rate at implant-level was 66% and 79.5% for case definition #1 and #2, respectively. APF group displayed more efficient disease resolution when considered success definition #1 (72%). Contrarily, when the data were adhered to success definition #2, STC group showed a slightly higher disease resolution rate (87%). For RES group, location, favoring anterior (P = 0.04) and defect type, favoring class II (P = 0.02) displayed statistical significance for therapeutic success. For REC group, implants exhibiting a wider band of keratinized mucosa (KM) demonstrated higher therapeutic success (P = 0.008). CONCLUSION: Implantoplasty as an adjunct to surgical therapy proved effective in terms of disease resolution and implant survival rate. Implant location, defect morphology as well as the buccal width of KM are indicators of therapeutic success.

Monitoring the formation of a colloidal lipid gel at the nanoscale: vesicle aggregation driven by a temperature-induced mechanism.

Colloidal gels made of lipid vesicles at highly diluted conditions have been recently described. The structure and composition of this type of material could be especially relevant for studies that combine model lipid membranes with proteins, peptides, or enzymes to replicate biological conditions. Details about the nanoscale events that occur during the formation of such gels would motivate their future application. Thus, in this work we investigate the gelation mechanism, which consists of a lipid dispersion of vesicles going through a process that involves freezing and heating. The appropriate combination of techniques (transmission electron microscopy, differential scanning calorimetry and synchrotron small angle X-ray scattering) allowed in-depth analysis of the different events that give rise to the formation of the gel. Results showed how freezing damaged the lipid dispersion, causing a polydisperse suspension of membrane fragments and vesicles upon melting. Heating above the lipids' main phase transition temperature promoted the formation of elongated tubular structures. After cooling, these lipid tubes broke down into vesicles that formed branched aggregates across the aqueous phase, obtaining a material with gel characteristics. These mechanistic insights may also allow finding new ways to interact with lipid vesicles to form structured materials. Future works might complement the presented results with molecular dynamics or nuclear magnetic resonance experiments.

The coming together of allosteric and phosphorylation mechanisms in the molecular integration of A2A heteroreceptor complexes in the dorsal and ventral striatal-pallidal GABA neurons.

The role of adenosine A2A receptor (A2AR) and striatal-enriched protein tyrosine phosphatase (STEP) interactions in the striatal-pallidal GABA neurons was recently discussed in relation to A2AR overexpression and cocaine-induced increases of brain adenosine levels. As to phosphorylation, combined activation of A2AR and metabotropic glutamate receptor 5 (mGluR5) in the striatal-pallidal GABA neurons appears necessary for phosphorylation of the GluA1 unit of the AMPA receptor to take place. Robert Yasuda (J Neurochem 152: 270-272, 2020) focused on finding a general mechanism by which STEP activation is enhanced by increased A2AR transmission in striatal-pallidal GABA neurons expressing A2AR and dopamine D2 receptor. In his Editorial, he summarized in a clear way the significant effects of A2AR activation on STEP in the dorsal striatal-pallidal GABA neurons which involves a rise of intracellular levels of calcium causing STEP activation through its dephosphorylation. However, the presence of the A2AR in an A2AR-fibroblast growth factor receptor 1 (FGFR1) heteroreceptor complex can be required in the dorsal striatal-pallidal GABA neurons for the STEP activation. Furthermore, Won et al. (Proc Natl Acad Sci USA 116: 8028-8037, 2019) found in mass spectrometry experiments that the STEP splice variant STEP61 can bind to mGluR5 and inactivate it. In addition, A2AR overexpression can lead to increased formation of A2AR-mGluR5 heterocomplexes in ventral striatal-pallidal GABA neurons. It involves enhanced facilitatory allosteric interactions leading to increased Gq-mediated mGluR5 signaling activating STEP. The involvement of both A2AR and STEP in the actions of cocaine on synaptic downregulation was also demonstrated. The enhancement of mGluR5 protomer activity by the A2AR protomer in A2AR-mGluR5 heterocomplexes in the nucleus accumbens shell appears to have a novel significant role in STEP mechanisms by both enhancing the activation of STEP and being a target for STEP61.