Novel imidazo[1,5-a]quinoxaline derivatives: SAR, selectivity and modeling challenges en route to the identification of an α5-GABAA receptor NAM.

Initial optimization of a series of novel imidazo[1,5-a]quinoxaline compounds originated from a heuristic approach combining two known structural moieties towards α5-GABAA receptor is shown. This work reveals one-digit nanomolar active compounds as well as positive and negative allosteric modulators resulted from our exploratory approach. To deepen our understanding, their diverse mechanistic nature resulted from in silico modeling is also disclosed.

Relative performance of various biomaterials used for maxillary sinus augmentation: A Bayesian network meta-analysis.

OBJECTIVES: To assess the histomorphometric outcomes obtained in randomized clinical trials (RCTs) with different biomaterials used for maxillary sinus augmentation (MSA). MATERIALS AND METHODS: A search of the existing medical literature until October 1, 2019, was performed. Inclusion criteria were (a) RCTs assessing a two-stage MSA from the lateral approach using autologous bone or biomaterials for grafting and (b) reported histomorphometric outcomes based on crestal bone core biopsy samples. The Bayesian method was used to perform pairwise meta-analyses and network meta-analysis (NMA). The primary outcome, the new bone percentage (NB %), was calculated as mean differences with 95% credible intervals. The interventions were ranked by their posterior probability by calculating the surface under the cumulative ranking curve values. RESULTS: Thirty-four RCTs (842 MSAs) were included in the analysis with a normal healing period (5-8 months). All comparisons were presented in a league table. On the basis of the ranking probability, the most effective bone grafting material for NB% was bovine xenograft + bone marrow concentrate (BMC) (81%), followed by bovine xenograft + platelet-rich plasma (PRP) (77%), bioactive glass ceramic + autologous bone 1:1 (70%), nanocrystalline hydroxyapatite in silica gel (70%), and bioactive glass ceramic (70%). Autologous bone graft alone took the twelfth position with 57%. CONCLUSION: Within the limitations of the present NMA, the analysis did not confirm autologous bone alone as the gold standard for MSA and showed superiority of composite grafts such as bovine xenograft + BMC after 5-8 months of healing.

The Effect of Platelet-Rich Fibrin Membrane in Surgical Therapy of Medication-Related Osteonecrosis of the Jaw.

PURPOSE: We examined the effect of the membranous form of platelet-rich fibrin (PRF) on patients with medication-related osteonecrosis of the jaw. MATERIALS AND METHODS: Our study included patients who underwent an operation because of second- or third-stage osteonecrosis of the jaw induced by antiresorptive therapy. The diagnosis of medication-related osteonecrosis of the jaw was based on the 2009 and 2014 recommendations of the American Association of Oral and Maxillofacial Surgeons. On the basis of the duration of treatment, we divided our patients into 2 groups. Patients in the first group (Gr1) underwent traditional surgical therapy between 2009 and 2014, whereas patients in the second group (Gr2) underwent PRF membrane-supplemented operations between 2015 and 2017. Outcomes were assessed based on patient recovery, stage improvement, and relapse rate. The follow-up period was a minimum of 1 year. RESULTS: Our study included 101 patients: 73 in Gr1 and 28 in Gr2. The results in Gr2 were significantly better than those in Gr1: recovery (P = .022), stage improvement (P = .005), and relapse rate (P < .001). CONCLUSIONS: In Gr2, significantly better results were achieved in terms of stage improvement, recovery, and relapse rate than in Gr1.

Entropy Affects the Competition of Ordered Phases.

The effect of entropy at low noises is investigated in five-strategy logit-rule-driven spatial evolutionary potential games exhibiting two-fold or three-fold degenerate ground states. The non-zero elements of the payoff matrix define two subsystems which are equivalent to an Ising or a three-state Potts model depending on whether the players are constrained to use only the first two or the last three strategies. Due to the equivalence of these models to spin systems, we can use the concepts and methods of statistical physics when studying the phase transitions. We argue that the greater entropy content of the Ising phase plays an important role in its stabilization when the magnitude of the Potts component is equal to or slightly greater than the strength of the Ising component. If the noise is increased in these systems, then the presence of the higher entropy state can cause a kind of social dilemma in which the players' average income is reduced in the stable Ising phase following a first-order phase transition.

[Chronic, nonbacterial, multicentric osteomyelitis in the mandible]. / Krónikus, nem bakteriális, multicentrikus osteomyelitis a mandibulában.

Chronic nonbacterial osteomyelitis is a sterile inflammatory osteitis that most commonly develops in the long bones, but it can occur in any bone. Mandibular lesions are found in 1.5-3% of disease foci in patients and it is poorly characterized in the maxillofacial surgery literature due to the use of inconsistent terminology. The purpose of this study was to present the clinical experience of chronic nonbacterial multicentric osteomyelitis and a collection of research and information of the disease. This is a retrospective study of 2 cases with mandibular lesions radiographically consistent with osteomyelitis without infection. Medical records were reviewed for history, clinical features, imaging and pathology. The study included 2 patients (2 females, age of 17 and 43 years). Both reported mandibular pain and swelling, radiographic finding of multifocal intraosseal inflammatory lesions. Computed tomography scans typically showed expansion of the affected mandible with sclerosis of the medullary space, small foci of poorly defined lytic destruction with lamellated periosteal reaction. Both patients showed a long ineffective antibiotic therapy and recurrent flare-ups of inflammation. After the proper course of treatment (nonsteroid and steroid therapy), a long painless period was reached. Chronic multicentric nonbacterial osteomyelitis has been reported to be uncommon in the mandible, but it may be more common with correct diagnosis, typified by recurrent pain and swelling with characteristic pathologic and radiologic features. The current treatment modalities include nonsteroidal anti-inflammatory drugs or steroids. Orv Hetil. 2018; 159(43): 1761-1766.

[The first 200 transcatheter aortic valve implantations in the Gottsegen Gyorgy Institute of Cardiology, Hungary]. / Az elso 200 transzkatéteres aortabillentyu-implantáció a Gottsegen György Országos Kardiológiai Intézetben.

INTRODUCTION: Transcatheter aortic valve implantation is a therapeutic alternative for contraindicated and high surgical risk patients with severe symptomatic aortic stenosis. This intervention is part of daily routine in the Institute of the authors. AIM: In the present work the results of the first 200 patients are discussed. METHOD: Until January, 2016, 200 patients (female 55%, mean age 79.9 years, average EuroSCORE 19.3%, left ventricular ejection fraction 54%, peak gradient 81.2 mmHg, mean aortic gradient 50.9 mmHg) underwent transcatheter aortic valve implantation. RESULTS: The procedure was performed with 99% success rate. Complications were evaluated according to VARC 2 definitions. Mortality was 5% at one month and 17.4% at one year. Cardiac mortality was 13.6 at one year. Cerebrovascular complications were 5% within one year, and 95% of patients were in NYHA I or II functional classes at one year. CONCLUSION: These findings are consistent with worldwide results. Orv. Hetil., 2016, 157(45), 1786-1792.

Clinical predictors of mortality following rotational atherectomy and stent implantation in high-risk patients: A single center experience.

OBJECTIVES: Our aim was to assess the procedural success and determine the clinical predictors of postprocedure mortality, following rotational atherectomy (RA) and stenting in high-risk patients. BACKGROUND: RA is mainly used to facilitate stenting in complex lesions. Outcomes involving RA and stenting have been investigated, yet high-risk patients have not been adequately described. METHODS: Data of 218 consecutive patients who underwent RA were evaluated in a prospective register. Primary endpoints were the angiographic success and long-term mortality. Secondary endpoints were procedural success, consumption of the angioplasty equipment, and periprocedural major adverse cardiac events. The impact of the relevant angiographic and clinical characteristics on long-term mortality was analyzed using uni- and multivariate Cox regression analysis. RESULTS: Mean age of the patients was 70 ± 8.2 years, diabetes was present in 44%, and chronic renal failure in 29%. Prior myocardial infarction and three-vessel disease amounted to 42.2% and 32.6%, respectively. Altogether, 52.8% of patients underwent RA after a failed, non-RA intervention attempt, and 30.7% of cases presented as acute coronary syndromes. Angiographic success was 100%, and all patients received stents after RA. Periprocedural major adverse cardiac events occurred in five (2.3%) patients. Postprocedural death was investigated, with a mean follow-up of 36 months. Mortality amounted to 37.2%. Multivariate analysis revealed that left ventricular ejection fraction < 50%, glomerular filtration rate < 60 ml/min, cardiogenic shock, and diabetes were the only independent mortality predictors. CONCLUSIONS: We have found that RA and stenting is feasible and viable in an elderly high-risk population, with exceptional procedural success and acceptable long-term results.

Transtelephonic electrocardiography in the management of patients with acute coronary syndrome.

BACKGROUND: The efficacy of the transtelephonic ECG system (TTECG) in the management of ST segment elevation myocardial infarction (STEMI) was examined with regard to the ambulance service- and percutaneous coronary intervention (PCI)-related delay times, the prehospital medical therapy and the in-hospital mortality rate. METHODS: The study was conducted as a collaborative effort between the University of Debrecen and the Hungarian National Ambulance Service. Altogether 397 patients were recruited in the TTECG group, while 378 patients transported to the PCI centre without TTECG served as controls. RESULTS: More accurate prehospital medical therapy was achieved in the TTECG group. The PCI-related delay times were significantly shorter, while the in-hospital mortality rate was significantly lower in the TTECG group than among the controls. CONCLUSIONS: The findings illustrate that TTECG is a valuable tool which may potentially improve the regional management of STEMI patients.

Surface analytical studies of maxillofacial implants: influence of the preoperational treatment and the human body on the surface properties of retrieved implants.

In the present work, surface analytical investigation of unimplanted as well as retrieved pyrolytic carbon-covered carbon/carbon composite implants and Ti osteosynthesis plates is reported. The Ti plates were covered by a 200-nm-thick, anodically and thermally formed TiO2 layer. Our results suggest that although the oxide layer on the Ti miniplates remained stable during the time spent in the human body, there is still material transport between the implant and the human body. In case of the carbon/carbon composite implants, damage of the carbon fibers constituting the material was found on one side of the sterile implant and attributed to the manufacturing process. The NaCl crystals originally present on the surface of the sterile material disappeared during the time spent in the human body. As a result of the interaction with the human body, a new surface layer (mainly constituted of carbon) appeared on the implant. The results indicate that both the time spent in the human organism and the preparation of the implants before operation can have detectable effects on the investigated surface properties. Surface analytical investigations could therefore provide information not only about the biocompatibility of these materials but also about the effect of their treatment before operation.

Evolutionarily stable payoff matrix in hawk-dove games.

BACKGROUND: Classical matrix game models aim to find the endpoint of behavioural evolution for a set of fixed possible interaction outcomes. Here, we introduce an evolutionary model in which not only the players' strategies but also the payoff matrix evolves according to natural selection. RESULTS: We start out from the hawk-dove matrix game and, in a way that is consistent with the monomorphic model setup of Maynard Smith and Price, introduce an evolving phenotypic trait that quantifies fighting ability and determines the probability of winning and the cost of losing escalated hawk-hawk fights. We define evolutionarily stable phenotypes as consisting of an evolutionarily stable strategy and an evolutionarily stable trait, which in turn describes a corresponding evolutionarily stable payoff matrix. CONCLUSIONS: We find that the maximal possible cost of escalating fights remains constant during evolution assuming a separation in the time scales of fast behavioural and slow trait selection, despite the fact that the final evolutionarily stable phenotype maximizes the payoff of hawk-hawk fights. Our results mirror the dual nature of Darwinian evolution whereby the criteria of evolutionary success, as well as the successful phenotypes themselves, are a product of natural selection.

Outcomes of treatment with short dental implants compared with standard-length implants: a retrospective clinical study.

BACKGROUND: The size of dental implants is a key success factor for appropriate osseointegration. Using shorter implants allows the possibility of avoiding complex surgical procedures and reduces the morbidity of treatment. Shorter implants also enable implant-prosthetic rehabilitation after maxillofacial reconstructions where only limited bone is available. In this study, the success rates of short implants were examined and compared to those of standard-sized implants. METHODS: Patients who received dental implants between 2007 and 2016 at the Department of Oro-Maxillofacial Surgery and Stomatology Semmelweis University were enrolled in the study. Several clinical parameters were recorded and supplemented with radiological examinations. The data were statistically analysed. RESULTS: Thirty-four patients with a total of 60 implants were included. The average time after prosthetic loading was 39.33 ± 21.96 months in the group with 8-mm implants and 41.6 ± 27.5 months in the group with > 8-mm implants. No significant differences were observed between the two groups in terms of probing depth (short implants, 2.84 ± 0.09 mm; standard implants, 2.91 ± 0.35 mm) or mean marginal bone loss (short implants, 1.2 ± 1.21-mm mesially and 1.36 ± 1.47-mm distally; standard implants: 0.63 ± 0.80-mm mesially and 0.78 ± 0.70-mm distally). CONCLUSIONS: In this study, the success rate of short dental implants was comparable to that of standard-sized implants. Consequently, it can be claimed that the long-term success of short dental implants does not differ significantly from the long-term success of standard implants.

Solitary ameloblastic fibroma with impacted teeth: A case report.

This case report aimed to describe a rare benign mandibular tumour and assess the outcomes of the most recent reviews, between January 2017 and August 2023. Presenting a detailed clinical case, this study advances our understanding of the diagnostic and therapeutic aspects, ultimately improving the management of similar cases in clinical practice. Orthopantomogram (OPG) revealed a well-defined unilocular radiolucency extending from the midline of the ramus and teeth 47 and 48 were submerged at the base of the mandible. In the presented case, a PLANMECA ROMEXIS PROMAX® three-dimensional (3D) maximum (MAX) cone-beam computed tomography (CBCT) device was used for the 3D examination. An intraoral approach was preferred and the tumour was removed in toto by creating a bone window using a W&H® Dentalwerk Bürmoos GmbH Piezomed piezoelectric device, and the bone plates were fixed with 4 MEDARTIS® microplates, with a primary flap closure. A PANORAMIC 1000, 3DHISTECH Ltd® device was employed for the histological investigation. Odontogenic tumours are rare and typically asymptomatic, often discovered incidentally during routine radiographic examinations. Most of these benign lesions heal well after complete excision and require long-term follow-up. Once diagnosed, ameloblastic fibroma (AF) should be treated immediately to avoid malignant transformation.

Coexistence of fraternity and egoism for spatial social dilemmas.

We have studied an evolutionary game with spatially arranged players who can choose one of the two strategies (named cooperation and defection for social dilemmas) when playing with their neighbors. In addition to the application of the usual strategies in the present model the players are also characterized by one of the two extreme personal features representing the egoist or fraternal behavior. During the evolution each player can modify both her own strategy and/or personal feature via a myopic update process in order to improve her utility. The results of numerical simulations and stability analysis are summarized in phase diagrams representing a wide scale of spatially ordered distribution of strategies and personal features when varying the payoff parameters. In most of the cases only two of the four possible options prevail and may form sublattice ordered spatial structure. The evolutionary advantage of the fraternal attitude is demonstrated within a large range of payoff parameters including the region of prisoner's dilemma where egoist defectors and fraternal cooperators form a role-separating chessboard like pattern.

Long-term clinical follow-up after drug-eluting stent implantation for bare metal in-stent restenosis.

OBJECTIVES: We aimed to evaluate the long-term safety and efficacy of drug-eluting stent (DES) implantation in the treatment of diffuse bare metal stent (BMS) restenosis as compared to the treatment of de novo coronary lesions in high restenosis risk patient population. BACKGROUND: To date limited long-term data are available about the treatment of BMS restenosis with DES. METHODS: Five hundred and fourteen consecutive patients who underwent DES implantation between January 2003 and October 2006 at our institute were studied: 201 patients received DES for treatment of BMS restenosis and 313 patients received DES for high restenosis risk de novo lesions. Outcomes were calculated using propensity score adjustment. Mean follow-up length was 45.6 ± 21.5 months. RESULTS: The rates of acute coronary syndrome, three-vessel disease, and diabetes were high in both restenosis and de novo groups: 44.8% versus 46.3%, 20.9% versus 28.7%, and 34.3% versus 38.9%, respectively. The incidence of ischemia-driven target lesion revascularization (TLR) yielded similar results in the restenosis group and de novo group at 4 years (10.4% vs 12.4%, P = 0.490). All-cause mortality was lower in the restenosis group at 4 years (7.4% vs 14.7%, P = 0.032); however, the incidence of definite and probable stent thrombosis did not differ (1.9% vs 1.6%, P = 0.708) between the 2 groups. CONCLUSIONS: DESs are safe in the treatment of diffuse BMS restenosis and the rate of additional TLR is acceptable as compared to the use of DES in de novo lesions.

SEM and EDS investigation of a pyrolytic carbon covered C/C composite maxillofacial implant retrieved from the human body after 8 years.

The long term effect of the human body on a pyrolytic carbon covered C/C composite maxillofacial implant (CarBulat(Tm)) was investigated by comparing the structure, the surface morphology and composition of an implant retrieved after 8 years to a sterilized, but not implanted one. Although the thickness of the carbon fibres constituting the implants did not change during the 8 year period, the surface of the implant retrieved was covered with a thin surface layer not present on the unimplanted implant. The composition of this layer is identical to the composition of the underlying carbon fibres. Calcium can only be detected on the surface as a trace element implying that the new layer is not formed by bone tissue. Residual soft tissue penetrating the bulk material between the carbon fibre bunches was found on the retrieved implant indicating the importance of the surface morphology in tissue growth and adhering to implants.

[Dental care and prevention possibilities for the mentally disabled currently]. / Az értelmi fogyatékkal élok fogászati kezelése és prevenciós lehetoségei napjainkban.

INTRODUCTION: In Hungary, dental care and prevention for mentally disabled individuals are becoming increasingly challenging. Currently, there are 100,000 intellectually disabled individuals in the country who require "special medical care". OBJECTIVE: The objective of this study was to develop and modify a relatively simple preventive procedure, adjusted to the mental capabilities of the patients, and implement it within a selected group. The study aimed to assess the results after 3 and 6 months, respectively, and to compare them with the international literature. METHOD: The preventive procedure was introduced to 49 patients admitted to the institute of Csömör Nursing Home and Daycare Institute of the Foundation for Equal Opportunities. To ensure the accuracy of the data, the patients were examined separately by 3 doctors. The program began with dental care training for both patients and nursing staff. The periodontal examinations were carried out by the team's periodontologist. The patients were checked after 3 and 6 months, respectively, and the data were recorded. RESULTS: No changes were registered in terms of the DMF-T index during this short period of time, therefore we applied the restorative index. However, a significant improvement was observed in the periodontal condition. DISCUSSION: The preventive procedure proved to be effective, considering the fact that all patients had periodontal problems due to neglected oral hygiene. As there was a significant improvement in the periodontal condition, an improvement of the DMF-T index dentition of the patients can also be expected in the future. CONCLUSION: Enhanced oral hygiene (advancing towards "normal oral hygiene" from the neglected oral hygiene of the patients) can bring about considerable improvement in the case of patients needing special medical care. To attain positive results, a proper approach and regular motivation are essential for both patients and caregivers. Orv Hetil. 2023; 164(37): 1456-1461.

Identification of Triazolopyridines as Selective α5-GABAA Receptor Negative Allosteric Modulators by a Hybridization Approach.

The identification and characterization of novel triazolopyridine derivatives with selective α5 subunit-containing GABAA receptor negative allosteric modulator (NAM) activity are disclosed. As a result of in silico screening of our corporate compound deck, we identified a moderately potent hit that was converted to an advanced hit bearing better physicochemical and pharmacological properties using a hybridization approach. Subsequent optimization led to the identification of in vitro potent and subtype-selective α5-GABAA receptor NAMs representing a new chemotype in this area.

Defense mechanisms of empathetic players in the spatial ultimatum game.

Experiments on the ultimatum game have revealed that humans are remarkably fond of fair play. When asked to share an amount of money, unfair offers are rare and their acceptance rate small. While empathy and spatiality may lead to the evolution of fairness, thus far considered continuous strategies have precluded the observation of solutions that would be driven by pattern formation. Here we introduce a spatial ultimatum game with discrete strategies, and we show that this simple alteration opens the gate to fascinatingly rich dynamical behavior. In addition to mixed stationary states, we report the occurrence of traveling waves and cyclic dominance, where one strategy in the cycle can be an alliance of two strategies. The highly webbed phase diagram, entailing continuous and discontinuous phase transitions, reveals hidden complexity in the pursuit of human fair play.

Selfishness, fraternity, and other-regarding preference in spatial evolutionary games.

Spatial evolutionary games are studied with myopic players whose payoff interest, as a personal character, is tuned from selfishness to other-regarding preference via fraternity. The players are located on a square lattice and collect income from symmetric two-person two-strategy (called cooperation and defection) games with their nearest neighbors. During the elementary steps of evolution a randomly chosen player modifies her strategy in order to maximize stochastically her utility function composed from her own and the co-players' income with weight factors 1-Q and Q. These models are studied within a wide range of payoff parameters using Monte Carlo simulations for noisy strategy updates and by spatial stability analysis in the low noise limit. For fraternal players (Q=1/2) the system evolves into ordered arrangements of strategies in the low noise limit in a way providing optimum payoff for the whole society. Dominance of defectors, representing the "tragedy of the commons", is found within the regions of prisoner's dilemma and stag hunt game for selfish players (Q=0). Due to the symmetry in the effective utility function the system exhibits similar behavior even for Q=1 that can be interpreted as the "lovers' dilemma".

Ventricular septal rupture caused by myocardial bridge, solved by interventional closure device.

Myocardial bridging is a common coronary anomaly, which is generally described as a benign phenomenon. However, a growing number of studies consider this anomaly a relevant pathophysiological phenomenon with serious pathological consequences. Here we report on the case of an 88-year-old woman suffering from myocardial infarction and ventricular septal rupture, lacking any recognizable coronary disease except for a myocardial bridge causing the systolic compression of the left anterior descending coronary artery. A wide range of diagnostic procedures, including coronarography, echocardiography, and magnetic resonance imaging were used. The septal rupture was finally closed by using a percutaneous closure device. This event indicates that myocardial bridges - at least in some cases - may have notable clinical relevance.