Application of transformer architectures in generative video modeling for neurosurgical education.

PURPOSE: This article explores the potential impact of OpenAI's Sora, a generative video modeling technology, on neurosurgical training. It evaluates how such technology could revolutionize the field by providing realistic surgical simulations, thereby enhancing the learning experience and proficiency in complex procedures for neurosurgical trainees. METHODS: The study examines the incorporation of this technology into neurosurgical education by leveraging transformer architecture and processing of video and image data. It involves compiling a neurosurgical procedure dataset for model training, aiming to create accurate, high-fidelity simulations. RESULTS: Our findings indicate significant potential applications in neurosurgical training, including immersive simulations for skill development and exposure to diverse surgical scenarios. The technology also promises to transform assessment and feedback, introducing a standardized, objective way to measure and improve trainee competencies. CONCLUSION: Integrating generative video modeling technology into neurosurgical education marks a progressive step toward enhancing training methodologies. Despite challenges in technical, ethical, and practical domains, continuous development and evaluation could lead to substantial advancements in surgical education, preparing neurosurgeons more effectively for their demanding roles.

Early versus Delayed Surgical Management of Ruptured Arteriovenous Brain Malformations in a Tertiary Referral Center in Colombia, South America.

BACKGROUND: Surgical timing after rupture of brain arteriovenous malformations (AVMs) is controversial. There is scarce literature on AVM surgical outcomes from developing countries. This study aims to determine if there is a difference between early and delayed surgical resection for patients with ruptured brain AVMs. METHODS: This single-center retrospective review included patients who underwent surgical resection for ruptured brain AVMs in Colombia. Patients were stratified by the timing of surgical intervention relative to the rupture into early (≤72 hours of bleeding) and delayed (>72 hours) resection. Continuous variables were analyzed using an independent t-test, and dichotomous variables were analyzed using a χ2 test. A linear regression analysis was performed with the final mRankin score at 2 years as the dependent variable; P < 0.05 was considered significant. RESULTS: Thirty-one patients were identified. The early treatment group included 14 (45.2%) patients, and the delayed group included 17 (54.8%) patients. The mean (SD) length of time between AVM rupture and surgical resection was 1.6 ± 1.2 days and 12.4 ± 8.4 days, respectively (P < 0.001). There were no differences regarding demographics, perioperative variables, and postoperative outcomes between groups. In the linear regression analysis, the only variable that had a significant association with the final mRankin score was the initial Glasgow Coma Scale, which had a ß coefficient of -0.6341 (95% confidence interval: -0.41,-0.017, P = 0.035). CONCLUSIONS: In this case series of 31 patients from a developing country, there were no differences in clinical outcomes at the final follow-up between acute and delayed surgical interventions for ruptured AVMs. The most important factor associated with the final outcomes was the initial Glasgow Coma Scale.

Long-term outcomes after surgical correction of anterior plagiocephaly secondary to isolated frontosphenoidal synostosis: a systematic review and two illustrative cases.

PURPOSE: Anterior plagiocephaly ( AP), secondary to isolated frontosphenoidal synostosis (IFS), represents one of the rarest forms of craniosynostosis documented in medical literature. Therefore, there is a lack of comprehensive understanding regarding the long-term (> 2 years) postoperative outcomes of this minor suture synostosis. METHODS: This study presents the long-term outcomes of two patients previously treated for IFS, detailing their clinical, imaging, and postoperative characteristics. Additionally, a systematic review was conducted following PRISMA criteria to summarize existing literature on the topic. The review specifically focuses on long-term aesthetic outcomes, reoperation rates, and complications following surgical intervention for IFS. RESULTS: Four articles encompassing 12 patients were included in the systematic review. The review highlights clinical features, postoperative complications, reoperation rates, and long-term aesthetic outcomes. The mean age at surgery was 17.5 months (range 9.5-24 months), with an average age at diagnosis of 9.3 months (range 6-10 months). Fronto-orbital advancement was the predominant surgical approach described across all cases. The reoperation rate among patients was 16.6%, with only two cases reporting postoperative complications. In one of our cases, an intraoperative CT scan was utilized to illustrate real-time improvement in frontal bone alignment according to the surgical plan, which significantly contributed to positive long-term clinical outcomes observed during a follow-up period exceeding 24 months. CONCLUSION: IFS, is a rare minor suture synostosis, significantly affects the aesthetic appearance of the forehead and necessitates consideration in the management of AP cases. Surgical intervention has shown minimal reoperation rates and excellent long-term prognosis. These findings are reinforced by recent institutional data and a comprehensive systematic review of the current literature.

Gamma knife radiosurgery for orbital cavernous hemangioma: a systematic review and single-arm meta-analysis.

PURPOSE: Gamma knife radiosurgery (GKRS) for orbital cavernous hemangioma (OCH) has emerged as a promising method due to its significant clinical improvement and low incidence of complications. This study aimed to evaluate the safety and efficacy of GKRS for the treatment of OCH. METHODS: In accordance with the PRISMA framework, we searched PubMed, Cochrane Central, and Embase for studies reporting outcomes of GKRS for OCH. Studies reporting complications, visual improvement, proptosis, tumor reduction rate, and tumor progression rate for OCH following GKRS were included. RESULTS: Six studies, out of 1856 search results, with 100 patients were included. Among them, only 5 minor complications were related to GKRS, including 3 with orbital pain and 2 with periorbital chemosis. Thus, the complication rate was 13% (95% CI, 7-25%). Visual acuity and visual field improvement rates after GKRS were 80% (95% CI, 63-96%) and 71% (95% CI, 47-95%) respectively. Proptosis improved in 94% of cases (95% CI, 83-100%). The tumor reduction rate was 77% after GKRS (95% CI, 69-85%). CONCLUSION: GKRS for OCH appears to be a safe technique, as evidenced by the rate of clinical improvement and radiological improvement. However, studies are limited by an absence of a control group. Additional studies are needed to evaluate the relative efficacy of GKRS as compared with alternative surgical modalities for OCH.

Efficacy and safety of sagittal synostosis surgery in older (> 12 months) patients: a systematic review and meta-analysis.

PURPOSE: Sagittal synostosis is the most common isolated craniosynostosis. Surgical treatment of this synostosis has been extensively described in the global literature, with promising outcomes when it is performed in the first 12 months of life. However, in some cases, patients older than 12 months arrive at the craniofacial center with this synostosis. A comprehensive study on efficacy and perioperative outcomes has yet to be fully explored in this population. This systematic review and meta-analysis aimed to assess the available evidence of surgical outcomes for the treatment of sagittal synostosis among older patients to analyze the efficacy and safety of synostosis surgery in this unique population. METHODS: PubMed, Embase, and Scopus were searched for studies published from inception to March 2024 reporting surgical outcomes of synostosis surgery in older patients (> 12 months) with isolated sagittal synostosis. The main outcome was the reoperation rate, with secondary endpoints including transfusion rates, aesthetic outcomes, and surgical complications. RESULTS: Nine studies were included in the final analysis. The pooled proportion of the reoperation rate was 1%. The rate of excellent aesthetic results was 95%. The need for transfusion associated with the procedures was 86%, and finally, surgical complications attained a pooled ratio of 2%, indicating minimal morbidity associated with the surgical repair. CONCLUSION: Sagittal synostosis surgery is a safe and effective procedure to perform in older patients; this meta-analysis suggests that open surgery confers a significant rate of excellent aesthetic results with a low reoperation rate and minimal complications associated with the intervention. Future research with direct comparisons among different techniques will validate the findings of this study, which will all contribute to the rigor of synostosis management.

History of pediatric neurosurgery in Latin America: the early years.

PURPOSE: Pediatric neurosurgical history in Latin America possesses rich and fascinating origins; the large number of neurosurgical societies that form the continent and the inspiring achievements of the pioneers in the field in every single Latin American country are described here. This unique text explores the aspects of this neurosurgical specialty since its beginnings by neurosurgeons trained outside Latin America, who brought the pediatric practice to their home countries, writing a new chapter in the neurosurgical history, constructing the foundations for the present pediatric practice and the few fellowships found in the continent. METHODS, RESULTS AND CONCLUSION: A formal search was performed in PubMed, Embase, and national libraries focused on the historical and biographical aspects of pioneers' pediatric neurosurgeons of Argentina, Brazil, Colombia, Venezuela, Peru, Chile, and Ecuador, with an important session that describes the fellowships' opportunities in pediatric neurosurgery found in the continent, dividing all the programs according to the countries that offer the subspecialty education.

How to become a pediatric neurosurgeon in Latin America: training opportunities, current status, and future challenges.

PURPOSE: To provide an analysis of pediatric neurosurgery educational opportunities in Latin America in order to characterize and evaluate the strengths, weaknesses, and limitations to assume a career in pediatric neurosurgery. METHODS: An online survey was distributed to pediatric neurosurgeons in Latin America to assess aspects of pediatric neurosurgical education, working conditions, and training opportunities. The survey was open to neurosurgeons that treat pediatric patients, whether or not they had completed fellowship training in pediatrics. A descriptive analysis was done with a subgroup analysis stratified the results among certified pediatric neurosurgeons and non-certified pediatric neurosurgeons. RESULTS: In total, 106 pediatric neurosurgeons completed the survey, of whose the vast majority completed their training in a Latin American pediatric neurosurgery program. A total of 19 accredited academic programs in pediatric neurosurgery were found in Latin America distributed in 6 different countries. On average, the pediatric neurosurgical training in America Latina has a duration of 278 years, ranging from 1 to > 6 years. CONCLUSIONS: This study is the first of its kind to review pediatric neurosurgical training in Latin America, in which both pediatric and general neurosurgeons provide neurosurgical care to children in the continent; however, we found that in the majority of the cases, children are treated by certified pediatric neurosurgeons, of whose the vast majority were trained in Latin American programs. On the other hand, we found areas of improvement in the specialty in the continent, including regulation of training opportunities, increased support for funding, and more opportunities for education among all countries.

Molecular Imprinted BiVO4 Microswimmers for Selective Target Recognition and Removal.

Analogous to photosynthetic systems, photoactive semiconductor-based micro/nanoswimmers display biomimetic features that enable unique light harvesting and energy conversion functions and interactions with their surroundings. However, these artificial swimmers are usually non-selective and provide ineffective target recognition, resulting in poor surface analyte binding that affects the overall reactivity and motion efficiency. Here, the surface engineering of light-driven BiVO4 microswimmers by molecular imprinting polymerization is presented. After embedding surface recognition sites, the modified microswimmers can self-propel in a solution of a target molecule, without requiring toxic fuels, and degrade the target selectively in a pollutant mixture. These findings show that optimizing the design of semiconductor-based microswimmers with specific target recognition cavities on their surface is a promising strategy to achieve selective capture and degradation of organic pollutants, which is otherwise impossible because of the non-selective behavior of photogenerated reactive radicals. Moreover, this study provides a unique strategy to enhance the motion capabilities of single-component photocatalytic microswimmers in a specific chemical environment.

Sustainable oxygen evolution electrocatalysis in aqueous 1 M H2SO4 with earth abundant nanostructured Co3O4.

Earth-abundant electrocatalysts for the oxygen evolution reaction (OER) able to work in acidic working conditions are elusive. While many first-row transition metal oxides are competitive in alkaline media, most of them just dissolve or become inactive at high proton concentrations where hydrogen evolution is preferred. Only noble-metal catalysts, such as IrO2, are fast and stable enough in acidic media. Herein, we report the excellent activity and long-term stability of Co3O4-based anodes in 1 M H2SO4 (pH 0.1) when processed in a partially hydrophobic carbon-based protecting matrix. These Co3O4@C composites reliably drive O2 evolution a 10 mA cm-2 current density for >40 h without appearance of performance fatigue, successfully passing benchmarking protocols without incorporating noble metals. Our strategy opens an alternative venue towards fast, energy efficient acid-media water oxidation electrodes.

Enhancement of electrocatalytic oxygen evolution by chiral molecular functionalization of hybrid 2D electrodes.

A sustainable future requires highly efficient energy conversion and storage processes, where electrocatalysis plays a crucial role. The activity of an electrocatalyst is governed by the binding energy towards the reaction intermediates, while the scaling relationships prevent the improvement of a catalytic system over its volcano-plot limits. To overcome these limitations, unconventional methods that are not fully determined by the surface binding energy can be helpful. Here, we use organic chiral molecules, i.e., hetero-helicenes such as thiadiazole-[7]helicene and bis(thiadiazole)-[8]helicene, to boost the oxygen evolution reaction (OER) by up to ca. 130 % (at the potential of 1.65 V vs. RHE) at state-of-the-art 2D Ni- and NiFe-based catalysts via a spin-polarization mechanism. Our results show that chiral molecule-functionalization is able to increase the OER activity of catalysts beyond the volcano limits. A guideline for optimizing the catalytic activity via chiral molecular functionalization of hybrid 2D electrodes is given.

Quantification of the Effect of an External Magnetic Field on Water Oxidation with Cobalt Oxide Anodes.

Here, we quantify the effect of an external magnetic field (ß) on the oxygen evolution reaction (OER) for a cobalt oxide|fluorine-doped tin oxide coated glass (CoOx|FTO) anode. A bespoke apparatus enables us to precisely determine the relationship between magnetic flux density (ß) and OER activity at the surface of a CoOx|FTO anode. The apparatus includes a strong NdFeB magnet (ßmax = 450 ± 1 mT) capable of producing a magnetic field of 371 ± 1 mT at the surface of the anode. The distance between the magnet and the anode surface is controlled by a linear actuator, enabling submillimeter distance positioning of the magnet relative to the anode surface. We couple this apparatus with a finite element analysis magnetic model that was validated by Hall probe measurements to determine the value of ß at the anode surface. At the largest tested magnetic field strength of ß = 371 ± 1 mT, a 4.7% increase in current at 1.5 V vs the normal hydrogen electrode (NHE) and a change in the Tafel slope of 14.5 mV/dec were observed. We demonstrate through a series of OER measurements at sequential values of ß that the enhancement consists of two distinct regions. The possible use of this effect to improve the energy efficiency of commercial water electrolyzers is discussed, and major challenges pertaining to the accurate measurement of the phenomenon are demonstrated.

Bifunctional Oxygen Electrocatalysis on Mixed Metal Phthalocyanine-Modified Carbon Nanotubes Prepared via Pyrolysis.

Non-precious-metal catalysts are promising alternatives for Pt-based cathode materials in low-temperature fuel cells, which is of great environmental importance. Here, we have investigated the bifunctional electrocatalytic activity toward the oxygen reduction reaction (ORR) and the oxygen evolution reaction (OER) of mixed metal (FeNi; FeMn; FeCo) phthalocyanine-modified multiwalled carbon nanotubes (MWCNTs) prepared by a simple pyrolysis method. Among the bimetallic catalysts containing nitrogen derived from corresponding metal phthalocyanines, we report the excellent ORR activity of FeCoN-MWCNT and FeMnN-MWCNT catalysts with the ORR onset potential of 0.93 V and FeNiN-MWCNT catalyst for the OER having EOER = 1.58 V at 10 mA cm-2. The surface morphology, structure, and elemental composition of the prepared catalysts were examined with scanning electron microscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. The FeCoN-MWCNT and FeMnN-MWCNT catalysts were prepared as cathodes and tested in anion-exchange membrane fuel cells (AEMFCs). Both catalysts displayed remarkable AEMFC performance with a peak power density as high as 692 mW cm-2 for FeCoN-MWCNT.

Redefining the Mechanistic Scenario of Carbon-Sulfur Nucleophilic Coupling via High-Valent Cp*CoIV Species.

The potential access to CoIV species for promoting transformations that are particularly challenging at CoIII still remains underexploited in the context of Cp*Co-catalyzed C-H functionalization reactions. Herein, we disclose a combined experimental and computational strategy for uncovering the participation of Cp*CoIV species in a Cp*Co-mediated C-S bond-reductive elimination. These studies support the intermediacy of high-valent Cp*Co species in C-H functionalization reactions, under oxidative conditions, when involving nucleophilic coupling partners.

Actividad lúpica en paciente con enfermedad renal terminal: reporte de caso / Lupus activity in a patient with end-stage renal disease: a case report

RESUMEN El lupus eritematoso sistémico (LES) es una enfermedad autoinmune que afecta múltiples órganos; el compromiso renal se encuentra en el 50% de los pacientes y es variable de acuerdo con el grupo racial y étnico. Se estima que el 10% de los pacientes con nefritis lúpica (NL) desarrollan enfermedad renal terminal (ERT) y, una vez que se da la progresión, el 80% de los pacientes negativizan los marcadores de actividad. Sin embargo, aunque es inusual, la reactivación de la enfermedad puede presentarse en compromiso renal avanzado y es importante diagnosticarla oportunamente para definir la causa, tratarla y evitar complicaciones. Presentamos el caso clínico de una paciente de 45 arios, con ERT en diálisis peritoneal, que se encontraba en remisión de la enfermedad y posteriormente desarrolló actividad lúpica.

ABSTRACT Systemic lupus erythematosus (SLE) is an autoimmune disease that affects multiple organs, and renal involvement is found in 50% of patients and is variable according to racial and ethnic group. It is estimated that 10% of patients with lupus nephritis (NL) develop end-stage renal disease (ERT), and once progression occurs, 80% of patients are negative for activity markers. However, although it is rare, the reactivation of the disease can occur in advanced renal involvement, and it is important to diagnose it in a timely manner to define the cause and treat it, avoiding complications.

Push-Pull Electronic Effects in Surface-Active Sites Enhance Electrocatalytic Oxygen Evolution on Transition Metal Oxides.

Sustainable electrocatalysis of the oxygen evolution reaction (OER) constitutes a major challenge for the realization of green fuels. Oxides based on Ni and Fe in alkaline media have been proposed to avoid using critical raw materials. However, their ill-defined structures under OER conditions make the identification of key descriptors difficult. Here, we have studied Fe-Ni-Zn spinel oxides, with a well-defined crystal structure, as a platform to obtain general understanding on the key contributions. The OER reaches maximum performance when: (i) Zn is present in the Spinel structure, (ii) very dense, equimolar 1 : 1 : 1 stoichiometry sites appear on the surface as they allow the formation of oxygen vacancies where Zn favors pushing the electronic density that is pulled by the octahedral Fe and tetrahedral Ni redox pair lowering the overpotential. Our work proves cooperative electronic effects on surface active sites as key to design optimum OER electrocatalysts.

Effect of Mechanochemical Recrystallization on the Thermal Hysteresis of 1D FeII-triazole Spin Crossover Polymers.

The thermal hysteresis in the cooperative spin crossover (SCO) polymer [Fe(trz)(Htrz)2]n[BF4]n (1) has been tuned by a simple ball milling grinding process. Mechanical treatment affects the size and morphology of the crystallite domains, as confirmed by multiple complementary techniques, including ESEM, DLS, and PXRD data. Upon milling, the regular cubic shape particles recrystallize with slightly different unit cell parameters and preferential orientation. This macroscopic change significantly modifies the thermally induced SCO behavior, studied by temperature-dependent magnetic susceptibility, X-ray diffraction, and DSC analysis. Transition temperatures downshift, closer to room temperature, while hysteresis widens, when particle sizes are actually decreasing. We relate this counterintuitive observation to subtle modifications in the unit cell, offering new alternatives to tune and enhance SCO properties in this class of 1D-cooperative polymers.

Non-redox doping boosts oxygen evolution electrocatalysis on hematite.

The oxygen evolution reaction (OER) is the major bottleneck to develop viable and cost-effective water electrolysis, a key process in the production of renewable fuels. Hematite, all iron α-Fe2O3, would be an ideal OER catalyst in alkaline media due to its abundance and easy processing. Despite its promising theoretical potential, it has demonstrated very poor OER activity under multiple experimental conditions, significantly worse than that of Co or Ni-based oxides. In the search for improving hematite performance, we have analysed the effect of doping with redox vs. non-redox active species (Ni or Zn). Our results indicate that Zn doping clearly outperforms Ni, commonly accepted as a preferred dopant. Zn-doped hematite exhibits catalytic performances close to the state-of-the-art for alkaline water splitting: reaching 10 mA cm-2 at just 350 mV overpotential (η) at pH 13, thus twenty times that of hematite. Such a catalytic enhancement can be traced back to a dramatic change in the reaction pathway. Incorporation of Ni, as previously suggested, decreases the energetic barrier for the OER on the available centres. In contrast, Zn facilitates the appearance of a dominant and faster alternative via a two-site reaction, where the four electron oxidation reaction starts on Fe, but is completed on Zn after thermodynamically favoured proton coupled electron transfer between adjacent metal centres. This unique behaviour is prompted by the non-redox character of Zn centres, which maintain the same charge during OER. Our results open an alternative role for dopants on oxide surfaces and provide a powerful approach for catalytic optimisation of oxides, including but not limited to highly preferred all-iron oxides.

Baja masa ósea y osteoporosis en pacientes con lupus eritematoso sistémico / Low bone mass and osteoporosis in patients with systemic lupus erythematosus

RESUMEN Introducción: El lupus eritematoso sistémico es una enfermedad autoinmune, multisistémica y crónica, de etiología desconocida, en la cual la frecuencia de alteraciones en la densidad mineral ósea varía entre 25-74%; si bien su diagnóstico no está estandarizado. Objetivo: Describir las alteraciones densitométricas en pacientes con lupus eritematoso sistémico, así como las características clínicas y demográficas en 2 centros de referencia del noroccidente colombiano. Materiales y métodos: Estudio transversal realizado entre enero de 2013 y diciembre de 2014. Variables incluidas: demográficas, estado de menopausia, consumo de tabaco y alcohol, autoanticuerpos, compromiso orgánico, medicamentos e índices de actividad y cronicidad (SLEDAI, SLICC). Alteraciones densitométricas definidas según la Organización Mundial de la Salud. Análisis estadístico: Frecuencias absolutas y relativas para variables cualitativas; mediana con rango intercuartílico (RIQ) para variables cuantitativas. Resultados: De 302 pacientes evaluados, 65 cumplieron criterios de elegibilidad. Treinta y uno por ciento de las pacientes premenopáusicas tenían baja masa ósea para la edad; un 50% de las mujeres posmenopáusicas tenían osteoporosis y un 27% baja masa ósea. Número de pacientes con alteraciones densitométricas según factores asociados: fracturas 4, consumo de alcohol 2, fumadores activos 3, anticuerpos anti-Ro 8, afección neurológica 7, falla renal crónica 4. Uso de prednisolona: 53,8%; mediana de dosis diaria: 10 mg (RIQ5-52). Medianas de SLEDAI y SLICC: 0 (RIQ= 0-4) y 0,5 (RIQ= 0-1,75), respectivamente. Conclusiones: Se encontraron pocas densitometrías óseas en pacientes con lupus; la frecuencia de las alteraciones minerales óseas fue independiente del estado de menopausia. La mediana de dosis de prednisolona fue alta, en sujetos en remisión y sin daño orgánico.

ABSTRACT Introduction: Systemic lupus erythematosus is a chronic, autoimmune, multisystem disease of unknown aetiology, and in which the frequency of alterations in bone mineral density varies between 25% and 74%, although its diagnosis is not standardised. Objective: To describe the densitometric changes in systemic lupus erythematosus patients, as well as the clinical and demographic characteristics from two reference centres northwestern Colombia. Materials and methods: A cross-sectional study was conducted between January 2013 and December 2014. The data collected included the demographic variables, menopausal status, use of tobacco and alcohol, autoantibodies, organ involvement, medications, as well as the activity and chronicity indices (SLEDAI, SLICC). Densitometric changes were defined according to World Health Organisation criteria. Statistical analyses: Absolute and relative frequencies were calculated for qualitative variables, and medians with interquartile range (IQR) for quantitative variables. Results: Of the total 302 patients evaluated, 65 met eligibility criteria. Thirty-one percent of premenopausal patients had low bone mass for age was observed in 31% of pre-menopausal women, with 50% of post-menopausal women showing osteoporosis, and 27% low bone mass. The number of patients with densitometric alterations according to associated factors was, fractures 4, alcohol consumption 2, active smokers 3, anti-Ro antibodies 8, neurological involvement 7, and chronic renal failure 4. Prednisone was used in 53.8%, with a median daily dose of 10mg (IQR5-52). The median SLEDAI and SLICC was 0 (IQR = 0-4) and 0.5 (IQR = 01.75), respectively. Conclusions: Few bone densitometry results were found in patients with systemic lupus erythematosus. The frequency of mineral bone disorders was independent of menopausal status. The median dose of prednisone was high in subjects in remission, and without organ damage.

8-Substituted 1,3-dimethyltetrahydropyrazino[2,1-f]purinediones: Water-soluble adenosine receptor antagonists and monoamine oxidase B inhibitors.

Multitarget approaches, i.e., addressing two or more targets simultaneously with a therapeutic agent, are hypothesized to offer additive therapeutic benefit for the treatment of neurodegenerative diseases. Validated targets for the treatment of Parkinson's disease are, among others, the A2A adenosine receptor (AR) and the enzyme monoamine oxidase B (MAO-B). Additional blockade of brain A1 ARs may also be beneficial. We recently described 8-benzyl-substituted tetrahydropyrazino[2,1-f]purinediones as a new lead structure for the development of such multi-target drugs. We have now designed a new series of tetrahydropyrazino[2,1-f]purinediones to extensively explore their structure-activity-relationships. Several compounds blocked human and rat A1 and A2AARs at similar concentrations representing dual A1/A2A antagonists with high selectivity versus the other AR subtypes. Among the best dual A1/A2AAR antagonists were 8-(3-(4-chlorophenyl)propyl)-1,3-dimethyl-6,7,8,9-tetrahydropyrazino[2,1-f]purine-2,4(1H,3H)-dione (41, Ki human A1: 65.5nM, A2A: 230nM; Ki rat A1: 352nM, A2A: 316nM) and 1,3-dimethyl-8-((2-(thiophen-2-yl)thiazol-4-yl)methyl)-6,7,8,9-tetrahydropyrazino[2,1-f]purine-2,4(1H,3H)-dione (57, Ki human A1: 642nM, A2A: 203nM; Ki rat A1: 166nM, A2A: 121nM). Compound 57 was found to be well water-soluble (0.7mg/mL) at a physiological pH value of 7.4. One of the new compounds showed triple-target inhibition: (R)-1,3-dimethyl-8-(2,1,3,4-tetrahydronaphthalen-1-yl)-6,7,8,9-tetrahydropyrazino[2,1-f]purine-2,4(1H,3H)-dione (49) was about equipotent at A1 and A2AARs and at MAO-B (Ki human A1: 393nM, human A2A: 595nM, IC50 human MAO-B: 210nM) thus allowing future in vivo explorations of the intended multi-target approach.