A Phase II, Open-Label, Randomized Trial of Durvalumab With Olaparib or Cediranib in Patients With Mismatch Repair-Proficient Colorectal or Pancreatic Cancer.

BACKGROUND: The use of immunotherapy in mismatch repair proficient colorectal cancer (pMMR-CRC) or pancreatic adenocarcinoma (PDAC) is associated with limited efficacy. DAPPER (NCT03851614) is a phase 2, basket study randomizing patients with pMMR CRC or PDAC to durvalumab with olaparib (durvalumab + olaparib) or durvalumab with cediranib (durvalumab + cediranib). METHODS: PDAC or pMMR-CRC patients were randomized to either durvalumab+olaparib (arm A), or durvalumab + cediranib (arm B). Co-primary endpoints included pharmacodynamic immune changes in the tumor microenvironment (TME) and safety. Objective response rate, progression-free survival (PFS) and overall survival (OS) were determined. Paired tumor samples were analyzed by multiplexed immunohistochemistry and RNA-sequencing. RESULTS: A total of 31 metastatic pMMR-CRC patients were randomized to arm A (n = 16) or B (n = 15). In 28 evaluable patients, 3 patients had stable disease (SD) (2 patients treated with durvalumab + olaparib and 1 patient treated with durvalumab + cediranib) while 25 had progressive disease (PD). Among patients with PDAC (n = 19), 9 patients were randomized to arm A and 10 patients were randomized to arm B. In 18 evaluable patients, 1 patient had a partial response (unconfirmed) with durvalumab + cediranib, 1 patient had SD with durvalumab + olaparib while 16 had PD. Safety profile was manageable and no grade 4-5 treatment-related adverse events were observed in either arm A or B. No significant changes were observed for CD3+/CD8+ immune infiltration in on-treatment biopsies as compared to baseline for pMMR-CRC and PDAC independent of treatment arms. Increased tumor-infiltrating lymphocytes at baseline, low baseline CD68+ cells and different immune gene expression signatures at baseline were associated with outcomes. CONCLUSIONS: In patients with pMMR-CRC or PDAC, durvalumab + olaparib and durvalumab + cediranib showed limited antitumor activity. Different immune components of the TME were associated with treatment outcomes.

Underdiagnosis, Undertreatment, and Noncompliance With Treatment in People Who Died by Suicide.

Background: This study explored the characteristics of people who die by suicide, comparing those who had depression with those who did not.Methods: Clinical data were collected through a postmortem proxy-based semistructured interview (psychological autopsy). Postmortem toxicological analysis provides data on the presence of substances or drugs in the blood of suicides. Participants were adults who died by suicide in the province of Seville, Spain, during 2006-2016. The main independent variables were previous diagnosis, postmortem diagnosis, prescribed treatment, and treatment found in blood. The primary outcome was the postmortem diagnosis of depression, after which the sample was divided into 2 groups according to DSM IV criteria to the presence or absence of major depressive episode (MDE).Results: Our sample is composed of 313 people, of which 200 (63.9%) had a diagnosis of MDE according to the psychological autopsy. Predeath diagnosis of depression was more frequent in MDE suicides than in non-MDE suicides (18.6% vs 3.5%, respectively; Χ2 = 23.420; df = 9; P = .005) and had more access to mental health treatment previous to death (67.7% vs 35.6%, respectively; Χ2 = 27.572; df = 1; P < .001). Antidepressants were prescribed in 21.5% of the MDE suicides, but only 8.5% of them were taking them at the time of death according to the toxicology exam.Conclusions: The underdiagnosis of depression in people who die by suicide is striking, as is the undertreatment. Further efforts must be made to train primary care physicians in the proper identification of persons at risk of suicide, as they are one of the main gatekeepers in the fight for suicide prevention.

A feasibility study of a Smart screening tool for people at risk of mental health issues: Response rate, and sociodemographic and clinical factors.

BACKGROUND: The use of Smart Screening tools to identify mental health problems has scarce empirical data on their effectiveness. This study aims to explore the response rate of patients to this tool and observe their socio-demographic and healthcare characteristics, and the tool's ability to detect potential mental health diagnoses. METHODS: The study employed an online survey within patient portal from patients of four teaching hospitals in Madrid. The sample included 8749 patients, comprising 66.77 % females and 31.21 % middle-aged adults. RESULTS: 60.56 % responded to the Smart Screening tool. Respondents were found to be predominantly middle-aged women who had been contacted by mental health services multiple times but had not exhibited suicidal behaviour. These patients demonstrated a higher appointment attendance rate and generated low healthcare costs. The tool identified probable low depression and mild anxiety (72.16 %), and individuals aged 50-65 exhibited higher levels of mental health problems, such as psychosis and suicidality, although these results were not all significant regarding previous mental health diagnoses. LIMITATIONS: The Smart Screening tool collects anonymous online data through short questionnaires to apply sophisticated algorithms and determine probable mental health diagnoses. CONCLUSIONS: The response rate to the Smart Screening tool was higher than in previous studies. The respondents' profile was middle-aged and older women with moderate mental health problems, although suicidality was also identified. Future research should focus on those who did not respond to the tool and explore the link between previous psychiatric diagnoses and the accuracy of the Smart Screening tool.

Cross-cultural validation and Spanish translation of the Boston Interview to evaluate severely obese patients seeking metabolic/bariatric surgery.

INTRODUCTION: obesity is a global health problem. Metabolic/Bariatric surgery (MBS) has proven to be one of the most effective methods for treating the most severe forms. However, a thorough evaluation and preparation of people seeking MBS is necessary. In Spain, there are no standardized interviews to carry out the psychosocial assessment of people seeking MBS. The Boston Interview for MBS (BIBS) is a recognized and flexible tool to evaluate the psychosocial factors. OBJECTIVE: to present the process of translation into Spanish and cross-cultural adaptation of the BIBS. MATERIALS AND METHODS: the reverse translation procedure was followed. To validate the translation, a multidisciplinary group of experts was formed. They were asked to rate the clarity of wording and cultural adaptation of the translation items. In addition, the translated interview was used to evaluate 173 patients seeking MBS who rated their satisfaction with the interview experience. RESULTS: the evaluation of the translation by a group of experts was favorable (global mode and median were 3-excellent, IQR of 1). The overall percentage agreement of the adequacy of "cultural adaptation" of the text was 85.8 % (95 % CI, 0.784, 0.932) and of the "clarity of wording" was 84.7 % (95 % CI, 0.7644; 0.9286). Furthermore, it was well accepted by the majority of the patients interviewed (p(50) 10 out of 10). CONCLUSIONS: the Spanish translation of the BIBS is available for the assessment of Spanish-speaking people seeking MBS. It was rated as having good fidelity to the original English version, and was deemed highly satisfactory by patients.

Preliminary Screening on Antibacterial Crude Secondary Metabolites Extracted from Bacterial Symbionts and Identification of Functional Bioactive Compounds by FTIR, HPLC and Gas Chromatography-Mass Spectrometry.

Secondary metabolites, bioactive compounds produced by living organisms, can unveil symbiotic relationships in nature. In this study, soilborne entomopathogenic nematodes associated with symbiotic bacteria (Xenorhabdus stockiae and Photorhabdus luminescens) were extracted from solvent supernatant containing secondary metabolites, demonstrating significant inhibitory effects against E. coli, S. aureus, B. subtilus, P. mirabilis, E. faecalis, and P. stutzeri. The characterization of these secondary metabolites by Fourier transforms infrared spectroscopy revealed amine groups of proteins, hydroxyl and carboxyl groups of polyphenols, hydroxyl groups of polysaccharides, and carboxyl groups of organic acids. Furthermore, the obtained crude extracts were analyzed by high-performance liquid chromatography for the basic identification of potential bioactive peptides. Gas chromatography-mass spectrometry analysis of ethyl acetate extracts from Xenorhabdus stockiae identified major compounds including nonanoic acid derivatives, proline, paromycin, octodecanal derivatives, trioxa-5-aza-1-silabicyclo, 4-octadecenal, methyl ester, oleic acid, and 1,2-benzenedicarboxylicacid. Additional extraction from Photorhabdus luminescens yielded functional compounds such as indole-3-acetic acid, phthalic acid, 1-tetradecanol, nemorosonol, 1-eicosanol, and unsaturated fatty acids. These findings support the potential development of novel natural antimicrobial agents for future pathogen suppression.

Penile prosthesis implantation is safe and effective in Peyronie's disease patients with and without erectile dysfunction.

Penile prosthesis (PP) is the mainstay of treatment in Peyronie's disease (PD) with co-existent refractory erectile dysfunction (ED). This study aimed to assess the clinical outcomes of patients who underwent PP as the first-line surgical treatment in PD without ED. A total of 636 patients underwent PP for PD from 2012 to 2022, but only 168 patients who underwent PP as first-line surgical management for PD with or without ED were included in the study. The mean (SD) age of 168 patients was 56.3 years (12.4). The mean curvature of the "PD with ED" group and the "PD without ED" group were 38.2 (5.6) degrees and 42.2 (5.9) degrees. The median (IQR) follow-up was 56.0 months (34.5- 61.4). Most (86.9%) patients underwent 3-piece inflatable PP. An important finding is that 33 patients (19.6%) without ED had undergone PP. Mechanical failure requiring revision surgery was less common in the 'without ED' group than in the ED group (6.8% vs. 10.2%, p 0.04). Most PD patients without ED (87.9%, 29/33) and with ED (88.9%, 120/135) were "satisfied" after PP implantation at six months, as defined by a score of ≥4 on a 5-point Likert scale. If surgery is offered in PD, PP may be considered a safe and effective first-line surgical treatment regardless of the ED, given the acceptable complications and high satisfaction rates. However, this new concept warrants further research.

Preparation of a heterogeneous biocatalyst through Thermomyces lanuginosus lipase immobilization on pore-expanded SBA-15.

Heterogeneous biocatalysts were prepared by adsorbing T. lanuginosus lipase (TLL) onto uncalcined (SBAUC-TLL) and calcined (SBAC-TLL) SBA-15, using ammonium fluoride as a pore expander to facilitate TLL immobilization. At an enzyme load of 1 mg/g, high immobilization yields (>90 %) and recovered activities (>80 % for SBAUC-TLL and 70 % for SBAC-TLL) were achieved. When increasing the enzyme load to 5 mg/g, the immobilization yield of SBAUC-TLL was 80 %, and the recovered activity was 50 %, while SBAC-TLL had a yield of 100 % and a recovered activity of 36 %. Crosslinking with glutaraldehyde (GA) was conducted to improve stability (SBAUC-TLL-GA and SBAC-TLL-GA). Although SBAC-TLL-GA lost 25 % of initial activity after GA modifications, it exhibited the highest thermal (t1/2 = 5.7 h at 65 °C), when compared to SBAC-TLL (t1/2 = 12 min) and the soluble enzyme (t1/2 = 36 min), and operational stability (retained 100 % activity after 5 cycles). Both biocatalysts presented high storage stability since they retained 100 % of initial activity for 30 days. These results highlight SBA-15's potential as an enzyme support and the protocol's efficacy in enhancing stability, with implications for industrial applications in the food, chemical, and pharmaceutical sectors.

Tolerability and Safety of Large-Volume Hyaluronidase-Facilitated Subcutaneous Immunoglobulin 10% Administered with or without Dose Ramp-Up: A Phase 1 Study in Healthy Participants.

PURPOSE: Facilitated subcutaneous immunoglobulin (fSCIG; immune globulin infusion 10% [human] with recombinant human hyaluronidase [rHuPH20]) permits high-volume subcutaneous immunoglobulin (SCIG) infusion, shorter infusion times and reduced dosing frequency relative to conventional SCIG. It is initiated by gradually increasing infusion volumes over time (dose ramp-up) to achieve target dose level (TDL). Whether ramp-up strategies have tolerability or safety advantages over direct initiation at full TDL has not been evaluated clinically. METHODS: This phase 1 open-label study assessed tolerability and safety of fSCIG 10% with accelerated or no ramp-up compared with conventional ramp-up in healthy adults (NCT04578535). Participants were assigned to one of the three ramp-up arms to achieve TDLs of 0.4 or 1.0 g/kg/infusion. The primary endpoint was the proportion of infusions completed without interruption or infusion rate reduction owing to treatment-emergent adverse events (TEAEs). Safety was assessed as a secondary endpoint. RESULTS: Of 51 participants enrolled, 50 (98.0%) tolerated all fSCIG 10% infusions initiated (n = 174). Infusion rate was reduced in one participant owing to headache in the 0.4 g/kg/infusion conventional ramp-up arm. Study discontinuations were higher in the no ramp-up arm (70%) versus the conventional (0%) and accelerated (22%) arms at the 1.0 g/kg/infusion TDL. Safety outcomes did not substantially differ between treatment arms. CONCLUSION: The favorable tolerability and safety profiles of fSCIG 10% in healthy participants support initiating treatment with fSCIG 10% with accelerated ramp-up at TDLs up to 1.0 g/kg. Data support no ramp-up at TDLs close to 0.4 g/kg but additional data are needed for higher doses.

Zeolites synthesis from phyllosilicates and their performance for CO2 adsorption.

Five phyllosilicates (kaolinite, montmorillonite, saponite, sepiolite and palygorskite) have been selected as starting materials for the synthesis of zeolites. Among them, kaolinite and montmorillonite display the lowest Si/Al molar ratio leading to aluminosilicates with high crystallinity. Thus, the hydrothermal treatment under basic conditions forms 4A zeolite when kaolinite is used as starting material while 13X zeolite is obtained when montmorillonite is used as starting material. The microporosity and CO2-adsorption capacity of the prepared zeolites are directly related to its crystallinity. Thus, in order to improve it, raw phyllosilicates were subjected to a microwave-assisted treatment to remove undesired Mg or Fe-species, which have a negative effect in the assembling of the zeolites by hydrothermal basic conditions in a second step. The highest adsorption value was 3.85 mmol/g at 25 °C and 760 mm of Hg for Mont-A-B sample after the consecutive treatments.

Descriptive study on substance uses and risk of sexually transmitted infections in the practice of Chemsex in Spain.

Background: In recent years, there has been an increasing use of sex-related substances (known as "Chemsex") to facilitate, intensify, and prolong the sexual experience of men who have sex with men. This phenomenon poses a public health problem, increasing the risk of sexually transmitted infections (STIs) and mental disorders. Objective: The primary aim of this study was to delve into the correlation between substance use and sexual health, specifically examining the association between different substances used and the risk of sexually transmitted infections (STIs) in the context of Chemsex in Spain. Methods: An observational, descriptive, cross-sectional study was conducted among 563 Spanish participants between January and April 2023. Non-probabilistic purposive sampling was used by the investigators. The researchers administered a questionnaire to men who have sex with men who use substances, especially in the sexual sphere, in all the autonomous communities of Spain. Results: 14.7% reported having practiced slamsex in the last year, and 17.94% were diagnosed with a Sexually Transmitted Infection in the previous 6 months. Of these, 21% were on PREP treatment, with the main STIs being gonorrhea (p < 0.001), chlamydia (p < 0.001), genital herpes (p = 0.020), and syphilis (p < 0.001). The 63.7% used methamphetamines as the main drug in the practice of chemsex. Discussion: Chemsex in Spain is linked to a high prevalence of STIs, especially gonorrhea and chlamydia, even among those on PrEP treatment. The use of various drugs during chemsex, such as amyl nitrite, GHB, ecstasy, and others, correlates with higher rates of STIs, highlighting the need for interventions to reduce risk and harm. The drugs most associated with slamsex include ketamine, mephedrone, and methamphetamine, underscoring the importance of addressing the risk behaviors associated with this activity. Conclusion: This study shows that chemsex appears to be associated with a high prevalence among men who have sex with men. Who use multiple substances in a sexual context, and are particularly exposed to sexually transmitted infections (STIs), indicating a particular need for STI prevention and care in this group.

Production of carbon-11 for PET preclinical imaging using a high-repetition rate laser-driven proton source.

Most advanced medical imaging techniques, such as positron-emission tomography (PET), require tracers that are produced in conventional particle accelerators. This paper focuses on the evaluation of a potential alternative technology based on laser-driven ion acceleration for the production of radioisotopes for PET imaging. We report for the first time the use of a high-repetition rate, ultra-intense laser system for the production of carbon-11 in multi-shot operation. Proton bunches with energies up to 10-14 MeV were systematically accelerated in long series at pulse rates between 0.1 and 1 Hz using a PW-class laser. These protons were used to activate a boron target via the 11 B(p,n) 11 C nuclear reaction. A peak activity of 234 kBq was obtained in multi-shot operation with laser pulses with an energy of 25 J. Significant carbon-11 production was also achieved for lower pulse energies. The experimental carbon-11 activities measured in this work are comparable to the levels required for preclinical PET, which would be feasible by operating at the repetition rate of current state-of-the-art technology (10 Hz). The scalability of next-generation laser-driven accelerators in terms of this parameter for sustained operation over time could increase these overall levels into the clinical PET range.

Fluctuation corrections to Lifshitz tails in disordered systems.

Quenched disorder in semiconductors induces localized electronic states at the band edge, which manifest as an exponential tail in the density of states. For large impurity densities, this tail takes a universal Lifshitz form that is characterized by short-ranged potential fluctuations. We provide both analytical expressions and numerical values for the Lifshitz tail of a parabolic conduction band including its exact fluctuation prefactor. Our analysis is based on a replica field integral approach, where the leading exponential scaling of the tail is determined by an instanton profile and fluctuations around the instanton determine the subleading preexponential factor. This factor contains the determinant of a fluctuation operator, and we avoid a full computation of its spectrum by using a Gel'fand-Yaglom formalism, which provides a concise general derivation of fluctuation corrections in disorder problems. We provide a revised result for the disorder band tail in two dimensions.

Cost-effectiveness analysis of the diagnosis of temporal arteritis.

Temporal arteritis (TA) is the most common form of systemic vasculitis. Its diagnosis is based on criteria proposed by the American College of Rheumatology (1990), and its treatment is high-dose corticosteroids. Our objective is to assess the cost of diagnosing TA, and secondarily, cost-effective analysis of different diagnostic strategies (clinical, biopsy, doppler ultrasound) and therapeutic strategies (corticosteroid suspension). MATERIAL AND METHOD: Observational, retrospective study has been carried out on patients with AT (2012-2021). Demographic data, comorbidities, signs and symptoms suggestive of AT were collected. AT was diagnosed with a score ≥ 3 according to American College of Rheumatoloy criteria (ACR-SCORE). The costs of diagnosis and treatment modification were analysed. RESULTS: Seventy-five patients have been included, median age 77 (46-87) years. Headache, temporal pain and jaw claudication were significant for the diagnosis of TA. Patients with a halo on Doppler ultrasound and a positive biopsy have significantly elevated ESR and CRP compared to patients who do not. The cost of the AT diagnosis was 414.7 euros/patient. If we use ACR-SCORE ≥ 3-echodoppler it is 167.2 є/patient (savings 59.6%) and ACR-SCORE ≥ 3-biopsy 339.75 є/patient (savings 18%). If the corticosteroid was removed and a biopsy was performed, 21.6 є/patient (94.7% savings), if the corticosteroid was removed and Doppler ultrasound was performed, 10.6 є/patient (97.4% savings). CONCLUSIONS: Headache, temporary pain and jaw claudication are predictors of AT. Elevated ESR and CRP are predictors of positive biopsy and presence of halo on ultrasound. The uses of ACR-SCORE ≥ 3 with Doppler ultrasound or biopsy, and with corticosteroid suspension, are cost-effective.

Análisis coste/efectivo del diagnóstico de la arteritis de la temporal / Cost-effectiveness analysis of the diagnosis of temporal arteritis

La arteritis de la temporal (AT) es la forma más frecuente de vasculitis sistémica, su diagnóstico está basado en criterios propuestos por el Colegio Americano de Reumatología (1990), y su tratamiento son corticoides a dosis elevadas. Nuestro objetivo es valorar el gasto del diagnóstico de la AT, y secundariamente análisis coste/efectivo de distintas estrategias diagnósticas (clínica, biopsia, eco-Doppler) y terapéuticas (suspensión del corticoide). Material y método: Estudio observacional, retrospectivo de pacientes con AT (2012-2021). Se recogieron datos demográficos, comorbilidades, signos y síntomas sugestivos de AT. Se diagnosticó AT con una puntuación ≥3 según los criterios del American College of Reumatology (ACR-SCORE). Se analizaron los gastos del diagnóstico y modificación de tratamiento. Resultados: Setenta y cinco pacientes, mediana edad 77 (6-87) años. Cefalea, dolor temporal y claudicación mandibular fueron significativos para el diagnóstico de AT. Los pacientes con halo en eco-Doppler y biopsia positiva, presentaron elevación de VSG y PCR de forma significativa en comparación con los pacientes que no. El gasto diagnóstico de AT fue de 414,7€/paciente. Si empleamos ACR-SCORE≥3-eco-Doppler serían 167,2€/paciente (ahorro del 59,6%) y ACR-SCORE≥3-biopsia 339,75€/paciente (ahorro del 18%). Si se retiraba corticoide y se realizaba biopsia hubiesen sido 21,6€/paciente (ahorro del 94,7%), si se retiraba corticoide y se realizaba eco-Doppler hubiesen sido 10,6€/paciente (ahorro del 97,4%). Conclusiones: Cefalea, dolor temporal y claudicación mandibular son predictores de AT. La elevación de VSG y PCR son predictores de biopsia positiva y presencia de halo en la ecografía.El empleo de ACR-SCORE≥3 con eco-Doppler o con biopsia, y con suspensión del corticoide son coste/efectivos.(AU)

Temporal arteritis (TA) is the most common form of systemic vasculitis. Its diagnosis is based on criteria proposed by the American College of Rheumatology (1990), and its treatment is high-dose corticosteroids. Our objective is to assess the cost of diagnosing TA, and secondarily, cost-effective analysis of different diagnostic strategies (clinical, biopsy, Doppler ultrasound) and therapeutic strategies (corticosteroid suspension).Material and method: Observational, retrospective study has been carried out on patients with TA (2012–2021). Demographic data, comorbidities, signs and symptoms suggestive of TA were collected. TA was diagnosed with a score ≥3 according to American College of Rheumatoloy criteria (ACR-SCORE). The costs of diagnosis and treatment modification were analysed. Results: Seventy-five patients have been included, median age 77 (46-87) years. Headache, temporal pain and jaw claudication were significant for the diagnosis of TA. Patients with a halo on Doppler ultrasound and a positive biopsy have significantly elevated ESR and CRP compared to patients who do not.: The cost of the TA diagnosis was 414.7 euros/patient. If we use ACR-SCORE≥3-echodoppler it is 167.2 €/patient (savings 59.6%) and ACR-SCORE≥3-biopsy 339.75 €/patient (savings 18%). If the corticosteroid was removed and a biopsy was performed, 21.6 €/patient (94.7% savings), if the corticosteroid was removed and Doppler ultrasound was performed, 10.6 €/patient (97.4% savings).Conclusions: Headache, temporary pain and jaw claudication are predictors of TA. Elevated ESR and CRP are predictors of positive biopsy and presence of halo on ultrasound. The uses of ACR-SCORE≥3 with Doppler ultrasound or biopsy, and with corticosteroid suspension, are cost-effective.(AU)

Examining the relationship between COVID-19 and suicide in media coverage through Natural Language Processing analysis

Background and objectives Suicide is a major public health concern, media can influence its awareness, contagion, and prevention. In this study, we evaluated the relationship between the COVID-19 pandemic and suicide in media coverage through Natural Language Processing analysis (NPL). Methods To study how suicide is depicted in news media, Artificial Intelligence and Big Data techniques were used to analyze news and tweets, to extract or classify the topic to which they belonged. Results A granger causality analysis showed with significant p-value that an increase in covid news at the beginning of the pandemic explains a later rise in suicide-related news. An analysis based on correlation and structural causal models show a strong relationship between the appearance of subjects “health” and “covid”, and also between “covid” and “suicide”. Conclusions Our analysis also uncovers that the inclusion of suicide-related news in the category health has grown since the outbreak of the pandemic. The COVID-19 pandemic has posed an inflection point in the way suicide-related news are reported. Our study found that the increased media attention on suicide during the COVID-19 pandemic may indicate rising social awareness of suicide and mental health, which could lead to the development of new prevention tools. (AU)

Evaluation of the toxicological effects of Neltuma alpataco (Prosopis alpataco) pod alkaloid extract.

The pods of Neltuma spp. have shown potential as a source of protein and energy in livestock. However, prolonged consumption of some of these species can lead to neurological symptoms in ruminants. This study aimed to determine the alkaloid content, as well as the in vitro and in vivo effects of an alkaloid-enriched extract (AEE) from N. alpataco pods. High performance liquid chromatography-high resolution mass spectrometry (HPLC-HRMS) identified juliprosine and juliprosopine as primary alkaloids, with juliprosine being most abundant. AEE from N. alpataco demonstrated dose-dependent cytotoxicity on glioma cells after 48 h, with a 50% cytotoxic concentration (CC50) of 24.69 µg/mL. However, the release of LDH was observed only at the highest tested concentration, indicating cellular damage. Further examination through phase-contrast microscopy and dual acridine orange/ethidium bromide fluorescence staining revealed morphological changes consistent with an apoptotic mechanism of cell death, ultimately leading to secondary necrosis. Finally, the LD50 after intraperitoneal injection in mice was determined to be 12.98 mg/kg. Taken together, these findings demonstrated for the first time the in vivo and in vitro toxicity of the AEE from N. alpataco pods.