Rare EIF4A2 variants are associated with a neurodevelopmental disorder characterized by intellectual disability, hypotonia, and epilepsy.

Eukaryotic initiation factor-4A2 (EIF4A2) is an ATP-dependent RNA helicase and a member of the DEAD-box protein family that recognizes the 5' cap structure of mRNAs, allows mRNA to bind to the ribosome, and plays an important role in microRNA-regulated gene repression. Here, we report on 15 individuals from 14 families presenting with global developmental delay, intellectual disability, hypotonia, epilepsy, and structural brain anomalies, all of whom have extremely rare de novo mono-allelic or inherited bi-allelic variants in EIF4A2. Neurodegeneration was predominantly reported in individuals with bi-allelic variants. Molecular modeling predicts these variants would perturb structural interactions in key protein domains. To determine the pathogenicity of the EIF4A2 variants in vivo, we examined the mono-allelic variants in Drosophila melanogaster (fruit fly) and identified variant-specific behavioral and developmental defects. The fruit fly homolog of EIF4A2 is eIF4A, a negative regulator of decapentaplegic (dpp) signaling that regulates embryo patterning, eye and wing morphogenesis, and stem cell identity determination. Our loss-of-function (LOF) rescue assay demonstrated a pupal lethality phenotype induced by loss of eIF4A, which was fully rescued with human EIF4A2 wild-type (WT) cDNA expression. In comparison, the EIF4A2 variant cDNAs failed or incompletely rescued the lethality. Overall, our findings reveal that EIF4A2 variants cause a genetic neurodevelopmental syndrome with both LOF and gain of function as underlying mechanisms.

Politicians polarize and experts depolarize public support for COVID-19 management policies across countries.

Political polarization impeded public support for policies to reduce the spread of COVID-19, much as polarization hinders responses to other contemporary challenges. Unlike previous theory and research that focused on the United States, the present research examined the effects of political elite cues and affective polarization on support for policies to manage the COVID-19 pandemic in seven countries (n = 12,955): Brazil, Israel, Italy, South Korea, Sweden, the United Kingdom, and the United States. Across countries, cues from political elites polarized public attitudes toward COVID-19 policies. Liberal and conservative respondents supported policies proposed by ingroup politicians and parties more than the same policies from outgroup politicians and parties. Respondents disliked, distrusted, and felt cold toward outgroup political elites, whereas they liked, trusted, and felt warm toward both ingroup political elites and nonpartisan experts. This affective polarization was correlated with policy support. These findings imply that policies from bipartisan coalitions and nonpartisan experts would be less polarizing, enjoying broader public support. Indeed, across countries, policies from bipartisan coalitions and experts were more widely supported. A follow-up experiment replicated these findings among US respondents considering international vaccine distribution policies. The polarizing effects of partisan elites and affective polarization emerged across nations that vary in cultures, ideologies, and political systems. Contrary to some propositions, the United States was not exceptionally polarized. Rather, these results suggest that polarizing processes emerged simply from categorizing people into political ingroups and outgroups. Political elites drive polarization globally, but nonpartisan experts can help resolve the conflicts that arise from it.

Validation of a predictive model for obstructive sleep apnea in people with Down syndrome.

Detecting obstructive sleep apnea (OSA) is important to both prevent significant comorbidities in people with Down syndrome (DS) and untangle contributions to other behavioral and mental health diagnoses. However, laboratory-based polysomnograms are often poorly tolerated, unavailable, or not covered by health insurance for this population. In previous work, our team developed a prediction model that seemed to hold promise in identifying which people with DS might not have significant apnea and, consequently, might be able to forgo a diagnostic polysomnogram. In this study, we sought to validate these findings in a novel set of participants with DS. We recruited an additional 64 participants with DS, ages 3-35 years. Caregivers completed the same validated questionnaires, and our study team collected vital signs, physical exam findings, and medical histories that were previously shown to be predictive. Patients then had a laboratory-based polysomnogram. The best modeling had a validated negative predictive value of 50% for an apnea-hypopnea index (AHI) > 1/hTST and 73.7% for AHI >5/hTST. The positive predictive values were 60% and 39.1%, respectively. As such, a clinically reliable screening tool for OSA in people with DS was not achieved. Patients with DS should continue to be monitored for OSA according to current healthcare guidelines.

COVID-19 Contagion Risk Estimation Model for Indoor Environments.

COVID-19 is an infectious disease mainly transmitted through aerosol particles. Physical distancing can significantly reduce airborne transmission at a short range, but it is not a sufficient measure to avoid contagion. In recent months, health authorities have identified indoor spaces as possible sources of infection, mainly due to poor ventilation, making it necessary to take measures to improve indoor air quality. In this work, an accurate model for COVID-19 contagion risk estimation based on the Wells-Riley probabilistic approach for indoor environments is proposed and implemented as an Android mobile App. The implemented algorithm takes into account all relevant parameters, such as environmental conditions, age, kind of activities, and ventilation conditions, influencing the risk of contagion to provide the real-time probability of contagion with respect to the permanence time, the maximum allowed number of people for the specified area, the expected number of COVID-19 cases, and the required number of Air Changes per Hour. Alerts are provided to the user in the case of a high probability of contagion and CO2 concentration. Additionally, the app exploits a Bluetooth signal to estimate the distance to other devices, allowing the regulation of social distance between people. The results from the application of the model are provided and discussed for different scenarios, such as offices, restaurants, classrooms, and libraries, thus proving the effectiveness of the proposed tool, helping to reduce the spread of the virus still affecting the world population.

Machine Learning Approach to Quadratic Programming-Based Microwave Imaging for Breast Cancer Detection.

In this work, a novel technique is proposed that combines the Born iterative method, based on a quadratic programming approach, with convolutional neural networks to solve the ill-framed inverse problem coming from microwave imaging formulation in breast cancer detection. The aim is to accurately recover the permittivity of breast phantoms, these typically being strong dielectric scatterers, from the measured scattering data. Several tests were carried out, using a circular imaging configuration and breast models, to evaluate the performance of the proposed scheme, showing that the application of convolutional neural networks allows clinicians to considerably reduce the reconstruction time with an accuracy that exceeds 90% in all the performed validations.

Delineating the molecular and phenotypic spectrum of the SETD1B-related syndrome.

PURPOSE: Pathogenic variants in SETD1B have been associated with a syndromic neurodevelopmental disorder including intellectual disability, language delay, and seizures. To date, clinical features have been described for 11 patients with (likely) pathogenic SETD1B sequence variants. This study aims to further delineate the spectrum of the SETD1B-related syndrome based on characterizing an expanded patient cohort. METHODS: We perform an in-depth clinical characterization of a cohort of 36 unpublished individuals with SETD1B sequence variants, describing their molecular and phenotypic spectrum. Selected variants were functionally tested using in vitro and genome-wide methylation assays. RESULTS: Our data present evidence for a loss-of-function mechanism of SETD1B variants, resulting in a core clinical phenotype of global developmental delay, language delay including regression, intellectual disability, autism and other behavioral issues, and variable epilepsy phenotypes. Developmental delay appeared to precede seizure onset, suggesting SETD1B dysfunction impacts physiological neurodevelopment even in the absence of epileptic activity. Males are significantly overrepresented and more severely affected, and we speculate that sex-linked traits could affect susceptibility to penetrance and the clinical spectrum of SETD1B variants. CONCLUSION: Insights from this extensive cohort will facilitate the counseling regarding the molecular and phenotypic landscape of newly diagnosed patients with the SETD1B-related syndrome.

Incidence and Factors Associated with Delirium in Children in a Single Pediatric Intensive Care Unit in Brazil.

PURPOSE: To identify the incidence of delirium in a Pediatric Intensive Care Unit (PICU); to determine the factors associated with the occurrence of delirium and the agreement between two scales used for detection of pediatric delirium in critically ill children. DESIGNS AND METHOD: Descriptive longitudinal study carried out in a PICU. The sample consisted of 65 critically ill children admitted to the PICU, with more than 24 h of hospitalization, excluding children with neurological or cognitive impairment, hearing and visual impairment, chronic encephalopathy and declining consent to participate in the study. Two scales were applied, the Cornell Assessment of Pediatric Delirium (CAPD) and the Sophia Observation Withdrawal Symptoms - Pediatric Delirium Scale (SOS_PD). Descriptive and inferential statistical analysis, with a 5% significance level was performed. RESULTS: Delirium was identified in 7.7% of children, with duration of the disorder of about 2 days. A very good agreement (Kappa = 1; p-value <0.001) between the two scales was identified. CAPD presented positive predictive value of 80.0%. There was a statistical association between the occurrence of delirium and age less than 2 years (p = 0.060); female gender (p = 0.057); use of mechanical pulmonary ventilation (p = 0.034); antiemetics (p = 0.002); anticholinergics (p = 0.044), and changes in serum sodium and potassium (p = 0.053). CONCLUSION: Demographic, clinical, and pharmacological conditions were associated with the occurrence of delirium. PRACTICE IMPLICATIONS: Routine monitoring is the first step to any delirium prevention strategies, so delirium screening by the bedside nurse must be valued through a commitment to education and training.

The prognostic role of hepatic venous pressure gradient in cirrhotic patients undergoing elective extrahepatic surgery.

BACKGROUND & AIMS: Surgery in cirrhosis is associated with a high morbidity and mortality. Retrospectively reported prognostic factors include emergency procedures, liver function (MELD/Child-Pugh scores) and portal hypertension (assessed by indirect markers). This study assessed the prognostic role of hepatic venous pressure gradient (HVPG) and other variables in elective extrahepatic surgery in patients with cirrhosis. METHODS: A total of 140 patients with cirrhosis (Child-Pugh A/B/C: 59/37/4%), who were due to have elective extrahepatic surgery (121 abdominal; 9 cardiovascular/thoracic; 10 orthopedic and others), were prospectively included in 4 centers (2002-2011). Hepatic and systemic hemodynamics (HVPG, indocyanine green clearance, pulmonary artery catheterization) were assessed prior to surgery, and clinical and laboratory data were collected. Patients were followed-up for 1 year and mortality, transplantation, morbidity and post-surgical decompensation were studied. RESULTS: Ninety-day and 1-year mortality rates were 8% and 17%, respectively. Variables independently associated with 1-year mortality were ASA class (American Society of Anesthesiologists), high-risk surgery (defined as open abdominal and cardiovascular/thoracic) and HVPG. These variables closely predicted 90-, 180- and 365-day mortality (C-statistic >0.8). HVPG values >16 mmHg were independently associated with mortality and values ≥20 mmHg identified a subgroup at very high risk of death (44%). Twenty-four patients presented persistent or de novo decompensation at 3 months. Low body mass index, Child-Pugh class and high-risk surgery were associated with death or decompensation. No patient with HVPG <10 mmHg or indocyanine green clearance >0.63 developed decompensation. CONCLUSIONS: ASA class, HVPG and high-risk surgery were prognostic factors of 1-year mortality in cirrhotic patients undergoing elective extrahepatic surgery. HVPG values >16 mmHg, especially ≥20 mmHg, were associated with a high risk of post-surgical mortality. LAY SUMMARY: The hepatic venous pressure gradient is associated with outcomes in patients with cirrhosis undergoing elective extrahepatic surgery. It enables a better stratification of risk in these patients and provides the foundations for potential interventions to improve post-surgical outcomes.

Relationship Between Maximum Pull-up Repetitions and First Repetition Mean Concentric Velocity.

Beckham, GK, Olmeda, JJ, Flores, AJ, Echeverry, JA, Campos, AF, and Kim, SB. Relationship between maximum pull-up repetitions and first repetition mean concentric velocity. J Strength Cond Res 32(7): 1831-1837, 2018-Mean concentric velocity (MCV) of exercise execution has been used by strength and conditioning professionals to improve exercise technique, provide accurate feedback, and predict exercise 1 repetition maximum. There is still limited research on velocity-based training and currently only one research study on the pull-up exercise. The primary purpose of this research was to determine whether the maximum number of pull-ups an individual can perform can be predicted by the MCV of a single pull-up repetition. Forty-nine healthy men and women were recruited who reported they could do at least 2 pull-ups. Each subject performed a standardized warm-up, then a single pull-up repetition, followed by one set of pull-up repetitions to failure. The GymAware PowerTool, a linear position transducer, was used to measure the MCV of each pull-up repetition. Both the MCV of the single repetition and first repetition of the set to failure were recorded, and the greater of the 2 was used in later analysis. Weighted least squares linear regression was used to estimate the relationship between the single-repetition MCV and maximum amount of pull-up repetitions. We observed a statistically significant linear relationship between the maximum number of pull-ups and the MCV of a single pull-up repetition (y = -6.661 + 25.556x, R = 0.841). Prediction of the maximum pull-up number by a single repetition rather than testing the maximal pull-up number may improve efficiency and effectiveness of exercise testing batteries for military, police, and other populations.

Case report: Extending the spectrum of clinical and molecular findings in FOXC1 haploinsufficiency syndrome.

FOXC1 is a ubiquitously expressed forkhead transcription factor that plays a critical role during early development. Germline pathogenic variants in FOXC1 are associated with anterior segment dysgenesis and Axenfeld-Rieger syndrome (ARS, #602482), an autosomal dominant condition with ophthalmologic anterior segment abnormalities, high risk for glaucoma and extraocular findings including distinctive facial features, as well as dental, skeletal, audiologic, and cardiac anomalies. De Hauwere syndrome is an ultrarare condition previously associated with 6p microdeletions and characterized by anterior segment dysgenesis, joint instability, short stature, hydrocephalus, and skeletal abnormalities. Here, we report clinical findings of two unrelated adult females with FOXC1 haploinsufficiency who have ARS and skeletal abnormalities. Final molecular diagnoses of both patients were achieved using genome sequencing. Patient 1 had a complex rearrangement involving a 4.9 kB deletion including FOXC1 coding region (Hg19; chr6:1,609,721-1,614,709), as well as a 7 MB inversion (Hg19; chr6:1,614,710-8,676,899) and a second deletion of 7.1 kb (Hg19; chr6:8,676,900-8,684,071). Patient 2 had a heterozygous single nucleotide deletion, resulting in a frameshift and a premature stop codon in FOXC1 (NM_001453.3): c.467del, p.(Pro156Argfs*25). Both individuals had moderate short stature, skeletal abnormalities, anterior segment dysgenesis, glaucoma, joint laxity, pes planovalgus, dental anomalies, hydrocephalus, distinctive facial features, and normal intelligence. Skeletal surveys revealed dolichospondyly, epiphyseal hypoplasia of femoral and humeral heads, dolichocephaly with frontal bossin gand gracile long bones. We conclude that haploinsufficiency of FOXC1 causes ARS and a broad spectrum of symptoms with variable expressivity that at its most severe end also includes a phenotype overlapping with De Hauwere syndrome.

Predatory activity of the fungus Duddingtonia flagrans in equine strongyle infective larvae on natural pasture in the Southern Region of Brazil.

Biological control is an alternative method to reduce the population of parasites through natural predators. A promising option of biological control in the reduction of infective larvae on pasture is the use of nematophagous fungi. In this study, the efficacy of the nematophagous fungus Duddingtonia flagrans in controlling gastrointestinal nematode parasites in field-raised horses was tested. Ten foals with an average age of 12 months were divided in two groups: five males constituted the treated group and five females constituted the control group. Each group was introduced in a field of mixed pasture with approximately 5 ha. The treated group received the fungus D. flagrans at a concentration of 10(6) chlamydospores per kilogramme of animal body weight daily, mixed with horse food for 5 months. The control group did not receive the fungus. Samples were collected to perform eggs per gramme (EPG) counts weekly. Coproculture and collection of pasture were done monthly for larvae counting. No significant difference was observed in the EPG counting and in the number of larvae recovered from coprocultures, where cyathostomines, Strongylus and Trichostrongylus spp. were found after monthly larvae counting. No significant difference was observed in the EPG counts, and Trichostrongylus sp. was identified. The number of recovered larvae on pasture was significantly lower in the treated group in the last month of treatment, showing a reduction of 73.5% (p < 0.05). As such, the fungus was able to reduce the number of infective larvae in the pasture. Nevertheless, this did not reflect in a decrease of parasitic infection during the 5-month study period.

Machine Learning Quantification of Amyloid Deposits in Histological Images of Ligamentum Flavum.

Wild-type transthyretin amyloidosis (ATTRwt) is an underdiagnosed and potentially fatal disease. Interestingly, ATTRwt deposits have been found to deposit in the ligamentum flavum (LF) of patients with lumbar spinal stenosis before the development of systemic and cardiac amyloidosis. In order to study this phenomenon and its possible relationship with LF thickening and systemic amyloidosis, a precise method of quantifying amyloid deposits in histological slides of LF is critical. However, such a method is currently unavailable. Here, we present a machine learning quantification method with Trainable Weka Segmentation (TWS) to assess amyloid deposition in histological slides of LF. Images of ligamentum flavum specimens stained with Congo red are obtained from spinal stenosis patients undergoing laminectomies and confirmed to be positive for ATTRwt. Amyloid deposits in these specimens are classified and quantified by TWS through training the algorithm via user-directed annotations on images of LF. TWS can also be automated through exposure to a set of training images with user-directed annotations, and then applied] to a set of new images without additional annotations. Additional methods of color thresholding and manual segmentation are also used on these images for comparison to TWS. We develop the use of TWS in images of LF and demonstrate its potential for automated quantification. TWS is strongly correlated with manual segmentation in the training set of images with user-directed annotations (R = 0.98; p = 0.0033) as well as in the application set of images where TWS was automated (R = 0.94; p = 0.016). Color thresholding was weakly correlated with manual segmentation in the training set of images (R = 0.78; p = 0.12) and in the application set of images (R = 0.65; p = 0.23). TWS machine learning closely correlates with the gold-standard comparator of manual segmentation and outperforms the color thresholding method. This novel machine learning method to quantify amyloid deposition in histological slides of ligamentum flavum is a precise, objective, accessible, high throughput, and powerful tool that will hopefully pave the way towards future research and clinical applications.

The Relationship Between Wild-Type Transthyretin Amyloid Load and Ligamentum Flavum Thickness in Lumbar Stenosis Patients.

BACKGROUND: One key contributor to lumbar stenosis is thickening of the ligamentum flavum (LF), a process still poorly understood. Wild-type transthyretin amyloid (ATTRwt) has been found in the LF of patients undergoing decompression surgery, suggesting that amyloid may play a role. However, it is unclear whether within patients harboring ATTRwt, the amount of amyloid is associated with LF thickness. METHODS: From an initial cohort of 324 consecutive lumbar stenosis patients whose LF specimens from decompression surgery were sent for analysis (2018-2019), 33 patients met the following criteria: 1) Congo red-positive amyloid in the LF, 2) ATTRwt by mass spectrometry-based proteomics, and 3) an available preoperative magnetic resonance imaging. Histological specimens were digitized, and amyloid load was quantified through Trainable Weka Segmentation machine learning. LF thicknesses were manually measured on axial T2-weighted preoperative magnetic resonance imaging scans at each lumbar level, L1-S1. The sum of thicknesses at every lumbar LF level (L1-S1) equals "lumbar LF burden". RESULTS: Patients had a mean age of 72.7 years (range = 59-87), were mostly male (61%) and white (82%), and predominantly had surgery at L4-L5 levels (73%). Amyloid load was positively correlated with LF thickness (R = 0.345, P = 0.0492) at the levels of surgical decompression. Furthermore, amyloid load was positively correlated with lumbar LF burden (R = 0.383, P = 0.0279). CONCLUSIONS: Amyloid load is positively correlated with LF thickness and lumbar LF burden across all lumbar levels, in a dose-dependent manner. Further studies are needed to validate these findings, uncover the underlying pathophysiology, and pave the way toward using therapies that slow LF thickening.

When election expectations fail: Polarized perceptions of election legitimacy increase with accumulating evidence of election outcomes and with polarized media.

The present study, conducted immediately after the 2020 presidential election in the United States, examined whether Democrats' and Republicans' polarized assessments of election legitimacy increased over time. In a naturalistic survey experiment, people (N = 1,236) were randomly surveyed either during the week following Election Day, with votes cast but the outcome unknown, or during the following week, after President Joseph Biden was widely declared the winner. The design unconfounded the election outcome announcement from the vote itself, allowing more precise testing of predictions derived from cognitive dissonance theory. As predicted, perceived election legitimacy increased among Democrats, from the first to the second week following Election Day, as their expected Biden win was confirmed, whereas perceived election legitimacy decreased among Republicans as their expected President Trump win was disconfirmed. From the first to the second week following Election Day, Republicans reported stronger negative emotions and weaker positive emotions while Democrats reported stronger positive emotions and weaker negative emotions. The polarized perceptions of election legitimacy were correlated with the tendencies to trust and consume polarized media. Consumption of Fox News was associated with lowered perceptions of election legitimacy over time whereas consumption of other outlets was associated with higher perceptions of election legitimacy over time. Discussion centers on the role of the media in the experience of cognitive dissonance and the implications of polarized perceptions of election legitimacy for psychology, political science, and the future of democratic society.

The life and legacy of William Beecher Scoville.

Dr. William Beecher Scoville (1906-1984) is a giant figure in the history of neurosurgery, well known by the public for his operation on Patient H.M. He developed dozens of neurosurgical instruments and techniques, with many tools named after him that are still widely used today. He founded numerous neurosurgical societies around the world. He led the movement in psychosurgery, developing the technique of selective orbital undercutting and performing hundreds of lobotomies throughout his career. However, his many contributions to the advancement of neurosurgery have not been well described in the medical literature. To bridge the knowledge gap, this article seeks to detail the life and career of William Beecher Scoville and bring to attention the enduring impact of his work.

Multiple resistance in equine cyathostomins: a case study from military establishments in Rio Grande do Sul, Brazil.

Semi-intensive equine breeding system favors gastrointestinal nematode infections. The treatment of these infections is based on the use of anthelmintics. However, the inappropriate use of these drugs has led to parasitic resistance to the available active principles. The objective of this study was to evaluate the efficacy of the main classes of antiparasitic (ATP) used in control in adult and young animals, including: benzimidazoles (fenbendazole), pyrimidines (pyrantel pamoate), macrocyclic lactones (ivermectin and moxidectin), as well as the combination of active ingredients (ivermectin + pyrantel pamoate). The study was carried out in two military establishments, located in Rio Grande do Sul (RS), from January to December, 2018. The intervals between the treatments of the animals were performed from 30 to 90 days. Coproparasitological evaluations were determined by the egg count reduction in the faeces. Cyatostomine larvae were identified in pre and post-treatment cultures. The results demonstrated the multiple parasitic resistance of cyathostomins to fenbendazole, moxidectin in young animals, and to fenbendazole, pyrantel pamoate in adult animals. Thus, it is necessary to define or diagnose parasitic resistance to assist in the creation of prophylactic parasitic control, using suppressive treatment with ATP associated with integrated alternatives. The progress of parasitic resistance can be slowed.

Young Children With Gender Nonconforming Behaviors and Preferences.

BACKGROUND: There is growing awareness and exposure in both the medical community and the lay media about the characteristics and complex needs of individuals who believe that their gender identity does not match their birth sex. Despite research and lay publications about teens with gender dysphoria and those who identify as transgender, little guidance is available regarding young (prepubertal) children with questions about their gender identity. Although many terms are used to describe these children, we have chosen to describe them as "gender nonconforming" (GNC). OBJECTIVE: Primary care and developmental-behavioral pediatric providers are often the first professionals with whom young gender nonconforming children and their families discuss their concerns about their emerging gender identity. It is important, therefore, that pediatric providers be knowledgeable about the dilemmas, conflicts, and choices that are typical of these children and their families to guide them appropriately. OVERVIEW: In this special article, we present observations, informed by clinical experience, an emerging body of research, and a developmental-behavioral pediatric framework, of the complex needs of prepubertal gender nonconforming children and their families and an approach to their care. The article begins by outlining the cognitive and biological bases for gender identity development, as well as the natural history of gender nonconforming preferences and behaviors. It then sets the context for understanding the care of GNC children as an area in which developmentally sophisticated providers can play a crucial role in support of the complex developmental patterns and need for advocacy in multiple settings among these children.

Cytotoxic effect of hydroalcoholic extract of Annona Muricata against a human cell line of gastric adenocarcinoma / Efecto citotóxico del extracto hidroalcoholico de la Annona Muricata frente a la línea celular humana de adenocarcinoma gástrico

Background: Therapeutic advances against cancer have not been as successful as expected and have adverse effects that patients rarely tolerate. A study in Peru identified favorable anticancer effects of Annona muricata (AM), a medicinal plant known as soursop, in C-678 mouse gastric adenocarcinoma. However, to date, no results have been reported in human cells. Objective: The objective of this study was to determine the cytotoxic effect of AM extract against a human gastric adenocarcinoma cell line (AGS). Methodology: Experimental in vitro analytical study using a hydroalcoholic extract of AM (AMOH) leaves collected in the Amazonas. Chemical functional groups were identified by phytochemical screening. To obtain the cytotoxic effect, different dilutions of extract were added to the plates containing the cell lines and the data were extrapolated to GraphPad employing an observation card. Finally, the cytotoxic effect was expressed as the half-maximal inhibitory concentration (IC50) and nonlinear regression analysis was performed to determine the growth inhibition of cancer cells. Results: Phytochemical screening showed the presence of reducing carbohydrates, alkaloids, phenols, tannins, triterpenes, steroids, saponins, flavonoids, proteins, cardiac glycosides, and anthocyanins. A calibration curve with gallic acid was used to determine the total phenol content and, quercetin was used to identify the flavonoid content. The AGS cell line showed cytotoxic activity with AMOH with an IC50 at 24 hours of 45.81 µg/mL and 19.05 µg/mL at 48 hours. Conclusion: Several chemical functional groups of AM were identified. In addition, the AMOH showed a cytotoxic effect against the AGS cell line

Antecedente: Los avances terapéuticos frente al cáncer no han tenido el éxito esperado y presentan efectos adversos pocas veces tolerados por el paciente. Un estudio en Perú identificó el efecto anticancerígeno de la Annona muricata (AM), planta medicinal conocida como guanábana, en adenocarcinoma gástrico de ratón C-678 con resultados favorables, sin embargo, no se ha encontrado evidencia previa en células humanas. Objetivo: El objetivo de este estudio fue determinar el efecto citotóxico del extracto de AM frente a la línea celular de adenocarcinoma gástrico humano (AGS). Materiales y métodos: Estudio experimental in vitro tipo analítico con extracto hidroalcohólico de hojas de AM (AMOH) recolectadas en Amazonas. Mediante screening fitoquímico se identificaron los grupos funcionales químicos. Para obtener el efecto citotóxico, se añadieron diferentes diluciones de extracto a las placas que contienen las líneas celulares y mediante una ficha de observación los datos fueron extrapolados a GraphPad. Finalmente se expresó como la concentración inhibitoria media máxima (IC50) y se hizo un análisis de regresión no lineal con la finalidad de encontrar la cantidad de inhibición de crecimiento de células oncológicas. Resultados: En el screening fitoquímico se pudo identificar la presencia de carbohidratos reductores, alcaloides, fenoles, taninos, tritérpenos y esteroides, saponinas, flavonoides, proteínas, glicósidos cardiotónicos y antocianinas. Para identificar el contenido total de fenoles se utilizó la curva de calibración con ácido gálico el cual nos comprobó la presencia de una buena cantidad de estos metabolitos. Adicionalmente se utilizó quercetina para identificar el contenido de flavonoides, obteniendo resultados favorables ya que se hizo evidente su presencia. La línea celular AGS mostró una actividad citotóxica frente al AMOH con un IC50 a las 24 horas de 45.81ug/mL y 19.05ug/mL a las 48 horas. Conclusión: Se identifica a los grupos funcionales de la AM. Además, AMOH demostró un efecto citotóxico contra la línea celular AGS