Assessing mucosal recovery in celiac disease - Time to diagnosis and histological severity as determining factors.

BACKGROUND AND OBJECTIVES: there is a huge disparity in mucosal recovery among celiac patients on a gluten-free diet. We report a study to identify associated factors. METHODS: celiac cases were collected that had positive celiac serology and villous atrophy at diagnosis, and had undergone a control biopsy after at least 12 months of follow-up. RESULTS: seventy celiac patients were included and had experienced symptoms for 9.05 ± 9.48 years before being diagnosed. After follow-up for 2.93 ± 1.94 years, 34.3 % had complete mucosal recovery and 57.1 % had partial mucosal recovery. In the comparative analysis, there was no relationship between mucosal recovery and sex, age, clinical manifestations or follow-up time from diagnosis to the second biopsy. Time with clinical manifestations before diagnosis was associated with a worse outcome: 2.64 years in patients with full recovery, 4.61 years in patients with partial recovery, and 14.26 years in patients with persistent villous atrophy. Higher transglutaminase antibody titers both at diagnosis and during follow-up were associated with poorer histologic outcomes. We observed higher mucosal recovery rates in patients with mild atrophy versus severe atrophy at diagnosis. CONCLUSIONS: in spite of a gluten-free diet, a significant proportion of patients have persistent histologic changes. Time with clinical manifestations before diagnosis is key for histological severity and recovery.

Accuracy of ultrasound and visual inspection in antral follicular count in crossbred Holstein cows raised under grazing systems at high altitude.

The objective of this research was to investigate the diagnostic accuracy of post-mortem ultrasound in antral follicle count (AFC) determination and compare it with visual AFC in grazing crossbred Holstein cows, at high altitude in Ecuador. Pre-mortem blood from 80 cows was collected, and AFC and ovarian characteristics were analysed post-mortem by ultrasound and visual techniques. AFC counts were stratified as high, medium or low by terciles. Mean AMH concentration in pre-mortem blood was 280.1 ± 15.53 pg/mL. The AFC obtained by visual inspection (26.9 ± 9.49 follicles) was 23.8% higher than by ultrasound (20.5 ± 7.53 follicles) in all ovaries. Body condition score, age and weight of the cattle did not interact with the count technique. In the low AFC group, visual inspection and ultrasound provided similar AFC results. However, in the Medium- and High-AFC groups, AFC by ultrasound was 14.9% lower than AFC by visual inspection. We confirm that ultrasound can be used with great accuracy for AFC >3 mm (close to the resolution limit) in grazing crossbred Holstein cows at high altitude.

Health-related quality of life decline in clinically stable inflammatory bowel disease patients during the COVID-19 outbreak.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) affects many aspects of a patient's life and impairs their health-related quality of life (HRQoL). The COVID-19 outbreak has led to important mobility restrictions and a dramatic re-adjustment of social habits and health systems. This study aimed to assess the influence of the outbreak and mobility restrictions on the HRQoL of IBD patients with stable clinical remission on biologic treatment. Their self-perceived stress scores during the outbreak were also assessed. METHODS: A prospective, observational study was performed in IBD patients on biologic treatment with stable clinical remission. Patients with both Crohn's disease and Ulcerative Colitis patients were included. Patients filled in the IBDQ9 and the Perceived stress scale (PSS) electronically. To determine any changes, the results of the IBDQ9 during the outbreak were compared with the last IBDQ9 before the outbreak. RESULTS: 106 patients in clinical remission were included, with a median age of 42 year, 42% were female and 77% had CD. Median preCOVID-19 IBDQ9 was 72.1[66.5-80.12] and decreased to 69.2 [63.1-77.10] during the outbreak (p<0.001). The median PSS score was 12 [9-19]. There was a significant negative correlation between the PSS and the outbreak IBDQ9 (r=-0.66, p< 0.001). Regression analysis showed that the PSS score was associated with a lower IBDQ-9 during the outbreak(p<0.001) Conclusion: There was a negative impact of the COVID19 outbreak on the HRQoL of IBD patients in remission, with higher self-perceived stress scores associated with a lower QoL. The COVID-19 outbreak may have long-term implications for the HRQoL in these patients.

CADMA-Chem: A Computational Protocol Based on Chemical Properties Aimed to Design Multifunctional Antioxidants.

A computational protocol aimed to design new antioxidants with versatile behavior is presented. It is called Computer-Assisted Design of Multifunctional Antioxidants and is based on chemical properties (CADMA-Chem). The desired multi-functionality consists of in different methods of antioxidant protection combined with neuroprotection, although the protocol can also be used to pursue other health benefits. The dM38 melatonin derivative is used as a study case to illustrate the protocol in detail. This was found to be a highly promising candidate for the treatment of neurodegeneration, in particular Parkinson's and Alzheimer's diseases. This also has the desired properties of an oral-drug, which is significantly better than Trolox for scavenging free radicals, and has chelates redox metals, prevents the ●OH production, via Fenton-like reactions, repairs oxidative damage in biomolecules (lipids, proteins, and DNA), and acts as a polygenic neuroprotector by inhibiting catechol-O-methyl transferase (COMT), acetylcholinesterase (AChE) and monoamine oxidase B (MAOB). To the best of our best knowledge, CADMA-Chem is currently the only protocol that simultaneously involves the analyses of drug-like behavior, toxicity, manufacturability, versatile antioxidant protection, and receptor-ligand binding affinities. It is expected to provide a starting point that helps to accelerate the discovery of oral drugs with the potential to prevent, or slow down, multifactorial human health disorders.

Gastrointestinal lymphoma, a rare endoscopic lesion.

We present the case of a 77-year-old male patient with iron deficiency anemia. His personal medical history is: dyslipidemia, high-grade diffuse centrofollicular lymphoma localized in the tonsil in 1984 and metastatic prostate cancer treated with hormone therapy.

Impact of the COVID-19 pandemic on the activity of advanced-practice nurses on a reference unit for inflammatory bowel disease.

OBJECTIVE: To report the impact of the COVID-19 pandemic on the activity of nurses working on an inflammatory bowel disease (IBD) unit and to identify reasons for telehealth care and its relationship to certain characteristics. BACKGROUND: The COVID-19 pandemic had led to an increase in demand for remote care in patients with inflammatory bowel disease who require monitoring and frequent access to health services. DESIGN - METHODS: A retrospective study of all activity (in person and by phone call or email) done on the unit during the acute phase of the pandemic at a reference hospital in Spain. Numbers of activities done by nurses, reasons for telehealth care and sociodemographic and clinical data were collected. Statistical analysis was performed using frequency, chi-squared and analysis of variance tests. RESULTS: A total of 1095 activities for 561 patients who received care were reported. Among them, 1042 (95.2%) were telemedicine activities, amounting to a 47.3% increase over the prior year. COVID-19-related activities numbered 588 (59.5%). Consultations due to disease flare-up numbered 134 (13.7%), representing a 145% increase compared to 2019. Significant differences were found between reasons for using telemedicine and diagnosis, occupational status, contact week and treatment. CONCLUSION: The acute phase of the pandemic has changed the activity managed by the nursing staff on the unit. Identifying and analysing these changes has yielded valuable information to achieve more efficient management and better care quality for patients in special situations.

Improving safety in blood transfusion using failure mode and effect analysis.

BACKGROUND: One of the medical areas where errors can have more serious consequences is the process of blood transfusion. We used failure mode and effect analysis (FMEA) for evaluating potential failures and improving transfusion safety in a medium-size urban hospital with a highly complex transfusion service. STUDY DESIGN AND METHODS: Each failure mode was evaluated using the likelihood of occurrence, severity of the effect, and probability of detection. The obtained results allowed each failure to be prioritized and decisions to be made in an organized manner to determine solutions. We define measures and indicators that allow the comparison of their results in a longer time period than most of the previous studies. RESULTS: The most important failures were those regarding 1) transmitting information about the transfusion request, 2) patient identification, 3) sample identification, 4) cross-matching ordered tests, 5) transfusing blood components, 6) completing and sending the transfusion control document, and 7) reporting of transfusion reactions. The application of the FMEA methodology allowed implementation of safety measures and monitoring of the measures using indicators, including the mandatory records of the hemovigilance system. There was a 56% improvement in the risk prioritization numbers in the second stage of the FMEA. CONCLUSION: FMEA allows for identification of factors that reduce safety in this hospital, analysis of the causes and consequences of these errors, design of corrective measures, and establishment of indicators to monitor their application. The FMEA methodology can help other institutions to identify their own specific vulnerabilities.

Ischemic gastritis due to oral iron.

Polypharmacy is a frequent phenomenon. For that reason, drugs side effects are increasing, including lesions in the gastrointestinal (GI) tract. Multiple drugs can induce damage to the GI mucosa. NSAIDs are the most characteristic, however there are other drugs, that can cause a harmful effect in the digestive tract, such as iron. We present the case of a 91-year-old man with hematemesis due to iron intake.

Paradoxical anaerobism in desert pupfish.

In order to estimate metabolic demands of desert pupfish for conservation purposes, we measured oxygen consumption in fish acclimated to the ecologically relevant temperatures of 28 or 33°C. For these experiments, we used fish derived from a refuge population of Devils Hole pupfish (Cyprinodon diabolis). Measurement of routine oxygen consumption (V̇O2,routine) revealed some 33°C-acclimated fish (10% of 295 assayed fish) periodically exhibited periods of no measurable oxygen consumption despite available ambient oxygen tensions that were above the critical PO2. We call this phenomenon paradoxical anaerobism. The longest observed continuous bout with no oxygen consumption was 149 min, although typical bouts were much shorter. Fish maintained normal posture and ventilation rate (>230 ventilations per minute) during paradoxical anaerobism. Fish rarely demonstrated a compensatory increase in oxygen use following a period of paradoxical anaerobism. In contrast, only one out of 262 sampled fish acclimated at 28°C spontaneously demonstrated paradoxical anaerobism. Muscle lactate concentration was not elevated during periods of paradoxical anaerobism. However, the amount of ethanol released by the 33°C-acclimated fish was 7.3 times greater than that released by the 28°C acclimation group, suggesting ethanol may be used as an alternative end product of anaerobic metabolism. Exposure to exogenous ethanol, in concentrations as low as 0.1%, produced periods of paradoxical anaerobism even in 28°C-acclimated fish.

Differences in gluten metabolism among healthy volunteers, coeliac disease patients and first-degree relatives.

Coeliac disease (CD) is an immune-mediated enteropathy resulting from exposure to gluten in genetically predisposed individuals. Gluten proteins are partially digested by human proteases generating immunogenic peptides that cause inflammation in patients carrying HLA-DQ2 and DQ8 genes. Although intestinal dysbiosis has been associated with patients with CD, bacterial metabolism of gluten has not been studied in depth thus far. The aim of this study was to analyse the metabolic activity of intestinal bacteria associated with gluten intake in healthy individuals, CD patients and first-degree relatives of CD patients. Faecal samples belonging to twenty-two untreated CD patients, twenty treated CD patients, sixteen healthy volunteers on normal diet, eleven healthy volunteers on gluten-free diet (GFD), seventy-one relatives of CD patients on normal diet and sixty-nine relatives on GFD were tested for several proteolytic activities, cultivable bacteria involved in gluten metabolism, SCFA and the amount of gluten in faeces. We detected faecal peptidasic activity against the gluten-derived peptide 33-mer. CD patients showed differences in faecal glutenasic activity (FGA), faecal tryptic activity (FTA), SCFA and faecal gluten content with respect to healthy volunteers. Alterations in specific bacterial groups metabolising gluten such as Clostridium or Lactobacillus were reported in CD patients. Relatives showed similar parameters to CD patients (SCFA) and healthy volunteers (FTA and FGA). Our data support the fact that commensal microbial activity is an important factor in the metabolism of gluten proteins and that this activity is altered in CD patients.

Micro- and nanoparticle generation during nanosecond laser ablation: correlation between mass and optical emissions.

The particulate emission during nanosecond ablation of gold targets was investigated at various fluences (10-100 Jcm(-2)) and vacuum levels (0.05-750 Torr). Atomic emission spectra were acquired during the ablation process and post-mortem characterization of particle spatial distribution was performed using scanning electron microscopy. The discussion of the results in the context of existing theoretical models permitted the identification of four distinct mass removal mechanisms. While the presence, shape and intensity of atomic emission lines is a telltale of the nanoparticle formation process, the fluctuations of the emission signal over a number of laser shots was linked to the production of microscopic debris.

Particle formation and plasma radiative losses during laser ablation suitability of the Sedov-Taylor scaling.

Deviations of the Sedov-Taylor scaling at three different laser ablation regimes (500 mJ in a 0.8 mm spot, 50 mJ in a 0.8 mm spot and 500 mJ in a 2.5 mm spot) were investigated using Schlieren photography in combination with optical scattering and optical emission spectrometry, among others. For each case, the time evolution of the shock front was related to the formation, expansion and properties of the plasma. Both, the time scale of the different radiative processes and that observed for vapor condensation into nanoparticles and sub-micron particles are compatible with the divergences found between the model and experimental data.

A multivariable analysis of patient dental satisfaction and oral health-related quality-of-life. A cross-sectional study based on DVSS and OHIP-14.

OBJECTIVE: The aim of this paper was to study the association between dental satisfaction and oral health-related quality-of-life (OHRQoL) when controlling for individual, clinical and psychological factors. MATERIALS: Secondary analysis was conducted using data from a large study carried out in the Swedish region of Värmland in 2004. The questionnaire included demographic variables, clinical assessment and the following instruments: the Dental Visit Satisfaction Scale (DVSS), the short version of Oral Health Impact Profile (OHIP-14) and a modified version of the revised helping alliance questionnaire. Internal consistency analysis was undertaken on the instruments to assess reliability; bivariate comparisons were assessed to compare DVSS scores with individual factors (age, gender and education). In addition, a three step hierarchical multiple regression analysis was performed with DVSS as a dependent variable. RESULTS: Data were completed for 485 randomly selected patients. The mean age of participants was 43.5 years, 54.6% were women,and 41.2% had high education. The median DVSS score was 48 (range 10-50) and the median OHIP was 3.0 (range 0-56). All the instruments showed good reliability. Bivariate analysis showed that females were more satisfied than males (p ≤ 0.01) and patients of 50 years or older were more satisfied than the younger ones (p ≤ 0.05). Finally, the following variables explained 31% of the variance of being very satisfied with dental visit: a good OHRQoL and patients' positive perceptions of the relationship with their care provider. CONCLUSION: This study showed positive associations between dental satisfaction and OHRQoL when controlling for related factors. The result suggests that care providers should take into account the various dimensions of OHRQoL rather than use only clinical measurements when they evaluate patient satisfaction.

Implementing integrated hypertension and diabetes management using the World Health Organization's HEARTS model: protocol for a pilot study in the Guatemalan national primary care system.

BACKGROUND: The HEARTS technical package was developed by the World Health Organization to address the implementation gap in cardiovascular disease prevention in low- and middle-income countries. Guatemala is a middle-income country that is currently implementing HEARTS. National authorities in Guatemala are interested in exploring how hypertension and diabetes management can be integrated in HEARTS implementation. The objective of this study is to conduct a feasibility and acceptability pilot trial of integrated hypertension and diabetes management based on HEARTS in the publicly funded primary care system in Guatemala. METHODS: A single-arm pilot trial for 6 months will be carried out in 11 Ministry of Health primary care facilities starting in September 2023. A planned sample of 100 adult patients diagnosed with diabetes (n = 45), hypertension (n = 45), or both (n = 10) will be enrolled. The intervention will consist of HEARTS-aligned components: Training health workers on healthy-lifestyle counseling and evidence-based treatment protocols, strengthening access to medications and diagnostics, training on risk-based cardiovascular disease management, team-based care and task sharing, and systems monitoring and feedback, including implementation of a facility-based electronic monitoring tool at the individual level. Co-primary outcomes of feasibility and acceptability will be assessed using an explanatory sequential mixed-methods design. Secondary outcomes include clinical effectiveness (treatment with medication, glycemic control, and blood pressure control), key implementation outcomes (adoption, fidelity, usability, and sustainability), and patient-reported outcome measures (diabetes distress, disability, and treatment burden). Using an implementation mapping approach, a Technical Advisory Committee will develop implementation strategies for subsequent scale-up planning. DISCUSSION: This trial will produce evidence on implementing HEARTS-aligned hypertension and diabetes care in the MOH primary care system in Guatemala. Results also will inform future HEARTS projects in Guatemala and other low- and middle-income countries. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT06080451. The trial was prospectively registered on October 12, 2023.

Combined precut in difficult biliary cannulation.

AIM: precut sphincterotomy refers to a variety of endoscopic techniques that are used in order to access the bile duct when conventional methods of cannulation have failed. There are not significant data (such as efficacy, safety) about the use of different techniques of precutting at the same session. We have described our experience with combined precut sphincterotomy (CPS) and we have compared our results to the use of an isolated precut. PATIENTS AND METHODS: we have performed 247 precuts of a total of 2.390 ERCPs. Patients were distributed according to the type of precut practiced: Needle-knife, transpancreatic and combined precut sphincterotomies. "Combined precut" consisted in performing first a transpancreatic sphincterotomy and, if the access was not achieved, then performing a needle-knife sphincterotomy in the same session. The data about safety and efficacy were prospectively collected. The complications were defined according to the consensus criteria. RESULTS: we performed precutting techniques in 247 patients. Needle-knife, transpancreatic, and combined precuts were performed in 125 (6.9%), 74 (4.1%) and 48 (2.6%) patients, respectively. Bile duct cannulation was successful in 48 patients (100%) in the group of combined precut, 121 patients (96.8%) in the transpancreatic group, and 67 patients (90.5%) in the needleknife group (p = 0.03). There were not differences in complications rates between the three groups. There was no pancreatitis in the combined precut group. The complications were successfully managed with conservative treatment. CONCLUSIONS: combined precut sphincterotomy seems to be a safe and successful technique in those cases of difficult bile duct cannulation.

Unrestricted component count in multiphase lattice Boltzmann: A fugacity-based approach.

Studies of multiphase fluids utilizing the lattice Boltzmann method (LBM) are typically severely restricted by the number of components or chemical species being modeled. This restriction is particularly pronounced for multiphase systems exhibiting partial miscibility and significant interfacial mass exchange, which is a common occurrence in realistic multiphase systems. Modeling such systems becomes increasingly complex as the number of chemical species increases due to the increased role of molecular interactions and the types of thermodynamic behavior that become possible. The recently introduced fugacity-based LBM [Soomro et al., Phys. Rev. E 107, 015304 (2023)2470-004510.1103/PhysRevE.107.015304] has provided a thermodynamically consistent modeling platform for multicomponent, partially miscible LBM simulations. However, until now, this fugacity-based LB model had lacked a comprehensive demonstration of its ability to accurately reproduce thermodynamic behavior beyond binary mixtures and to remove any restrictions in a number of components for multiphase LBM. In this paper we closely explore these fugacity-based LBM capabilities by showcasing comprehensive, thermodynamically consistent simulations of multiphase mixtures of up to ten chemical components. The paper begins by validating the model against the Young-Laplace equation for a droplet composed of three components. The model is then applied to study mixtures with a range of component numbers from one to six, showing agreement with rigorous thermodynamic predictions and demonstrating linear scaling of computational time with the number of components. We further investigate ternary systems in detail by exploring a wide range of temperature, pressure, and overall composition conditions to produce various characteristic ternary diagrams. In addition, the model is shown to be unrestricted in the number of phases as demonstrated through simulations of a three-component three-phase equilibrium case. The paper concludes by demonstrating simulations of a ten-component, realistic hydrocarbon mixture, achieving excellent agreement with thermodynamics for both flat interface vapor-liquid equilibrium and curved interface spinodal decomposition cases. This study represents a significant expansion of the scope and capabilities of multiphase LBM simulations that encompass multiphase systems of keen interest in engineering.

Fugacity-based lattice Boltzmann method for multicomponent multiphase systems.

The free-energy model can extend the lattice Boltzmann method to multiphase systems. However, there is a lack of models capable of simulating multicomponent multiphase fluids with partial miscibility. In addition, existing models cannot be generalized to honor thermodynamic information provided by any multicomponent equation of state of choice. In this paper, we introduce a free-energy lattice Boltzmann model where the forcing term is determined by the fugacity of the species, the thermodynamic property that connects species partial pressure to chemical potential calculations. By doing so, we are able to carry out multicomponent multiphase simulations of partially miscible fluids and generalize the methodology for use with any multicomponent equation of state of interest. We test this fugacity-based lattice Boltzmann method for the cases of vapor-liquid equilibrium for two- and three-component mixtures in various temperature and pressure conditions. We demonstrate that the model is able to reliably reproduce phase densities and compositions as predicted by multicomponent thermodynamics and can reproduce different characteristic pressure-composition and temperature-composition envelopes with a high degree of accuracy. We also demonstrate that the model can offer accurate predictions under dynamic conditions.

[Relationship of demographic and dietary hygiene factors with the pathology found in outpatient colonoscopies performed in a Castilla y León Health Service center]. / Relación de los factores demográficos e higiénico-dietéticos con la patología hallada en las colonoscopias ambulatorias realizadas en un centro del Servicio Castellano y Leonés de Salud.

Introduction: Background: colorectal cancer (CRC) is one of the most frequent tumors in terms of incidence and mortality. Several elements, both inherited and environmental, have been related with its pathogenesis. Aims: to analyze the influence of age, gender and nutritional factors on the diagnosis of colonic polyps and CRC. Methods: a prospective, descriptive study over outpatients from the Health Area of León who took a colonoscopy between 09/09/2012 and 06/30/2013. Patients were asked to fill a semiquantitative food frecuency questionnaire with data such a sociodemographic, toxic and dietetic facts. Differences in diagnosis according to sociodemographic and hygiene-dietetic data were analyzed with a multivariate analysis by forward stepwise logistic regression. Results: data were collected from 1390 patients. Mean age was 57.88 (15.17) years and 47.8 % were male. CRC was diagnosed in 5 % of colonoscopies, and polyps in 20.4 %, with 9.4 % of them being HRA. Risk of polyps and HRA was higher in males (26.9 % vs 14.5 %) and (12.6 % vs 6.3 %), respectively (p < 0.001). Mean age was significantly higher in patients who presented polyps (56.51 (15.45) vs 63.22 (12.69) years; p < 0.001). Among the group who reported intake of smoked and salted food, the risk of polyps doubled (2.9 % vs 6.7 %, p = 0.002). In relation to alcohol intake we found that subjects with daily alcohol consumption showed a higher incidence of polyps whe compared to occasional drinkers and teetotallers (32 % vs 20 % vs 18.6 %, p = 0.002) Conclusions: age correlated with higher risk of polyps, HRA and CRC. Moreover, male gender also was associated with a high risk of polyps and HRA. Alcohol and red and processed meat intake increased polyp risk.

Introducción: Introducción: el cáncer colorrectal (CCR) es un tumor muy frecuente en términos de incidencia y mortalidad. Su patogenia se ha relacionado con diversos factores ambientales y hereditarios. Objetivos: analizar la asociación de edad, sexo y factores dietéticos con el diagnóstico de adenomas y CCR. Métodos: se realizó un estudio descriptivo prospectivo con los pacientes del Área Sanitaria de León que se sometieron a una colonoscopia ambulatoria entre 09/09/2012 y 30/06/2013. Mediante un formulario autoadministrado se recogieron datos sociodemográficos, tóxicos y dietéticos usando un cuestionario alimentario de frecuencia semicuantitativo. Se analizaron las diferencias en el diagnóstico según los datos sociodemográficos e higiénico-dietéticos, con análisis multivariante mediante regresión logística por pasos hacia delante. Resultados: se recogieron datos de 1390 pacientes cuya edad media fue de 57 (15) años; de ellos, el 47,8 % eran varones. Se diagnosticaron CCR en el 5 % de los pacientes y pólipos en el 20,4 % (9,4 % de adenomas de alto riesgo (AAR)). El hallazgo de pólipos y AAR fue más frecuente en los varones (26,9 % vs. 14,5 % y 12,6 % vs. 6,3 %, respectivamente (p < 0,001)). La edad media fue significativamente superior en los pacientes que presentaban pólipos (56.51 (15.45) vs. 63.22 (12.69) años; p < 0,001). En la población que refirió un consumo diario de carnes procesadas se duplicaba la proporción de pólipos detectados (2,9 % vs. 6,7 %; p = 0,02). Aquellos pacientes que consumían alcohol diariamente tenían mayor incidencia de pólipos frente al consumo ocasional y los abstemios (32 % vs. 20 % vs. 18,6 %; p = 0,002). Conclusiones: la edad se relacionaba con un mayor riesgo de pólipos, AAR y CCR. Los varones también tenían más riesgo de pólipos y AAR. El consumo de alcohol, carnes rojas y procesadas incrementaba el riesgo de pólipos.

Rational Design of Multifunctional Ferulic Acid Derivatives Aimed for Alzheimer's and Parkinson's Diseases.

Ferulic acid has numerous beneficial effects on human health, which are frequently attributed to its antioxidant behavior. In this report, many of them are reviewed, and 185 new ferulic acid derivatives are computationally designed using the CADMA-Chem protocol. Consequently, their chemical space was sampled and evaluated. To that purpose, selection and elimination scores were used, which are built from a set of descriptors accounting for ADME properties, toxicity, and synthetic accessibility. After the first screening, 12 derivatives were selected and further investigated. Their potential role as antioxidants was predicted from reactivity indexes directly related to the formal hydrogen atom transfer and the single electron transfer mechanisms. The best performing molecules were identified by comparisons with the parent molecule and two references: Trolox and α-tocopherol. Their potential as polygenic neuroprotectors was investigated through the interactions with enzymes directly related to the etiologies of Parkinson's and Alzheimer's diseases. These enzymes are acetylcholinesterase, catechol-O-methyltransferase, and monoamine oxidase B. Based on the obtained results, the most promising candidates (FA-26, FA-118, and FA-138) are proposed as multifunctional antioxidants with potential neuroprotective effects. The findings derived from this investigation are encouraging and might promote further investigations on these molecules.