[Anaphylaxis due to legumes: case report]. / Anafilaxia por leguminosas: reporte de un caso.

BACKGROUND: Legumes belonging to the family Fabaceae of the order Fabales are a widely consumed source of protein. IgE-mediated hypersensitivity reactions to legumes have been described, the most studied allergens being peanuts and soybeans. In the Mediterranean region and India, lentils, chickpeas and peas have been considered important allergens and legumes have been reported to represent the fifth most common cause of food allergy in children under 5 years of age in Spain. In Latin America, there are few reports of allergy to legumes other than peanuts, and these are especially in the paediatric population. OBJECTIVE: To describe a case of IgE-mediated legume allergy in an adult female patient. CASE REPORT: We describe the case of a 65-year-old female patient who reports a 20-year history of generalized urticaria, accompanied by angioedema and dyspnea occurring immediately after consumption of lentils, beans, chickpeas, soya beans and cold meats, requiring admission to the emergency department for this cause. Tolerates peanuts. She does not report anaphylaxis in any context other than those described. He has presented generalized pruritus with exposure to fumes from cooking beans. Pathological history: Hypertension, type II diabetes mellitus, hypothyroidism. Allergic: Anaphylaxis due to penicillin at the age of 30. Other history: extensive local reaction to hymenoptera sting. Prick test trophoallergens: soya 3 mm. Prick to prick protein based on commercial soybean 7mm, chickpea 5mm, lentil 6mm and bean 7mm. He was negative for wheat and peanut (Image 1) (Attached in separate file). It has a normal tryptase report. Indication was given for adequate adrenaline and strict avoidance of legumes, except peanuts. CONCLUSIONS: Legume allergy is little known in our environment and mainly affects children. Clinical manifestations include mild reactions and anaphylaxis. A high degree of cross-reactivity among legumes has been reported. Lentils have cross-reactivity with chickpeas and beans. Peanut allergy may also be associated with allergy to lentils, chickpeas, and peas, but is less frequently reported.

ANTECEDENTES: Las leguminosas pertenecientes a la familia Fabaceae del orden Fabales, son una fuente de proteína de amplio consumo. Se han descrito reacciones de hipersensibilidad mediadas por IgE a las leguminosas, siendo los alérgenos más estudiados el maní y la soya. En la región mediterránea y en India, las lentejas, garbanzos y arvejas se han considerado alérgenos importantes, y se ha informado que las leguminosas representan la quinta causa más común de alergia alimentaria en niños menores de cinco años en España. En América Latina, hay pocos reportes de alergia a las leguminosas diferentes al maní, y éstos son, especialmente, en población pediátrica. OBJETIVO: Describir el caso de alergia mediada por IgE a leguminosas, en una paciente adulta. REPORTE DE CASO: Se describe el caso de una paciente de 65 años, quien reporta un cuadro de 20 años con evolución consistente de urticaria generalizada, acompañada de angioedema y disnea, que ocurre, en forma inmediata, tras el consumo lentejas, fríjoles, garbanzos, soya y carnes frías; y requiere de ingresos al servicio de urgencias por esta causa. Tolera maní. No se reporta anafilaxia en otro contexto diferente a los descritos. Ha presentado prurito generalizado con la exposición a vapores de la cocción de fríjoles. Antecedentes patológicos: hipertensión arterial, diabetes mellitus tipo II, hipotiroidismo. Alérgicos: Anafilaxia por Penicilina a los 30 años. Otros antecedentes: Reacción local extensa con picadura de himenópteros. Prick test trofoalérgenos: soya 3 mm. Prick to prick proteína a base de soya comercial 7mm, garbanzo 5mm, lenteja 6mm y fríjol 7mm. Fue negativa para trigo y maní (Imagen 1). (Adjunta en archivo separado). Tiene reporte de triptasa normal. Se dio indicación de porte adecuado de adrenalina y evitación estricta de leguminosas, excepto maní. CONCLUSIONES: La alergia a las leguminosas es poco conocida en nuestro medio, y afecta principalmente a los niños. Sus manifestaciones clínicas incluyen reacciones leves y anafilaxia. Se ha informado, un alto grado de reactividad cruzada entre las leguminosas. Las lentejas tienen reactividad cruzada con garbanzos y fríjoles. La alergia al maní también puede estar asociada con la alergia a lentejas, garbanzos y guisantes, pero se informa con menos frecuencia.

Machine Learning-Driven Classification of Urease Inhibitors Leveraging Physicochemical Properties as Effective Filter Criteria.

Urease, a pivotal enzyme in nitrogen metabolism, plays a crucial role in various microorganisms, including the pathogenic Helicobacter pylori. Inhibiting urease activity offers a promising approach to combating infections and associated ailments, such as chronic kidney diseases and gastric cancer. However, identifying potent urease inhibitors remains challenging due to resistance issues that hinder traditional approaches. Recently, machine learning (ML)-based models have demonstrated the ability to predict the bioactivity of molecules rapidly and effectively. In this study, we present ML models designed to predict urease inhibitors by leveraging essential physicochemical properties. The methodological approach involved constructing a dataset of urease inhibitors through an extensive literature search. Subsequently, these inhibitors were characterized based on physicochemical properties calculations. An exploratory data analysis was then conducted to identify and analyze critical features. Ultimately, 252 classification models were trained, utilizing a combination of seven ML algorithms, three attribute selection methods, and six different strategies for categorizing inhibitory activity. The investigation unveiled discernible trends distinguishing urease inhibitors from non-inhibitors. This differentiation enabled the identification of essential features that are crucial for precise classification. Through a comprehensive comparison of ML algorithms, tree-based methods like random forest, decision tree, and XGBoost exhibited superior performance. Additionally, incorporating the "chemical family type" attribute significantly enhanced model accuracy. Strategies involving a gray-zone categorization demonstrated marked improvements in predictive precision. This research underscores the transformative potential of ML in predicting urease inhibitors. The meticulous methodology outlined herein offers actionable insights for developing robust predictive models within biochemical systems.

Unveiling Novel Urease Inhibitors for Helicobacter pylori: A Multi-Methodological Approach from Virtual Screening and ADME to Molecular Dynamics Simulations.

Helicobacter pylori (Hp) infections pose a global health challenge demanding innovative therapeutic strategies by which to eradicate them. Urease, a key Hp virulence factor hydrolyzes urea, facilitating bacterial survival in the acidic gastric environment. In this study, a multi-methodological approach combining pharmacophore- and structure-based virtual screening, molecular dynamics simulations, and MM-GBSA calculations was employed to identify novel inhibitors for Hp urease (HpU). A refined dataset of 8,271,505 small molecules from the ZINC15 database underwent pharmacokinetic and physicochemical filtering, resulting in 16% of compounds for pharmacophore-based virtual screening. Molecular docking simulations were performed in successive stages, utilizing HTVS, SP, and XP algorithms. Subsequent energetic re-scoring with MM-GBSA identified promising candidates interacting with distinct urease variants. Lys219, a residue critical for urea catalysis at the urease binding site, can manifest in two forms, neutral (LYN) or carbamylated (KCX). Notably, the evaluated molecules demonstrated different interaction and energetic patterns in both protein variants. Further evaluation through ADMET predictions highlighted compounds with favorable pharmacological profiles, leading to the identification of 15 candidates. Molecular dynamics simulations revealed comparable structural stability to the control DJM, with candidates 5, 8 and 12 (CA5, CA8, and CA12, respectively) exhibiting the lowest binding free energies. These inhibitors suggest a chelating capacity that is crucial for urease inhibition. The analysis underscores the potential of CA5, CA8, and CA12 as novel HpU inhibitors. Finally, we compare our candidates with the chemical space of urease inhibitors finding physicochemical similarities with potent agents such as thiourea.

[Characterization of patients with anaphylaxis in a tertiary hospital in Medellin, Colombia (2009-2019)]. / Identificación de pacientes con anafilaxia en una institución de salud de tercer nivel de Medellín, Colombia (2009-2019).

OBJECTIVE: To characterize demographically and clinically the patients with anaphylaxis treated in a third level health institution in Medellin, Colombia. METHODS: A cross-sectional descriptive observational study was carried out, which includedpatients were diagnosed with anaphylaxis between 2009 and 2019. Information was retrieved from medical records through a collection instrument. Subsequently, a descriptive statistical analysis of proportions and measures of central tendency of the variables of interest was performed. RESULTS: A total of 1820 records were reviewed and data from 253 patients were included. Among the reported comorbidities, drug allergy was the most prevalent (28%). The most frequent manifestations of anaphylaxis were cutaneous and respiratory. Most of the cases presented basal tryptase values ≤ 11.4 ng/mL (94.7%). Different etiological agents (food, drugs, insects and latex) were reported, and their frequency varied according to age. Adrenaline, steroids, and antihistamines were the treatments of choice in 39.9, 34.3, and 39.9% of cases, respectively. CONCLUSIONS: The characteristics of anaphylaxis in a medical center in Colombia coincide with those reported in Latin American. The treatment of anaphylaxis is not standardized, which makes it necessary to educate the health personnel and develop national guidelines.

OBJECTIVO: Identificar las características clínicas y demográficas de pacientes con anafilaxia, atendidos en un hospital de tercer nivel de Medellín, Colombia. MÉTODOS: Estudio observacional, descriptivo, de corte transversal, al que se incluyeron pacientes con diagnóstico con anafilaxia entre 2009 y 2019. La información de los pacientes se obtuvo a partir de los expedientes clínicos, mediante un instrumento de recolección. Se realizó un análisis estadístico descriptivo, de proporciones y medidas de tendencia central de las variables de interés. RESULTADOS: Se revisaron 1820 expedientes y se incluyeron los datos de 253 pacientes. Los agentes etiológicos más frecuentes fueron: medicamentos (52.1%), alimentos (34.7%), picadura de insectos (13.8%) y agentes no especificados (17.7%). Las manifestaciones cutáneas y respiratorias fueron las más frecuentes asociadas con anafilaxia. El 94.7% de los casos tuvo concentraciones normales de triptasa. La adrenalina, los corticosteroides y antihistamínicos fueron los fármacos de elección en el 39.9, 34.3 y 39.9% de los casos, respectivamente. CONCLUSIONES: Las características de anafilaxia coinciden con las reportadas en la mayor parte de los estudios en Latinoamérica. Aunque existen guías mundiales de tratamiento de la anafilaxia, no suelen aplicarse de forma uniforme, lo que hace necesario adiestrar al personal de salud y desarrollar guías nacionales al respecto.

Counteracting the Toxic Hidroarsenicism Effects upon Reproductive-Physiological Outcomes in Male Goats: The Selenium and Vitamin-E Mitigation Approach.

This study was to evaluate whether selenium and vitamin-E counteract the toxic effects of arsenic on reproductive aspects and physiological conditions of male goats. Male goats [Criollo, n = 20, 4-5 yr-old, 72 kg live weight (LW)] were distributed in homogeneous groups (n = 5), and received during 12 weeks: (1) Sodium arsenite 2 mg/kg of LW/day (AG, LW = 69 kg); (2) Sodium selenite 6 mg + vitamin-E 420 I.U. every 14 days during the 12 weeks (SG, LW = 68 kg); (3) Both AG and SG treatments (ASG, LW = 77 kg); and (4) 1 mL of physiological solution every 14 days during the 12 weeks (CG, LW = 72 kg). The animals had access to water from a well with a concentration of 35 µg/L of arsenic. The SG had the highest percentage of sperm viability (80.6%) followed by the CG, ASG (74.7; p > 0.05), and AG (64.3; p ≤ 0.05). The ASG and SG had a lower heart rate as compared to the CG and AG (58.8, 58 vs. 65.4, 63.5; respectively, p ≤ 0.05). The CG and SG showed a lower respiratory rate than the AG and ASG (19.2, 18.7 vs. 22.1, 21.0, respectively; p ≤ 0.05). Selenium and vitamin-E were efficient in reducing the damage caused by sodium arsenite in sperm quality and maintaining heart and respiratory rates and increases in odor in male goats.

Comparative Biomonitoring of Arsenic Exposure in Mothers and Their Neonates in Comarca Lagunera, Mexico.

Multiple comorbidities related to arsenic exposure through drinking water continue to be public problems worldwide, principally in chronically exposed populations, such as those in the Comarca Lagunera (CL), Mexico. In addition, this relationship could be exacerbated by an early life exposure through the placenta and later through breast milk. This study conducted a comparative analysis of arsenic levels in multiple biological samples from pregnant women and their neonates in the CL and the comparison region, Saltillo. Total arsenic levels in placenta, breast milk, blood, and urine were measured in pregnant women and their neonates from rural areas of seven municipalities of the CL using atomic absorption spectrophotometry with hydride generation methodology. The average concentrations of tAs in drinking water were 47.7 µg/L and 0.05 µg/L in the exposed and non-exposed areas, respectively. Mean levels of tAs were 7.80 µg/kg, 77.04 µg/g-Cr, and 4.30 µg/L in placenta, blood, urine, and breast milk, respectively, in mothers, and 107.92 µg/g-Cr in neonates in the exposed group, which were significantly higher than those in the non-exposed area. High levels of urinary arsenic in neonates were maintained 4 days after birth, demonstrating an early arsenic exposure route through the placenta and breast milk. In addition, our study suggested that breastfeeding may reduce arsenic exposure in infants in arsenic-contaminated areas. Further studies are necessary to follow up on comorbidities later in life in neonates and to provide interventions in this region.

Reacciones adversas asociadas a vacunas contra la COVID-19 / Adverse reactions associated with vaccines against COVID-19

Resumen Con el advenimiento de la pandemia por COVID-19 se generó la necesidad de diseñar estrategias que ayudaran a mitigar la morbimortalidad causada por el virus y una de las más prometedoras es la vacunación masiva. Sin embargo, la vacunación puede asociarse a reacciones adversas, entre ellas, reacciones de hipersensibilidad a los componentes de las diferentes vacunas, por lo que es fundamental conocer dichos componentes y la población que requiere una valoración previa por Alergología. Todo paciente que lo requiera se debe remitir oportunamente con el fin de reconocer el componente implicado en la reacción por medio de pruebas adecuadas y ofrecer una conducta que permita continuar un esquema de vacunación que sea seguro. Este artículo busca recopilar los datos de reacciones adversas, con énfasis en reacciones de hipersensibilidad, que se han presentado en ensayos clínicos con la aplicación de las vacunas contra el SARS-CoV-2 para ser aplicadas en Colombia. Adicionalmente, se realiza una propuesta de abordaje de los pacientes con antecedentes de reacciones de hipersensibilidad con respecto a la conducta que se debe tomar para su vacunación.

Abstract With the occurrence of the COVID-19 pandemic, the need to design strategies to help mitigate the morbimortality caused by the virus arose and one of the most promising is mass vaccination. However, vaccination may be associated with adverse reactions, including hypersensitivity reactions to the components of the different vaccines, so it is essential to know these components and the population that requires prior assessment by Allergology. Any patient who requires it should be referred in a timely manner, in order to recognize the component involved in the reaction by means of appropriate tests and to offer a course of action that allows continuing a safe vaccination schedule. This article seeks to compile data on adverse reactions, with emphasis on hypersensitivity reactions, which have occurred in clinical trials with the application of vaccines against SARS-CoV-2 to be applied in Colombia. Additionally, a proposal is made to approach patients with a history of hypersensitivity reactions with respect to the conduct that should be taken for their vaccination.

Pulmonary nodule in pediatrics: Beyond the infection. / Nódulo pulmonar en pediatría: Más allá de la infección.

INTRODUCTION: The study of a pulmonary nodule in pediatrics is a diagnostic challenge where multiple pathologies must be taken into account, especially infections. In developing countries, where tuberculosis infec tion is endemic, it is one of the most likely diagnoses; however, the diagnostic possibility of malig nancy should never be overlooked. OBJECTIVE: To describe a case report of a patient with a pulmonary nodule, that after ruling out the most frequent causes, a primary malignant tumor was diagnosed. CLINICAL CASE: 17-year-old female patient with a one-month history of cough, dyspnea, and hemop tysis, without other symptoms. Since she did not respond to conventional antibiotic management, a chest CT scan with contrast was performed which showed a pulmonary nodule with irregular con tours, and with the bronchoalveolar lavage pulmonary infections were ruled out (pulmonary tuber culosis, fungal infection, and others bacteria). Biopsy of the lesion was performed to complete the study which histopathology was compatible with a mucoepidermoid carcinoma (MEC). The patient underwent right low lobectomy and lymph node resection with good clinical response during three years of follow-up. CONCLUSION: Pulmonary nodule in pediatrics is a finding usually associated with infection, nevertheless, neoplastic conditions have to be considered, not only metastasis but also pri mary pulmonary malignant lesions due to prognosis implications.

Metabolomics analysis of bronchoalveolar lavage fluid samples in horses with naturally-occurring asthma and experimentally-induced airway inflammation.

The present work characterized the metabolomic profile of bronchoalveolar lavage fluid (BALF) in healthy horses, experimentally-induced airway inflammation by lipopolysaccharide (LPS) nebulization, and naturally-occurring asthma (n = 3 in each group). All animals underwent clinical and upper airway endoscopic examinations, and bronchoalveolar lavage. BALF supernatant samples were subjected to metabolic analysis based on gas chromatography-mass spectrometry (GC-MS). Overall, 67 peaks were obtained from BALF GC-MS analysis, corresponding to 53 metabolites which were categorized according to chemical class, such as organic acids, fatty acids, nucleosides or their derivatives, amino acids, peptides or their derivatives, carbohydrates, and other compounds. Our results showed that the airway inflammation induction model with LPS produced the same pattern of metabolite changes as in horses with naturally occurring asthma. Metabolic pathway analysis was done by means of Fisher's exact test, for detection of metabolites over-represented in asthma affected-horses and LPS-induced airway inflammation as compared with healthy horses. The most significant altered metabolic pathways were fatty acid biosynthesis, galactose metabolism and citrate cycle. These results suggest that the airway inflammation induction model with LPS is a good study model for asthma-affected horses, due to the similarity of the profile of inflammatory cells (specifically neutrophils) and similar metabolic alterations found in BALF that occur during the inflammatory process of the airways. Further research may increase understanding of metabolomics disturbances and their significance in the pathogenesis of equine asthma.

Changes in the vaginal microbiota across a gradient of urbanization.

The vaginal microbiota of healthy women typically has low diversity, which increases after perturbations. Among these, lifestyle associated with certain sexual and antimicrobial practices may be associated with higher diversity. To test this hypothesis, we characterized the vaginal microbiota in the cervicovaginal and introital sites in sexually active Amerindians (N = 82) spanning urbanization, and in urban mestizos (N = 29), in the Venezuelan Amazonas. HPV status was also considered. Sampling was performed in an urban gradient from remote villages to a town, and women were individually classified by the degree of urbanization (low, medium, and high). Amerindian cervicovaginal and introital microbiota diversity were not associated with major changes in urbanization or ethnicity. There was a non-significant trend of increased diversity with urbanization, with a few taxa found overrepresented in urban Amerindians (Brevibacterium linens and Peptoniphilus lacrimalis) or mestizos (Mobiluncus mulieris and Prevotella sp.). Among all women, cervicovaginal and introital samples clustered, respectively, in four and two community state types (CSTs), where most profiles were dominated by Lactobacillus iners, Gardnerella vaginalis or were highly diverse profiles. HPV status did not associate with microbial diversity. In conclusion, no association was found between urban level and the vaginal microbiome in Amerindian women, and little difference was found between ethnicities. L. iners and high diversity profiles, associated with vaginal health outcomes, prevail in these populations.

Pre-conditioning of Equine Bone Marrow-Derived Mesenchymal Stromal Cells Increases Their Immunomodulatory Capacity.

Mesenchymal stem/stromal cells (MSCs) are increasingly explored for the treatment of degenerative and inflammatory diseases in human and veterinary medicine. One of the key characteristics of MSCs is that they modulate inflammation mainly through the secretion of soluble mediators. However, despite widespread clinical use, knowledge regarding the effector mechanisms of equine MSCs, and consequently their effectiveness in the treatment of diseases, is still unknown. The objectives of this study were to determine the mechanisms underlying inhibition of lymphocyte proliferation by equine bone marrow-derived MSCs, and to evaluate the effect of pre-conditioning of equine MSCs with different pro-inflammatory cytokines on inhibition of lymphocyte proliferation. We determined that inhibition of lymphocyte proliferation by equine MSCs depends on activity of prostaglandin-endoperoxide synthase 2 and indoleamine 2,3-dioxygenase. Additionally, pre-conditioning of MSCs with TNF-α, IFN-γ or their combination significantly increased the expression of prostaglandin-endoperoxide synthase 2, indoleamine 2,3-dioxygenase, iNOS and IL-6. This upregulation correlated with an increased inhibitory effect of MSCs on lymphocyte proliferation. In conclusion, pre-conditioning of bone marrow-derived MSC increases their inhibitory effect on lymphocyte proliferation in horses.

Tamoxifen and its metabolites induce mitochondrial membrane depolarization and caspase-3 activation in equine neutrophils.

Neutrophils participate in innate immunity as the first line of host defence against microorganisms. However, persistent neutrophil activity and delayed apoptosis can be harmful to surrounding tissues; this problem occurs in diverse inflammatory diseases, including asthma-affected horses. Previous studies in horses with acute lung inflammation indicated that treatment with tamoxifen (TX), a selective oestrogen receptor modulator, produces a significant decrease in bronchoalveolar lavage fluid (BALF) neutrophil content. The aim of this study was to investigate the effect of tamoxifen and its metabolites (N-desmethyltamoxifen and endoxifen) on the mitochondrial membrane potential assay by flow cytometry, and the activation of effector caspase-3 through immunoblotting, in peripheral blood neutrophils obtained from healthy horses (n = 5). Results show that tamoxifen, N-desmethyltamoxifen and endoxifen depolarize the mitochondrial membrane and activate caspase-3 in healthy equine neutrophils in vitro. These findings suggest that tamoxifen and its metabolites may activate the intrinsic apoptotic pathway in equine neutrophils. However, more studies are necessary to further explore the signalling pathways of these drugs in the induction of apoptosis.

Toxicity in Goats Exposed to Arsenic in the Region Lagunera, Northern Mexico.

The Region Lagunera, a region in northeast Mexico, is undergoing significant problems with the quality of its groundwater, which exceeds the permissible limits of contaminants and/or heavy metals stipulated in Mexican legislation. The present study evaluated chronic toxicity in male goats exposed to arsenic via one ex situ Group 1 (n = 5) and one in situ female goats Group 3 (n = 10). The treatment in Group 1 was carried out in the La Laguna experimental field of the Instituto Nacional de Investigaciones Forestales, Agrícolas y Pecuarias (INIFAP), located in Matamoros, Coahuila, Mexico. Sodium arsenite (2 mg/kg) was orally administered for 84 days to five male Creole goats, aged between four and five years old and weighing between 60 and 70 kg, in order to determine its effect on urine toxicity, libido, and physiological condition, an untreated group (n = 5) was included (Group 2). The experiment in group 3 was conducted on ten female Creole goats, aged between four and six years old and weighing between 40 and 49 kg, in both the contaminated sampling area in the rural community of El Venado and the control sampling area in the rural community of Nuevo Reynosa (Group 4 (n = 5)), in which the arsenic levels were measured in the urine of the exposed goats, as was their physiological condition. Significant differences (p < 0.01) between the groups were found in both the arsenic concentration in the urine and the physiological condition observed in both experimental groups.

Possible Genetic Determinants of Response to Phenytoin in a Group of Colombian Patients With Epilepsy.

BACKGROUND: Epilepsy is a serious health problem worldwide. Despite the introduction of new antiepileptic drugs (AEDs) almost 30% of these patients have drug-resistant forms of the disease (DRE), with a significant increase in morbi-mortality. OBJECTIVE: Our objective was to assess the impact of some genetic factors and its possible association with treatment response and adverse drug reactions (ADRs) to phenytoin in 67 adult Colombian patients with epilepsy. METHODS: We conducted an analytical, observational, prospective cohort study to screen four polymorphisms in pharmacogenes: CYP2C9*2-c.430C>T (rs1799853), CYP2C9*3-c.1075A>C (rs1057910), ABCB1-c.3435T>C (rs1045642), and SCN1A-IVS5-91G>A (rs3812718), and their association with treatment response. Patients were followed for 1 year to confirm the existence of DRE (non-response) and ADRs using an active pharmacovigilance approach, followed by a consensus in order to classify ADRs according to causality, preventability, intensity and their relation with phenytoin dose, the duration of treatment, and susceptibility factors (DoTS methodology). RESULTS: A little more than half of evaluated subjects (52.2%) were non-responding to phenytoin. Regarding the genotype-phenotype correlation there was no association between polymorphisms of SCN1A and ABCB1 and DRE (non-response) (p = 0.34), and neither with CYP2C9 polymorphisms and the occurrence of ADRs (p = 0.42). We only found an association between polymorphic alleles of CYP2C9 and vestibular-cerebellar ADRs (dizziness, ataxia, diplopia, and dysarthria) (p = 0.001). Alleles CYP2C9*2-c.430C>T and CYP2C9*3-c.1075A>C were identified as susceptibility factors to ADRs in 24% of patients. CONCLUSIONS: Decreased function alleles of CYP2C9 were highly predictive of vestibular-cerebellar ADRs to phenytoin in our study (p = 0.001). However, the genetic variants CYP2C9*2-c.430C>T, CYP2C9*3-c.1075A>C, ABCB1-c.3435T>C, and SCN1A-IVS5-91G>A, were not associated with treatment response in our study.

Doped Poly(3-hexylthiophene) Coatings onto Chitosan: A Novel Approach for Developing a Bio-Based Flexible Electronic.

Conductive and flexible bio-based materials consisting of chitosan films coated with conductive poly(3-hexylthiophene) (P3HT) were prepared. Thermal, optical, mechanical, morphological, wettability, and conductive properties were analyzed. In a very simple and effective method of chitosan film modification, a controlled volume of a P3HT solution was deposited onto a previously formed chitosan film, assisted by the spin coating method. Later, P3HT-coated chitosan films were doped by simple contact with an aqueous solution of HAuCl4. The use of HAuCl4 becomes attractive because the reports on the doping process in this type of material using this reagent are still scarce and recent to date. In addition, since this acid is a well-known metal nanoparticle precursor, its use opens new future perspectives for these materials into new applications. The effect of P3HT concentration and doping times on film properties was studied. Attenuated total reflectance spectroscopy and UV-Vis spectroscopy allowed us to demonstrate that the presence of the P3HT coating and its doping induce significant changes in the vibrational modes and optoelectronic properties of samples. Additionally, the images obtained by scanning electron microscopy showed a well-distributed and homogeneous coating on the surface of chitosan films. Measured conductivity values of doped film samples fall in the range from 821.3 to 2017.4 S/m, representing, to the best of our knowledge, the highest values reported in the literature for chitosan/chitin-based materials. Indeed, these values are around or even higher than those obtained for some materials purely consisting of conductive polymers.

Tamoxifen induces apoptosis and inhibits respiratory burst in equine neutrophils independently of estrogen receptors.

Neutrophils play an important role in the exacerbation and maintenance of severe equine asthma; persistent neutrophil activity and delayed apoptosis can be harmful to surrounding tissues. Tamoxifen (TX) is a nonsteroidal estrogen receptor modulator with immunomodulatory effects and induces early apoptosis of blood and bronchoalveolar lavage neutrophils from horses with acute lung inflammation. This study investigated if the in vitro effects of tamoxifen are produced by its action on nuclear (α and ß) and membrane (GPR30) estrogen receptors in healthy equine neutrophils. Results showed that TX inhibits neutrophil respiratory burst induced by opsonized zymosan in a dose-dependent manner. Nuclear (17-ß-Estradiol) and GPR30 cell membrane (G1) estrogen receptor agonists and their antagonists (ICI 182,780 and G15, respectively) do not block or reproduce the effect of TX. Therefore, TX does not inhibit respiratory burst through estrogen receptors. TX (8.5 µM) also increased phosphatidylserine translocation, a marker of early apoptosis, which did not occur with any of the estrogen receptor agonists or antagonists. Thus, tamoxifen generates dose-dependent inhibition of respiratory burst and increased early apoptosis in healthy equine neutrophils, independently of nuclear or membrane estrogen receptors. Further studies are necessary to explore the signaling pathways of tamoxifen-induced ROS inhibition and phosphatidylserine translocation.

Tamoxifen inhibits chemokinesis in equine neutrophils.

Neutrophils are terminally differentiated innate effector cells at the first line of host defense. Neutrophil migration within tissues is complex and involves several steps, during which these cells must be able to interpret a variety of chemical and physical signals. Exacerbated neutrophil activity can be harmful to surrounding tissues; this is important in a range of diseases, including equine asthma. Tamoxifen (TX) is a non-steroidal estrogen receptor modulator with effects on cell growth and survival. Previous studies showed that TX treatment in horses with induced acute pulmonary inflammation promoted early apoptosis of blood and bronchoalveolar lavage fluid (BALF) neutrophils, reduction of BALF neutrophil content, and improvement in animals' clinical status. Further, TX dampens chemotactic index and respiratory burst production in vitro. The aim of this study was to provide information on the effect of TX on chemokinesis in peripheral blood neutrophils from five healthy horses. Results showed that neutrophils increased migration and travelled distance in response to IL-8; but in the presence of TX, IL-8 did not produce neutrophil migration. This suggests that TX has an inhibitory effect on the kinesis of equine peripheral blood neutrophils stimulated with IL-8. However, further studies are required to fully understand the signaling pathways of TX on neutrophil chemokinesis.

High Rate of Infection by Only Oncogenic Human Papillomavirus in Amerindians.

Human papillomavirus (HPV), an etiological agent of cervical cancer (CC), has infected humans since ancient times. Amerindians are the furthest migrants out of Africa, and they reached the Americas more than 14,000 years ago. Some groups still remain isolated, and some migrate to towns, forming a gradient spanning urbanization. We hypothesized that, by virtue of their history, lifestyle, and isolation from the global society, remote Amerindian women have lower HPV diversity than do urban women (Amerindian or mestizo). Here we determined the diversity of the 25 most relevant cervical HPV types in 82 Amerindians spanning urbanization (low, medium, and high, consistent with the exposure to urban lifestyles of the town of Puerto Ayacucho in the Venezuelan Amazonas State), and in 29 urban mestizos from the town. Cervical, anal, oral, and introitus samples were taken, and HPVs were typed using reverse DNA hybridization. A total of 23 HPV types were detected, including 11 oncogenic or high-risk types, most associated with CC. Cervical HPV prevalence was 75%, with no differences by group, but Amerindians from low and medium urbanization level had significantly lower HPV diversity than mestizos did. In Amerindians, but not in mestizos, infections by only high-risk HPVs were higher than coinfections or by exclusively low-risk HPVs. Cervical abnormalities only were observed in Amerindians (9/82), consistent with their high HPV infection. The lower cervical HPV diversity in more isolated Amerindians is consistent with their lower exposure to the global pool, and transculturation to urban lifestyles could have implications on HPV ecology, infection, and virulence.IMPORTANCE The role of HPV type distribution on the disparity of cervical cancer (CC) incidence between human populations remains unknown. The incidence of CC in the Amazonas State of Venezuela is higher than the national average. In this study, we determined the diversity of known HPV types (the viral agent of CC) in Amerindian and mestizo women living in the Venezuelan Amazonas State. Understanding the ecological diversity of HPV in populations undergoing lifestyle transformations has important implication on public health measures for CC prevention.

La transición a la agricultura y la industrialización cambiaron la cara del ser humano: ¿puede el vegetarianismo ser un nuevo factor de cambio?: revisión de la literatura / The transition to agriculture and industrialization changed the human face: can vegetarianism be a new factor of change?: review of the literature

RESUMEN: Hace aproximadamente once mil años el ser humano pasó de alimentarse de los animales que cazaba o pescaba y los frutos y plantas que recolectaba, a aquellos que podía crecer a voluntad mediante la agricultura. Este cambio alteró dramáticamente la forma de la cabeza ósea y particularmente de la cara, que se hizo más grácil, y además se redujo el aporte de nutrientes claves. Con la industrialización, hubo un gran deterioro de la salud oral. Al abandono de una dieta cazadora recolectora incluso se le ha atribuido el origen de maloclusiones dentales, debido a la reducción del estrés masticatorio y con ello un menor tamaño relativo del maxilar y la mandíbula respecto a los dientes. Hoy en día, existiendo una mayor conciencia de la población respecto de sus cuidados y de su entorno, la adopción de dietas que excluyen cierto tipo de alimentos como los animales ha ganado adeptos. La dieta vegetariana presenta varias características que pueden afectar el metabolismo general y el óseo en particular, de manera similar a como lo hizo la agricultura en el pasado. La presente revisión busca analizar los cambios de la dieta humana, del punto de vista nutricional y mecánico y cómo estos afectaron la forma de la cara. Esto con el objetivo de comprender los posibles efectos de la introducción de alimentaciones de tipo restrictivas, como la vegetariana, en el organismo y particularmente en la anatomía facial.

SUMMARY: Approximately eleven thousand years ago humans beings went from feeding on animals they hunted or fished and fruits and plants they gathered, to crops they could grow through agriculture. This change dramatically altered the shape of the skull, particularly the face, which became more gracile, and also reduced the contribution of key nutrients. Along with industrialization, there was great deterioration of oral health. Leaving behind the hunter-gatherer diet has even been attributed to the origins of dental malocclusions, as masticatory stress was reduce, and reducing the size of the maxilla and mandible with respect to the teeth. Nowadays, there is greater awareness in the general population regarding personal care and their surroundings. Diets that exclude certain types of foods such as animal products are becoming more prevalent. The vegetarian diet has several characteristics that can affect metabolism, particularly the bones, as did the change from hunter-gatherer to agriculture in the past. The present review seeks to analyze the changes of the human diet, from the nutritional and mechanical point of view and how these have affected the shape of the face. This in order to understand the possible effects of the introduction of restrictive type feeds, such as the vegetarian diet in the body, particularly in facial anatomy.

Mapeo y ablación por radiofrecuencia a cielo abierto: un caso de taquicardia ventricular refractaria en anomalía de Ebstein / Open-heart mapping and radiofrequency ablation: a case of refractory ventricular tachycardia in Ebstein's anomaly

Resumen La anomalía de Ebstein es una enfermedad congénita, caracterizada por el desplazamiento y la adherencia de la válvula tricúspide. Las valvas septal y posterior se implantan en posiciones más inferiores, causando insuficiencia tricuspídea, esta condición de forma progresiva genera dilatación y deterioro de la función sistólica ventricular derecha. Comúnmente se asocia a otras entidades, principalmente, a la comunicación interauricular y las arritmias mediadas por vías accesorias. La muerte súbita ocurre en estadios avanzados, usualmente relacionados con episodios de taquicardia ventricular. Este reporte describe un caso de anomalía de Ebstein y tormenta arrítmica, que se sometió a ablación del sustrato arrítmico endo y epicárdico en la porción atrializada del ventrículo derecho, que presentó como complicación intraprocedimiento la perforación del ventrículo, el taponamiento cardiaco y la necesidad urgente de la reparación quirúrgica, realizándose en el intraoperatorio una segunda ablación por radiofrecuencia a cielo abierto con el objetivo de eliminar los potenciales tardíos y los fragmentados remanentes en el área de bajo voltaje de la escara. Veintidós semanas después de la ablación se implantó un cardiodesfibrilador subcutáneo para prevención secundaria de la muerte súbita; en el seguimiento a 14 meses no hubo terapias apropiadas del dispositivo.

Abstract Ebstein's anomaly is a congenital disease characterised by the displacement and adherence of the tricuspid valve. Septal and posterior valves are implanted in lower positions, thus causing tricuspid insufficiency. This condition gradually generates dilation and deterioration of the right ventricular systolic function. It is commonly associated to other conditions, mainly atrial septal defect and accessory pathway arrhythmias. Sudden death occurs in the advanced stages, usually related to episodes of ventricular tachycardia. This report describes a case of Ebstein's anomaly and arrhythmic storm who underwent ablation of the arrhythmic endo- and epicardial substract in the atrialized portion of the right ventricle, that developed as an intrasurgical complication the perforation of the ventricle, cardiac tamponade and urgent need of surgical repair. During the surgery a second open-heart radiofrequency ablation was conducted with the goal of eliminating potentially late and fragmented remnants in the low voltage area of the scars. Twenty two weeks after the ablation a subcutaneous cardioverterdefibrillator was implanted for secondary prevention of sudden death; in the follow-up after 14 months there were no appropriate therapies of the device.