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Peptides are promising drug development frameworks that have been hindered by intrinsic undesired properties including hemolytic activity. We aim to get a better insight into the chemical space of hemolytic peptides using a novel approach based on network science and data mining. Metadata networks (METNs) were useful to characterize and find general patterns associated with hemolytic peptides, whereas Half-Space Proximal Networks (HSPNs), represented the hemolytic peptide space. The best candidate HSPNs were used to extract various subsets of hemolytic peptides (scaffolds) considering network centrality and peptide similarity. These scaffolds have been proved to be useful in developing robust similarity-based model classifiers. Finally, using an alignment-free approach, we reported 47 putative hemolytic motifs, which can be used as toxic signatures when developing novel peptide-based drugs. We provided evidence that the number of hemolytic motifs in a sequence might be related to the likelihood of being hemolytic.
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Minería de Datos , Hemólisis , Péptidos , Minería de Datos/métodos , Hemólisis/efectos de los fármacos , Humanos , Biología Computacional/métodosRESUMEN
OBJECTIVE: The study aimed to determine the association between serum magnesium and Vitamin D levels with the severity and mortality by coronavirus disease 19 (COVID-19) in hospitalized patients. METHOD: Men and women over 18 years of age with probable COVID-19 were enrolled in a case-control study. Patients with a positive or negative test for Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were allocated into case or control groups, respectively. Vitamin D deficiency was defined by concentrations < 20 ng/mL and hypomagnesemia by serum levels < 1.8 mg/dL. RESULTS: A total of 54 patients, 30 women and 24 men, were enrolled and allocated into the groups with (n = 27) and without (n = 27) COVID-19. The logistic regression analysis showed that Vitamin D deficiency (odds ratio [OR] = 6.13; 95% confidence intervals [CI]: 1.32-28.34) and insufficiency (OR = 0.12; 95% CI: 0.02-0.60) are significantly associated with hospitalization. However, Vitamin D disorders and hypomagnesemia were not associated with mortality. CONCLUSIONS: The results of the present study revealed that Vitamin D disturbances, but not hypomagnesemia, are associated with the severity of SARS-CoV-2.
OBJETIVO: Determinar la asociación entre los niveles séricos de vitamina D y de magnesio con la gravedad y la mortalidad de la COVID-19 en pacientes hospitalizados. MÉTODO: Hombres y mujeres mayores de 18 años con probable COVID-19 fueron enrolados en un estudio de casos y controles. Los pacientes con una prueba positiva o negativa para SARS-CoV-2 fueron asignados en los grupos de casos y de controles, respectivamente. RESULTADOS: Un total de 54 pacientes, 30 mujeres y 24 hombres, fueron enrolados y asignados a los grupos COVID-19 (n = 27) y control (n = 27). El análisis de regresión logística mostró que la deficiencia de vitamina D (odds ratio [OR]: 6.13; intervalo de confianza del 95% [IC95%]: 1.32-28.34) y la insuficiencia de vitamina D (OR: 0.12; IC95%: 0.02-0.60) se asocian significativamente con hospitalización. Sin embargo, las alteraciones de la vitamina D y la hipomagnesemia no se asociaron con mortalidad. CONCLUSIONES: Los resultados del presente estudio revelaron que las alteraciones de la vitamina D, pero no la hipomagnesemia, se asocian con la gravedad de la COVID-19.
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COVID-19 , Deficiencia de Magnesio , Magnesio , Índice de Severidad de la Enfermedad , Deficiencia de Vitamina D , Vitamina D , Humanos , COVID-19/sangre , COVID-19/mortalidad , COVID-19/complicaciones , Masculino , Femenino , Magnesio/sangre , Persona de Mediana Edad , Estudios de Casos y Controles , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/epidemiología , Vitamina D/sangre , Vitamina D/análogos & derivados , Anciano , Deficiencia de Magnesio/sangre , Deficiencia de Magnesio/complicaciones , Deficiencia de Magnesio/epidemiología , Adulto , Hospitalización/estadística & datos numéricos , SARS-CoV-2RESUMEN
In this work, a quantum dissipative model is employed to investigate the influence of a perpendicular magnetic field on the photoluminescence (PL) spectrum of a quantum well embedded within a microcavity. This model incorporates both the exact electron-hole interaction within the semiconductor and the light-matter coupling between the fundamental photonic mode and the fermionic particles. The loss and pumping mechanisms are described using the quantum master equation, and the PL spectrum is determined via the quantum regression theorem. Our findings demonstrate that the magnetic field acts as a control mechanism in the polariton emission energy, the emission linewidth and the intensity distribution along the emission line. Finally, it is observed that the magnetic field can redistribute the density matrix occupations leading to modifications in the average number of polaritons in the system.
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The prediction of possible lead compounds from already-known drugs that may present DPP-4 inhibition activity imply a advantage in the drug development in terms of time and cost to find alternative medicines for the treatment of Type 2 Diabetes Mellitus (T2DM). The inhibition of dipeptidyl peptidase-4 (DPP-4) has been one of the most explored strategies to develop potential drugs against this condition. A diverse dataset of molecules with known experimental inhibitory activity against DPP-4 was constructed and used to develop predictive models using different machine-learning algorithms. Model M36 is the most promising one based on the internal and external performance showing values of Q2CV = 0.813, and Q2EXT = 0.803. The applicability domain evaluation and Tropsha's analysis were conducted to validate M36, indicating its robustness and accuracy in predicting pIC50 values for organic molecules within the established domain. The physicochemical properties of the ligands, including electronegativity, polarizability, and van der Waals volume were relevant to predict the inhibition process. The model was then employed in the virtual screening of potential DPP4 inhibitors, finding 448 compounds from the DrugBank and 9 from DiaNat with potential inhibitory activity. Molecular docking and molecular dynamics simulations were used to get insight into the ligand-protein interaction. From the screening and the favorable molecular dynamic results, several compounds including Skimmin (pIC50 = 3.54, Binding energy = -8.86â¯kcal/mol), bergenin (pIC50 = 2.69, Binding energy = -13.90â¯kcal/mol), and DB07272 (pIC50 = 3.97, Binding energy = -25.28â¯kcal/mol) seem to be promising hits to be tested and optimized in the treatment of T2DM. This results imply a important reduction in cost and time on the application of this drugs because all the information about the its metabolism is already available.
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Dipeptidil Peptidasa 4 , Inhibidores de la Dipeptidil-Peptidasa IV , Descubrimiento de Drogas , Aprendizaje Automático , Simulación de Dinámica Molecular , Inhibidores de la Dipeptidil-Peptidasa IV/química , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Dipeptidil Peptidasa 4/metabolismo , Dipeptidil Peptidasa 4/química , Humanos , Estructura Molecular , Diabetes Mellitus Tipo 2/tratamiento farmacológicoRESUMEN
BACKGROUND: Guided by Andersen's Behavioral Model of Health Services Use (BMHSU), this study aimed to identify determinants of post-migration healthcare use among a sample of Mexican immigrants in a US-Mexico border region in Southern Arizona, while considering pre-migration health and healthcare experiences. METHODS: A non-probabilistic convenience sample of 300 adult Mexican immigrants completed a telephone survey to assess healthcare practices. Multivariable logistic regressions were fitted to determine adjusted relationships between frequency of care and predisposing, enabling, need, and contextual factors as well as personal health practices. RESULTS: Overall, participants had a 79% probability of receiving healthcare "at least once a year" after migrating to Southern Arizona. Receiving post-migration healthcare was associated with predisposing, enabling, need, contextual factors, and personal health practices (p < 0.05). DISCUSSION: Consistent with BMHSU, our findings suggest that frequency of healthcare is not only a function of having post-migration health insurance but is also shaped by a complex array of other factors. The results of this study shed light onto potential areas to be leveraged by multifactorial sociocultural interventions to increase Mexican immigrants' frequency of healthcare services use.
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The Cupressaceae family includes species considered to be medicinal. Their essential oil is used for headaches, colds, cough, and bronchitis. Cedar trees like Chamaecyparis lawsoniana (C. lawsoniana) are commonly found in urban areas. We investigated whether C. lawsoniana exerts some of its effects by modifying airway smooth muscle (ASM) contractility. The leaves of C. lawsoniana (363 g) were pulverized mechanically, and extracts were obtained by successive maceration 1:10 (w:w) with methanol/CHCl3. Guinea pig tracheal rings were contracted with KCl, tetraethylammonium (TEA), histamine (HIS), or carbachol (Cch) in organ baths. In the Cch experiments, tissues were pre-incubated with D-600, an antagonist of L-type voltage-dependent Ca2+ channels (L-VDCC) before the addition of C. lawsoniana. Interestingly, at different concentrations, C. lawsoniana diminished the tracheal contractions induced by KCl, TEA, HIS, and Cch. In ASM cells, C. lawsoniana significantly diminished L-type Ca2+ currents. ASM cells stimulated with Cch produced a transient Ca2+ peak followed by a sustained plateau maintained by L-VDCC and store-operated Ca2+ channels (SOCC). C. lawsoniana almost abolished this last response. These results show that C. lawsoniana, and its active metabolite quercetin, relax the ASM by inhibiting the L-VDCC and SOCC; further studies must be performed to obtain the complete set of metabolites of the extract and study at length their pharmacological properties.
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Calcio , Chamaecyparis , Contracción Muscular , Músculo Liso , Extractos Vegetales , Quercetina , Tráquea , Animales , Cobayas , Músculo Liso/efectos de los fármacos , Músculo Liso/metabolismo , Contracción Muscular/efectos de los fármacos , Quercetina/farmacología , Quercetina/química , Tráquea/efectos de los fármacos , Tráquea/metabolismo , Extractos Vegetales/farmacología , Extractos Vegetales/química , Chamaecyparis/química , Calcio/metabolismo , Masculino , Bloqueadores de los Canales de Calcio/farmacología , Histamina/metabolismo , Canales de Calcio Tipo L/metabolismo , Hojas de la Planta/químicaRESUMEN
Notwithstanding the wide adoption of the OECD principles (or best practices) for QSAR modeling, disparities between in silico predictions and experimental results are frequent, suggesting that model predictions are often too optimistic. Of these OECD principles, the applicability domain (AD) estimation has been recognized in several reports in the literature to be one of the most challenging, implying that the actual reliability measures of model predictions are often unreliable. Applying tree-based error analysis workflows on 5 QSAR models reported in the literature and available in the QsarDB repository, i.e., androgen receptor bioactivity (agonists, antagonists, and binders, respectively) and membrane permeability (highest membrane permeability and the intrinsic permeability), we demonstrate that predictions erroneously tagged as reliable (AD prediction errors) overwhelmingly correspond to instances in subspaces (cohorts) with the highest prediction error rates, highlighting the inhomogeneity of the AD space. In this sense, we call for more stringent AD analysis guidelines which require the incorporation of model error analysis schemes, to provide critical insight on the reliability of underlying AD algorithms. Additionally, any selected AD method should be rigorously validated to demonstrate its suitability for the model space over which it is applied. These steps will ultimately contribute to more accurate estimations of the reliability of model predictions. Finally, error analysis may also be useful in "rational" model refinement in that data expansion efforts and model retraining are focused on cohorts with the highest error rates.
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Algoritmos , Relación Estructura-Actividad Cuantitativa , Reproducibilidad de los ResultadosRESUMEN
Viruses comprise the most abundant genetic material in the biosphere; however, global viral genomic population (virome) has been largely underestimated. Recently, high-throughput sequencing (HTS) has provided a powerful tool for the detection of known viruses and the discovery of novel viral species from environmental and individual samples using metagenomics and ecogenomics approaches, respectively. Viruses with circular DNA single-stranded (ssDNA) genomes belonging to the begomovirus genera (family Geminiviridae) constitute the largest group of emerging plant viruses worldwide. The knowledge of begomoviruses viromes is mostly restricted to crop plant systems; nevertheless, it has been described that noncultivated plants specifically at the interface between wild and cultivated plants are important reservoirs leading to viral evolution and the emergence of new diseases. Here we present a protocol that allows the identification and isolation of known and novel begomoviruses species infecting cultivated and noncultivated plant species. The method consists of circular viral molecules enrichment by rolling circle amplification (RCA) from begomovirus-positive total plant DNA, followed by NGS-based metagenomic sequencing. Subsequently, metagenomic reads are processed for taxonomic classification using Viromescan software and a customized Geminiviridae family database, and begomovirus-related reads are used for contigs assembly and annotation using Spades software and Blastn algorithm, respectively. Then, the obtained begomovirus-related signatures are used as templates for specific primers design and implemented for PCR-based ecogenomic identification of individual samples harboring the corresponding viral species. Lastly, full-length begomovirus genomes are obtained by RCA-based amplification from total plant DNA of selected individual samples, cloning, and viral molecular identity corroborated by Sanger sequencing. Conclusively, the identification and isolation of a novel monopartite begomovirus species native to the New World (NW) named Gallium leaf deformation virus (GLDV) is shown.
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Begomovirus , ADN Viral , ADN Viral/genética , Filogenia , Plantas/genética , Begomovirus/genética , Genoma Viral , Metagenómica/métodos , ADN de Plantas , ADN Circular/genética , Enfermedades de las PlantasRESUMEN
BACKGROUND: Sudden Sensorineural Hearing Loss was described by Mc. Cabe in 1979 and, since then, many authors have tried to define, explain and correctly treat this disease. The National Institute on Deafness and Other Communication Disorders defines it as sudden sensorineural hearing loss of at least 30 dB in three contiguous audiometric frequencies in a period of 72 hours. Among the therapeutic strategies, corticosteroids have been shown to have the greatest benefit due to their anti-inflammatory and anti-cellular stress effects. OBJECTIVE: To determine the hearing results with combined steroid therapy in patients with sudden sensorineural hearing loss (SSHL), according to the Siegel recovery criteria scale. METHOD: Study carried out in the otorhinolaryngology and head and neck surgery service of the Centro Médico Naval, Ciudad de México, where 150 patients diagnosed with SSHL and who received combined therapy with intratympanic dexamethasone and systemic prednisone were included. RESULTS: Therapeutic effectiveness was demonstrated by correlating therapeutic success in 82% of cases and therapeutic failure in 18% of cases, by correlating it with the Siegel recovery criteria scale. When evaluating the general average of the pure tone average levels at the beginning and 6 weeks after treatment, a statistically significant difference was obtained (p = 0.001). The average of the speech audiometry at the beginning and 6 weeks later had a statistically significant difference (p = 0.001). CONCLUSIONS: Initial combined steroid treatment for SSHL has been shown to have beneficial results according to Siegel recovery criteria scale.
ANTECENDENTES: La Hipoacusia Neurosensorial Súbita Idiopática fue descrita por Mc. Cabe en 1979 y, desde entonces, muchos autores han tratado de definir, explicar y tratar correctamente esta enfermedad. El Nacional Institute on Deafness and Other Communication Disorders la define como pérdida auditiva neurosensorial brusca de al menos 30 dB en tres frecuencias audiométricas contiguas en un periodo de 72 horas. Entre las estrategias terapéuticas, los corticosteroides han demostrado tener mayor beneficio por sus efectos antiinflamatorios y antiestrés celular. OBJETIVO: Determinar los resultados auditivos con la terapia de esteroides combinados en pacientes con hipoacusia neurosensorial súbita idiopática (HNSI), de acuerdo a la escala de criterios de recuperación de Siegel. MÉTODO: Estudio realizado en el servicio de otorrinolaringología y cirugía de cabeza y cuello del Centro Médico Naval, en Ciudad de México, en el que se incluyeron 150 pacientes con diagnóstico de HNSI y que recibieron terapia combinada con dexametasona intratimpánica y prednisona sistémica. RESULTADOS: Se demostró una efectividad terapéutica al correlacionar el éxito terapéutico en el 82% de los casos y un fracaso terapéutico en el 18% de los casos según la escala de criterios de recuperación de Siegel. Al evaluar el promedio general de los niveles de promedio de tonos puros al inicio y 6 semanas posterior al tratamiento se obtuvo una diferencia estadísticamente significativa (p = 0.001). El promedio de las logoaudiometrías al inicio y 6 semanas posterior al tratamiento tuvo una diferencia estadísticamente significativa (p = 0.001). CONCLUSIONES: El tratamiento combinado con esteroides de manera inicial para la HNSI ha demostrado tener resultados benéficos de acuerdo con la escala de criterios de recuperación de Siegel.
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Pérdida Auditiva Sensorineural , Pérdida Auditiva Súbita , Humanos , Resultado del Tratamiento , Antiinflamatorios/uso terapéutico , Pérdida Auditiva Súbita/tratamiento farmacológico , Pérdida Auditiva Súbita/diagnóstico , Pérdida Auditiva Sensorineural/tratamiento farmacológico , Pérdida Auditiva Sensorineural/inducido químicamente , Audición , Esteroides/uso terapéutico , Audiometría de Tonos Puros , Dexametasona/uso terapéutico , Glucocorticoides/uso terapéutico , Estudios RetrospectivosRESUMEN
OBJECTIVE: Determine the effectiveness of endoscopy in cochlear implantation as compared to microscopy. METHOD: Study comparing microscopy and endoscopy in cochlear implant placement in 34 patients (23 endoscopic implants and 20 implants via microscopy), between 2014 and 2019, at the Centro Medico Naval, Mexico City. The study was performed under informed consent and according to the Council for International Organizations of Medical Sciences (CIOMS). RESULTS: Of the 34 patients, 12 were children or adolescents and 22 were adults. The visualization of the round window classified via microscopy per St. Thomas Hospital's classification showed that type IIB prevailed in 30.2% of patients, and type III in 41.9%, and when using the endoscope, the round window was observed in full in 82.6% of patients (type I), and type IIA was only observed in 17.4% (four patients). The number of attempts made to place the cochlear implant was greater with the microscope. The time to insertion of the electrode was 1.6 minutes. No differences were observed (p > 0.05) in the number of inpatient days. Cochleostomy was more frequent when using the microscope. CONCLUSIONS: Endoscopy is an effective resource in cochlear implantation for posterior tympanotomy, with no complications observed, offering greater safety in inserting the electrode through the round window.
OBJETIVO: Determinar la efectividad de la endoscopía en la implantación coclear en comparación con la técnica microscópica. MÉTODO: Se comparó la microscopía frente a la endoscopía en la colocación de implante coclear en 34 pacientes (23 endoscópicos y 20 microscópicos), del año 2014 al año 2019, en el Centro Médico Naval de la Ciudad de México. El estudio se realizó bajo consentimiento informado y apegado a las normas del Council for International Organizations of Medical Sciences. RESULTADOS: De los 34 pacientes, 12 eran niños o adolescentes y 22 eran adultos. La visualización de la ventana redonda fue clasificada con microscopio según la clasificación del St. Thomas Hospital, predominando la tipo IIB (30.2%) y la III (41.9%), y al utilizar el endoscopio se observó completa en el 82.6% (tipo I) y tipo IIA en tan solo el 17.4% (cuatro pacientes). El número de intentos en la colocación del implante coclear fue mayor con el microscopio. El tiempo en el que se insertó el electrodo fue de 1.6 minutos. No hubo diferencias (p > 0.05) en la estancia hospitalaria. Fue más frecuente la cocleostomía cuando se uso el microscopio. CONCLUSIONES: La endoscopía es un instrumento efectivo en la implantación coclear por timpanotomía posterior, sin presentarse complicaciones y dando mayor seguridad para insertar el electrodo por la ventana redonda.
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Implantación Coclear , Implantes Cocleares , Niño , Adulto , Adolescente , Humanos , Ventana Redonda/cirugía , Endoscopía Gastrointestinal , MéxicoRESUMEN
Introducción: El cáncer de tiroides es la neoplasia endocrina más prevalente y el tercer tumor más frecuente en las mujeres colombianas. Tiene buen pronóstico en ausencia de metástasis. Los pulmones son el tejido más comprometido por metástasis en pacientes con cáncer de tiroides. El objetivo del trabajo fue describir la prevalencia de las metástasis torácicas en pacientes con cáncer de tiroides en un centro de referencia en cáncer de la ciudad de Bogotá entre 2016 y 2019. Material y métodos: El estudio fue de corte transversal con muestreo no probabilístico de casos consecutivos en pacientes mayores de 18 años con cáncer de tiroides que asistieron a consulta externa de del Instituto Nacional de Cancerología entre 2016 y 2019. Resultados: Se incluyeron 241 pacientes; 53 presentaron metástasis torácicas. Dentro de los pacientes con metástasis el promedio de edad fue de 59,6 años (DE ± 12,7), 77,3% fueron mujeres, y el 90,5% presentó carcinoma papilar. La prevalencia de metástasis torácicas fue del 21,9%. Las comorbilidades más frecuentes fueron hipertensión arterial (32,08%). El síntoma más frecuente fue la disnea en un 15%. El 34% presentaron tiroglobulina mayor de 38 ng/mL y un 22% tenían anticuerpos antitiroglobulina detectables. Las variables asociadas a metástasis torácicas fueron la edad (p = 0,002), el peso (p = 0,019), adenopatías cervicales (p = 0,007), presencia de disnea (p = 0,004) y tiroglobulina mayor de 38 ng/mL (p < 0,001). La presencia de adenopatías cervicales se encontró en el 86% de los pacientes con metástasis, lo que sugiere que se trata de un marcador de riesgo de metástasis. Conclusiones: El presente estudio permite establecer datos locales, cuyos resultados promueven futuros estudios prospectivos que identifiquen variables asociadas y factores pronósticos en pacientes con cáncer de tiroides.
Introduction: Thyroid cancer is the most prevalent endocrine neoplasm and the third most common tumor in Colombian women. It has a good prognosis in the absence of metastasis. The lungs are the most affected tissue by metastasis in patients with thyroid cancer. The objective of this work was to describe the prevalence of thoracic metastases in patients with thyroid cancer in a cancer reference hospital from Bogotá, between 2016 and 2019. Materials and methods: The study was cross-sectional, with non-probabilistic sampling of consecutive cases in patients older than 18 with thyroid cancer who were attended at the National Cancer Institute between 2016 and 2019. Results: 241 patients were included in the study; 53 had thoracic metastases. The mean age of patients with metastasis was 59.6 years (SD ± 12.7); 77.3% were female and 90.5% showed papillary carcinoma. The prevalence of thoracic metastases was 21.9%. The most common comorbidity was arterial hypertension (32.08%). The most common symptom was dyspnea, with 15%. 34% of patients had thyroglobulin of more than 38 ng/ml and 22% had detectable anti-thyroglobulin antibodies. Variables associated with thoracic metastases were age (p = 0.002), weight (p = 0.019), cervical adenopathies (p = 0.007), presence of dyspnea (p = 0.004), and thyroglobulin values greater than 38 ng/ml (p < 0.001). Cervical adenopathies were found in 86% of patients with metastasis, suggesting the fact that they are a risk marker for metastasis. Conclusions: This study allows us to establish local data, whose results promote future prospective studies that identify associated variables and prognostic factors in patients with thyroid cancer.
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FemeninoRESUMEN
Porcine circovirus type 3 (PCV3) is a nonenveloped virus of the Circoviridae family. This virus has been identified in pigs of different ages and pigs with several clinical manifestations of the disease or even in apparently healthy pigs. While PCV3 was first reported in 2015, several retrospective studies have reported the virus before that year. The earliest report indicates that PCV3 has been circulated in swine farms since 1996. In this study, we evaluated the presence of PCV3 in samples collected in Mexico in 2008, 2015, 2020, and 2021. This study assessed PCV3 DNA by qPCR and antibodies against CAP protein by indirect ELISA. The results showed that PCV3 (DNA and anti-CAP antibodies) was detected in the samples collected from 2008 to 2021. The highest prevalence was in 2008 (100%), and the lowest was in 2015 (negative). Genetic analysis of ORF2 showed that the virus identified belonged to genotype a, as most of the viruses identified thus far. PCV3 was detected in samples from piglets with respiratory signs and growth retardation, sows with reproductive failure, or asymptomatic piglets and sows. Pigs with respiratory signs, growth retardation, or reproductive failure had a higher prevalence of antibodies and qPCR-positive samples. In conclusion, this study showed that PCV3 has been circulating in Mexico since 2008 and that PCV3 DNA and antibodies were more prevalent in samples from pigs with clinical manifestations of diseases.
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Infecciones por Circoviridae , Circovirus , Enfermedades de los Porcinos , Animales , Porcinos , Femenino , Estudios Retrospectivos , Enfermedades de los Porcinos/epidemiología , Infecciones por Circoviridae/epidemiología , Infecciones por Circoviridae/veterinaria , Circovirus/genética , México/epidemiología , Anticuerpos , ADN , Trastornos del Crecimiento , FilogeniaRESUMEN
Vasculogenic mimicry (VM), a process in which aggressive cancer cells form tube-like structures, plays a crucial role in providing nutrients and escape routes. Highly plastic tumor cells, such as those with the triple-negative breast cancer (TNBC) phenotype, can develop VM. However, little is known about the interplay between the cellular components of the tumor microenvironment and TNBC cells' VM capacity. In this study, we analyzed the ability of endothelial and stromal cells to induce VM when interacting with TNBC cells and analyzed the involvement of the FGFR/PI3K/Akt pathway in this process. VM was corroborated using fluorescently labeled TNBC cells. Only endothelial cells triggered VM formation, suggesting a predominant role of paracrine/juxtacrine factors from an endothelial origin in VM development. Via immunocytochemistry, qPCR, and secretome analyses, we determined an increased expression of proangiogenic factors as well as stemness markers in VM-forming cancer cells. Similarly, endothelial cells primed by TNBC cells showed an upregulation of proangiogenic molecules, including FGF, VEGFA, and several inflammatory cytokines. Endothelium-dependent TNBC-VM formation was prevented by AZD4547 or LY294002, strongly suggesting the involvement of the FGFR/PI3K/Akt axis in this process. Given that VM is associated with poor clinical prognosis, targeting FGFR/PI3K/Akt pharmacologically may hold promise for treating and preventing VM in TNBC tumors.
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[This corrects the article DOI: 10.1016/j.heliyon.2023.e18451.].
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La dermatitis herpetiforme es una enfermedad autoinmune que se caracteriza por la presencia de lesiones vesiculares y prurito en la superficie extensora de las extremidades, nalgas y parte baja de la espalda. Se presenta el caso clínico de una mujer de 21 años, natural y procedente de Iquitos, que presentó múltiples vesículas dolorosas, pruriginosas, de base eritematosa y purulentas en ambos codos durante un mes. Posteriormente, estas lesiones se diseminaron a ambas rodillas y se agregó prurito intenso. La paciente experimentó períodos alternantes de remisión y exacerbación. La correlación del cuadro clínico, resultados serológicos y de biopsia, junto con respuesta terapéutica a la dapsona confirmaron el diagnóstico de dermatitis herpetiforme, con una evolución favorable y remisión de la enfermedad.
Dermatitis herpetiforme is an autoimmune disease characterized by the presence of vesicular lesions and itching on the extensor surface of the limbs, buttocks, and lower back. The clinical case of a 21-year-old woman, a native of and from Iquitos, is presented. She presented multiple painful, itchy vesicles with an erythematous and purulent base on both elbows for a month. Subsequently, these lesions spread to both knees, and intense itching was added. The patient experienced alternating periods of remission and exacerbation. The correlation of the clinical picture, serological and biopsy results, along with the therapeutic response to dapsona, confirmed the diagnosis of dermatitis herpetiforme, with a favorable evolution and remission of the disease.
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The racemization of biomolecules in the active site can reduce the biological activity of drugs, and the mechanism involved in this process is still not fully comprehended. The present study investigates the impact of aromaticity on racemization using advanced theoretical techniques based on density functional theory. Calculations were performed at the ωb97xd/6-311++g(d,p) level of theory. A compelling explanation for the observed aromatic stabilization via resonance is put forward, involving a carbanion intermediate. The analysis, employing Hammett's parameters, convincingly supports the presence of a negative charge within the transition state of aromatic compounds. Moreover, the combined utilization of natural bond orbital (NBO) analysis and intrinsic reaction coordinate (IRC) calculations confirms the pronounced stabilization of electron distribution within the carbanion intermediate. To enhance our understanding of the racemization process, a thorough examination of the evolution of NBO charges and Wiberg bond indices (WBIs) at all points along the IRC profile is performed. This approach offers valuable insights into the synchronicity parameters governing the racemization reactions.
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Aminoácidos Aromáticos , Enlace de HidrógenoRESUMEN
This work investigates the impact of decoherence induced by pure dephasing and phonon-assisted tunneling mechanisms on the optical and quantum properties of two quantum dots. Special attention is given to the density matrix at steady state, and a detailed analysis of populations, coherences, optical transitions and the emission spectrum is performed. Additionally, we study the influence of both phonon-decoherence mechanisms on bipartite entanglement and the degree of mixedness of the system. In particular, our findings indicate that the phonon-assisted tunneling mechanism partially affects the coherences of the system and quantum properties when the imbalance of phonon absorption and emission is significant. Conversely, the pure dephasing mechanism does not affect the populations but strongly entangles the quantum dots and the reservoir, inducing maximally mixed states and significantly reducing the spectral splitting in the emission spectrum of the system.
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Herpesvirus reactivates from a latent infection in older adults and critically ill and immunocompromised individuals. Herpes zoster ophthalmicus (HZO) is a latent infection that affects the fifth cranial nerve. It is an infrequent cause of increased intraocular pressure. We present the case of a 50-year-old man with a reactivation of latent varicella-zoster virus infection involving the ophthalmic branch of the fifth cranial nerve. The patient was initially managed as an outpatient with an antiviral, but his clinical evolution worsened and required urgent surgical decompression. Lateral canthotomy was performed with cantholysis of the inferior crus of the lateral canthal tendon. Only partial decompression was achieved, so cantholysis of the upper crus was performed with significant tissue tension release. The patient evolved well and was discharged after 6 days without symptoms for outpatient management.
RESUMEN
Landfill gas (LFG) is related to the biochemical processes generating heat and releasing CH4, CO2, and other gases in lower concentrations, which result in environmental impacts and risk of local explosion. Thermal infrared imagery (TIR) is employed to detect CH4 leakage as a risk control approach. However, the challenge for LFG leakage detection using TIR is establishing a relation between the gas flux and the ground temperature. This study evaluates the problem of a heated gas flowing through a porous medium column where the upward surface exchanges heat by radiation and convection to the environment. A heat transfer model that considers the upward LFG flow is proposed, and a sensibility analysis is developed to relate the flux to the ground temperature level in the condition of non-income solar radiation. An explicit equation to predict CH4 fugitive flow as a function of temperature anomalies of the ground was presented for the first time. The results show that the predicted ground surface temperatures are consistent with the literature's experimental observations. Moreover, the model was complementarily applied to a Brazilian landfill, with in situ TIR measurements in an area with a slightly fractured cover. In this field observation, the predicted CH4 flux was around 9025 g m-2 d-1. Model limitations concerning the soil homogeneity, the transient variation of atmospheric conditions or local pressure, and soil temperature difference in low-flux conditions (related to TIR-cameras accuracy) require further validation. Results could help landfill monitoring in conditions of a high-temperature ground anomaly in dry seasons.
Asunto(s)
Metano , Eliminación de Residuos , Metano/análisis , Instalaciones de Eliminación de Residuos , Gases/análisis , Temperatura , Suelo , Eliminación de Residuos/métodosRESUMEN
The selective photocatalytic oxidation with O2 as oxidant of valencene and thymol was evaluated using nanostructured TiO2 under UV-Vis radiation at atmospheric conditions. The effect of the morphology and optical properties of TiO2 nanotubes and aminate nanoparticles was studied. Different scavengers were used to detect the presence of positive holes (h+), electrons (e-), hydroxyl radicals (â¢OH), and the superoxide radical anion (O2-) during the photooxidation reaction. Superoxide anion radical is the main oxidizing specie formed, which is responsible for the selective formation of nootkatone and thymoquinone using aminated TiO2 nanoparticles under 400 nm radiation.