RESUMO

Solid-state nanochannels (SSNs) have emerged as promising platforms for controlling ionic transport at the nanoscale. SSNs are highly versatile, and this feature can be enhanced through their combination with porous materials such as Metal-Organic Frameworks (MOF). By selection of specific building blocks and experimental conditions, different MOF architectures can be obtained, and this can influence the ionic transport properties through the nanochannel. Herein, we study the effects of confined synthesis of Zr-based UiO-66 MOF on the ion transport properties of single bullet-shaped poly(ethylene terephthalate) (PET) nanochannels. We have found that emerging textural properties from the MOF phase play a determinant role in controlling ionic transport through the nanochannel. We demonstrate that a transition from ion current saturation regimes to diode-like regimes can be obtained by employing different synthetic approaches, namely, counterdiffusion synthesis, where MOF precursors are kept separate and forced to diffuse through the nanochannel, and one-pot synthesis, where both precursors are placed at both ends of the channel. Also, by considering the dependence of the charge state of the UiO-66 MOF on the protonation degree, pH changes offered a mechanism to tune the iontronic output (and selectivity) among different regimes, including anion-driven rectification, cation-driven rectification, ion current saturation, and ohmic behavior. Furthermore, Poisson-Nernst-Planck (PNP) simulations were employed to rationalize the different iontronic outputs observed experimentally for membranes modified by different methods. Our results demonstrate a straightforward tool to synthesize MOF-based SSN membranes with tunable ion transport regimes.

RESUMO

In this study, the transport of salt with moderate solubility through bioinspired solid-state nanochannels was comprehensively investigated. For this purpose, bullet-shaped channels were fabricated and exposed to KClO4, a monovalent salt with moderate solubility. These channels displayed the typical rectifying behavior characteristic of asymmetrical channels but with one remarkable difference, the iontronic output exhibited a negative incremental resistance phenomenon of high gating efficiency when the transmembrane voltage in the open state was increased enough, giving rise to an inactivated state characterized by a low and stable ion current. The behavior is attributed to salt precipitation inside the channel and remarkably, it is not observed in other geometries such as cylindrical or cigar-shaped channels. Considering the central role of the surface in precipitation formation, the influence of several parameters such as electrolyte concentration, pH, and channel size was studied. Under optimized conditions, this system can alternate among three different conductance states (closed, open, and inactivated) and exhibits gating ratios higher than 20. Beyond its potential application in fields related to electronics or sensing, this study provides valuable insight into the fundamental principles behind ion rectifying behavior in solid-state channels and highlights the implications of surface phenomena at the nanoscale.

RESUMO

RESUMEN Antecedentes: las metástasis pancreáticas, si bien son poco frecuentes, representan una entidad clínica cuyo diagnóstico probablemente se incrementará en el futuro por el aumento de los programas de seguimiento oncológico. Objetivo: describir los resultados quirúrgicos y oncológicos de una serie de pacientes operados por metástasis pancreáticas. Materiales y métodos: se realizó un estudio de cohorte retrospectivo, descriptivo, multicéntrico, de los pacientes sometidos a resecciones pancreáticas por metástasis entre enero de 2016 y diciembre de 2022, en tres efectores de salud por el mismo grupo quirúrgico. Resultados: fueron operados 19 pacientes, con una media de edad de 59 años (45-79), 11 de sexo femenino, en buen estado general y sin otra evidencia de enfermedad oncológica. El origen de los tumores primarios fue 14 en riñón (7 diagnosticados durante el seguimiento), uno carcinoma mamario, uno melanoma, uno testicular, uno colorrectal y uno de cuello de útero. Las técnicas quirúrgicas empleada fueron: 7 esplenopancreatectomías (5 videolaparoscópicas y 2 convencionales), 4 enucleaciones (3 convencionales y 1 videolaparoscópica), 3 duodenopancreatectomías cefálicas convencionales, 2 duodenopancreatectomías totales convencionales, 2 pancreatectomías centrales convencionales, y una pancreatectomía corporocaudal con preservación del bazo. No se registró mortalidad operatoria (dentro de los 90 días posoperatorios), y presentaron una supervivencia global y libre de enfermedad de 58 y 53 meses, respectivamente. Conclusión: la resección de metástasis pancreáticas, en casos seleccionados, con un abordaje multidisciplinario, y en centros de alto volumen de patología hepatobiliopancreática, es segura y permite buenos resultados oncológicos y de supervivencia global.

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ABSTRACT Background: Pancreatic metastases are rare but are likely to be diagnosed more frequently in the future due to the increase in oncology surveillance programs. Objective: The aim of this study was to describe the surgical and oncologic outcomes of a series of patients undergoing surgery for pancreatic metastases. Materials and methods: We conducted a retrospective, descriptive, and multicenter cohort study on patients who underwent pancreatic resections for metastases in the pancreas by the same surgical group between January 2016 and December 2022 in three healthcare providers. Results: A total of 19 patients were operated on, mean age was 59 years (45-79), and 11 were women with good performance status and no other evidence of oncologic disease. Clear cell renal cell carcinoma was the primary tumor in 14 cases (7 diagnosed during surveillance), and the remaining primary tumors were one case of breast ductal carcinoma, one testicular cancer, one colorectal cancer, one melanoma and one cervical cancer. The surgical techniques used were pancreatectomies and splenectomies in 7 patients (5 via laparoscopy and 2 conventional procedures), 4 enucleations (3 conventional procedures and 1 laparoscopic surgery), 3 conventional cephalic pancreaticoduodenectomies, 2 conventional central pancreatectomies and one spleen-preserving distal pancreatectomy. No deaths were reported within 90 days of surgery, and overall survival and disease-free survival were 58 and 53 months, respectively. Conclusion: Resection of pancreatic metastases is safe and provides good oncologic outcomes and overall survival when performed with a multidisciplinary approach in centers with a high volume of hepatobiliary and pancreatic surgeries and in selected cases.

RESUMO

PURPOSE: There is a lack of clinical and epidemiological knowledge about nonconvulsive status epilepticus (NCSE) in developing countries including Mexico, which has the highest prevalence of epilepsy in the Americas. Our aim was to describe the clinical findings, EEG features, and outcomes of NCSE in a tertiary center in Mexico. METHODS: We conducted a retrospective case series study (2010-2020) including patients (≥15 years old) with NCSE according to the modified Salzburg NCSE criteria 2015 with at least 6 months of follow-up. We extracted the clinical data (age, sex, history of epilepsy, antiseizure medications, clinical manifestations, triggers, and etiology), EEG patterns of NCSE, and outcome. Descriptive statistics and multinomial logistic regression were used. RESULTS: One hundred thirty-four patients were analyzed; 74 (54.8%) women, the total mean age was 39.5 (15-85) years, and 71% had a history of epilepsy. Altered state of consciousness was found in 82% (including 27.7% in coma). A generalized NCSE pattern was the most common (32.1%). The NCSE etiology was mainly idiopathic (56%), and previous uncontrolled epilepsy was the trigger in 48% of patients. The clinical outcome was remission with clinical improvement in 54.5%. Multinomial logistic regression showed that the patient's age (P = 0.04), absence of comorbidities (P = 0.04), history of perinatal hypoxia (P = 0.04), absence of clinical manifestations (P = 0.01), and coma (P = 0.03) were negatively correlated with the outcome and only the absence of generalized slowing in the EEG (P = 0.001) had a significant positive effect on the prognosis. CONCLUSIONS: Age, history of perinatal hypoxia, coma, and focal ictal EEG pattern influence negatively the prognosis of NCSE.

Assuntos

Epilepsia , Estado Epiléptico , Gravidez , Humanos , Feminino , Adulto , Adolescente , Masculino , México/epidemiologia , Coma , Países em Desenvolvimento , Estudos Retrospectivos , Estado Epiléptico/diagnóstico , Estado Epiléptico/epidemiologia , Estado Epiléptico/terapia , Prognóstico , Hipóxia , Eletroencefalografia

RESUMO

The orphan nuclear receptor Nur77 is involved in diverse cellular processes such as inflammation, proliferation, differentiation and survival. Stimuli like lipopolysaccharide (LPS) and tumor necrosis factor (TNF) increase Nur77 expression in human and murine macrophages, and it has been proposed that Nur77 plays a major role in dampening the inflammatory response. Here, we evaluated the expression and function of Nur77 in human anti-inflammatory and pro-inflammatory macrophages derived from blood monocytes cultured with macrophage colony-stimulating factor (M-MDMs) or granulocyte/macrophage colony-stimulating factor (GM-MDMs), respectively. Nur77 mRNA expression was significantly enhanced in M-MDMs compared with GM-MDMs, both constitutively and upon exposure to Toll-like receptor (TLR)2, 3, and 4 ligands. Nur77 activation with the agonist Cytosporone B (CsnB) significantly suppressed the production of TNF, interleukin (IL)-1ß, IL-6, and IL-8 in GM-MDMs stimulated with LPS. In contrast, it tended to enhance the production of the anti-inflammatory cytokine IL-10. This effect was associated with reduced NF-κB p65 nuclear translocation. Similarly, Nur77 knockdown enhanced TNF production in GM-MDMs. CsnB effectively stimulated the transactivation activity of Nur77 in M-MDMs, but it did not alter cytokine synthesis or p65 nuclear translocation. However, Nur77 seemed to have a role in maintaining the anti-inflammatory profile of M-MDMs, since Nur77-deficient M-MDMs constitutively produced higher levels of TNF transcripts. Thus, in the absence of exogenous agonists, Nur77 activity favors the anti-inflammatory function of M-MDMs, whereas agonistic activation of this receptor preferentially drives attenuation of inflammation in inflammatory macrophages.

Assuntos

Macrófagos , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares , Fenilacetatos , Humanos , Citocinas/metabolismo , Inflamação/metabolismo , Lipopolissacarídeos , Fator Estimulador de Colônias de Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares/agonistas , Fenilacetatos/farmacologia

RESUMO

The differential diagnosis of the metastatic axillary lymphadenopathies of breast cancer with which they occur secondary to the Pfizer-BioNTech vaccine against COVID-19, is imperative. In a series of cases, we analyzed the characteristics of unilateral axillary lymphadenopathy in patients after Pfizer-BioNTech vaccination. Axillary lymphadenopathy were observed ipsilateral to the vaccination arm. The axillary ultrasound defined these as reactive and that they disappeared in 3 weeks. The pathological findings were benign. The anamnesis, the place and date of vaccination and the radiological findings, play an essential role to carry out a correct differential diagnosis and follow-up of these adenopathies.

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El diagnóstico diferencial de las adenopatías axilares metastásicas del cáncer de mama con las que se producen secundarias a la vacuna de Pfizer-BioNTech contra la COVID-19 es imperioso. Analizamos una serie de casos con las características de las adenopatías axilares unilaterales tras la administración de la vacuna de Pfizer-BioNTech. Se observaron adenopatías axilares homolaterales al brazo de vacunación. La ecografía axilar las definió como reactivas y que desaparecían en 3 semanas. Los hallazgos anatomopatológicos fueron de benignidad. La anamnesis, el lugar y la fecha de vacunación, así como los hallazgos radiológicos, desempeñan un papel esencial para realizar un correcto diagnóstico deferencial y el seguimiento de estas adenopatías.

Assuntos

Neoplasias da Mama , COVID-19 , Linfadenopatia , Neoplasias da Mama/patologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Feminino , Humanos , Linfadenopatia/etiologia , Metástase Linfática , SARS-CoV-2 , Vacinação

RESUMO

Brownian particles interacting sequentially with distinct temperatures and driving forces at each stroke have been tackled as a reliable alternative for the construction of engine setups. However, they can behave very inefficiently depending on the driving used for the work source and/or when temperatures of each stage are very different from each other. Inspired by some models for molecular motors and recent experimental studies, a coupling between driving and velocities is introduced and detail investigated from stochastic thermodynamics. Exact expressions for thermodynamic quantities and distinct maximization routes have been obtained. The search of an optimal coupling provides a substantial increase of engine performance (mainly efficiency), even for large ΔT. A simple and general argument for the optimal coupling can be estimated, irrespective of the driving and other model details.

Assuntos

Temperatura , Termodinâmica

RESUMO

Filtering and smoothing algorithms are key tools to develop decision-making strategies and parameter identification techniques in different areas of research, such as economics, financial data analysis, communications, and control systems. These algorithms are used to obtain an estimation of the system state based on the sequentially available noisy measurements of the system output. In a real-world system, the noisy measurements can suffer a significant loss of information due to (among others): (i) a reduced resolution of cost-effective sensors typically used in practice or (ii) a digitalization process for storing or transmitting the measurements through a communication channel using a minimum amount of resources. Thus, obtaining suitable state estimates in this context is essential. In this paper, Gaussian sum filtering and smoothing algorithms are developed in order to deal with noisy measurements that are also subject to quantization. In this approach, the probability mass function of the quantized output given the state is characterized by an integral equation. This integral was approximated by using a Gauss-Legendre quadrature; hence, a model with a Gaussian mixture structure was obtained. This model was used to develop filtering and smoothing algorithms. The benefits of this proposal, in terms of accuracy of the estimation and computational cost, are illustrated via numerical simulations.

Assuntos

Algoritmos , Funções Verossimilhança , Distribuição Normal

RESUMO

BACKGROUND: Even though targeted therapies are available for cancers expressing oncogenic epidermal growth receptor (EGFR) and (or) human EGFR2 (HER2), acquired or intrinsic resistance often confounds therapy success. Common mechanisms of therapy resistance involve activating receptor point mutations and (or) upregulation of signaling downstream of EGFR/HER2 to Akt and (or) mitogen activated protein kinase (MAPK) pathways. However, additional pathways of resistance may exist thus, confounding successful therapy. METHODS: To determine novel mechanisms of EGFR/HER2 therapy resistance in breast cancer, gefitinib or lapatinib resistant variants were created from SKBR3 breast cancer cells. Syngenic therapy sensitive and resistant SKBR3 variants were characterized for mechanisms of resistance by mammosphere assays, viability assays, and western blotting for total and phospho proteins. RESULTS: Gefitinib and lapatinib treatments reduced mammosphere formation in the sensitive cells, but not in the therapy resistant variants, indicating enhanced mesenchymal and cancer stem cell-like characteristics in therapy resistant cells. The therapy resistant variants did not show significant changes in known therapy resistant pathways of AKT and MAPK activities downstream of EGFR/HER2. However, these cells exhibited elevated expression and activation of the small GTPase Rac, which is a pivotal intermediate of GFR signaling in EMT and metastasis. Therefore, the potential of the Rac inhibitors EHop-016 and MBQ-167 to overcome therapy resistance was tested, and found to inhibit viability and induce apoptosis of therapy resistant cells. CONCLUSIONS: Rac inhibition may represent a viable strategy for treatment of EGFR/HER2 targeted therapy resistant breast cancer.

Assuntos

Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias da Mama/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Proteínas rac de Ligação ao GTP/antagonistas & inibidores , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apoptose , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Carbazóis/farmacologia , Carbazóis/uso terapêutico , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Feminino , Mutação com Ganho de Função , Gefitinibe/farmacologia , Gefitinibe/uso terapêutico , Regulação Neoplásica da Expressão Gênica , Humanos , Lapatinib , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/genética , Mutação Puntual , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , Receptor ErbB-2/antagonistas & inibidores , Receptor ErbB-2/genética , Esferoides Celulares , Regulação para Cima

RESUMO

Many human emergent and re-emergent diseases have a sylvatic cycle. Yet, little effort has been put into discovering and modeling the wild mammal reservoirs of dengue (DENV), particularly in the Americas. Here, we show a species-level susceptibility prediction to dengue of wild mammals in the Americas as a function of the three most important biodiversity dimensions (ecological, geographical, and phylogenetic spaces), using machine learning protocols. Model predictions showed that different species of bats would be highly susceptible to DENV infections, where susceptibility mostly depended on phylogenetic relationships among hosts and their environmental requirement. Mammal species predicted as highly susceptible coincide with sets of species that have been reported infected in field studies, but it also suggests other species that have not been previously considered or that have been captured in low numbers. Also, the environment (i.e., the distance between the species' optima in bioclimatic dimensions) in combination with geographic and phylogenetic distance is highly relevant in predicting susceptibility to DENV in wild mammals. Our results agree with previous modeling efforts indicating that temperature is an important factor determining DENV transmission, and provide novel insights regarding other relevant factors and the importance of considering wild reservoirs. This modeling framework will aid in the identification of potential DENV reservoirs for future surveillance efforts.