Light-Emitting Probes for Labeling Peptides

[Abstract] Peptides are versatile biopolymers composed of 2–100 amino acid residues that present a wide range of biological functions and constitute potential therapies for numerous diseases, partly due to their ability to penetrate cell membranes. However, their mechanisms of action have not been fully elucidated due to the lack of appropriate tools. Existing light-emitting probes are limited by their cytotoxicity and large size, which can alter peptide structure and function. Here, we describe the available fluorescent, bioluminescent, and chemiluminescent probes for labeling peptides, with a focus on minimalistic options.Estados Unidos. National Institute of General Medical Sciences; R35GM138201Fundação de Amparo à Pesquisa do Estado de São Paulo; 2016/10585-4Fundação de Amparo à Pesquisa do Estado de São Paulo; 2019/15871-3Xunta de Galicia; ED481A-2019/08

Iris prosthesis in traumatic aniridia as an attempt to control refractory glaucoma induced by silicone oil in the anterior chamber: case report

The objective of this report is to demonstrate the effectiveness of an iris prosthesis to treat a refractory glaucoma induced by silicone oil in the anterior chamber. This case is about a patient who suffered a trauma caused by firearm shrapnel. A vitreous-retinal surgery was performed to remove intraocular foreign matter and to realign the retina that was detached. Due to the partial traumatic aniridia, silicone oil that was introduced in the vitreous chamber to keep the retina in place migrated to the anterior chamber, resulting in the decrease of endothelium cells and uncontrollable intraocular pressure. We performed transscleral fixation of the iris prosthesis to correct these problems. After a 45-month period of evolution, sight became stable at the 1 meter finger-count distance and intra-ocular pressure at 14 mmHg We may conclude that the triad that consists of lack of: iris diaphragm, aphakia and silicone oil that could not be removed because of inexorable occurrence of detachment of the retina should lead the surgeon to consider transscleral fixation of the iris prosthesis. This procedure might control intraocular pressure and/or preserve corneal transparency, preventing silicone oil from contact with the trabecular net and the corneal endothelium.O objetivo deste trabalho é demonstrar a eficácia da prótese iriana na resolução do glaucoma refratário, provocado pela presença de óleo de silicone na câmara anterior. Trata-se de paciente que sofreu trauma por estilhaços de projétil de arma de fogo. A cirurgia vítreo-retiniana visou a remoção dos corpos estranhos intra-oculares e posicionamento da retina, que se encontrava descolada. Devido à ausência parcial do tecido iriano e a afacia, o óleo de silicone introduzido na câmara vítrea, para manter a retina colada, migrou para a câmara anterior e provocou gradativa diminuição do número de células endoteliais e aumento da pressão intra-ocular incontrolável clinicamente. Optamos pela fixação transescleral da prótese de íris para corrigir tais complicações. Após 45 meses de evolução, a acuidade visual estabilizou-se em conta dedos a 1 metro e a pressão intra-ocular em 14 mmHg. Concluímos que a tríade composta pela ausência do diafragma iriano, afacia e impossibilidade da remoção do óleo de silicone, devido a inexorável recorrência de descolamento de retina, deve levar o cirurgião a ponderar sobre a fixação transescleral da prótese de íris. Esta conduta poderá controlar a pressão intra-ocular e/ou preservar a transparência corneana, impedindo o contato do óleo de silicone com a malha trabecular e com o endotélio corneano.Universidade Federal de São Paulo (UNIFESP) Instituto da VisãoCentro Oftalmológico de CuritibaFaculdade Evangélica do ParanáUniversidade Federal de Minas GeraisUniversidade Federal do ParanáUNIFESP, Instituto da VisãoSciEL

Further Remarks on Irrational Systems and Their Applications †

Irrational Systems (ISs) are transfer functions that include terms with irrational exponents. Since such systems are ubiquitous and can be seen when solving partial differential equations, fractional-order differential equations, or non-linear differential equations; their nature seems to be strongly linked with a low-order description of distributed parameter systems. This makes ISs an appealing option for model-reduction applications and controls. In this work, we review some of the fundamental concepts behind a set of ISs that are of core importance in their stability analysis and control design. Specifically, we introduce the notion of multivalued functions, branch points, time response, and stability regions, as well as some practical applications where these systems can be encountered. The theory is accompanied by some numerical examples or simulations

Dentoalveolar comparative study between removable and fixed cribs, associated to chincup, in anterior open bite treatment

OBJECTIVE: The aim of this prospective study was to compare the dentoalveolar effects produced by two types of palatal crib, removable (Rpc+C) and fixed (Fpc+C), combined with chincup in growing patients with anterior open bite. MATERIAL AND METHODS: each group comprised 30 patients, in the mixed dentition phase, with similar cephalometric characteristics and skeletal ages. Group 1 (Rpc+C) presented initial mean age of 8.3 years and mean anterior open bite of 4.0 mm. Group 2 (Fpc+C) presented initial mean age of 8.54 years and mean anterior open bite of 4.3 mm. The evaluation period comprised 12 months between initial (T1) and second lateral radiograph (T2). The T2-T1 changes were compared cephalometrically in the 2 groups using the non-paired t-test. RESULTS: Vertical changes in the posterior dentoalveolar region were similar between the groups (about 1 mm) and no significant differences were found in molar mesialization. The Fpc+C group had in average 1.6 mm more improvement of the overbite as a result of greater maxillary incisor extrusion (1.3 mm). Patients in this group also presented less lingual tipping of maxillary incisors and more mandibular incisors uprighting. CONCLUSIONS: The Fpc+C combination was more efficient in the correction of the negative overbite mainly due to greater extrusion of the maxillary incisors. However, the Rpc+C appliance promoted better upper and lower incisor inclination, resulting in a more adequate overjet

In Vitro and In Vivo Validation of EP2-Receptor Agonism to Selectively Achieve Inhibition of Mast Cell Activity

Agonism of the prostaglandin E2 receptor, E-prostanoid receptor 2 (EP2), may represent an alternative protective mechanism in mast cell (MC)-mediated diseases. Previous studies have suggested that activation of the MC EP2 receptor prevents pathological changes in the murine models of allergic asthma. This work aimed to analytically validate the EP2 receptor on MCs as a therapeutic target. Murine MC lines and primary cultures, and MCs bearing the human immunoglobulin E (IgE) receptor were subjected to IgE-mediated activation subsequent to incubation with selective EP2 agonists. Two molecularly unrelated agonists, butaprost and CP-533536, were tested either in vitro or in 2 in vivo models of allergy. The diverse range of MC populations was consistently inhibited through selective EP2 agonism in spite of exhibiting a heterogeneous phenotype. Such inhibition occurred in both mouse and human IgE (hIgE)-mediated activation. The use of molecularly unrelated selective EP2 agonists allowed for the confirmation of the specificity of this protective mechanism. This effect was further demonstrated in 2 in vivo murine models of allergy where MCs are a key to pathological changes: cutaneous anaphylaxis in a transgenic mouse model expressing the hIgE receptor and aeroallergen-induced murine model of asthma. Selective EP2 agonism is a powerful pharmacological strategy to prevent MCs from being activated through IgE-mediated mechanisms and from causing deleterious effects. The MC EP2 receptor may be an effective pharmacological target in allergic and other MC-mediated conditions

El termómetro del distrés como prueba de cribado de ansiedad y depresión en pacientes oncológicos recién diagnosticados

Objective: The Distress Thermometer (DT) is one of the most used and studied screening tests of psychological distress in cancer patients. However, it includes many false positives. Furthermore, it has not been adequately studied with Spanish populations or with recently diagnosed patients. This research examines the diagnostic performance of the DT with a sample of Spanish recently diagnosed cancer patients. Method: The diagnostic performance of DT was assessed in a sample of 135 recently diagnosed cancer patients using the Hospital Anxiety and Depression Scale (HADS) and a semi-structured diagnostic interview as gold standard. Results: The diagnostic performance of DT was acceptable (AUC=0.79) to detect psychological distress using the HADS as gold standard. The optimal cut-off score was 4 (Sensitivity=0.89; Specificity=0.56). The diagnostic performance of DT using the HADS plus the diagnostic interview as gold standard was good (AUC=0.86).The optimal cut-off score was 6 (sensitivity=0.82; Specificity=0.76). Discussion: The DT is an appropriate screening test to detect anxiety and depressive disorders in recently diagnosed cancer patients. Increasing the cut-off score up to 6 points boosts its specificity, proving to be more useful for the detection of clinically significant distress.Objetivo: El Termómetro del Distrés (TD) es una de las pruebas de cribado de malestar emocional más utilizadas y estudiadas en pacientes oncológicos. Sin embargo, genera numerosos falsos positivos. Además, aún no ha sido convenientemente estudiado con población española, ni en muestras de pacientes recién diagnosticados. El presente estudio analiza el rendimiento diagnóstico del TD en una muestra española de pacientes oncológicos recién diagnosticados. Método: Se evaluó el rendimiento diagnóstico del TD en una muestra de 135 pacientes con diagnóstico oncológico empleando como pruebas de referencia la Escala de Ansiedad y Depresión Hospitalaria (HADS) y una entrevista diagnóstica semiestructurada. Resultados: El TD mostró un rendimiento diagnóstico aceptable (Área Bajo la Curva, ABC=0,79) para detectar malestar emocional usando la HADS como referencia. El punto de corte óptimo fue de 4 puntos (Sensibilidad=0,89; Especificidad=0,56). El rendimiento diagnóstico del TD empleando la combinación de la entrevista clínica y la HADS como referencia fue bueno (ABC=0,86). El punto de corte óptimo fue de 6 puntos (Sensibilidad=0,82; Especificidad=0,76). Conclusiones: El TD constituye una prueba de cribado adecuada para detectar trastornos ansiosos y depresivos en pacientes recién diagnosticados de cáncer. Incrementar el punto de corte a 6 supone un incremento en su especificidad, resultando más útil para la detección del malestar emocional con significación clínica

Diseño de una red con dispositivo Cisco

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Prostaglandin E2 Prevents Hyperosmolar-Induced Human Mast Cell Activation through Prostanoid Receptors EP2 and EP4.

Background: Mast cells play a critical role in allergic and inflammatory diseases, including exercise-induced bronchoconstriction (EIB) in asthma. The mechanism underlying EIB is probably related to increased airway fluid osmolarity that activates mast cells to the release inflammatory mediators. These mediators then act on bronchial smooth muscle tocause bronchoconstriction. In parallel, protective substances such as prostaglandin E2 (PGE2) are probably also released and could explain the refractory period observed in patients with EIB. Objective: This study aimed to evaluate the protective effect of PGE2 on osmotically activated mast cells, as a model of exercise-induced bronchoconstriction. Methods: We used LAD2, HMC-1, CD34-positive, and human lung mast cell lines. Cells underwent a mannitol challenge, and the effects of PGE2 and prostanoid receptor (EP) antagonists for EP14 were assayed on the activated mast cells. Betahexosaminidase release, protein phosphorylation, and calcium mobilization were assessed. Results: Mannitol both induced mast cell degranulation and activated phosphatidyl inositide 3-kinase and mitogenactivated protein kinase (MAPK) pathways, thereby causing de novo eicosanoid and cytokine synthesis. The addition of PGE2 significantly reduced mannitol-induced degranulation through EP2 and EP4 receptors, as measured by betahexosaminidase release, and consequently calcium influx. Extracellular-signal-regulated kinase 1/2, c-Jun N-terminal kinase,and p38 phosphorylation were diminished when compared with mannitol activation alone. Conclusions: Our data show a protective role for the PGE2 receptors EP2 and EP4 following osmotic changes, through the reduction of human mast cell activity caused by calcium influx impairment and MAP kinase inhibition

Activity of the cyclooxygenase 2-prostaglandin-E prostanoid receptor pathway in mice exposed to house dust mite aeroallergens, and impact of exogenous prostaglandin E2

<p>Abstract</p> <p>Background</p> <p>Prostaglandin E₂(PGE₂), experimentally administered to asthma patients or assayed in murine models, improves allergen-driven airway inflammation. The mechanisms are unknown, but fluctuations of the endogenous cyclooxygenase (COX)-2/prostaglandin/E prostanoid (EP) receptor pathway activity likely contribute to the clinical outcome. We analyzed the activity of the pathway in mice sensitized to aeroallergens, and then studied its modulation under exogenous PGE₂.</p> <p>Methods</p> <p>Mice were exposed to house dust mite (HDM) aeroallergens, a model that enable us to mimic the development of allergic asthma in humans, and were then treated with either subcutaneous PGE₂or the selective EP1/3 receptor agonist sulprostone. Simultaneously with airway responsiveness and inflammation, lung COX-2 and EP receptor mRNA expression were assessed. Levels of PGE₂, PGI₂, PGD₂were also determined in bronchoalveolar lavage fluid.</p> <p>Results</p> <p>HDM-induced airway hyperreactivity and inflammation were accompanied by increased COX-2 mRNA production. In parallel, airway PGE₂and PGI₂, but not PGD₂, were upregulated, and the EP2 receptor showed overexpression. Subcutaneous PGE₂attenuated aeroallergen-driven airway eosinophilic inflammation and reduced endogenous PGE₂and PGI₂production. Sulprostone had neither an effect on airway responsiveness or inflammation nor diminished allergen-induced COX-2 and PGE₂overexpression. Finally, lung EP2 receptor levels remained high in mice treated with PGE₂, but not in those treated with sulprostone.</p> <p>Conclusion</p> <p>The lung COX-2/PGE₂/EP2 receptor pathway is upregulated in HDM-exposed mice, possibly as an effort to attenuate allergen-induced airway inflammation. Exogenous PGE₂downregulates its endogenous counterpart but maintains EP2 overexpression, a phenomenon that might be required for administered PGE₂to exert its protective effect.</p

Delivery VET - Tu mascota, en nuestras manos siempre sanas y felices

Las mascotas en general se consideran por muchos dueños como una parte de su núcleo familiar y por consecuencia existe un gran interés y angustia por su atención, indagando que se les ofrezca productos y servicios de gran calidad a un mejor costo. Por lo que se aprecia, es un buen segmento de negocio que viene acrecentando en los recientes años continuamente y en relación a diversos análisis elaborados por consultoras nacionales y extranjeros se avizora que continua un ritmo de crecimiento existente durante los años venideros. El actual trabajo que presentamos de investigación tiene como meta evolucionar un plan de marketing estratégico-operativo, financiero con indicadores; que admita integrar las múltiples herramientas del Plan de Negocio para ratificar la sostenibilidad y crecimiento del negocio. Nuestra Clínica Veterinaria “Delivery VET – Tu Mascota, en nuestras manos siempre sanas y felices”, se encuentra ubicado en Magdalena, provincia de Lima y departamento de Lima; y es una compañía que dará servicios con inversión oriunda peruana (inversionistas), con un préstamo de capital de trabajo; que propone servicios de veterinaria prioritariamente de consultas médicas en nuestro local de forma delivery para mascotas caninas. De acuerdo a la evaluación financiera en su segundo año de funcionamiento se ha de presentar un desarrollo positivo en sus ingresos. Para este contenido del actual trabajo de investigación se ha llevado a cabo una búsqueda apoyada en informaciones iniciales y secundarias. Las informaciones secundarias usadas fueron la base de datos de encuestas de las clínicas veterinarias aledañas a Magdalena (Lince y Jesús María), diversos libros, artículos, recortes de revistas, algunas tesis que guardan relación, informaciones en varios medios locales, cuadros estadísticos, algunas normas legales que están vigentes y exploraciones en Internet. Las raíces de testimonio inicial usadas son las entrevistas a personas con mascotas. Algunas de estas entrevistas fueron realizadas a médicos veterinarios que laboran o son dueños de clínicas enfocadas a veterinarias y también fueron elaboradas a clientes de gran potencial (dueños de mascotas), con el propósito de conseguir un dato relevante que a su vez permita hacer un diseño con diferentes y mejores maniobras y acciones que deben de establecerse por el negocio. Luego de un estudio de la empresa: se definen las metas, maniobras, acciones e hitos de control para el negocio; con el fin de garantizar el sostén y el aumento de forma progresiva de este negocio con un análisis a 5 años. Además, a través de esta investigar, es posible definir el rasgo de nuestro cliente y las particularidades de la sección del mercado objetivo; ya que a partir de ello debamos determinar la meta a pequeño, medio y extenso plazo. Por lo tanto, se define un plan de marketing estratégico-operativo, financiero con indicadores, con unas acciones a pequeño plazo que tendrá que desarrollar el negocio para poder cumplir con las diversas exigencias de los usuarios e inclusive rebasar sus propias posibilidades. En vista que varios usuarios valoran a su animal como un integrante de su familia, debe tenerse en mención el temperamento emocional (como base) cuando se tomen definiciones por parte del dueño de las mascotas, al instante de elegir la compra de un producto o servicio. Como punto final, se encontró que el clima (estacionalidad) es un buen factor que interviene en la continuidad de visitas a las diversas clínicas de veterinaria, punto que se debe considerar en nuestra propuesta de servicio delivery (pero se deberá manejar con estrategias adecuadas de comunicación, marketing y promociones) que tiene que impactar de manera positiva en los ingresos del negocio.Trabajo de investigaciónCampus Lima Centr