Programa educativo “Amigo de la madre, el niño y la niña” en el nivel de conocimiento sobre lactancia materna en madres primiparas en el programa de crecimiento y desarrollo del niño en el Hospital Domingo Olavegoya – Jauja - 2019

La tesis “Programa educativo “Amigo de la madre, el niño y la niña” en el nivel de conocimiento sobre lactancia materna en madres primíparas en el Programa de Crecimiento y Desarrollo del niño en el Hospital Domingo Olavegoya – Jauja – 2019”, el desarrollo de intervenciones educativas para la promoción y prevención de la enfermedad, es una de las acciones más importantes que desarrolla el profesional de enfermería, ya que garantiza una calidad de vida adecuada, como es el caso de la buena nutrición de los recién nacidos mediante el uso de la lactancia materna. Esta investigación tuvo como objetivo Determinar el efecto del programa educativo “Amigo de la madre, el niño y la niña” sobre el nivel de conocimiento de lactancia materna en madres primíparas atendidas en el Programa de Crecimiento y Desarrollo del niño en el Hospital Domingo Olavegoya, Jauja, 2019. el tipo de investigación fue Explicativo, longitudinal, prospectivo, pre experimental y cuantitativa. La población estuvo conformada por 46 madres, por el tamaño mínimo de población no se trabajó en muestra, solo se tuvo en cuenta los criterios de inclusión y exclusión, llegando a aplicarse a 40 madres primíparas. La técnica utilizada para la recolección de datos fue la encuesta con un cuestionario para evaluar el nivel de conocimientos, se evaluó las siguientes dimensiones: aspectos generales, técnicas de amamantamiento y extracción de la leche materna; Los datos obtenidos a través de los cuestionarios fueron procesados con el programa Excel y SPSS. Los resultados muestran que el nivel de conocimientos sobre aspectos generales de la lactancia materna, el 78.38% de madres con nivel de conocimiento bajo en el pre test, presentan un nivel de conocimiento alto en el post test (p<0.05), sobre técnicas de lactancia materna, el 75.0% de madres con nivel de conocimiento 10 bajo en el pre test, presentan un nivel de conocimiento alto en el post test (p<0.05), sobre técnicas de extracción de leche materna, el 36.7% de madres con nivel de conocimiento bajo en el pre test, presentan un nivel de conocimiento alto en el post test. (p< 0.05).Tesis de segunda especialida

Amiloidosis Secundaria o Sistemática: Diagnóstico por la Biopsia Oral y por Patología Clínica en Relación con Pacientes Portadores de Enfermedades Crónicas en Especial TBC Crónica

The present investigation incluided: 100 samples, 20 control groups (Universidad Nacional Agraria students), and 80 patients infected with HIVIAIDS; 25 with level If, 35 with level III, and 20patients with level IV. Average proteinic fractions and salivary percentage were taken: Albumin 45.15%, SALIVARY ALBUMIN 15.2%, GAMMAGLOBULIN 75.94% (SIGNIFICANCE LEVEL 1.00%). Problem Sample.- In the problem sample we can see a considerable alteration in the serical electrophorelics proteins. Spit: level II, 22.12% albumin, gammaglobulin 77.64%, level III, albumin 16.35%, gammaglobulin 83.49%. IV 7.71% albumin and 92.37% gammaglobulim. There is a diferrential relationship between normal values of serical gammaglobulim and salivary ones, in HIV/AIDS infected patiens and there is an increase of bucal pathologies.Tiene caracteres investigatorios ver el depósito anormal de sustancial amiloide en la mucosa oral, mediante la biopsia inocua de las áreas lateral gingival y dérmica (psoriatica) en 20 casos patológicos de pacientes enfermedad inflamatoria crónica, de larga evolución. Así como la aplicación de una adecuada historia clínica implementada en todos los pacientes en los diferentes hospitales y centros asistenciales donde practicando las incisiones operatorias, donde comunicamos y solicitamos el adecuado permiso para nuestra investigación clínica anátomo patológica, con la asepsia adecuada; la aplicación de anestésicos de cirugía menor anticoagulantes y la fijación posterior del espécimen quirúrgico en formalina neutra al 10% para su inclusión de parafina, cortes de pocas micras y las coloraciones de hematoxilina-Eosina y la especifica de Rojo de Congo para buscar en ellos la presencia de amiloide secundaria a proceso inflamatorio especifico y no especifico.Se determinó en la Historia clínica de cada uno de los pacientes todos los datos nosográficos de edad, raza, talla, tiempo de evolución de ella como la T.B.C. terciaria, reumatismo, abscesos, alteraciones de la gingiva y del peridontio para correlacionar el tiempo del depósito y el probable factor etiopatogénico inmunológico de dicha enfermedad y con ello sugerir alguna medida terapéutica clínica aplicar a dichos pacientes, con proyección a la comunidad de pueblos jóvenes donde imperan estos tipos de enfermedades como la TBC y nefritis que pueden provocar un incremento de la morbilidad y mortalidad, como insuficiencias renales o respiratorias y hacer factor de prevención y promoción clínica de estos males clínicos que estamos llanos a curarlos con mucho tiempo de anticipación o prevención terapéutica con tuberculostativos gratuitos y antibióticos de alta degeneraci6n y con ello evitar la hemodiálisis y la intubación traqueal o toráxica en graves problemas de Anoxia e Hipoxia, de alto costo y son tratamientos finales paliativos

Significant benefits of AIP testing and clinical screening in familial isolated and young-onset pituitary tumors

Context Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs). Objective To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients. Design 12-year prospective, observational study. Participants & Setting We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases. Interventions & Outcome AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310). Results Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650). Conclusions Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course

Development and Testing of Pharmacological Tools to Evaluate the Role of Protease-Activated Receptor-2 in Allergic Asthma

Despite the variety of asthma pharmacotherapy options that exist, a large subset of asthma patients present with poorly controlled disease. Extensive studies supporting a central role for Protease-Activated Receptor-2 (PAR2) in allergic asthma pathophysiology have promoted drug development efforts towards this molecular target. I report here that PAR2 antagonist C391 blocks signaling and symptoms caused by the asthma causing allergen Alternaria alternata. I show C391 effectively inhibits A. alternata-induced PAR2-MAPK and -Ca2+ signaling in vitro and attenuates asthma symptom development (e.g. airway hyperresponsiveness, excessive mucus production, and inflammation) in a murine model of asthma. Use of in vitro studies enable the cell-specific examination of PAR2 contribution to A. alternata-induced airway inflammation. I show PAR2 signaling plays an important role in the initiation of asthma through the finding that PAR2 signaling is required for full cytokine and chemokine release from A. alternata-exposed epithelial cells when I compare release from parental cells and CRISPR-produced PAR2 knockout cells. C391 inhibition of PAR2 signaling in A. alternata-induced lymphocyte migration reveal PAR2 signaling is required for effective chemotaxis. Finally, I show development and screening of three novel PAR2 ligands, C732, C781 and C782. Cell impedance screening and PAR2 binding assessment highlight C781 as a lead compound for asthma therapy. Further PAR2 signaling characterization reveals C781 to be a PAR2-specific, biased MAPK antagonist. My studies demonstrate for the first time that a PAR2-specific antagonist provides pharmacological control of asthma in a pre-clinical model and presents novel lead compounds for improved drug development.Release after 11/20/201

The HSP90 Inhibitor Ganetespib Synergizes with the MET Kinase Inhibitor Crizotinib in both Crizotinib-Sensitive and -Resistant MET-Driven Tumor Models

The proto-oncogene MET is aberrantly activated via overexpression or mutation in numerous cancers, making it a prime anticancer molecular target. However, the clinical success of MET-directed tyrosine kinase inhibitors (TKI) has been limited due, in part, to mutations in the MET kinase domain that confer therapeutic resistance. Circumventing this problem remains a key challenge to improving durable responses in patients receiving MET-targeted therapy. MET is an HSP90-dependent kinase, and in this report we show that HSP90 preferentially interacts with and stabilizes activated MET, regardless of whether the activation is ligand-dependent or is a consequence of kinase domain mutation. In contrast, many MET-TKI show a preference for the inactive form of the kinase, and activating mutations in MET can confer resistance. Combining the HSP90 inhibitor ganetespib with the MET-TKI crizotinib achieves synergistic inhibition of MET, its downstream signaling pathways, and tumor growth in both TKI-sensitive and -resistant MET-driven tumor models. These data suggest that inclusion of an HSP90 inhibitor can partially restore TKI sensitivity to previously resistant MET mutants, and they provide the foundation for clinical evaluation of this therapeutic combination in patients with MET-driven cancers. (C)2013 AACR

PAR2 antagonist C391

Background and purposeProteinase-activated receptor-2 (PAR2) is a GPCR linked to diverse pathologies, including acute and chronic pain. PAR2 is one of the four PARs that are activated by proteolytic cleavage of the extracellular amino terminus, resulting in an exposed, tethered peptide agonist. Several peptide and peptidomimetic agonists, with high potency and efficacy, have been developed to probe the functions of PAR2, in vitro and in vivo. However, few similarly potent and effective antagonists have been described.Experimental approachWe modified the peptidomimetic PAR2 agonist, 2-furoyl-LIGRLO-NH2 , to create a novel PAR2 peptidomimetic ligand, C391. C391 was evaluated for PAR2 agonist/antagonist activity to PAR2 across Gq signalling pathways using the naturally expressing PAR2 cell line 16HBE14o-. For antagonist studies, a highly potent and specific peptidomimetic agonist (2-aminothiazo-4-yl-LIGRL-NH2 ) and proteinase agonist (trypsin) were used to activate PAR2. C391 was also evaluated in vivo for reduction of thermal hyperalgesia, mediated by mast cell degranulation, in mice.Key resultsC391 is a potent and specific peptidomimetic antagonist, blocking multiple signalling pathways (Gq -dependent Ca2+ , MAPK) induced following peptidomimetic or proteinase activation of human PAR2. In a PAR2-dependent behavioural assay in mice, C391 dose-dependently (75 μg maximum effect) blocked the thermal hyperalgesia, mediated by mast cell degranulation.Conclusions and implicationsC391 is the first low MW antagonist to block both PAR2 Ca2+ and MAPK signalling pathways activated by peptidomimetics and/or proteinase activation. C391 represents a new molecular structure for PAR2 antagonism and can serve as a basis for further development for this important therapeutic target

Client Proteins and Small Molecule Inhibitors Display Distinct Binding Preferences for Constitutive and Stress-Induced HSP90 Isoforms and Their Conformationally Restricted Mutants.

The two cytosolic/nuclear isoforms of the molecular chaperone HSP90, stress-inducible HSP90α and constitutively expressed HSP90β, fold, assemble and maintain the three-dimensional structure of numerous client proteins. Because many HSP90 clients are important in cancer, several HSP90 inhibitors have been evaluated in the clinic. However, little is known concerning possible unique isoform or conformational preferences of either individual HSP90 clients or inhibitors. In this report, we compare the relative interaction strength of both HSP90α and HSP90β with the transcription factors HSF1 and HIF1α, the kinases ERBB2 and MET, the E3-ubiquitin ligases KEAP1 and RHOBTB2, and the HSP90 inhibitors geldanamycin and ganetespib. We observed unexpected differences in relative client and drug preferences for the two HSP90 isoforms, with HSP90α binding each client protein with greater apparent affinity compared to HSP90β, while HSP90β bound each inhibitor with greater relative interaction strength compared to HSP90α. Stable HSP90 interaction was associated with reduced client activity. Using a defined set of HSP90 conformational mutants, we found that some clients interact strongly with a single, ATP-stabilized HSP90 conformation, only transiently populated during the dynamic HSP90 chaperone cycle, while other clients interact equally with multiple HSP90 conformations. These data suggest different functional requirements among HSP90 clientele that, for some clients, are likely to be ATP-independent. Lastly, the two inhibitors examined, although sharing the same binding site, were differentially able to access distinct HSP90 conformational states