Effects of lack of microRNA-34 on the neural circuitry underlying the stress response and anxiety

Stress-related psychiatric disorders, including anxiety, are complex diseases that have genetic, and environmental causes. Stressful experiences increase the release of prefrontal amygdala neurotransmitters, a response that is relevant to cognitive, emotional, and behavioral coping. Moreover, exposure to stress elicits anxiety-like behavior and dendritic remodeling in the amygdala. Members of the miR-34 family have been suggested to regulate synaptic plasticity and neurotransmission processes, which mediate stress-related disorders. Using mice that harbored targeted deletions of all 3 members of the miR-34-family (miR-34-TKO), we evaluated acute stress-induced basolateral amygdala (BLA)-GABAergic and medial prefrontal cortex (mpFC) aminergic outflow by intracerebral in vivo microdialysis. Moreover, we also examined fear conditioning/extinction, stress-induced anxiety, and dendritic remodeling in the BLA of stress-exposed TKO mice. We found that TKO mice showed resilience to stress-induced anxiety and facilitation in fear extinction. Accordingly, no significant increase was evident in aminergic prefrontal or amygdala GABA release, and no significant acute stress-induced amygdalar dendritic remodeling was observed in TKO mice. Differential GRM7, 5-HT2C, and CRFR1 mRNA expressionwas noted in the mpFC and BLA between TKO andWT mice. Our data demonstrate that the miR-34 has a critical function in regulating the behavioral and neurochemical response to acute stress and in inducing stress-related amygdala neuroplasticity

Efecto protector de oleuropeina en inflamación intestinal

La colitis ulcerosa (CU) es un desorden inflamatorio intestinal crónico que se caracteriza por la inflamación recurrente del colon. Debido a su desconocida etiología, la búsqueda de nuevos tratamientos farmacológicos está enfocada a mejorar la calidad de vida de los pacientes y reducir la inflamación. Sin embargo, aún con un amplio espectro de medicamentos, un cierto porcentaje de pacientes son resistentes a estas terapias, y además, los efectos secundarios asociados son elevados y, algunos de ellos muy graves. A esto se le suma la aparición de cáncer colorectal asociado a colitis en un 25-40% de los pacientes, tras 40 años de enfermedad. En este sentido, la búsqueda en la medicina complementaria alternativa, en concreto en el uso de plantas medicinales y productos naturales, ha resurgido en los últimos años. Oleuropeina es un secoiridoide aislado de las hojas del olivo y los frutos verdes de Olea oleuropaea L. El efecto antiinflamatorio de oleuropeina se ha comprobado en numerosos modelos de inflamación y en la presente Tesis Doctoral, se evalúa el efecto protector de oleuropeina en inflamación intestinal. Tras llevar a cabo un modelo de colitis aguda inducida por dextrano sulfato sódico (DSS) al 5% en ratones Balb/C, la administración de 1% de oleuropeina en la dieta protege frente los signos cínicos de la inflamación, reduce la concentración en tejido de marcadores inflamatorios e inhibe la activación de distintas vías de señalización. Por otra parte, el incremento de la expresión génica de la proteína antiinflamatoria anexina A1, deja entrever un posible efecto sobre los mecanismos protectores endógenos. Además, en este mismo modelo, reduce la respuesta th17. En un modelo de colitis crónica inducida por 4 ciclos de DSS al 1-2% en ratones C57BL/6, se volvió a comprobar que oleuropeina, en este caso a 0,25% suplementada en la dieta, reduce la inflamación intestinal, inhibe la liberación y expresión de proteínas proinflamatorias, aumenta la expresión de anexina A1, reduce la fosforilación de p38 MAPK y aumenta la activación del factor Nrf2, encargado de sintetizar enzimas anti-oxidantes. Una vez observada la actividad antiinflamatoria de oleuropeina en la inflamación intestinal, se procede al estudio del efecto quimiopreventivo del compuesto en un modelo de CRC asociado a CU inducido por azoximetano (AOM) y DSS en ratones C57BL/6. El tratamiento de oleuropeina a 100 mg/kg reduce la aparición de tumores en el colon y mejora los síntomas clínicos asociados al CRC. Además, inhibe la proliferación celular en el intestino, reduce los niveles de citocinas y proteínas inflamatorias, y actúa sobre la activación de vías de señalización implicadas en el CRC. Oleuropeina también posee un efecto cicatrizante, tal y como se demuestra en un modelo de cicatrización en placa con la línea celular IEC-18. Sin embargo, en macrófagos peritoneales, se observa que oleuropeina no presenta ningún efecto, sino que es su metabolito, el hidroxitirosol, el que inhibe la activación de las células. En resumen, oleuropeina presenta un efecto protector frente a la inflamación intestinal, actúa como agente quimiopreventivo en un modelo de CRC en animales, lo que podría presentarse como un tratamiento potencial para la colitis ulcerosa

Legius syndrome: Case report and review of literature

A 8-month-old child was referred to our Dermatologic Unit for suspected Neurofibromatosis type 1 (NF 1), because of the appearance, since few days after birth, of numerous caf\ue9-au-lait spots (seven larger than 5 mm); no other sign evocative of NF 1 was found. Her family history was remarkable for the presence of multiple caf\ue9-au-lait spots in the mother, the grandfather and two aunts. The family had been already examined for NF 1, but no sign evocative of the disease was found. We then suspected Legius syndrome, a dominant disease characterized by a mild neurofibromatosis 1 phenotype. The diagnosis was confirmed by the finding of a mutation in SPRED1 gene, a feedback regulator of RAS/MAPK signaling. Here, we discuss the differential diagnosis of caf\ue8-au-lait spots and we briefly review the existing literature about Legius syndrome

El Liderazgo Transformacional y el Desempeño Docente de los Profesores de la Institución Particular San Antonio Huamancaca Chico - 2018

El presente trabajo de investigación titulada, responde a la interrogante ¿Cuál es la relación que existe entre el liderazgo transformacional y el desempeño docente de los profesores de la Institución Educativa Particular San Antonio de Huamancaca Chico, en el periodo 2018? y tiene como propósito principal determinar la relación que existe entre el liderazgo transformacional y el desempeño docente de los profesores de la Institución Educativa Particular San Antonio de Huamancaca Chico, en el periodo 2018. El trabajo es de tipo básica, de nivel correlacional, de diseño no experimental, específicamente transeccional, cuya hipótesis planteada es: La relación que existe entre el liderazgo transformacional y el desempeño docente de los profesores de la Institución Educativa Particular San Antonio de Huamancaca Chico, en el periodo 2018, es significativa; la población de docentes evaluados validacoionson 15, los instrumentos utilizados fueron el cuestionario y la guía de entrevista las cuales fueron validados por juicio de expertos y el Alfa de Cronbach. Como resultado final el nivel de significancia y los criterios de aceptación y rechazo de la hipótesis nula, concluimos que existe suficiente evidencia estadística para aceptar la hipótesis general (alterna) y rechazar la hipótesis nula. Ya que el nivel de significancia (bilateral) es menor al nivel de significancia (0,002 < 0,05), y al 95% de confianza el coeficiente (0,539) indica que existe una correlación positiva media

Coeliac disease in the ERA of the new ESPGHAN and BSPGHAN guidelines: a prospective cohort study

To evaluate the consequences of the last European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) guidelines for the diagnosis of coeliac disease (CD) by means of a prospective study

Iron Metabolism in the Disorders of Heme Biosynthesis

Given its remarkable property to easily switch between different oxidative states, iron is essential in countless cellular functions which involve redox reactions. At the same time, uncon- trolled interactions between iron and its surrounding milieu may be damaging to cells and tissues. Heme—the iron-chelated form of protoporphyrin IX—is a macrocyclic tetrapyrrole and a coordina- tion complex for diatomic gases, accurately engineered by evolution to exploit the catalytic, oxygen- binding, and oxidoreductive properties of iron while minimizing its damaging effects on tissues. The majority of the body production of heme is ultimately incorporated into hemoglobin within mature erythrocytes; thus, regulation of heme biosynthesis by iron is central in erythropoiesis. Additionally, heme is a cofactor in several metabolic pathways, which can be modulated by iron- dependent signals as well. Impairment in some steps of the pathway of heme biosynthesis is the main pathogenetic mechanism of two groups of diseases collectively known as porphyrias and congenital sideroblastic anemias. In porphyrias, according to the specific enzyme involved, heme precursors accumulate up to the enzyme stop in disease-specific patterns and organs. Therefore, different por- phyrias manifest themselves under strikingly different clinical pictures. In congenital sideroblastic anemias, instead, an altered utilization of mitochondrial iron by erythroid precursors leads to mito- chondrial iron overload and an accumulation of ring sideroblasts in the bone marrow. In line with the complexity of the processes involved, the role of iron in these conditions is then multifarious. This review aims to summarise the most important lines of evidence concerning the interplay be- tween iron and heme metabolism, as well as the clinical and experimental aspects of the role of iron in inherited conditions of altered heme biosynthesis

Manifestaciones corneales en las enfermedades sistémicas

Systemic diseases affecting the cornea have a wide range of manifestations. The detailed study of all pathologies that cause corneal alteration is unapproachable, so we have centered our interest in the most prevalent or characteristic of them. In this paper we have divided these pathologies in sections to facilitate their study. Pulmonar and conective tissue (like colagen, rheumatologic and idiopathic inflamatory diseases), dermatologic, cardiovascular, hematologic, digestive and hepatopancreatic diseases with corneal alteration are described. Endocrine and metabolic diseases, malnutrition and carential states are also studied, as well as some otorhinolaryngologic and genetic diseases that affect the cornea. Finally, a brie

Clinicopathological findings and risk factors associated with Cytauxzoon spp. infection in cats : A case-control study (2008-2021)

In Europe, Cytauxzoon spp. infection was documented in domestic and wild felids. Cats often develop a subclinical infection, while fatal disease is rare. Currently, information on the epidemiology, risk factors and clinicopathological findings of Cytauxzoon spp. infection remains limited and obtained by a single subject or small groups of cats. The objective of this case-control study was to evaluate clinicopathological findings and to describe risk factors associated with Cytauxzoon spp. infection in domestic cats. Infected cats (n = 39) and non-infected (n = 190) cats were selected from the database of the referral San Marco Veterinary Laboratory between 2008 and 2021. Demographic information, a preset questionnaire considering lifestyle, environment, and clinical status, and a CBC performed contextually with the PCR analysis were recorded for all cats. Data on the biochemical profile and serum protein electrophoresis were also evaluated when available. Compared to the control group, infection was more likely to occur in stray cats (24/39, 61.5%, P < 0.001), living totally/partially outdoors (36/39, 92.3%, P < 0.001), in an urban context (37/39, 94.9%, P = 0.002), taken or recently adopted from colonies (34/35, 97.1, P < 0.001), with irregular or absent parasite preventive treatments (39/39, 100%, p = 0.005), without fleas (28/35, 80%, P = 0.047) and without clinical signs (22/39, 56.4%, p = 0.026) at the time of medical evaluation. Anemia was not associated with infection, but in cats without clinical signs, the percentage of anemic-infected cats (7/22, 31.8%, P = 0.009) was higher compared to non-infected cats (5/65, 7.7%). Furthermore, a decrease in total iron serum concentration approximating the lowest reference interval [median values (IQR): 79 μg/dL (52.25) vs. 50.5 μg/dL (34), P = 0.007] was likely in infected cats. No other laboratory findings were associated with infection. Interestingly, a partial/total outdoor lifestyle was a risk factor for infection (OR: 8.58, 95% CI: 2.90-37.0, P < 0.001). In conclusion, the present study revealed that Cytauxzoon spp. infection manifests itself prevalently as a subclinical infection, based on physical examination and laboratory findings, in domestic European cats. However, subclinical infected cats were more likely to be anemic compared to non-infected

Inducción y su relación con el compromiso laboral de los colaboradores del Hotel San Eduardo E.I.R.L. Chiclayo

La investigación titulada “Inducción y su relación con el Compromiso Laboral de los Colaboradores del Hotel San Eduardo E.I.R.L. Chiclayo” tuvo como objetivo Determinar la relación entre la inducción y el compromiso laboral en el Hotel San Eduardo E.I.R.L – Chiclayo. El presente estudio muestra una metodología con diseño no experimental y de corte transversal, de tipo descriptivo - correlacional, con enfoque cuantitativo y un alcance exploratorio. Los sujetos de estudio fueron los colaboradores del Hotel, teniendo como muestra 10 colaboradores a quiénes se les aplicó un cuestionario por variable, diseñado en la escala de Likert. Los resultados revelan que mediante el coeficiente de Spearman se obtuvo la prueba de hipótesis que se realizó, donde (R = 0,227; P- Valor =0,126); lo que indica que no hay una relación estadísticamente entre la variable inducción y compromiso laboral, por lo que no se rechaza la H0 y tampoco se afirma que sea verdadera. Se concluye, que en esta investigación el Hotel aún no cuenta con un proceso adecuado de inducción para que los colaboradores realicen de manera correcta sus labores; asimismo, la productividad dentro de la empresa no es positiva a causa de la falta de compromiso laboral

Alternative splicing of the angiogenesis associated extra-domain B of fibronectin regulates the accessibility of the B-C loop of the type III repeat 8

BACKGROUND: Fibronectin (FN) is a multi-domain molecule involved in many cellular processes, including tissue repair, embryogenesis, blood clotting, and cell migration/adhesion. The biological activities of FN are mediated by exposed loops located mainly at the interdomain interfaces that interact with various molecules such as, but not only, integrins. Different FN isoforms arise from the alternative splicing of the pre-mRNA. In malignancies, the splicing pattern of FN pre-mRNA is altered; in particular, the FN isoform containing the extra-domain B (ED-B), a complete FN type III repeat constituted by 91 residues, is undetectable in normal adult tissues, but exhibits a much greater expression in fetal and tumor tissues, and is accumulated around neovasculature during angiogenic processes, thus making ED-B one of the best markers and targets of angiogenesis. The functions of ED-B are still unclear; however, it has been postulated that the insertion of an extra-domain such as ED-B modifies the domain-domain interface and may unmask loops that are otherwise cryptic, thus giving FN new potential activities. METHODOLOGY: We used the mAb C6, which reacts with ED-B containing FN, but not with ED-B-free FN and various recombinant FN fragments containing mutations, to precisely localize the epitopes recognized by the mAb C6. CONCLUSION: We formally demonstrated that the inclusion of the alternatively spliced angiogenesis-associated ED-B leads to the unmasking of the FNIII 8 B-C loop that is cryptic in FN molecules lacking ED-B. Thus, the mAb C6, in addition to providing a new reagent for angiogenesis targeting, represents a new tool for the study of the potential biological functions of the B-C loop of the repeat FNIII 8 that is unmasked during angiogenic processes