Neurological and neuropsychological sequelae of Zika virus infection in children in León, Nicaragua / Secuelas neurológicas y neuropsicológicas de la infección por el virus del Zika en niños y niñas en León, Nicaragua / Sequelas neurológicas e neuropsicológicas da infecção pelo vírus zika em crianças em León, Nicarágua

ABSTRACT Objectives. To describe the presence and persistence of neurological and neuropsychological sequelae among children with acquired Zika virus infection and assess whether those sequelae were more common in children infected with Zika virus compared to uninfected children. Methods. We conducted a prospective cohort study of children with and without Zika virus infection in León, Nicaragua, using a standard clinical assessment tool and questionnaire to collect data on symptoms at three visits, about 6 months apart, and a battery of standardized instruments to evaluate neurocognitive function, behavior, depression, and anxiety at the last two visits. Results. Sixty-two children were enrolled, with no significant differences in demographics by infection group. Children infected with Zika virus had a range of neurological symptoms, some of which persisted for 6 to 12 months; however, no consistent pattern of symptoms was observed. At baseline a small percentage of children infected with Zika virus had an abnormal finger-to-nose test (13%), cold touch response (13%), and vibration response (15%) versus 0% in the uninfected group. Neurocognitive deficits and behavioral problems were common in both groups, with no significant differences between the groups. Children infected with Zika virus had lower cognitive efficiency scores at the 6-month visit. Anxiety and depression were infrequent in both groups. Conclusions. Larger studies are needed to definitively investigate the relationship between Zika virus infection and neurological symptoms and neurocognitive problems, with adjustment for factors affecting cognition and behavior, including mood and sleep disorders, home learning environment, history of neuroinvasive infections, and detailed family history of neuropsychological problems.

RESUMEN Objetivos. Describir la presencia y persistencia de secuelas neurológicas y neuropsicológicas en pacientes pediátricos que contrajeron la infección por el virus del Zika y evaluar si dichas secuelas fueron más comunes en los infectados con el virus del Zika en comparación con los no infectados. Métodos. Se realizó un estudio de cohorte prospectivo en pacientes pediátricos con y sin infección por el virus del Zika en León (Nicaragua), con una herramienta de evaluación clínica estándar y un cuestionario para recopilar datos sobre los síntomas en tres visitas, con aproximadamente seis meses de diferencia, y un conjunto de instrumentos estandarizados para evaluar la función neurocognitiva, el comportamiento, la depresión y la ansiedad en las últimas dos visitas. Resultados. Participaron 62 niños y niñas sin diferencias significativas en la demografía por grupo de infección. Los participantes infectados con el virus del Zika mostraron una variedad de síntomas neurológicos, algunos de los cuales persistieron entre 6 y 12 meses; no obstante, no se observó un patrón sistemático en los síntomas. Al inicio del estudio, un pequeño porcentaje de participantes infectados con el virus del Zika mostró resultados anormales a las pruebas dedo-nariz (13%), respuesta al tacto (frío) (13%) y respuesta a la vibración (15%), frente a un 0% en el grupo no infectado. Los déficits neurocognitivos y los problemas de comportamiento fueron comunes en ambos grupos, sin diferencias significativas entre los grupos. Los participantes infectados con el virus del Zika mostraron puntuaciones de eficiencia cognitiva más bajas en la visita a los 6 meses. La ansiedad y la depresión fueron poco frecuentes en ambos grupos. Conclusiones. Son necesarios estudios más amplios para investigar definitivamente la relación entre la infección por el virus del Zika y los síntomas neurológicos y los problemas neurocognitivos, haciendo ajustes para los factores relacionados con la cognición y el comportamiento, incluidos los trastornos del estado de ánimo y el sueño, el entorno de aprendizaje en el hogar, los antecedentes de infecciones neuroinvasivas y los antecedentes familiares detallados de problemas neuropsicológicos.

RESUMO Objetivos. Descrever a presença e a persistência de sequelas neurológicas e neuropsicológicas em crianças com infecção pelo vírus zika e avaliar se essas sequelas foram mais comuns em crianças infectadas pelo vírus zika em comparação com crianças não infectadas. Métodos. Realizamos um estudo de coorte prospectivo em crianças com e sem infecção pelo vírus zika em León, Nicarágua, usando uma ferramenta de avaliação clínica padrão e um questionário para coletar dados de sintomas em três consultas, com cerca de 6 meses de intervalo, além de um conjunto de ferramentas padronizadas para avaliar função neurocognitiva, comportamento, depressão e ansiedade nas duas últimas consultas. Resultados. Foram incluídas 62 crianças, sem diferenças significativas nas características demográficas por grupo de infecção. As crianças infectadas pelo vírus zika tinham uma gama de sintomas neurológicos, alguns dos quais persistiram por 6 a 12 meses. Entretanto, não se observou nenhum padrão consistente de sintomas. No início do estudo, uma pequena porcentagem de crianças infectadas com o vírus zika apresentou resultado anormal na prova índex-nariz (13%), resposta ao toque frio (13%) e sensibilidade vibratória (15%), em comparação a 0% no grupo não infectado. Déficits neurocognitivos e problemas comportamentais foram frequentes em ambos os grupos, mas sem diferenças significativas entre eles. As crianças infectadas com o vírus zika tiveram resultados mais baixos de eficiência cognitiva na consulta de 6 meses. Ansiedade e depressão não foram observadas com frequência em ambos os grupos. Conclusões. São necessários estudos mais amplos para investigar a relação exata entre a infecção pelo vírus zika e sintomas neurológicos e problemas neurocognitivos, com ajuste para fatores que afetam a cognição e o comportamento, incluindo distúrbios do humor e do sono, ambiente de aprendizagem em casa, história de infecções neuroinvasivas e história familiar detalhada de problemas neuropsicológicos.

Acciones para la preparación pedagógica de los alumnos ayudante en ciencias básicas biomédicas / Actions aimed at the pedagogical training of student teachers of basic biomedical sciences

Introducción: El proceso de formación docente en las ciencias médicas, específicamente en las ciencias básicas biomédicas, exige de nuevas concepciones teóricas y metodológicas en la actualidad. Objetivo: Elaborar acciones que favorezcan la preparación de los alumnos ayudantes en ciencias básicas biomédicas desde una perspectiva pedagógica. Métodos: Se realizó un estudio descriptivo, con enfoque cualicuantitativo en la Facultad de Ciencias Médicas de Artemisa, en el período comprendido desde noviembre de 2018 hasta octubre de 2019. Se utilizaron métodos teóricos: análisis-síntesis e inducción-deducción para los referentes teóricos del tema; y empíricos: revisión documental, encuesta a estudiantes, observación científica y entrevista a informantes clave. Resultados: Los resultados mostraron que existen insuficiencias en los alumnos ayudante de ciencias básicas biomédicas acerca del conocimiento de sus funciones pedagógicas, la mayoría no mostró motivación para impartir docencia, no poseen los conocimientos esenciales básicos sobre la pedagogía y el proceso de enseñanza-aprendizaje, necesarias para su desempeño, por lo que se elaboraron acciones científico-metodológicas para resolver estas carencias. Conclusiones: Las acciones elaboradas fortalecen el dominio de la pedagogía en la formación de los alumnos ayudantes para su futuro desempeño como profesionales de las ciencias de la salud, vinculados a la docencia de las ciencias básicas biomédicas y fueron valoradas por los especialistas como pertinentes, factibles y de gran valor pedagógico

Introduction: At present the teacher training process in medical sciences, particularly in basic biomedical sciences, requires new theoretical and methodological foundations. Objective: Develop actions contributing to the training of student teachers of basic biomedical sciences from a pedagogical perspective. Methods: A descriptive qualitative-quantitative study was conducted at the School of Medical Sciences of Artemisa from November 2018 to October 2019. The theoretical methods applied were analysis-synthesis and induction-deduction for the theoretical referents of the topic. The empirical methods used were document review, a survey with students, scientific observation and an interview with key informants. Results: Results point to the existence of deficiencies among student teachers of basic biomedical sciences concerning knowledge about their pedagogical functions. Most did not show any motivation to teach and do not have the basic essential knowledge about pedagogy and the teaching-learning process required for their work. Scientific-methodological actions were developed to correct such deficiencies. Conclusions: The actions developed strengthen the command of pedagogy in the training of student teachers for their future work as health science professionals involved in the teaching of basic biomedical sciences. These actions were evaluated by specialists as relevant, feasible and of great pedagogical value

Calidad de los formatos escritos del consentimiento informado en pacientes graves / Quality of written forms of informed consent in critically ill patients

RESUMEN Fundamentación: el consentimiento informado es un proceso cuyo objetivo es el respeto a la autonomía del paciente y consta de la aceptación verbal y escrita de una intervención médica, después que el médico le haya informado de forma adecuada. Objetivo: evaluar la calidad de los formatos escritos de consentimiento informado en pacientes graves. Métodos: se realizó un estudio descriptivo trasversal con 335 formatos escritos del consentimiento informado aplicados a familiares y pacientes ingresados en la Unidad de Cuidados Intensivos del Hospital Joaquín Albarrán Domínguez, La Habana, Cuba, del 30 de septiembre de 2017 al 22 de septiembre de 2018. Se realizó la prueba de Chi cuadrado a las frecuencias de los cumplimientos. Fue significativo un valor de p ≤ 0,05. Resultados: aunque el predominio de los formatos escritos fue en pacientes con perfil clínico, los mejores documentos fueron los de perfil quirúrgico. El cumplimiento de los datos generales de los formatos escritos fue adecuado, sin embargo, los formularios del perfil clínico, no cumplieron adecuadamente con la información respecto a los procederes médicos, fue pobre la evacuación de las dudas respecto a la condición médica de los pacientes. En ningún caso se solicitó el autorizo para investigaciones médicas ni se entregó copia del documento escrito a los interesados. Conclusiones: la calidad de los formatos fue mala, aún hay que mejorar la calidad de la información e implementar de manera habitual la solicitud para investigaciones médicas y mecanismos que faciliten la entrega de una copia del documento escrito.

ABSTRACT Background: Informed Consent is the acceptance of a medical intervention by a patient, in a free, voluntary and conscious way, after the doctor has informed him of the nature of the intervention, risks, benefits and alternatives. Objective: to assess the quality of structure and content of the informed consent forms in severe patients. Methods: cross-sectional retrospective descriptive study was carried out with 335 IC written forms applied to family members and/or patients admitted to the Intensive Care Unit of the Joaquín Albarrán Domínguez Hospital, Havana, Cuba, from September 30, 2017 to September 22, 2018. The Chi-square test was performed the frequencies of compliance. A value of p ≤ 0.05 was significant. Results: predominantly, the written formats in patients with a clinical profile complied with the completion of the document and the best were those of surgical profile. In compliance with the general data in the IC written format, there was an adequate compliance, in the forms of the clinical profile, they did not comply with writing the name and description of medical procedures. There was no consent forms to authorize medical researches and it was not delivered a copy of the written document to the interested persons. Conclusions: the quality of the formats was bad, we still have to improve the information offered, clarify the doubts, as well as the request for authorization for medical research and implement mechanisms that facilitate the delivery of a copy of the written document.

The expression of oxidative stress response genes is modulated by a combination of resveratrol and N-acetylcysteine to ameliorate ototoxicity in the rat cochlea.

Aminoglycoside antibiotics are used widely in medicine despite their ototoxic side-effects. Oxidative stress and inflammation are key mechanisms determining the extent and severity of the damage. Here we evaluate the protective effect of a treatment with resveratrol plus N-acetylcysteine on the ototoxic actions of kanamycin and furosemide in the rat. Resveratrol (10 mg/kg) and N-acetylcysteine (400 mg/kg) were administered together to Wistar rats on 5 consecutive days. The second day, a concentrated solution of kanamycin and furosemide was placed on the round window to induce ototoxicity. Hearing was assessed by recording auditory brainstem responses before and 5, 16 and 23 days after the beginning of the treatment. Cochlear samples were taken at day 5 (end of the treatment) and at day 23, and targeted PCR arrays or RT-qPCR were performed to analyze oxidative balance and inflammation related genes, respectively. In addition, the cytoarchitecture and the presence of apoptosis, oxidative stress and inflammation markers were evaluated in cochlear sections. Results indicate that administration of resveratrol plus N-acetylcysteine reduced the threshold shifts induced by ototoxic drugs at high frequencies (≈10 dB), although this protective effect fades after the cessation of the treatment. Gene expression analysis showed that the treatment modulated the expression of genes involved in the cellular oxidative (Gpx1, Sod1, Ccs and Noxa1) and inflammatory (Il1b, Il4, Mpo and Ncf) responses to injury. Thus, co-administration of resveratrol and NAC, routinely used individually in patients, could reduce the ototoxic secondary effects of aminoglycosides.

Current indications for the osteoplastic flap.

INTRODUCTION AND OBJECTIVES: Endoscopic sinus surgery is the technique of choice in most of the frontal sinus diseases, both inflammatory and tumour-related. This is why the external approach using osteoplastic flap (OF) would be limited to cases with a difficult endoscopic approach. Our aim was to review the current indications of the osteoplastic flap in the treatment of frontal sinus pathology, through a retrospective study of patients undergoing this technique. METHODS: We performed a retrospective study of 14 patients who were treated with the osteoplastic flap procedure. All the surgical indication criteria, type of sinus disease, presence or absence of prior endoscopic surgery, surgical findings, complications and recurrence were reviewed. RESULTS: The pathologies found were 1 osteoma (7.1%), 3 inverted papilloma (21.4%) and 10 mucoceles (71.4%). Nine patients had a prior endoscopic surgery and 10 patients had an orbital dehiscence (9 mucocele, 1 papilloma). Frontal osteoma was Grade IV and the papilloma cases were Krouse Stage III. Surgical revision was required for 21.4%. CONCLUSIONS: The main indications for an OF in patients with inflammatory disease are lateral extension and frontal recess neo-osteogenesis. In osteoma cases, it depends on the size of the tumour. In inverted papilloma cases, the indication is multifocal implantation with origin in the anterior and lateral wall. In all cases, performing the osteoplastic flap must be individualised.

The role of gene variants of the inflammatory markers CRP and TNF-α in cardiovascular heart disease: systematic review and meta-analysis.

It is widely acknowledged that cardiovascular heart disease (CHD) has a genetic influence. Several studies have investigated the role of inflammatory markers like C-reactive protein (CRP) and tumor necrosis factor α (TNF-α) in the causation of cardiovascular diseases. Although there have been several positive studies associating CRP and TNF-α genes with CHD, the evidence is not entirely consistent. Therefore, we performed a meta-analysis to gain a better understanding into this issue. The meta-analysis was conducted with 22 articles of genetic association studies of CRP (G1059C rs1800947, C1444T rs1130864, C717T rs2794521 and G3872A rs1205) and TNF-α (C857T rs1799724, C863A rs1800630 and T1031C rs1799964) genes. To analyze the association of these variants with CHD we used the following models: allelic, additive, dominant and recessive. In addition, we performed a sub-group analysis by Caucasian population using the same four models. CRP and TNF-α gene polymorphisms showed a positive significant association with CHD. This study provides evidence that rs2794521 of the CRP gene and rs1799724, rs1800630 and rs1799964 of the TNF-α gene polymorphisms may be risk factors to manifest CHD. The analysis of rs1800947 and rs1205 of the CRP gene yielded a protective effect in the pathogenesis of this disease. Only the analysis of the rs1130864 polymorphism showed a lack of association with CHD. To have conclusive outcomes it is necessary to integrate more studies to confirm our findings.

Cell death during crisis is mediated by mitotic telomere deprotection.

Tumour formation is blocked by two barriers: replicative senescence and crisis. Senescence is triggered by short telomeres and is bypassed by disruption of tumour-suppressive pathways. After senescence bypass, cells undergo crisis, during which almost all of the cells in the population die. Cells that escape crisis harbour unstable genomes and other parameters of transformation. The mechanism of cell death during crisis remains unexplained. Here we show that human cells in crisis undergo spontaneous mitotic arrest, resulting in death during mitosis or in the following cell cycle. This phenotype is induced by loss of p53 function, and is suppressed by telomerase overexpression. Telomere fusions triggered mitotic arrest in p53-compromised non-crisis cells, indicating that such fusions are the underlying cause of cell death. Exacerbation of mitotic telomere deprotection by partial TRF2 (also known as TERF2) knockdown increased the ratio of cells that died during mitotic arrest and sensitized cancer cells to mitotic poisons. We propose a crisis pathway wherein chromosome fusions induce mitotic arrest, resulting in mitotic telomere deprotection and cell death, thereby eliminating precancerous cells from the population.

Efecto del tratamiento con extracto de propóleos rojo oral en la esteatohepatitis no alcohólica / Effect of treatment with oral red propolis extract on nonalcoholic teatohepatitis

Introducción: la esteatohepatitis no alcohólica es frecuente y puede evolucionar hacia la cirrosis. Sus opciones de tratamiento farmacológico son poco eficaces. Se conoce que los propóleos tienen acción antioxidante y antiinflamatoria y se han reportado efectos beneficiosos de los propóleos. Objetivo: identificar los cambios histológicos hepáticos en pacientes con esteatohepatitis tratados con extracto hidroalcohólico al 5 por ciento de propóleos rojo oral cubano durante un año. Métodos: se realizó un ensayo clínico aleatorizado, a doble ciegas, con grupo control, en 40 individuos de ambos sexos, entre 20 y 65 años, con índice de Kleiner entre 6 y 8, divididos en 2 grupos: propóleos y placebo. Las pruebas estadísticas aplicadas fueron chi-cuadrado y la prueba no paramétrica. Resultados: el Kleiner total en el grupo propóleos se redujo de 6 ± 0,65 a 3,15 ± 071 y en el grupo placebo de 6 ± 0,65 a 6,1 ± 0,97. En el grupo propóleos se redujeron la esteatosis, inflamación, balonamiento y fibrosis y los cambios en las enzimas hepáticas y las lipoproteínas plasmáticas fueron favorables. Conclusiones: el propóleos rojo puede ser una alternativa terapéutica para detener la progresión de la esteatohepatitis...

Introduction: nonalcoholic steatohepatitis is a common condition which may lead to cirrhosis. The existing drug therapy options are not very effective. It is a well known fact that propolis has an antioxidant and antiinflammatory effect. Reports on the benefits of propolis may be found in the literature. Objective: identify histological hepatic changes in patients with steatohepatitis treated with 5 percent hydroalcoholic oral extract of Cuban red propolis for a year. Methods: a double-blind randomized controlled clinical trial was conducted with 40 patients of both sexes aged 20-65 with 6-8 Kleiner index, who were divided in 2 groups: propolis and placebo. Statistical analysis was based on chi-square and nonparametric tests. Results: total Kleiner decreased from 6 ± 0.65 to 3.15 ± 071 in the propolis group and from 6±0.65 to 6.1±0.97 in the placebo group. In the propolis group there was also a decrease in steatosis, inflammation, ballooning and fibrosis. Changes in liver enzymes and plasmatic lipoproteins were favorable. Conclusions: red propolis may be a therapeutic alternative to stop the progress of esteatohepatitis...

Kikuchi disease with skin lesions mimicking lupus erythematosus.

BACKGROUND: Kikuchi disease (Kikuchi-Fujimoto disease, histiocytic necrotizing lymphadenitis) is a systemic illness of unkown etiology. It is characterized by cervical lymphadenopathy and fever. The skin is the most frequently affected extranodal organ. Cuta-neous Kikuchi-Fujimoto disease can mimic both clinically and histolo-gically skin lesions in lupus erythema-tosus, a disorder with which it seems to be closely related. A close follow up is required as systemic lupus erythema-tosus develop-ment has been reported. MAIN OBSERVATION: We report a case of a 23-year-old woman, who was admitted to our depart-ment with high fever, skin lesions and arthralgia. Scaly and erythematous plaques were noted on both cheeks and earlobes. In pads of feet and hands and periungual area, multiple purple papules with a perilesional erythematous halo were evident. A thoraco-abdominal computed tomography scan revealed lateral cervical, mediastinal, paratracheal, subcarinal and submandi-bular lympha-denopathy. Excisional node biopsy was consisten with Kikuchi disease with skin involvement. CONCLUSION: It has to be kept in mind that Kikuchi disease is a differential diag-nosis in case of fever, lymphade-nopathy and lupus-like skin lesions. Skin lesions in this disease and may resemble clinically and histologically to those of subacute lupus erythema-tosus or systemic erythema-tosus lupus.

p85ß phosphoinositide 3-kinase subunit regulates tumor progression.

PIK3R2 encodes a ubiquitous regulatory subunit (p85ß) of PI3K, an enzyme that generates 3-polyphosphoinositides at the plasma membrane. PI3K activation triggers cell survival and migration. We found that p85ß expression is elevated in breast and colon carcinomas and that its increased expression correlates with PI3K pathway activation and tumor progression. p85ß expression induced moderate PIP(3) generation at the cell membrane and enhanced cell invasion. In accordance, genetic alteration of pik3r2 expression levels modulated tumor progression in vivo. Increased p85ß expression thus represents a cellular strategy in cancer progression.

Drug delivery to the inner ear: strategies and their therapeutic implications for sensorineural hearing loss.

Hearing aids or cochlear implants constitute almost exclusively the treatment options currently available to patients suffering from sensorineural hearing loss and related conditions, such as noise-induced hearing loss, ototoxicity or autoimmune inner ear disease. While some systemic treatments exist, they generally exert adverse secondary effects and their efficacy is hampered by the blood-cochlear barrier that limits drug access to the inner ear. Hence, the new therapies that are being developed for hearing loss focus on strategies for direct drug delivery to the inner ear. The passive and active methods for local delivery can be categorized into two general groups: intratympanic or intracochlear. The intratympanic approach is a non-invasive method that preserves hearing and takes advantage of the permeability of the round window to gain access to the cochlea. However, this technique is limited by not knowing the dose of the drug that reaches the cochlea, (a handicap which might be overcome by the use of tagged drugs). While direct access to the inner ear by intracochlear administration avoids this problem, this method requires surgery. Currently, laboratory animals are being used to explore which therapeutic approaches are best suited to address this problem. These include cochleostomy and the insertion of devices that pump drugs into the inner ear without inducing cochlear damage. In this article, we review the different techniques under evaluation in animal models of deafness, and their potential use for drug delivery and treatment of human inner ear diseases.

Xenopus HJURP and condensin II are required for CENP-A assembly.

Centromeric protein A (CENP-A) is the epigenetic mark of centromeres. CENP-A replenishment is necessary in each cell cycle to compensate for the dilution associated to DNA replication, but how this is achieved mechanistically is largely unknown. We have developed an assay using Xenopus egg extracts that can recapitulate the spatial and temporal specificity of CENP-A deposition observed in human cells, providing us with a robust in vitro system amenable to molecular dissection. Here we show that this deposition depends on Xenopus Holliday junction-recognizing protein (xHJURP), a member of the HJURP/Scm3 family recently identified in yeast and human cells, further supporting the essential role of these chaperones in CENP-A loading. Despite little sequence homology, human HJURP can substitute for xHJURP. We also report that condensin II, but not condensin I, is required for CENP-A assembly and contributes to retention of centromeric CENP-A nucleosomes both in mitosis and interphase. We propose that the chromatin structure imposed by condensin II at centromeres enables CENP-A incorporation initiated by xHJURP.

Colonic anastomosis and colonic polyp mucosal metastasis of signet ring cell gastric adenocarcinoma.

The mucosal metastasis of adenocarcinomas located in colonic mucosa is not infrequent. We present a clinical report of a patient diagnosed with a gastric multifocal signet ring cell adenocarcinoma without any evidence of visceral dissemination with the exception of mucosal infiltration of signet ring cell adenocarcinoma in a colonic polyp and in the mucosa of previous colonic anastomosis. The histopathological study of suspect lesions in the colonic mucosa is necessary to correctly approach the treatment of these patients.

Pedunculated polyp removal by means of larynx fiberendoscopic surgery.

To evaluate the stroboscopic and acoustic results obtained with larynx fiberendoscopic surgery (LFS) to remove pedunculated vocal fold polyps. Prospective study, comparing before and after surgery results. We used a series of 31 patients, with a pedicled vocal fold polyp. To remove the pedunculated polyp, we used LFS. This technique consists of excising vocal fold injuries under local anaesthesia by means of micro tweezers using a canal larynx fiberscope. Subjects were evaluated on three occasions: before surgery, 2 and 4 weeks after surgery. After surgery, improvement obtained in stroboscopy examination was statistically significant (p < 0.001) and 100% of the patients had recovered a mucosal wave. After 4 weeks of surgery, all acoustic parameters reached normality ranges. LFS used for the removal of pedunculated vocal fold polyps produces acoustic and stroboscopic improvements, comparable to those obtained using direct laryngoscopy.

The dimeric structure and the bivalent recognition of H3K4me3 by the tumor suppressor ING4 suggests a mechanism for enhanced targeting of the HBO1 complex to chromatin.

The INhibitor of Growth (ING) family of tumor suppressors regulates the transcriptional state of chromatin by recruiting remodeling complexes to sites with histone H3 trimethylated at position K4 (H3K4me3). This modification is recognized by the plant homeodomain (PHD) present at the C-terminus in the five members of the ING family. ING4 facilitates histone H3 acetylation by the HBO1 complex. Here, we show that ING4 forms homodimers through its N-terminal domain, which folds independently into an elongated coiled-coil structure. The central region of ING4, which contains the nuclear localization sequence, is disordered and flexible and does not directly interact with p53, or does it with very low affinity, in contrast to previous findings. The NMR analysis of the full-length protein reveals that the two PHD fingers of the dimer are chemically equivalent and independent of the rest of the molecule. The detailed NMR analysis of the full-length dimeric protein binding to histone H3K4me3 shows essentially the same binding site and affinity as the isolated PHD finger. Therefore, the ING4 dimer has two identical and independent binding sites for H3K4me3 tails, which, in the context of the chromatin, could belong to the same or to different nucleosomes. These results show that ING4 is a bivalent reader of the chromatin H3K4me3 modification and suggest a mechanism for enhanced targeting of the HBO1 complex to specific chromatin sites. This mechanism could be common to other ING-containing remodeling complexes.

[Nasosinusal schwannoma]. / Schwannoma nasosinusal.

Schwannomas are tumours which grow from the most external layer of the peripheral nerves. They can appear in any part of the human anatomy, but are especially common in the head and neck region. Within this area, the most frequent location is the VIII cranial nerve (80%). Treatment is surgical.

Aplicación del propóleos en el tratamiento de la parotiditis crónica del niño / Use of propolis in pediatric chronic parotitis treatment

Objetivo: Analizar los resultados obtenidos al aplicar el propóleos como tratamiento de la parotiditis bacteriana crónica recurrente. Se aplicó propóleos como agente terapéutico y profilàctico de la parotiditis crónica recurrente, en 12 pacientes pediàtricos, a razón de 10 gotas del propóleos hidroalcohólico al 10 por ciento, con el que realizó una buchada de 2 minutos y después lo deglutió, una vez al día, durante un mes y se repitió el ciclo a los 2 meses. Se realizó seguimiento por 6 meses. La muestra estuvo dividida en 2 grupos de edades: de 18 meses a 5 años (58,3 por ciento) y mayores de 5 y hasta 12 años (41,7 por ciento). Los varones constituyeron el 41,7 por ciento de la muestra. La gravedad de la enfermedad: grave (33,3 por ciento), moderada (58,3 por ciento) y leve (8,4 por ciento). El 75 por ciento de los pacientes fueron curados y mejorados el 25 por ciento. El uso del propóleos fue eficaz en el tratamiento de la parotiditis crónica recurrente del niño, disminuyendo el uso de antibióticos convencionales(AU)

Objective: To analyze the results obtained applying the propolis in treatment of recurrent chronic bacterial parotitis. Propolis was administered as a therapeutical and prophylactic agent in 12 pediatric patients (10 drops of 10 percent hydroalcoholic propolis) with a 2 min mouthful and then swallowed, daily over a month and cycle was repeated at two months. We made a 6 month follow up. Sample was divided into 2 age groups: from 18 months to 5 years (58.3 percent) and over 5 and up to 12 years (41.7 percent). Male sex accounted for the 41.7 percent of sample. Disease severity: Severe (33.3 percent), moderate (58.3 percent) and light (8.4 percent). The 75 percent of patients were cured and the 25 percent improved, since they had some signs without need of antibiotic-therapy. The propolis use was efficacious in pediatric recurrent chronic parotitis treatment, decreasing the conventional antibiotic use(AU)

Direct drug application to the round window: a comparative study of ototoxicity in rats.

OBJECTIVE: To assess the validity of inducing ototoxicity in rats by applying a sponge soaked in kanamycin and furosemide on the round window. STUDY DESIGN: Basic, randomized, nonblind experimental study. SETTING: Animal models of cochlear damage and reliable methods of local drug delivery are fundamental to study hearing loss and to design new therapies. SUBJECTS AND METHODS: Four experimental groups of six Wistar rats with different methods of drug administration were used: (1) injection of subcutaneous kanamycin (400 mg/kg) and intravenous furosemide (100 mg/kg); (2) local application of a sponge soaked in saline close to the round window; (3) animals for which the sponge was soaked in a solution containing kanamycin (200 mg/mL) and furosemide (50 mg/mL); and (4) sham-operated rats. The tympanic bulla was exposed using a ventral approach, and a bullostomy was performed to visualize the round window membrane. Cochlear function was assessed by measuring the auditory brainstem response, and hearing thresholds in response to click and tone burst stimuli were determined as peak and interpeak latencies. At the end of the study, cochlear histology was analyzed. RESULTS: Systemic administration of kanamycin and furosemide induced profound hearing loss and severe hair cell damage. Local delivery of these ototoxic drugs caused comparable damage but avoided the systemic side effects of the drug. Sham-operated and saline control animals did not experience functional alterations. CONCLUSION: Situating a sponge soaked in kanamycin and furosemide on the round window membrane through the ventral approach is a reliable method to provoke local ototoxicity in rats.

[Endoscopic sinonasal surgery: study of 110 patients with nasal polyposis and chronic rhinosinusitis]. / Cirugía endoscópica nasosinusal: estudio de 110 pacientes con rinosinusitis crónica con pólipos.

INTRODUCTION AND OBJECTIVES: Nasal polyposis with chronic rhinosinusitis is classified as a subset of chronic rhinosinusitis. The goal of this study is to assess the results of endoscopic sinonasal surgery at our hospital for nasal polyposis with chronic rhinosinusitis. PATIENTS AND METHOD: In this review of 110 patients affected by chronic rhinosinusitis and nasal polyps treated with endoscopic sinus surgery, we focus on symptoms, degree of involvement, sinus opacity (Lund-Mackay grading system), complications, rate of improvements, and recurrences. RESULTS: Major complications did not occur. Minor complications occurred in 21 patients (19 %) with the most frequent being adhesion. Patients who suffered from asthma, aspirin intolerance, or both were related to a greater rate of recurrences. The endoscopic surgery of recurrences was not linked to a greater rate of failures. In our study, the complications rate was not related to revision surgery. The severity grading used in nasal endoscopy correlated well to the grading assigned by computerized tomography. CONCLUSIONS: The presence of asthma, aspirin intolerance, or both adversely affect endoscopic sinus surgery outcome. In this review, the rate of complications is not related to revision surgery. The staging used relates well the degree of occupation shown by the nasal endoscopy to that given by computerized tomography.

Seroepidemiological and clinical study of Chagas diseases in Nicaragua

Con el objetivo de determinar la prevalencia, perfil imunologico de la poblacion y conocer las alteraciones electrocardiograficas; se realizo un estudio seroepidemiologico y clinico de la enfermedad de Chagas en tres localidades ubicadas al Norte, Oriente y Occidente de Nicaragua. Como muestra se tomo suero a 803 personas, a las que se les realizo busqueda de anticuerpos anti T. cruzi por Immunoflurescencia (IFI) y hemaglutinacion indirecta (HAI)...