Quiste epidermoide en región parotídea. Reporte de caso y revisión de la literatura / Epidermoid cyst in the parotid region. A case report and review of the literature

Los quistes epidermoides son lesiones quísticas benignas que se desarrollan de componentes epiteliales anormales de tejido ectodérmico formado durante el periodo fetal (congénito) o por epitelio implantado después de una cirugía o trauma (adquirido). El quiste epidermoide es considerado una lesión benigna que afecta la región del pericráneo, cara, cuello, espalda y torso, el 7% de estos quistes ocurren en la región de la cabeza y el cuello y solo el 1,6% representa la cavidad oral. A continuación, se presenta un caso clínico con diagnóstico histopatológico de quiste epidermoide en la región parotídea, el cual no presentó un compromiso del parénquima glandular, el cual fue tratado mediante escisión quirúrgica completa, sin alteración o daño al nervio facial, con seguimiento postoperatorio de tres años sin recidiva.

Epidermoid cysts are benign cystic lesions that develop from abnormal epithelial components of ectodermal tissue formed during the fetal period (congenital) or from epithelium implanted after surgery or trauma (acquired). The epidermoid cyst is considered a benign lesion that usually affects the scalp, face, neck, back, and torso. 7% of these cysts occur in the head and neck, whereas the oral cavity represents only 1.6%. A clinical case is presented with a histopathological diagnosis of an epidermoid cyst in the parotid region, which did not present compromise of the glandular parenchyma, that was treated with complete surgical excision, without alteration or damage to the facial nerve, with a three-year postoperative follow-up without recurrence.

Genetic variability of populations of the white-eared opossum, Didelphis albiventris Lund 1840 (Didelphimorphia; Didelphidae) in Brazil / Variabilidade genética de populações de gambá de orelha branca, Didelphis albiventris Lund 1840 (Didelphimorphia; Didelphidae) no Brasil

Abstract Didelphis albiventris are found throughout Northeast and Central Brazil to central-southern Uruguay and it was subject of few studies in a population level. Given this, the present study investigated the genetic variability of the species using the mitochondrial molecular marker cytochrome oxidase c subunit I. We analyzed samples from the different biomes within three Brazilian regions: Northeast (Caatinga , Cerrado, and Atlantic Forest), Southeast (Cerrado , Atlantic Forest, Cerrado/Atlantic Forest, and Cerrado/Caatinga ecotones) and South (Pampa and Atlantic Forest). Software BAPs retrieved five distinct demes: dm 1, dm 2, and dm 5 that occurs in South, Northeast and Southeast regions respectively and the dm 3 and dm 4 are wide distributed in Northeast and Southeast. Population analysis performed with AMOVA, haplotype network and Mantel test estimated the veracity of the demes. The FST shows structuring for the five demes, with dm 1 (South region) isolated from the others, however the other analysis showed the Northeast/Southeast demes (dm 2-5) united, diagnosing gene flow between them, mainly at the transitional zones, in areas as far away as areas with similar latitude interval (Southeast vs South) that was not detected gene flow. In the haplotype network, the mutational steps was conclusive in split dm1 from dm 2-5 with 15 mutational steps and the Mantel test was moderated, which is explained by genetic similarity despite the great geographic distances (Northeast/Southeast). Thus, our analysis recognized two different lineages (South and Northeast/Southeast) and indicate that the biomes were not decisive in their isolation. The sharing of demes at the transitional zones and in areas with high latitudinal intervals reflects a recent ancestral polymorphism for D. albiventris. The plasticity in the occupation of the space by this species contributes in its wide dispersion capability, that is, geographical distribution. Our results revealed important implications for the management of D. albiventris in these transitional zones areas where demes were shared.

Resumo Didelphis albiventris é encontrada em todo o Nordeste e região central do Brasil até o centro-sul do Uruguai e foi alvo de poucos estudos em nível populacional. Dessa forma, o presente estudo, investiga a variabilidade genética da espécie usando o marcador molecular citocromo c oxidase subunidade I. Analisou-se amostras de diferentes biomas de três regiões brasileiras: Nordeste (Caatinga, Cerrado e Floresta Atlântica), Sudeste (Cerrado, Floresta Atlântica, ecótonos Cerrado/Floresta Atlântica e Cerrado/Caatinga) e Sul (Pampa e Floresta Atlântica). O software BAPs recuperou cinco demes distintos: dm 1, dm 2 e dm 5, que ocorrem nas regiões Sul, Nordeste e Sudeste, respectivamente, e os dm 3 e dm 4, que são amplamente distribuído no Nordeste e Sudeste. Análises populacionais realizadas com AMOVA, rede de haplótipo e teste de Mantel estimaram a veracidade das demes. O FST mostrou estruturação para as cinco demes, com dm 1 (região Sul) isolada das demais, entretanto as outras análises mostraram as demes Nordeste/Sudeste (dm 2-5) unidos, diagnosticando fluxo gênico entre elas, principalmente em zonas de transição, em áreas tão distante quanto áreas com similar intervalo de latitude (Sudeste e Sul), onde não foram detectado fluxo gênico. Na rede de haplótipo, os passos mutacionais foram conclusivos em separar dm 1 do dm 2-5 com 15 passos mutacionais, e o teste de Mantel foi moderado, o que é explicado pela similaridade genética apesar da grande distância geográfica (Nordeste/Sudeste). Assim, duas linhagens diferentes (Sul e Sudeste/Nordeste) foram encontradas, indicando que os biomas não foram decisivos em seus isolamentos. Os compartilhamentos das demes, em zonas de transição e em áreas com elevados intervalos de latitude, refletem um polimorfismo ancestral recente para D. albiventris. A plasticidade na ocupação do espaço por esta espécie contribui em sua ampla capacidade de dispersão, ou seja, distribuição geográfica. Nossos resultados revelam importantes implicações para o manejo de D. albiventris nessas áreas de zonas de transição, onde as demes são compartilhadas.

Genetic variability of populations of the white-eared opossum, Didelphis albiventris Lund 1840 (Didelphimorphia; Didelphidae) in Brazil

Abstract Didelphis albiventris are found throughout Northeast and Central Brazil to central-southern Uruguay and it was subject of few studies in a population level. Given this, the present study investigated the genetic variability of the species using the mitochondrial molecular marker cytochrome oxidase c subunit I. We analyzed samples from the different biomes within three Brazilian regions: Northeast (Caatinga , Cerrado, and Atlantic Forest), Southeast (Cerrado , Atlantic Forest, Cerrado/Atlantic Forest, and Cerrado/Caatinga ecotones) and South (Pampa and Atlantic Forest). Software BAPs retrieved five distinct demes: dm 1, dm 2, and dm 5 that occurs in South, Northeast and Southeast regions respectively and the dm 3 and dm 4 are wide distributed in Northeast and Southeast. Population analysis performed with AMOVA, haplotype network and Mantel test estimated the veracity of the demes. The FST shows structuring for the five demes, with dm 1 (South region) isolated from the others, however the other analysis showed the Northeast/Southeast demes (dm 2-5) united, diagnosing gene flow between them, mainly at the transitional zones, in areas as far away as areas with similar latitude interval (Southeast vs South) that was not detected gene flow. In the haplotype network, the mutational steps was conclusive in split dm1 from dm 2-5 with 15 mutational steps and the Mantel test was moderated, which is explained by genetic similarity despite the great geographic distances (Northeast/Southeast). Thus, our analysis recognized two different lineages (South and Northeast/Southeast) and indicate that the biomes were not decisive in their isolation. The sharing of demes at the transitional zones and in areas with high latitudinal intervals reflects a recent ancestral polymorphism for D. albiventris. The plasticity in the occupation of the space by this species contributes in its wide dispersion capability, that is, geographical distribution. Our results revealed important implications for the management of D. albiventris in these transitional zones areas where demes were shared.

Resumo Didelphis albiventris é encontrada em todo o Nordeste e região central do Brasil até o centro-sul do Uruguai e foi alvo de poucos estudos em nível populacional. Dessa forma, o presente estudo, investiga a variabilidade genética da espécie usando o marcador molecular citocromo c oxidase subunidade I. Analisou-se amostras de diferentes biomas de três regiões brasileiras: Nordeste (Caatinga, Cerrado e Floresta Atlântica), Sudeste (Cerrado, Floresta Atlântica, ecótonos Cerrado/Floresta Atlântica e Cerrado/Caatinga) e Sul (Pampa e Floresta Atlântica). O software BAPs recuperou cinco demes distintos: dm 1, dm 2 e dm 5, que ocorrem nas regiões Sul, Nordeste e Sudeste, respectivamente, e os dm 3 e dm 4, que são amplamente distribuído no Nordeste e Sudeste. Análises populacionais realizadas com AMOVA, rede de haplótipo e teste de Mantel estimaram a veracidade das demes. O FST mostrou estruturação para as cinco demes, com dm 1 (região Sul) isolada das demais, entretanto as outras análises mostraram as demes Nordeste/Sudeste (dm 2-5) unidos, diagnosticando fluxo gênico entre elas, principalmente em zonas de transição, em áreas tão distante quanto áreas com similar intervalo de latitude (Sudeste e Sul), onde não foram detectado fluxo gênico. Na rede de haplótipo, os passos mutacionais foram conclusivos em separar dm 1 do dm 2-5 com 15 passos mutacionais, e o teste de Mantel foi moderado, o que é explicado pela similaridade genética apesar da grande distância geográfica (Nordeste/Sudeste). Assim, duas linhagens diferentes (Sul e Sudeste/Nordeste) foram encontradas, indicando que os biomas não foram decisivos em seus isolamentos. Os compartilhamentos das demes, em zonas de transição e em áreas com elevados intervalos de latitude, refletem um polimorfismo ancestral recente para D. albiventris. A plasticidade na ocupação do espaço por esta espécie contribui em sua ampla capacidade de dispersão, ou seja, distribuição geográfica. Nossos resultados revelam importantes implicações para o manejo de D. albiventris nessas áreas de zonas de transição, onde as demes são compartilhadas.

Use of serum levels of high sensitivity troponin T, galectin-3 and C-terminal propeptide of type I procollagen at long term follow-up in heart failure patients with reduced ejection fraction: Comparison with soluble AXL and BNP.

BACKGROUND: Prognostic biomarkers are needed to improve the management of the heart failure (HF) epidemic, being the brain natriuretic peptides the most valuable. Here we evaluate 3 biomarkers, high sensitivity troponin T (hs-TnT), galectin-3 (Gal-3) and C-terminal propeptide of type I procollagen (CICP), compare them with a recently described new candidate (sAXL), and analyze their relationship with BNP. METHODS: HF patients with reduced ejection fraction (n=192) were included in this prospective observational study, with measurements of candidate biomarkers, functional, clinical and echocardiographic variables. A Cox regression model was used to determine predictors for clinical events, i.e. all-cause mortality and heart transplantation. RESULTS: Hs-TnT circulating values were correlated to clinical characteristics indicative of more advanced HF. When analyzing the event-free survival at a mean follow-up of 3.6years, patients in the higher quartile of either BNP, hs-TnT, CICP and sAXL had increased risk of suffering a clinical event, but not Gal-3. Combination of high sAXL and BNP values had greater predictive value (HR 6.8) than high BNP alone (HR 4.9). In a multivariate Cox regression analysis, BNP, sAXL and NYHA class were independent risk factors for clinical events. CONCLUSIONS: In this HF cohort, hs-TnT is a good HF marker and has a very significant prognostic value. The prognostic value of CICP and sAXL was of less significance. However, hs-TnT did not add predictive value to BNP, while sAXL did. This suggests that elevated troponin has a common origin with BNP, while sAXL could represent an independent pathological mechanism.

Parâmetros e ganhos genéticos em características de crescimento de bovinos Tabapuã da Bahia / Parameters and gains in genetic characteristics of Bahia Tabapuã bovine Growth

Compararam-se dois modelos (com ou sem o efeito materno) na estimativa de parâmetros genéticos por meio do fator de Bayes (FB) e do critério de informação da deviance (DIC). Adicionalmente, avaliaram-se as tendências genéticas, maternas e fenotípicas em características de crescimento de bovinos da raça Tabapuã do estado da Bahia. O modelo que incluiu o efeito materno proporcionou menores valores de FB (167629,2; 117341,2 e 124804,8) e DIC (174550,0; 120242,7 e 128037,2) para pesos aos 205 (P205), 365 (P365) e 550 (P550) dias de idade, respectivamente. As estimativas médias, a posteriori, das herdabilidades diretas e maternas foram 0,33; 0,43 e 0,44 e 0,15; 0,14 e 0,16 para as três características, respectivamente. As tendências genéticas para o efeito direto foram de 0,4415 e 0,3613kg/ano para P205 e P365 e representam incrementos de apenas 0,25 e 0,15% nas médias das características ao ano. As tendências genéticas maternas para as três características demonstraram perdas e indicam ausência de seleção de matrizes para boa habilidade materna. Apesar de existir variabilidade genética suficiente para justificar ganhos genéticos via seleção, estes e os ganhos fenotípicos foram pequenos, sugerindo necessidade de melhorias genéticas e ambientais.(AU)

We compared two models (with or without maternal effect) in the estimation of genetic parameters through Bayes Factor (BF) and the Deviance Information Criterion (DIC). Additionally, we evaluated the genetic, maternal and phenotypic trends in Tabapuã bovine growth characteristics in the state of Bahia. The model that included the maternal effect provided smaller BF values (167,629.2; 117,341.2 and 124,804.8) and DIC (174,550.0; 120,242.7 and 128,037.2) for weights at 205 (W205), 365 (W365) and 550 (W550) days of age, respectively. The average estimates, a posteriori, the direct and maternal heritability (0.33, 0.43 and 0.44) and (0.15, 0.14 and 0.16) for the three characteristics, respectively. Genetic trends for direct effect were 0.4415 and 0.3613kg/year for W205 and W365 and presented increases of 0.25 and 0.15% in the average characteristics of the year. The phenotypic trend for W205 was 0.7039kg/year. Maternal genetic trends for the three characteristics showed losses and indicate absence of selection matrices for good maternal ability. Despite the magnitude of the estimated direct and maternal heritability, they indicate genetic gain opportunities, genetic and phenotypic trends indicated few direct gains and no gains for maternal ability.(AU)

NPM1, FLT3 and CEBPA mutations in pediatric patients with AML from Argentina: incidence and prognostic value.

Mutations in NPM1, FLT3 and CEBPA genes are found in 25-35 % of adult acute myeloblastic leukemia (AML) cases and correlate with prognosis. To date, there have been no reports about these mutations in pediatric AML from Argentina. The aims of the present study were to describe the incidence of NPM1, FLT3 and CEBPA mutations and to analyze their prognostic impact in this population. The incidences of these mutations within a population of 216 pediatric AML cases were: NPM1-mutated 4.2 %, CEBPA-mutated 1.9 %, FLT3-ITD 10.2 % and FLT3-TKD 7.9 %. Among 33 patients with normal karyotype, we found significantly higher frequencies for NPM1-mutated 24.2 % and CEBPA-mutated 12.1 %. Overall survival (pOS) for the 163 eligible non-acute promyelocytic leukemia cases was 46.2 ± 4.3 %, while leukemia-free survival probability was 51.0 ± 4.4 % (n = 135). The NPM1-mutated/FLT3-ITD-negative genotype showed better outcome than any other combined NPM1/FLT3 genotype; this difference was statistically significant within the group of high-risk patients (pOS ± SE 83.3 ± 15.2 % versus 33.1 ± 4.7 %; p = 0.0251). This is the first report of the frequencies of these mutations in Argentina. Despite the limited number of patients, a favorable prognosis of AML with genotype NPM1-mutated/FLT3-ITD-negative was confirmed. This is especially relevant within the high-risk group of patients, as it may contribute to the detection of patients with better prognosis, and thus avoid unnecessary treatment intensification.

A comprehensive profile of recurrent glioblastoma.

In spite of relentless efforts to devise new treatment strategies, primary glioblastomas invariably recur as aggressive, therapy-resistant relapses and patients rapidly succumb to these tumors. Many therapeutic agents are first tested in clinical trials involving recurrent glioblastomas. Remarkably, however, fundamental knowledge on the biology of recurrent glioblastoma is just slowly emerging. Here, we review current knowledge on recurrent glioblastoma and ask whether and how therapies change intra-tumor heterogeneity, molecular traits and growth pattern of glioblastoma, and to which extent this information can be exploited for therapeutic decision-making. We conclude that the ability to characterize and predict therapy-induced changes in recurrent glioblastoma will determine, whether, one day, glioblastoma can be contained in a state of chronic disease.

Laparoscopic management of pancreatic pseudocysts: experience at a general hospital in Mexico City.

BACKGROUND: Invasive management of pancreatic pseudocysts (PP) is currently indicated in those patients with symptoms or complications. Treatment options are classified as surgical (open and laparoscopic) and non-surgical (endoscopic and radiologic). AIM: To describe the morbidity, mortality, and efficacy in terms of technical and clinical success of the laparoscopic surgical approach in the treatment of patients with PP in the last 3 years at our hospital center. METHODS: We included patients with PP treated with laparoscopic surgery within the time frame of January 2012 and December 2014. The morbidity and mortality associated with the procedure were determined, together with the postoperative results in terms of effectiveness and recurrence. RESULTS: A total of 38 patients were diagnosed with PP within the last 3 years, but only 20 of them had invasive treatment. Laparoscopic surgery was performed on 17 of those patients (mean pseudocyst diameter of 15.3, primary drainage success rate of 94.1%, complication rate of 5.9%, and a 40-month follow-up). CONCLUSIONS: The results obtained with the laparoscopic technique used at our hospital center showed that this approach is feasible, efficacious, and safe. Thus, performed by skilled surgeons, it should be considered a treatment option for patients with PP.

It's all in your head: sinus node dysfunction secondary to a sphenoid wing meningioma.

BACKGROUND: A 57-year-old man presented with recurrent episodes of dizziness, weakness of legs, and presyncope. The electrocardiogram showed a sinus bradycardia and recurrent sinus pauses. RESULTS: Cardiac evaluation revealed a normal left ventricular ejection fraction without ischemic, structural, or valvular heart disease. Pronounced limb weakness prompted neurological consultation. Cranial magnetic resonance imaging showed a large right-sided intracranial tumor adjacent to the medial sphenoid wing. Surgical removal of the tumor was accomplished successfully after application of a transient cardiac pacemaker, while decision upon permanent pacemaker implantation was postponed. Histopathology provided evidence of a meningothelial meningioma. Postoperative assessment displayed the absence of sinus node dysfunction after tumor removal. CONCLUSION: Careful differential diagnostic assessment of patients with symptomatic bradycardias needs to rule out reversible causes before implantation of permanent devices.

Analysis of iron superoxide dismutase-encoding DNA vaccine on the evolution of the Leishmania amazonensis experimental infection.

The present work aimed to evaluate the immunogenicity of Leishmania amazonensis iron superoxide dismutase (SOD)-encoding DNA experimental vaccine and the protective properties of this DNA vaccine during infection. The SOD gene was subcloned into the pVAX1 plasmid, and it was used to immunize BALB/c mice. Twenty-one days after the last immunization, mice were sacrificed (immunogenicity studies) or subcutaneously challenged with L. amazonensis (studies of protection), and alterations in cellular and humoral immune responses were evaluated, as well as the course of infection. Mice only immunized with pVAX1-SOD presented increased frequencies of CD4(+) IFN-γ(+), CD8(+)IFN-γ(+) and CD8(+)IL-4(+) lymphocytes; moreover, high levels of IgG2a were detected. After challenge, mice that were immunized with pVAX1-SOD had increased frequencies of the CD4(+)IL-4(+), CD8(+)IFN-γ(+) and CD8(+)IL-4(+) T lymphocytes. In addition, the lymph node cells produced high amounts of IFN-γ and IL-4 cytokines. Increased IgG2a was also detected. The pattern of immunity induced by pVAX1-SOD partially protected the BALB/c mice from a challenge with L. amazonensis, as the animals presented reduced parasitism and lesion size when compared to controls. Taken together, these results indicate that leishmanial SOD modulates the lymphocyte response, and that the elevation in IFN-γ possibly accounted for the decreased skin parasitism observed in immunized animals.

Microorganismos involucrados en las infecciones respiratorias de pacientes con fibrosis quísitca / Microorganisms involved in respiratory infections in cystic fibrosis patients

La fibrosis quística es la enfermedad autosómica recesiva letal más frecuente en la infancia. Se caracteriza por presentar una evolución crónica, progresiva y compromiso multisistémico. El objetivo de este trabajo fue conocer la frecuencia de los microorganismos implicados en las infecciones respiratorias de pacientes fibroquísticos atendidos en el Hospital de Pediatría Prof. Dr. Juan P. Garrahan durante el año 2012 y su resistencia a los antimicrobianos. Para la identificación bacteriana se utilizaron pruebas bioquímicas convencionales, sistemas automatizados y semiautomatizados. En la identificación de miembros del complejo Burkholderia cepacia se utilizaron además métodos moleculares. De esta manera se pudo lograr la clasificación genética de las especies incluidas dentro de ese complejo presentes en los pacientes fibroquísticos de nuestro medio. Este trabajo nos permitió conocer la situación microbiológica actual de las infecciones respiratorias en los pacientes fibroquísticos. Tanto el estudio minucioso de los cultivos convencionales como la caracterización molecular de las especies de B. cepacia deben seguirse en los pacientes colonizados por microorganismos multirresistentes y son imprescindibles en el control postratamiento después del aislamiento de estos patógenos (AU)

Cystic fibrosis is the most common lethal autosomal recessive disease in childhood. It is characterized by a chronic, progressive evolution and multisystemic involvement. The aim of this study was to assess the incidence of the microorganisms involved in respiratory infections of patients with cystic fibrosis seen at the Pediatric Hospital Prof. Dr. Juan P. Garrahan in 2012 and their resistance to antimicrobial agents. To identify the microorganisms conventional biochemical tests with automatized and semiautomatized systems were used. For the identification of members of the Burkholderia cepacia complex molecular studies were additionally used. Species of this complex found in cystic fibrosis patients in our setting were genetically classified allowing for the definition of the current microbiological situation of respiratory infections in cystic fibrosis patients. Careful study of conventional cultures as well as molecular typing of the B. cepacia species should be routinely performed in patients colonized by multiresistant microorganisms and is fundamental in the post-treatment monitoring after the isolation of these pathogens (AU)

AXL receptor tyrosine kinase is increased in patients with heart failure.

BACKGROUND: AXL is a membrane receptor tyrosine kinase highly expressed in the heart and has a conspicuous role in cardiovascular physiology. The role of AXL in heart failure (HF) has not been previously addressed. METHODS AND RESULTS: AXL protein was enhanced 6-fold in myocardial biopsies of end-stage HF patients undergoing heart transplantation compared to controls from heart donors (P<0.0001). Next, we performed a transversal study of patients with chronic HF (n=192) and a group of controls with no HF (n=67). sAXL and BNP circulating levels were quantified and clinical and demographic data were collected. sAXL levels in serum were higher in HF (86.3 ± 2.0 ng/mL) than in controls (67.8 ± 2.0 ng/mL; P<0.0001). Also, sAXL correlated with several parameters associated with worse prognosis in HF. Linear regression analysis indicated that serum creatinine, systolic blood pressure and atrial fibrillation, but not BNP levels, were predictive of sAXL levels. Cox regression analysis indicated that high sAXL values at enrollment time were related to the major HF events (all-cause mortality, heart transplantation and HF hospitalizations) at one year follow-up (P<0.001), adding predictive value to high BNP levels. CONCLUSIONS: Myocardial expression and serum concentration of AXL is elevated in HF patients compared to controls. Furthermore, peripheral sAXL correlates with parameters associated with the progression of HF and with HF events at short term follow-up. All together these results suggest that sAXL could belong to a new molecular pathway involved in myocardial damage in HF, independent from BNP.

Pesticide residue analyses and biomarker responses of native Costa Rican fish of the Poeciliidae and Cichlidae families to assess environmental impacts of pesticides in Palo Verde National Park.

Pesticide chemical residues in water samples and biomarker responses in transplanted fish were used to monitor environmental hazards of pesticides in Palo Verde National Park (Costa Rica). The Costarican fish, Parachromis dovii (Ciclhidae) and Poecilia gillii (Poecillidae), were selected as sentinel species. Contaminant analyses detected up to 15 different pesticide residues in water with hexachlobenzene (2261 ng l(-1)), phorate (473 ng l(-1)), epoxiconazole (314) and bromacil (117 ng l(-1)) being the compounds found in higher concentrations. Biomarker responses evidenced impacts on cholinesterase activities in transplanted fish at Barbudal site probably due to the presence of organophosphate insecticides such as phorate. High enzyme activities of glutathione S-transferase and catalase and elevated levels of lipid peroxides were also observed at a site impacted by rice fields (Cabuyo); those effects could be associated with the presence of hexachloro benzene and triazole fungicides. In general, P. dovii biomarkers were affected to a greater extent than those of P. gillii in fish transplanted to sites associated with agriculture, which suggests the former species is a good candidate for future surveys.

Characterization of NF1 allele containing two nonsense mutations in exon 37 that segregates with neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) is a common autosomal dominant disease caused by mutations in the NF1 gene. The mutation rate of NF1 is one of the highest known for human genes and the mutational analysis has revealed a wide variety of changes, a significant proportion of which affect normal pre-mRNA splicing. Here, we describe two truncating mutations in exon 37 of NF1, the recurrent c.6792C>A and the novel c.6799C>T change, that occur in cis and segregate with NF1 in a large family. The double mutation induces defective splicing of exon 37 and thus, we performed quantitative comparisons of transcripts harboring single (c.6792C>G or c.6792C>A) and double (c.6792C>A and c.6799C>T) mutations to assess their effects on exon 37 splicing. Skipping of exon 37 was greater and there were fewer mutant full-length transcripts in samples with the double mutation than in those carrying single mutations. Thus, the combination of the c.6792C>A and c.6799C>T mutations augmented exon 37 skipping. These findings suggest that, in addition to the previously described exonic splicing enhancer in the c.6791_6795 region, c.6799 lies within an additional regulatory element that influences the splicing of exon 37.

Environmental hazards of pesticides from pineapple crop production in the Río Jiménez watershed (Caribbean Coast, Costa Rica).

This study aimed to characterize environmental hazards of pesticides from pineapple production in riparian communities along the Jiménez River watershed. To achieve our objectives riparian ecological quality indices on riparian habitat and macroinvertebrate assemblages were combined with toxicity assays, fish biomarkers, physico-chemical water analysis and pesticide environmental hazards. During two consecutive years and two periods (July and October), three reference and four impacted sites were monitored. The ecological quality of benthic macroinvertebrates and of riparian habitats deteriorated from the reference sites downstream to the polluted reaches along the Jiménez River area affected by pineapple plantations. The toxicity of water to Daphnia magna also increased towards downstream reaches. Biomarkers of fish of the species Poecilia gillii and Bryconamericus scleroparius transplanted across the studied sites evidenced a clear anticholinergic effect towards downstream sites as well as increased levels of lipid peroxidation. Different pesticide residues were frequently detected in water samples collected across the Jiménez River watershed with herbicides (ametryn, bromacil, diuron), organophosphorus insecticides (diazinon and ethoprophos) and triazole fungicides being the greatest reaching levels above 1 µg L(-1) in downstream sites. Principal component and environmental hazard analysis of physico-chemical and biological responses established clear relationships among habitat deterioration and the ecological quality of macroinvertebrate communities, high levels of herbicides and poor plant growth, high levels of organophosphorus insecticides in water and anticholinesterase effects on fish, D. magna mortality and deterioration of macroinvertebrate communities. Fungicide and herbicide residue levels were also related with high levels of lipid peroxidation and high activities of glutathione S transferase in fish liver, respectively. These results indicated, thus, that riparian habitat deterioration due to deforestation and land use for agriculture and pesticide contamination are affecting river ecosystems.

[Laparoscopic drainage of a pancreatic pseudocyst: a case report]. / Drenaje laparoscópico de un seudoquiste pancreático: reporte de caso.

Pancreatic pseudocysts are defined as homogeneous pancreatic or peripancreatic collections that are not associated with necrotic tissue and are surrounded by granulated or fibrous tissue with no epithelium. Management has been classified as surgical (conventional and laparoscopic) and nonsurgical (endoscopic and radiologic). The aim of this report is to describe our initial experience in the management of a pancreatic pseudocyst by means of laparoscopic posterior cyst-gastrostomy anastomosis, performed at the Pancreas Clinic of the Hospital General "Dr. Manuel Gea González" in Mexico City. New techniques and instrumentation have contributed to the relatively recent development of laparoscopic pancreatic surgery. Our technique has practical advantages that have been confirmed by other authors, such as simple hemostasis, a wide viewing angle enabling adequate necrosectomy, anastomosis that does not require the use of staples, and the possibility of resolving other associated intra-abdominal pathologies, as in this case.

Thiolated DAB dendrimer/ZnSe nanoparticles for C-reactive protein recognition in human serum.

A nanocomposite obtained by a thiol DAB-dendrimer (generation 5), coated with fluorescent ZnSe quantum dots, was successfully synthesized for the selective recognition of C-reactive protein. The procedure presented was carried out by a novel, cheap and non-toxic bottom up synthesis. The nanocomposite showed an excitation at 180 nm, with two emission bands at 411 and 465 nm, with a full-width at half-maximum of 336 nm. The Stokes shift was influenced by the presence of coating molecules and the intensity was dependent on pH due to the presence of a charge transfer process. The transmission electron microscopy images demonstrated that the spherical nanoparticles obtained displayed a regular shape of 30 nm size. The fluorescence intensity was markedly quenched by the presence of C-reactive protein, with a dynamic Stern-Volmer constant of 0.036 M(-1). The quenching profile shows that about 51% of the ZnSe QDs are located in the external layer of the thiol dendrimer accessible to the quencher. The precision of the method obtained as relative standard deviation was 3.76% (4 mg L(-1), n=3). This water soluble fluorescent nanocomposite showed a set of favorable properties to be used as a sensor for the C-reactive protein in serum samples, at concentrations of risk levels.

Epigenetic screen of human DNA repair genes identifies aberrant promoter methylation of NEIL1 in head and neck squamous cell carcinoma.

Aberrant promoter methylation of different DNA repair genes has a critical role in the development and progression of various cancer types, including head and neck squamous cell carcinomas (HNSCCs). A systematic analysis of known human repair genes for promoter methylation is however missing. We generated quantitative promoter methylation profiles in single CpG units of 160 human DNA repair genes in a set of DNAs isolated from fresh frozen HNSCC and normal tissues using MassARRAY technology. Ninety-eight percent of these genes contained CpG islands (CGIs) in their promoter region; thus, DNA methylation is a potential regulatory mechanism. Methylation data were obtained for 145 genes, from which 15 genes exhibited more than a 20% difference in methylation levels between tumor and normal tissues, manifested either as hypermethylation or as hypomethylation. Analyses of promoter methylation with mRNA expression identified the DNA glycosylase NEIL1 (nei endonuclease VIII-like 1) as the most prominent candidate gene. NEIL1 promoter hypermethylation was confirmed in additional fresh frozen HNSCC samples, normal mucosa, HNSCC cell lines and primary human skin keratinocytes. The investigation of laser-microdissected tissues further substantiated increased methylation levels in tumor versus matched non-tumor cells. Immunohistological analysis revealed significantly less NEIL1 protein expression in tumor tissues. 5-Aza-2'-deoxycytidine treatment and DNMT1 knockdown resulted in the re-expression of NEIL1 in HNSCC cell lines, which initially carried hypermethylated promoter regions. In conclusion, our results suggest that DNA methylation contributes to the downregulation of NEIL1 expression and might thus have a role in modulating the response to therapies of HNSCC.

Notch1 signaling promotes survival of glioblastoma cells via EGFR-mediated induction of anti-apoptotic Mcl-1.

The Notch1-mediated signaling pathway has a central role in the maintenance of neural stem cells and contributes to growth and progression of glioblastomas, the most frequent malignant brain tumors in adults. Here, we demonstrate that the Notch1 receptor promotes survival of glioblastoma cells by regulation of the anti-apoptotic Mcl-1 protein. Notch1-dependent regulation of Mcl-1 occurs cell type dependent at a transcriptional or post-translational level and is mediated by the induction of epidermal growth factor receptor (EGFR). Inhibition of the Notch1 pathway overcomes apoptosis resistance and sensitizes glioblastoma cells to apoptosis induced by ionizing radiation, the death ligand TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) or the Bcl-2/Bcl-XL inhibitor ABT-737. In conclusion, targeting Notch1 might represent a promising novel strategy in the treatment of glioblastomas.