Clinical, immunological, and genetic description of a Mexican cohort of patients with DOCK8 deficiency.

PURPOSE: We aimed to describe the clinical, immunological, and genetic features of patients with DOCK8 deficiency (DOCK8-Def) in a tertiary care center for children. METHODS: Retrospective chart review of patients' clinical, immunological, and genetic characteristics with DOCK8-Def. Genetic analysis was performed with targeted- or whole-exome sequencing; we also assessed DOCK8 protein expression and a lymphoproliferation assay and analyzed survival by the Kaplan-Meier method. RESULTS: We described 11 patients from 8 unrelated kindreds. The median age at symptoms' onset was 10 months (range 1-54 months). The median follow-up time was 53.4 months (4.8-118.8). All patients presented eczema and recurrent sinopulmonary and cutaneous infections. Besides those symptoms, the most frequent manifestations were bronchiectases (8/11), food allergies (6/11), and severe infections (6/11). Infrequent characteristics were detection of CMV in bronchial lavage, C. parvum-driven sclerosing cholangitis, Takayasu vasculitis, neurological syndromes, pulmonary tuberculosis, and lymphomatoid granulomatosis. CONCLUSION: DOCK8-Def has a broad spectrum of manifestations, including allergy, autoimmunity, inflammation, infection, and cancer. The hallmark of this inborn error of immunity is IEI-associated eczema with eosinophilia and increased IgE. Here, we report six new mutations causing human DOCK8 deficiency and symptoms previously unrecognized to occur in DOCK8-Def. Therefore, an early diagnosis of DOCK8-Def is essential to facilitate an adequate treatment such as HSCT.

Accuracy and Survival Outcomes after National Implementation of Sentinel Lymph Node Biopsy in Early Stage Endometrial Cancer.

BACKGROUND: Sentinel lymph node (SLN) biopsy has recently been accepted to evaluate nodal status in endometrial cancer at early stage, which is key to tailoring adjuvant treatments. Our aim was to evaluate the national implementation of SLN biopsy in terms of accuracy to detect nodal disease in a clinical setting and oncologic outcomes according to the volume of nodal disease. PATIENTS AND METHODS: A total of 29 Spanish centers participated in this retrospective, multicenter registry including patients with endometrial adenocarcinoma at preoperative early stage who had undergone SLN biopsy between 2015 and 2021. Each center collected data regarding demographic, clinical, histologic, therapeutic, and survival characteristics. RESULTS: A total of 892 patients were enrolled. After the surgery, 12.9% were suprastaged to FIGO 2009 stages III-IV and 108 patients (12.1%) had nodal involvement: 54.6% macrometastasis, 22.2% micrometastases, and 23.1% isolated tumor cells (ITC). Sensitivity of SLN biopsy was 93.7% and false negative rate was 6.2%. After a median follow up of 1.81 years, overall surivial and disease-free survival were significantly lower in patients who had macrometastases when compared with patients with negative nodes, micrometastases or ITC. CONCLUSIONS: In our nationwide cohort we obtained high sensitivity of SLN biopsy to detect nodal disease. The oncologic outcomes of patients with negative nodes and low-volume disease were similar after tailoring adjuvant treatments. In total, 22% of patients with macrometastasis and 50% of patients with micrometastasis were at low risk of nodal metastasis according to their preoperative risk factors, revealing the importance of SLN biopsy in the surgical management of patients with early stage EC.

Síndrome del incisivo central maxilar medio único en neonato / Solitary median maxillary central incisor syndrome in neonates / Síndrome do incisivo central maxilar médio solitário em neonatos

Introducción: el síndrome del incisivo central maxilar medio único (SMMCI) es un trastorno de etiología desconocida, con base genética heterogénea, que se caracteriza por la erupción de un único incisivo central en el maxilar y que se puede relacionar con multitud de patologías y síndromes, entre los que destacan las alteraciones de la línea media, obstrucción nasal congénita, disfunción hipofisaria, talla baja y holoprosencefalia. Caso clínico: neonato mujer con síndrome dismórfico no filiado y obstrucción nasal congénita, que es diagnosticada de SMMCI tras consultar en repetidas ocasiones por cuadros de dificultad respiratoria y problemas para alimentarse. Conclusiones: el conocimiento de este raro síndrome es fundamental para la realización de un diagnóstico precoz por parte del equipo pediátrico y obstétrico, ya que un diagnóstico temprano es posible, mejorando la evaluación prenatal ecográfica, así como el adecuado manejo posnatal multidisciplinar posterior de nuestros pacientes.

Introduction: the Solitary Median Maxillary Central Incisor Syndrome (SMMCI) is a disorder of unknown etiology, with a heterogeneous genetic basis, characterized by the eruption of a single central incisor in the maxilla and that can be linked to various pathologies and syndromes, among which the alterations of the midline, congenital nasal obstruction, pituitary dysfunction, short stature and holoprosencephaly stand out. Clinical case: female newborns with unknown dysmorphic syndrome and congenital nasal obstruction, diagnosed with SMMCI after repeated consultations due to respiratory distress and feeding problems. Conclusions: understanding this rare syndrome is essential for an early diagnosis to be carried out by the pediatric and obstetric team, since it will improve the ultrasound prenatal assessment, as well as the adequate subsequent multidisciplinary postnatal patient management procedures.

Introdução: a síndrome do incisivo central maxilar médio solitário (SICMMS) é uma desordem de etiologia desconhecida, com base genética heterogênea, caracterizada pela erupção de um único incisivo central na maxila e que pode estar relacionada a uma infinidade de patologias e síndromes. onde se destacam alterações da linha média, obstrução nasal congênita, disfunção hipofisária, baixa estatura e holoprosencefalia. Caso clínico: recém-nascida com síndrome dismórfica de origem desconhecida e obstrução nasal congênita, diagnosticada com SICMSS após várias consultas por desconforto respiratório e problemas de alimentação. Conclusões: o conhecimento desta rara síndrome é essencial para que a equipe pediátrica e obstétrica possa fazer um diagnóstico precoce, pois ele pode melhorar a avaliação ultrassonográfica pré-natal, bem como o adequado manejo pós-natal multidisciplinar pós-natal dos pacientes.

Tuberculosis of the ribcage by dissemination of Koch bacilli.

INTRODUCTION: Tuberculosis (TB) is an infectious, transmissible and immune disease caused by the Mycobacterium tuberculosis-complex (MTBC). Although osteoarticular tuberculosis (OATB) has been widely described, the ribcage variety remains a rare form. CASE REPORT: A thirteen-month-old male and a twenty-month-old female, both with pain and increased volume of anterolateral left rib cage were described. Physical examination revealed the presence of a soft consistent mass at the level of the 9th and 5th costal arches in the male and female patients respectively. Upon clinical evaluation, tuberculosis was suspected, which was confirmed by X-ray and histopathological studies. After confirmation, the management, based on anti-tuberculosis therapy was started as follows: nine months of anti-tuberculosis therapy for the male patient and fourteen months for the female. The outcomes were favorable for both patients. However, further interventions, consisting of abscess drainage in the male patient and excisional biopsy in the female patient were necessary. With these therapeutic interventions, to date, the patients are without any evidence of active TB.

Estenosis congénita de venas pulmonares y malformación vascular broncopulmonar / Congenital pulmonary vein stenosis and bronchopulmonary vascular malformation

Resumen El objetivo es mostrar el diagnóstico y la evolución de una paciente con estenosis de venas pulmonares y secuestro pulmonar. Se trata de una niña de 1 año de edad, con bronconeumonías de repetición, acrocianosis, 2R intenso, cardiomegalia, hipertensión venocapilar pulmonar, con diagnóstico clínico de comunicación interauricular. El ecocardiograma mostró estenosis de venas pulmonares izquierdas. El cateterismo cardiaco detectó fístulas arteriovenosas en la región apical del pulmón derecho. La imagen de resonancia magnética y la angiografía mostraron un vaso arterial aberrante paralelo a la aorta abdominal y con flujo dirigido al lóbulo pulmonar derecho. La angiotomografía reportó confluencia de las venas pulmonares del lado derecho. Se realizó lobectomía derecha. La paciente falleció en el posoperatorio debido a una hemorragia masiva pulmonar. Esta paciente es la primera descrita en la literatura con estenosis de venas pulmonares congénita asociada a secuestro pulmonar. La ecocardiografía es el estudio diagnóstico ideal inicial en los pacientes con estenosis congénita de venas pulmonares.

Abstract The objective is demonstrate the diagnostic process and evolution of a patient with a diagnosis of congenital pulmonary vein stenosis and broncho-pulmonary vascular malformation. One year old female patient with repeated bronchopneumonia, acrocyanosis, split S2, cardiomegaly, pulmonary hypertension, with a clinical diagnosis of atrial septal defect. The echocardiogram demonstrated left sided vein pulmonary stenosis. The cardiac catheterization demonstrated arterial-venous fistulas apical on the right lung. Magnetic Resonance image and angiography showed an aberrant arterial vessel parallel to the abdominal aorta which flow the right pulmonary lobe. The cardiac tomography angiography reported confluence of right-sided pulmonary veins. A lobectomy is performed. Patient died in post-operative due to massive pulmonary hemorrhaging. This is the first patient mentioned in written literature with pulmonary vein stenosis associated with pulmonary sequestration, with normal venous connection. Echocardiography represents the specific standard study ideal for initial diagnostic for patients with pulmonary vein stenosis.

Efectividad de una intervención cognitivo-conductual para dejar de fumar combinada con vareniclina / Effectiveness of a Cognitive-Behavioral Intervention to Smoking Cessation Combined with Varenicline

Resumen Diferentes investigaciones han evidenciado que el tratamiento con vareniclina es efectivo para dejar de fumar cuando se combina con un tratamiento psicológico. Sin embargo, existe una carencia de estudios respecto a cuánta efectividad aporta la vareniclina al tratamiento psicológico. El objetivo del presente estudio piloto fue evaluar si la efectividad de una intervención psicológica cognitivo-conductual incrementa con la inclusión de la vareniclina. La muestra de este estudio la conformaron 22 fumadores (M edad = 30.5; de = 15.4 años), con un consumo diario promedio de 12.29 (de = 5.7) cigarrillos. Cada participante eligió una de dos intervenciones: 11 fumadores recibieron la Intervención Breve Motivacional para Dejar de Fumar (ibmdf) y 11 la misma intervención más vareniclina. Los resultados indican que no hay diferencias significativas entre las intervenciones. Así, la inclusión de la vareniclina no incrementó la efectividad de la intervención psicológica. Las conclusiones de este estudio deben ser tomadas con cautela debido al tamaño de la muestra, por lo tanto, es necesario aumentar las investigaciones al respecto.

Abstract Different studies have shown that treatment with varenicline is effective for smoking cessation when it is combined with psychological treatment. However, there are few studies on the effectiveness that varenicline adds to psychological treatment. The aim of this pilot study was to assess if the effectiveness of a cognitive behavioral intervention increases with the inclusion of varenicline. The sample of this study were 22 smokers (M age = 39.5, SD = 15.4 years), with an average daily consumption of 12.29 cigarettes (SD = 5.7). Each participant chose one of the two interventions: 11 smokers received the Motivational Smoking Cessation Brief Intervention (mscbm) and 11 the same intervention plus varenicline. The results showed no significant differences between interventions. Thus, the inclusion of varenicline did not increase the effectiveness of psychological intervention. The findings of this study should be taken with caution due to the sample size. More research is therefore needed.

Case Report: Chest Wall Tuberculosis without Pulmonary Involvement in Three Pediatric Immunocompetent Patients.

Primary rib cage tuberculosis (TB) is an infrequent form of presentation and represents 1% of all cases of osteoarticular TB. We report three cases of children who were previously healthy and who began with swelling of the anterior surface of the rib as initial manifestation of TB. The most important clinical presentations in this series were swelling and pain, with lytic lesions and a soft tissue mass in image studies simulating oncologic pathologies. Because none of the cases had positive epidemiological contact, TB was initially not considered, so the delay in diagnosis from the onset of symptoms was 4, 1, and 2 months, respectively. The diagnosis was made through histomorphological analyses. Treatment was administered during 12, 10, and 9 months. Posttreatment studies did not show any evidence of extrapulmonary TB and until date, the patients remained without relapse or active disease. The findings in our cases illustrate that the diagnosis of chest wall TB should be suspected in all patients from endemic areas who present rib injury.

Development of a quantitative method to measure EV uptake.

The outstanding potential of Extracellular Vesicles (EVs) in medicine, deserves a detailed study of the molecular aspects regulating their incorporation into target cells. However, because EV size lies below the limit of resolution of optical techniques, quantification together with discrimination between EV binding to the target cell and uptake is usually not completely achieved with current techniques. Human tetraspanins CD9 and CD63 were fused to a dual EGFP-Renilla-split tag. Subcellular localization and incorporation of these fusion proteins into EVs was assessed by western-blot and fluorescence microscopy. EV binding and uptake was measured using either a classical Renilla substrate or a cytopermeable one. Incubation of target cells expressing DSP2 with EVs containing the complementary DSP1 portion could not recover fluorescence or luciferase activity. However, using EVs carrying the fully reconstituted Dual-EGFP-Renilla protein and the cytopermeable Renilla luciferase substrate, we could distinguish EV binding from uptake. We provide proof of concept of the system by analysing the effect of different chemical inhibitors, demonstrating that this method is highly sensitive and quantitative, allowing a dynamic follow-up in a high-throughput scheme to unravel the molecular mechanisms of EV uptake in different biological systems.

Exosome Analysis in Tumor-Draining Pulmonary Vein Identifies NSCLC Patients with Higher Risk of Relapse after Curative Surgery.

Since tumor-draining pulmonary vein blood (PV) is enriched in tumor-secreted products, we hypothesized that it would also be enriched in tumor-derived exosomes, which would be important in the metastasis process. We characterized exosomes from PV of 61 resected non-small cell lung cancer (NSCLC) patients to evaluate its potential as relapse biomarkers. Exosomes were characterized using transmission electron microscopy, western blot and nanoparticle tracking analysis and we examined time to relapse (TTR) and overall survival (OS). Differences between PV and peripheral vein were found. PV was enriched in smaller exosomes than the paired peripheral vein (p = 0.01). Moreover, PV exosome size mode was able to identify relapsed patients (Area under the curve [AUC] = 0.781; 95%CI: 0.6641⁻0.8978), in whom exosome size was smaller (<112 nm; p < 0.001). The combination of PV exosome size and N (lymph node involvement) showed an AUC of 0.89 (95%CI: 0.80⁻0.97). Moreover, smaller PV exosome size was associated with shorter TTR (28.3 months vs. not reached, p < 0.001) and OS (43.9 months vs. not reached, p = 0.009). Multivariate analyses identified PV exosome size and stage as independent prognostic markers for TTR and OS. PV exosome size is a promising relapse biomarker after surgery that can add valuable information to clinical variables.

Detection of carbapenem resistance genes in Pseudomonas aeruginosa isolates with several phenotypic susceptibility profiles / Detección de genes de resistencia a carbapenémicos en aislados de Pseudomonas aeruginosa con diferentes perfiles de susceptibilidad fenotípica

Abstract Introduction: Pseudomonas aeruginosa display several resistance mechanisms to carbapenems and such variety makes it difficult to infer from the antibiogram. The aim of this study was to determine the carbapenem resistance genes in P. aeruginosa isolates with different profiles of phe-notypic susceptibility to these antibiotics. Materials and methods: From a microbial collection of P aeruginosa isolates from infected patients, 40 isolates with different carbapenem resistance profiles were selected. The carbapenemases genes, and expression of the OprD porin, the MexAB-OprM efflux pump and the p-lactamase AmpC were determined. Results: From a total of 40 isolates evaluted, in 21 (52.5%) any mechanism of resistance evaluated were detected. In the meropenem-resistant group, overexpression of AmpC (n = 1) and decreased expression of MexAB-OprM (n = 2) and OprD (n = 1) were found. A decrease in the expression of MexAB-OprM was observed in imipenem-resistant group (n = 3) and mutations in the gene encoding the OprD porin (n = 1). Finally, the presence of carbapenemases (VIM, n= 3, KPC-2 / VIM, n = 1) was detected in imipenem-meropenem resistant isolates. Conclusion: The phenotypic susceptibility profiles in P aeruginosa isolates were not explained by the molecular mechanisms explored, with the exception of carbapenemase-producing isolates. These results evidence the complexity of the antibiotic resistance mechanisms involved in this bacterium.

Resumen Introducción: Pseudomonas aeruginosa presenta diferentes mecanismos de resistencia a los carbapenémicos, dificultando su inferencia a partir del antibiograma. El objetivo fue determinar los genes de resistencia a car-bapenémicos en aislados de Pseudomonas aeruginosa con diferentes perfiles de susceptibilidad a estos antibióticos. Materiales y métodos: A partir de una colección microbiana de aislados de P. aeruginosa provenientes de pacientes infectados se seleccionaron 40 aislados con diferentes perfiles de resistencia a carbapenémicos y en los cuales se determinaron los genes de car-bapenemasas, la expresión de la porina OprD, la bomba de expulsión MexAB-OprM y la betalactamasa AmpC. Resultados: El 52,5 % de los aislados no presentó ninguno de los mecanismos de resistencia evaluados. En los resistentes a meropenem se encontró sobreexpresión de AmpC (n=1) y disminución de la expresión de MexAB-OprM (n=2) y OprD (n=1). En los resistentes a imipenem se observó disminución en la expresión de MexAB-OprM (n=3) y mutaciones en el gen que codifica la porina OprD (n=1). En aislados resistentes a imipenem y meropenem se detectó la presencia de carbapenemasas (VIM, n=3, KPC/VIM, n=1). Conclusión: Los mecanismos moleculares hallados no explican el fenotipo de resistencia a carbapenémicos, excepto en los aislados productores de carbapenemasas. Estos resultados evidencian la complejidad de los mecanismos implicados en la resistencia antibiótica en esta bacteria.

Role of lymphadenectomy in intermediate-risk endometrial cancer: a matched-pair study.

OBJECTIVE: To assess the impact of lymph node dissection (LND) on morbidity, survival, and cost for intermediate-risk endometrial cancers (IREC). METHODS: A multicenter retrospective cohort of 720 women with IREC (endometrioid histology with myometrial invasion <50% and grade 3; or myometrial invasion ≥50% and grades 1-2; or cervical involvement and grades 1-2) was carried out. All patients underwent hysterectomy and bilateral salpingo-oophorectomy. A matched pair analysis identified 178 pairs (178 with LND and 178 without it) equal in age, body mass index, co-morbidities, American Society of Anesthesiologist score, myometrial invasion, and surgical approach. Demographic data, pathology results, perioperative morbidity, and survival were abstracted from medical records. Disease-free survival (DFS) and overall survival (OS) was analyzed using Kaplan-Meier curves and multivariate Cox regression analysis. Cost analysis was carried out between both groups. RESULTS: Both study groups were homogeneous in demographic data and pathologic results. The mean follow-up in patients free of disease was 61.7 months (range, 12.0-275.5). DFS (hazard ratio [HR]=1.34; 95% confidence interval [CI]=0.79-2.28) and OS (HR=0.72; 95% CI=0.42-1.23) were similar in both groups, independently of nodes count. In LND group, positive nodes were found in 10 cases (5.6%). Operating time and late postoperative complications were higher in LND group (p<0.05). Infection rate was significantly higher in no-LND group (p=0.035). There were no statistical differences between both groups regarding operative morbidity and hospital stay. The global cost was similar for both groups. CONCLUSION: Systematic LND in IREC has no benefit on survival, although it does not show an increase in perioperative morbidity or global cost.

NKX2-1 expression as a prognostic marker in early-stage non-small-cell lung cancer.

BACKGROUND: NKX2-1, a key molecule in lung development, is highly expressed in non-small cell lung cancer (NSCLC), particularly in lung adenocarcinoma (ADK), where it is a diagnostic marker. Studies of the prognostic role of NKX2-1 in NSCLC have reported contradictory findings. Two microRNAs (miRNAs) have been associated with NKX2-1: miR-365, which targets NKX2-1; and miR-33a, which is downstream of NKX2-1. We have examined the effect of NKX2-1, miR-365 and miR-33a on survival in a cohort of early-stage NSCLC patients and in sub-groups of patients classified according to the mutational status of TP53, KRAS, and EGFR. METHODS: mRNA and miRNA expression was determined using TaqMan assays in 110 early-stage NSCLC patients. TP53, KRAS, and EGFR mutations were assessed by Sanger sequencing. RESULTS: NKX2-1 expression was upregulated in never-smokers (P = 0.017), ADK (P < 0.0001) and patients with wild-type TP53 (P = 0.001). A negative correlation between NKX2-1 and miR-365 expression was found (ρ = -0.287; P = 0.003) but there was no correlation between NKX2-1 and miR-33a expression. Overall survival (OS) was longer in patients with high expression of NKX2-1 than in those with low expression (80.8 vs 61.2 months (P = 0.035), while a trend towards longer OS was observed in patients with low miR-365 levels (P = 0.07). The impact of NKX2-1 on OS and DFS was higher in patients with neither TP53 nor KRAS mutations. Higher expression of NKX2-1 was related to higher OS (77.6 vs 54 months; P = 0.017) and DFS (74.6 vs 57.7 months; P = 0.006) compared to low expression. The association between NKX2-1 and OS and DFS was strengthened when the analysis was limited to patients with stage I disease (P = 0.005 and P=0.003 respectively). CONCLUSIONS: NKX2-1 expression impacts prognosis in early-stage NSCLC patients, particularly in those with neither TP53 nor KRAS mutations.

Epigenetic regulation mechanisms of microRNA expression.

MicroRNAs (miRNAs) are single-stranded RNAs of 18-25 nucleotides that regulate gene expression at the post-transcriptional level. They are involved in many physiological and pathological processes, including cell proliferation, apoptosis, development and carcinogenesis. Because of the central role of miRNAs in the regulation of gene expression, their expression needs to be tightly controlled. Here, we summarize the different mechanisms of epigenetic regulation of miRNAs, with a particular focus on DNA methylation and histone modification.

HPLC-MS profiling of the multidrug-resistance modifying resin glycoside content of Ipomoea alba seeds

ABSTRACT High performance liquid chromatography profiling with mass spectrometry detection was applicable to identify known and novel multidrug-resistance glycolipid inhibitors from the complex resin glycosides mixture of Ipomoea alba L., Convolvulaceae, seeds. Albinosides X and XI were purified by recycling liquid chromatography and their structural elucidation was accomplished by nuclear magnetic resonance. Albinoside XI exerted a strong potentiation of vinblastine susceptibility in multidrug-resistant human breast carcinoma cells.

Resin Glycosides from Ipomoea alba Seeds as Potential Chemosensitizers in Breast Carcinoma Cells.

Multidrug resistance is the expression of one or more efflux pumps, such as P-glycoprotein, and is a major obstacle in cancer therapy. The use of new potent and noncytotoxic efflux pump modulators, coadministered with antineoplastic agents, is an alternative approach for increasing the success rate of therapy regimes with different drug combinations. This report describes the isolation and structure elucidation of six new resin glycosides from moon vine seeds (Ipomoea alba) as potential mammalian multidrug-resistance-modifying agents. Albinosides IV-IX (1-6), along with the known albinosides I-III (7-9), were purified from the CHCl3-soluble extract. Degradative chemical reactions in combination with NMR spectroscopy and mass spectrometry were used for their structural elucidation. Four new glycosidic acids, albinosinic acids D-G (10-13), were released by saponification of natural products 3-6. They were characterized as tetrasaccharides of either convolvulinolic (11S-hydroxytetradecanoic) or jalapinolic (11S-hydroxyhexadecanoic) acids. The potentiation of vinblastine susceptibility in multidrug-resistant human breast carcinoma cells of albinosides 1-6 was evaluated by modulation assays. The noncytotoxic albinosides VII (4) and VIII (5), at a concentration of 25 µg/mL, exerted the strongest potentiation of vinblastine susceptibility, with a reversal factor (RFMCF-7/Vin+) of 201- and >2517-fold, respectively.

Acute effects of restraint, shock and training in the elevated t-maze on noradrenaline and serotonin systems of the prefrontal cortex / Efectos agudos de la restricción, choque y entrenamiento en el laberinto elevado en T en los sistemas de noradrenalina y serotonina en la corteza prefrontal / Efeitos agudos da restrição, choque e treinamento no labirinto elevado em T nos sistemas de noradrenalina e serotonina no córtex pré-frontal

The prefrontal cortex (PFC) participates in cognitive functions and stress regulation. Noradrenaline (NA) and serotonin (5-HT) levels in some regions of the central nervous system are modified by acute stress. The effects depend on the type of stressor and the time elapsed between the presence of the stressor and the assessment. The aims of the present study were to assess the acute effect of different stressors on NA and 5-HT activities in the PFC and its relation with corticosterone levels. Independent groups of male Wistar rats (250-280 g) were submitted to restraint, footshock or training in the elevated T-maze (ETMT). The animals were sacrificed immediately (T0) or one hour (T1) after stress exposure. An untreated group sacrificed concurrently with treated animals was included as control. Samples of the PFC were dissected and the concentration of NA, 5-HT and their metabolites were measured by HPLC. Corticosterone levels were measured in serum. None of the treatments modified NA levels in the PFC. Animals exposed to footshock or ETMT showed significantly higher concentrations of 5-HT at T0. Restraint and footshock treatments were associated with higher corticosterone levels at T0 and T1 after the respective treatment. Taken together the results show that in the PFC, the noradrenergic and serotonergic systems, and the corticosterone levels respond in different ways to different stressors.

La corteza prefrontal (CPF) participa en las funciones cognitivas y la regulación del estrés. Las concentraciones de noradrenalina (NA) y serotonina (5-HT) en algunas regiones en el sistema nervioso central son modificadas por el estrés agudo. El efecto depende del estresor y del tiempo que transcurra entre el estresor y la evaluación. El objetivo del presente estudio fue evaluar el efecto agudo de diferentes estresores en la actividad de la NA y 5-HT en la CPF y su relación con los niveles de corticosterona. Grupos independientes de ratas (250-270 g) fueron sometidos a restricción, choque o entrenamiento en el laberinto elevado en T (ELET). Los animales fueron sacrificados inmediatamente (T0) o una hora (T1) después de la exposición al estrés. Un grupo no tratado, sacrificado al mismo tiempo que los animales tratados, se incluyó como control. Las muestras de la CPF fueron disecadas y la concentración de NA, 5-HT y sus metabolitos fue detectada por la técnica de HPLC. Las concentraciones de corticosterona fueron medidas en el suero. Ninguno de los tratamientos modificó las concentraciones de NA en la CPF. Al T0 los animales expuestos a choque o al ELET mostraron concentraciones de 5-HT significativamente mayores que el control. Los tratamientos de restricción y choque estuvieron asociados con altas concentraciones de corticosterona al T0 y a T1 después del tratamiento respectivo. En conjunto, los resultados mostraron que en la CPF los sistemas noradrenérgico y serotonérgico y la concentración de corticosterona responden en forma diferente a los distintos estresores.

O córtex pré-frontal (CPF) participa nas funções cognitivas e na regulação do estresse. As concentrações de noradrenalina (NA) e serotonina (5-HT) em algumas regiões do sistema nervoso central são modificadas pelo estresse agudo. O efeito depende do estressor e do tempo que transcorra entre o estressor e a avaliação. O objetivo do presente estudo foi avaliar o efeito agudo de diferentes estressores na atividade da NA e 5-HT no PFC e sua relação com os níveis de corticosterona. Grupos independentes de ratos (250-270 g) foram submetidos a restrição, choque ou treinamento no labirinto elevado em T (ELET). Os animais foram sacrificados imediatamente (T0) ou uma hora (T1) depois da exposição ao estresse. Um grupo não tratado, sacrificado ao mesmo tempo que os animais tratados, incluiu-se como controle. As mostras do PFC foram dissecadas e a concentração de NA, 5-HT e seus metabolitos foi detectada pela técnica de HPLC. As concentrações de corticosterona foram medidas no soro. Nenhum dos tratamentos modificou as concentrações de NA no PFC. Em T0 os animais expostos a choque o ao ELET mostraram concentrações de 5-HT significativamente maiores que o controle. Os tratamentos de restrição e choque estiveram associados com altas concentrações de corticosterona em T0 e em T1 depois do tratamento respectivo. Em conjunto, os resultados mostraram que no PFC os sistemas noradrenérgico e serotonérgico e a concentração de corticosterona respondem de maneira diferente aos diferentes estressores.

Surgical outcome of extraperitoneal paraaortic lymph node dissections compared with transperitoneal approach in gynecologic cancer patients.

STUDY OBJECTIVE: To evaluate the surgical outcome of extraperitoneal paraaortic lymph node dissection compared with the traditional transperitoneal approach. DESIGN: Retrospective review (Canadian Task Force classification III). SETTING: University hospital. PATIENTS: Women with gynecologic malignancies admitted to our hospital between 2007 and 2011 who underwent laparoscopic paraaortic lymphadenectomy. INTERVENTIONS: Indication, diagnosis, and outcome according to type of surgery were evaluated. MEASUREMENTS AND MAIN RESULTS: Of 47 patients who underwent laparoscopic paraaortic lymphadenectomy because of gynecologic indications, 28 patients underwent extraperitoneal paraaortic lymph node dissection and 19 underwent the same procedure via the classic transperitoneal technique. The most frequent indication for extraperitoneal lymph node dissection was cervical cancer (71.4%), and for the transperitoneal technique was endometrial cancer (47.4%). The mean (SD) duration of surgery was 211 (38) minutes in the transperitoneal approach group, and 173 (51) minutes in the extraperitoneal lymphadenectomy group (p = .009). No significant differences between groups were found in the number of lymph nodes removed (15 [5.9] nodes in the extraperitoneal group vs 17.4 [8.6] in the transperitoneal group; p = .25). However, a higher rate of positive nodes was observed in the extraperitoneal group than in the transperitoneal group (42.8% vs 36.2%, respectively [p = .001]), and a significantly shorter stay in the intensive care unit in the extraperitoneal group (0.59 [0.5] vs 1.1 [0.5] days, respectively; p = .02). No significant differences in complication rate were found between groups. CONCLUSIONS: Extraperitoneal paraaortic lymph node dissection is a minimally invasive procedure that is an excellent and safe approach to the paraaortic area, with a low complication rate, sufficient number of lymph nodes, and short hospital stay. It seems to be a good alternative to the classic transperitoneal approach.