A detailed study of resampling algorithms for cyberattack classification in engineering applications.

The evolution of engineering applications is highly relevant in the context of protecting industrial systems. As industries are increasingly interconnected, the need for robust cybersecurity measures becomes paramount. Engineering informatics not only provides tools for knowledge representation and extraction but also affords a comprehensive spectrum of developing sophisticated cybersecurity solutions. However, safeguarding industrial systems poses a unique challenge due to the inherent heterogeneity of data within these environments. Together with this problem, it's crucial to acknowledge that datasets that simulate real cyberattacks within these diverse environments exhibit a high imbalance, often skewed towards certain types of traffics. This study proposes a system for addressing class imbalance in cybersecurity. To do this, three oversampling (SMOTE, Borderline1-SMOTE, and ADASYN) and five undersampling (random undersampling, cluster centroids, NearMiss, repeated edited nearest neighbor, and Tomek Links) methods are tested. Particularly, these balancing algorithms are used to generate one-vs-rest binary models and to develop a two-stage classification system. By doing so, this study aims to enhance the efficacy of cybersecurity measures ensuring a more comprehensive understanding and defense against the diverse range of threats encountered in industrial environments. Experimental results demonstrates the effectiveness of proposed system for cyberattack detection and classification among nine widely known cyberattacks.

Development of a clinical and translational research curriculum for undergraduate students.

Introduction: Research participation during undergraduate years has a powerful influence on career selection and attitudes toward scientific research. Most undergraduate research programs in academic health centers are oriented toward basic research or address a particular disease focus or research discipline. Undergraduate research programs that expose students to clinical and translational research may alter student perceptions about research and influence career selection. Methods: We developed an undergraduate summer research curriculum, anchored upon a clinical and translational research study developed to address a common unmet needs in neonatal nurseries (e.g., assessment of neonatal opioid withdrawal syndrome). Program topics reflected the cross-disciplinary expertise that contributed to the development of this "bedside to bench" study, including opioid addiction, vulnerable populations, research ethics, statistics, data collection and management, assay development, analytical laboratory analysis, and pharmacokinetics. The curriculum was delivered through three offerings over 12 months, using Zoom video-conferencing due to restrictions imposed by the COVID-19 pandemic. Results: Nine students participated in the program. Two-thirds reported the course enhanced their understanding of clinical and translational research. Over three-quarters reported the curriculum topics were very good or excellent. In open-ended questions, students reported that the cross-disciplinary nature of the curriculum was the strongest aspect of the program. Conclusion: The curriculum could be readily adapted by other Clinical and Translational Science Award programs seeking to provide clinical and translational research-oriented programs to undergraduate students. Application of cross-disciplinary research approaches to a specific clinical and translational research question provides students with relevant examples of translational research and translational science.

CYP2E1 overexpression protects COS-7 cancer cells against ferroptosis.

Ferroptosis is a recently described form of regulated cell death initiated by the iron-mediated one-electron reduction of lipid hydroperoxides (LOOH). Cytochrome P450 2E1 (CYP2E1) induction, a consequence of genetic polymorphisms or/and gene induction by xenobiotics, may promote ferroptosis by contributing to the cellular pool of LOOH. However, CYP2E1 induction also increases the transcription of anti-ferroptotic genes that regulate the activity of glutathione peroxidase 4 (GPX4), the main ferroptosis inhibitor. Based on the above, we hypothesize that the impact of CYP2E1 induction on ferroptosis depends on the balance between pro- and anti-ferroptotic pathways triggered by CYP2E1. To test our hypothesis, ferroptosis was induced with class 2 inducers (RSL-3 or ML-162) in mammalian COS-7 cancer cells that don't express CYP2E1 (Mock cells), and in cells engineered to express human CYP2E1 (WT cells), and the impact on viability, lipid peroxidation and GPX4 was assessed. CYP2E1 overexpression protected COS-7 cancer cells against ferroptosis, evidenced by an increase in the IC50 and a decrease in lipid ROS in WT versus Mock cells after exposure to class 2 inducers. CYP2E1 overexpression produced an 80% increase in the levels of the GPX4 substrate glutathione (GSH). Increasing GSH in Mock cells protected cells against ferroptosis by ML-162. Depleting GSH, or inhibiting Nrf2 in WT cells reverted the protective effect mediated by CYP2E1, causing a decrease in the IC50 and an increase in lipid ROS after exposure to ML-162. These results show that CYP2E1 overexpression protects COS-7 cancer cells against ferroptosis, an effect probably mediated by Nrf2-dependent GSH induction.

MRI-computer vision on fresh and frozen-thawed beef: Optimization of methodology for classification and quality prediction.

This study aims to evaluate the capability of Magnetic Resonance Imaging (MRI) and computer vision techniques to classify fresh (raw F) (n = 12) and frozen-thawed (FT) (n = 12) beef and predict physico-chemical, texture and sensory characteristics by optimization the methodology for image analysis (algorithm) and data analysis (regressor), testing different algorithm-regressor combinations. The accuracy of the classification and prediction results especially depend on the algorithm. Different optimum combinations were found for classification (Fractal with CForest, RF or SVM) and prediction of quality parameters of raw FT (Fractal-CForest or Fractal-RF) and cooked FT samples (Classic-RF). Thus, the computational analysis of MRI, especially the algorithm to analyze the image, may be set as a function of the aim (classification or prediction) and of the type of sample (raw or cooked), while the analysed characteristic is not relevant. This study firstly showed the capability of MRI to classify beef (raw F vs. raw FT) and to determine quality characteristics in a non-destructive way.

Optimization of the image acquisition procedure in low-field MRI for non-destructive analysis of loin using predictive models.

The use of low-field magnetic resonance imaging (LF-MRI) scanners has increased in recent years. The low economic cost in comparison to high-field (HF-MRI) scanners and the ease of maintenance make this type of scanner the best choice for nonmedical purposes. However, LF-MRI scanners produce low-quality images, which encourages the identification of optimization procedures to generate the best possible images. In this paper, optimization of the image acquisition procedure for an LF-MRI scanner is presented, and predictive models are developed. The MRI acquisition procedure was optimized to determine the physicochemical characteristics of pork loin in a nondestructive way using MRI, feature extraction algorithms and data processing methods. The most critical parameters (relaxation times, repetition time, and echo time) of the LF-MRI scanner were optimized, presenting a procedure that could be easily reproduced in other environments or for other purposes. In addition, two feature extraction algorithms (gray level co-occurrence matrix (GLCM) and one point fractal texture algorithm (OPFTA)) were evaluated. The optimization procedure was validated by using several evaluation metrics, achieving reliable and accurate results (r > 0.85; weighted absolute percentage error (WAPE) lower than 0.1%; root mean square error of prediction (RMSEP) lower than 0.1%; true standard deviation (TSTD) lower than 2; and mean absolute error (MAE) lower than 2). These results support the high degree of feasibility and accuracy of the optimized procedure of LF-MRI acquisition. No other papers present a procedure to optimize the image acquisition process in LF-MRI. Eventually, the optimization procedure could be applied to other LF-MRI systems.

Antioxidant and pro-oxidant mechanisms of (+) catechin in microsomal CYP2E1-dependent oxidative stress.

The objectives of this work were to evaluate the effects of catechin on cytochrome P450 2E1 (CYP2E1)-dependent oxidative stress. Microsomes co-expressing human CYP2E1 with NADPH cytochrome P450 reductase and cytochrome b5 were incubated with NADPH and DTPA at pH 7.0. Superoxide anion generation was specifically detected by spin-trapping with DEPMPO. Generation of the DEPMPO-OOH adduct was not observed in the absence of CYP2E1 and in the presence of superoxide dismutase (SOD) or catechin, while catalase was ineffective. Reactive oxygen species generation was detected with 1-hydroxy-3-carboxy-2,2,5,5-tetramethylpyrrolidine (CPH) by the EPR-detection of its oxidation product, 3-carboxy-proxyl radical (CP●). CP● generation was not observed in the absence of CYP2E1 and in the presence of SOD, while catalase was ineffective. In contrast, catechin increased CPH oxidation, an effect that was not observed in the absence of CYP2E1 or in the presence of SOD (but not catalase), and was not associated with an increase in oxygen consumption. Catechin also increased the non-specific oxidation of the probes CPH and hydroethidine by the superoxide anion-generating system xanthine plus xanthine oxidase. Catechin oxidized CPH in the presence of horseradish peroxidase plus hydrogen peroxide, a catechin radical-generating system. In conclusion, catechin exhibits both antioxidant (superoxide-scavenging) and pro-oxidant effects under CYP2E1-dependent oxidative stress.

Encephalitis Associated to Metabotropic Glutamate Receptor 5 (mGluR5) Antibodies in Cerebrospinal Fluid.

A 68-years-old Hispanic man, complained of night sweats, low grade fewer, unexplained weight loss, and memory problems over 3 months. Abdominal tomography showed multiple intra-abdominal adenopathy and biopsy confirmed classic Hodgkin's lymphoma. He commenced treatment with chemotherapy. Three months later, he had acute onset of inattention, auditory hallucinations and alterations of anterograde memory. The patient developed psychomotor agitation, unresponsive to a combination of neuroleptics and benzodiazepines. Brain MRI showed a small established cerebellar infarction. Electroencephalogram was normal. Tests for toxic metabolic encephalopathy were negative. One oligoclonal IgG bands was found in the Cerebrospinal fluid (CSF), which was not observed in corresponding serum, but cell count and protein were normal. Extensive testing for infectious encephalitis was unremarkable. CSF testing for commercially available neural and non-neural autoantibodies was negative. The patient fulfilled the Gultekin diagnostic criteria for paraneoplastic limbic encephalitis and methylprednisolone IV 1g/d for 5 days was given. He recovered rapidly, with progressive improvement in memory and psychomotor agitation. After treatment commenced, results for antibodies to mGluR5 in CSF taken prior to treatment were returned as positive. mGluR5 is found on post-synaptic terminals of neurons and microglia and is expressed primarily in the hippocampus and amygdala. This case highlights the difficulties in diagnosing this type of encephalitis: the CSF did not show pleocytosis, the MRI showed only chronic change and the electroencephalogram was normal. The dramatic recovery after methylprednisolone help to better characterized the clinical spectrum of auto-immune encephalitis. Diagnosing anti mGlutR5 encephalitis may lead to potentially highly effective treatment option and may anticipate the diagnostic of a cancer. A high index of suspicion is needed to avoid missed diagnosis. In patients with unexplained encephalitis, testing for antibodies to mGluR5 in CSF and serum should be considered. When there is a reasonable index of suspicion of auto-immune encephalitis, treatment should not be delayed for the antibody results.

Iron overload prevents oxidative damage to rat brain after chlorpromazine administration.

The hypothesis tested is that Fe administration leads to a response in rat brain modulating the effects of later oxidative challenges such as chlorpromazine (CPZ) administration. Either a single dose (acute Fe overload) or 6 doses every second day (sub-chronic Fe overload) of 500 or 50 mg Fe-dextran/kg, respectively, were injected intraperitoneally (ip) to rats. A single dose of 10 mg CPZ/kg was injected ip 8 h after Fe treatment. DNA integrity was evaluated by quantitative PCR, lipid radical (LR·) generation rate by electron paramagnetic resonance (EPR), and catalase (CAT) activity by UV spectrophotometry in isolated brains. The maximum increase in total Fe brain was detected after 6 or 2 h in the acute and sub-chronic Fe overload model, respectively. Mitochondrial and nuclear DNA integrity decreased after acute Fe overload at the time of maximal Fe content; the decrease in DNA integrity was lower after sub-chronic than after acute Fe overload. CPZ administration increased LR· generation rate in control rat brain after 1 and 2 h; however, CPZ administration after acute or sub-chronic Fe overload did not affect LR· generation rate. CPZ treatment did not affect CAT activity after 1-4 h neither in control rats nor in acute Fe-overloaded rats. However, CPZ administration to rats treated sub-chronically with Fe showed increased brain CAT activity after 2 or 4 h, as compared to control values. Fe supplementation prevented brain damage in both acute and sub-chronic models of Fe overload by selectively activating antioxidant pathways.

Prediction of pork quality parameters by applying fractals and data mining on MRI.

This work firstly investigates the use of MRI, fractal algorithms and data mining techniques to determine pork quality parameters non-destructively. The main objective was to evaluate the capability of fractal algorithms (Classical Fractal algorithm, CFA; Fractal Texture Algorithm, FTA and One Point Fractal Texture Algorithm, OPFTA) to analyse MRI in order to predict quality parameters of loin. In addition, the effect of the sequence acquisition of MRI (Gradient echo, GE; Spin echo, SE and Turbo 3D, T3D) and the predictive technique of data mining (Isotonic regression, IR and Multiple linear regression, MLR) were analysed. Both fractal algorithm, FTA and OPFTA are appropriate to analyse MRI of loins. The sequence acquisition, the fractal algorithm and the data mining technique seems to influence on the prediction results. For most physico-chemical parameters, prediction equations with moderate to excellent correlation coefficients were achieved by using the following combinations of acquisition sequences of MRI, fractal algorithms and data mining techniques: SE-FTA-MLR, SE-OPFTA-IR, GE-OPFTA-MLR, SE-OPFTA-MLR, with the last one offering the best prediction results. Thus, SE-OPFTA-MLR could be proposed as an alternative technique to determine physico-chemical traits of fresh and dry-cured loins in a non-destructive way with high accuracy.

1,3-Butadiene-induced mitochondrial dysfunction is correlated with mitochondrial CYP2E1 activity in Collaborative Cross mice.

Cytochrome P450 2E1 (CYP2E1) metabolizes low molecular weight hydrophobic compounds, including 1,3-butadiene, which is converted by CYP2E1 to electrophilic epoxide metabolites that covalently modify cellular proteins and DNA. Previous CYP2E1 studies have mainly focused on the enzyme localized in the endoplasmic reticulum (erCYP2E1); however, active CYP2E1 has also been found in mitochondria (mtCYP2E1) and the distribution of CYP2E1 between organelles can influence an individual's response to exposure. Relatively few studies have focused on the contribution of mtCYP2E1 to activation of chemical toxicants. We hypothesized that CYP2E1 bioactivation of 1,3-butadiene within mitochondria adversely affects mitochondrial respiratory complexes I-IV. A population of Collaborative Cross mice was exposed to air (control) or 200ppm 1,3-butadiene. Subcellular fractions (mitochondria, DNA, and microsomes) were collected from frozen livers and CYP2E1 activity was measured in microsomes and mitochondria. Individual activities of mitochondrial respiratory complexes I-IV were measured using in vitro assays and purified mitochondrial fractions. In air- and 1,3-butadiene-exposed mouse samples, mtDNA copy numbers were assessed by RT-PCR, and mtDNA integrity was assessed through a PCR-based assay. No significant changes in mtDNA copy number or integrity were observed; however, there was a decrease in overall activity of mitochondrial respiratory complexes I, II, and IV after 1,3-butadiene exposure. Additionally, higher mtCYP2E1 (but not erCYP2E1) activity was correlated with decreased mitochondrial respiratory complex activity (in complexes I-IV) in the 1,3-butadiene-exposed (not control) animals. Together, these results represent the first in vivo link between mitochondrial CYP2E1 activity and mitochondrial toxicity.

Non-destructive analysis of sensory traits of dry-cured loins by MRI-computer vision techniques and data mining.

BACKGROUND: Magnetic resonance imaging (MRI) combined with computer vision techniques have been proposed as an alternative or complementary technique to determine the quality parameters of food in a non-destructive way. The aim of this work was to analyze the sensory attributes of dry-cured loins using this technique. For that, different MRI acquisition sequences (spin echo, gradient echo and turbo 3D), algorithms for MRI analysis (GLCM, NGLDM, GLRLM and GLCM-NGLDM-GLRLM) and predictive data mining techniques (multiple linear regression and isotonic regression) were tested. RESULTS: The correlation coefficient (R) and mean absolute error (MAE) were used to validate the prediction results. The combination of spin echo, GLCM and isotonic regression produced the most accurate results. In addition, the MRI data from dry-cured loins seems to be more suitable than the data from fresh loins. CONCLUSIONS: The application of predictive data mining techniques on computational texture features from the MRI data of loins enables the determination of the sensory traits of dry-cured loins in a non-destructive way. © 2016 Society of Chemical Industry.

Subcellular localization of rat CYP2E1 impacts metabolic efficiency toward common substrates.

Cytochrome P450 2E1 (CYP2E1) detoxifies or bioactivates many low molecular-weight compounds. Most knowledge about CYP2E1 activity relies on studies of the enzyme localized to endoplasmic reticulum (erCYP2E1); however, CYP2E1 undergoes transport to mitochondria (mtCYP2E1) and becomes metabolically active. We report the first comparison of in vitro steady-state kinetic profiles for erCYP2E1 and mtCYP2E1 oxidation of probe substrate 4-nitrophenol and pollutants styrene and aniline using subcellular fractions from rat liver. For all substrates, metabolic efficiency changed with substrate concentration for erCYP2E1 reflected in non-hyperbolic kinetic profiles but not for mtCYP2E1. Hyperbolic kinetic profiles for the mitochondrial enzyme were consistent with Michaelis-Menten mechanism in which metabolic efficiency was constant. By contrast, erCYP2E1 metabolism of 4-nitrophenol led to a loss of enzyme efficiency at high substrate concentrations when substrate inhibited the reaction. Similarly, aniline metabolism by erCYP2E1 demonstrated negative cooperativity as metabolic efficiency decreased with increasing substrate concentration. The opposite was observed for erCYP2E1 oxidation of styrene; the sigmoidal kinetic profile indicated increased efficiency at higher substrate concentrations. These mechanisms and CYP2E1 levels in mitochondria and endoplasmic reticulum were used to estimate the impact of CYP2E1 subcellular localization on metabolic flux of pollutants. Those models showed that erCYP2E1 mainly carries out aniline metabolism at all aniline concentrations. Conversely, mtCYP2E1 dominates styrene oxidation at low styrene concentrations and erCYP2E1 at higher concentrations. Taken together, subcellular localization of CYP2E1 results in distinctly different enzyme activities that could impact overall metabolic clearance and/or activation of substrates and thus impact the interpretation and prediction of toxicological outcomes.

Prooxidant and antioxidant properties of salicylaldehyde isonicotinoyl hydrazone iron chelators in HepG2 cells.

BACKGROUND: Salicylaldehyde isonicotinoyl hydrazone (SIH) is an iron chelator of the aroylhydrazone class that displays antioxidant or prooxidant effects in different mammalian cell lines. Because the liver is the major site of iron storage, elucidating the effect of SIH on hepatic oxidative metabolism is critical for designing effective hepatic antioxidant therapies. METHODS: Hepatocyte-like HepG2 cells were exposed to SIH or to analogs showing greater stability, such as N'-[1-(2-Hydroxyphenyl)ethyliden]isonicotinoyl hydrazide (HAPI), or devoid of iron chelating properties, such as benzaldehyde isonicotinoyl hydrazone (BIH), and toxicity, oxidative stress and antioxidant (glutathione) metabolism were evaluated. RESULTS: Autoxidation of Fe(2+)in vitro increased in the presence of SIH or HAPI (but not BIH), an effect partially blocked by Fe(2+) chelation. Incubation of HepG2 cells with SIH or HAPI (but not BIH) was non-toxic and increased reactive oxygen species (ROS) levels, activated the transcription factor Nrf2, induced the catalytic subunit of γ-glutamate cysteine ligase (Gclc), and increased glutathione concentration. Fe(2+) chelation decreased ROS and inhibited Nrf2 activation, and Nrf2 knock-down inhibited the induction of Gclc in the presence of HAPI. Inhibition of γ-glutamate cysteine ligase enzymatic activity inhibited the increase in glutathione caused by HAPI, and increased oxidative stress. CONCLUSIONS: SIH iron chelators display both prooxidant (increasing the autoxidation rate of Fe(2+)) and antioxidant (activating Nrf2 signaling) effects. GENERAL SIGNIFICANCE: Activation by SIH iron chelators of a hormetic antioxidant response contributes to their antioxidant properties and modulates the anti- and pro-oxidant balance.

N-acetylcysteine inhibits the up-regulation of mitochondrial biogenesis genes in livers from rats fed ethanol chronically.

BACKGROUND: Chronic ethanol (EtOH) administration to experimental animals induces hepatic oxidative stress and up-regulates mitochondrial biogenesis. The mechanisms by which chronic EtOH up-regulates mitochondrial biogenesis have not been fully explored. In this work, we hypothesized that oxidative stress is a factor that triggers mitochondrial biogenesis after chronic EtOH feeding. If our hypothesis is correct, co-administration of antioxidants should prevent up-regulation of mitochondrial biogenesis genes. METHODS: Rats were fed an EtOH-containing diet intragastrically by total enteral nutrition for 150 days, in the absence or presence of the antioxidant N-acetylcysteine (NAC) at 1.7 g/kg/d; control rats were administered isocaloric diets where carbohydrates substituted for EtOH calories. RESULTS: EtOH administration significantly increased hepatic oxidative stress, evidenced as decreased liver total glutathione and reduced glutathione/glutathione disulfide ratio. These effects were inhibited by co-administration of EtOH and NAC. Chronic EtOH increased the expression of mitochondrial biogenesis genes including peroxisome proliferator-activated receptor gamma-coactivator-1 alpha and mitochondrial transcription factor A, and mitochondrial DNA; co-administration of EtOH and NAC prevented these effects. Chronic EtOH administration was associated with decreased mitochondrial mass, inactivation and depletion of mitochondrial complex I and complex IV, and increased hepatic mitochondrial oxidative damage, effects that were not prevented by NAC. CONCLUSIONS: These results suggest that oxidative stress caused by chronic EtOH triggered the up-regulation of mitochondrial biogenesis genes in rat liver, because an antioxidant such as NAC prevented both effects. Because NAC did not prevent liver mitochondrial oxidative damage, extra-mitochondrial effects of reactive oxygen species may regulate mitochondrial biogenesis. In spite of the induction of hepatic mitochondrial biogenesis genes by chronic EtOH, mitochondrial mass and function decreased probably in association with mitochondrial oxidative damage. These results also predict that the effectiveness of NAC as an antioxidant therapy for chronic alcoholism will be limited by its limited antioxidant effects in mitochondria, and its inhibitory effect on mitochondrial biogenesis.

Características de pacientes con pancreatitis aguda en pediatría: hallazgos clínicos e imaginológicos / Characteristics of Pediatric Patients with Acute Pancreatitis: Clinical and Imaging Findings

Introducción: La pancreatitis aguda (PA) es un proceso inflamatorio pancreático que cursa con dolor abdominal y vómito. Es una entidad infrecuente en pediatría, por lo que existen pocos estudios en la literatura. Las principales causas son trauma, infecciones, fármacos y litiasis. En diversos estudios aparece como primera causa la idiopática; la causa litiásica es infrecuente. El estudio imaginológico se inicia con Ultrasonido (US) y se puede complementar con Tomografía computalizada (TC). Objetivo: Describir los hallazgos imaginológicos y las características epidemiológicas de los pacientes pediátricos con PA. Metodología: Análisis retrospectivo de las características clínicas y radiológicas de niños con PA, durante los años 2004-2012. Se obtuvo un total de 11 casos, 5 varones (45%) y 6 mujeres (55%), todos evaluados con algún método imaginológico. Resultados: Las formas de presentación fueron: aguda, 73%; recurrente, 9%; insuficiencia pancreática, 18%. Los principales síntomas fueron: dolor abdominal, 100%; vómito, 72,7%; fiebre, 9%; diarrea, 18%; ictericia, 9%. Las etiologías fueron: litiásica, 36,4%; idiopática, 27,3%; farmacológica, 18,2%; autoinmune, 9%; hipertrigliceridemia, 9%. Los hallazgos imagenológicos fueron: páncreas aumentado de tamaño, 63,6%; líquido libre, 45,5%; colelitiasis, 36,4%; derrame pleural, 18,2%; colecciones, 18,2%; vía biliar dilatada, 9%. Conclusión: A diferencia de otros estudios, la causa más frecuente de PA en esta serie es la litiásica, lo que concuerda con el alto índice de colelitiasis en la población adulta del país. En este contexto se hace relevante el estudio etiológico de las PA con métodos de imágenes para precisar el tratamiento adecuado.

Introduction: Acute pancreatitis (AP) is an inflammatory pancreatic disease that presents with abdominal pain and vomiting. It is a rare entity in the pediatric population, thus, there are few studies reported in literature. The main etiologies are trauma, infection, drugs, and lithiasis among others. In several studies, the main reported cause is idiopathic, and biliary causes are infrequent. Imaging study usually begins with an abdominal ultrasound, which can be complemented with CT. Objective: The objective is to describe the imaging findings and epidemiological characteristics of children with AP. Method: We performed a retrospective analysis of clinical and radiological features of pediatric patients with AP, between the years 2004-2012. We obtained a total of 11 cases, 5 males (45%) and 6 females (55%), all evaluated with an imaging study. Results: The three forms of presentation were acute 73%, recurrent 9% and pancreatic insufficiency 18%. The main symptoms were abdominal pain 100%, vomiting 72.7%, fever 9%, diarrhea 18%, and jaundice 9%. The most frequent etiology was lithiasic (36.4%), idiopathic (27.3%), drugs (18.2%), autoimmune (9%), and hypertriglyceridemia 9%. The imaging findings were enlarged pancreas 63.6%, free fluid 45.5%, cholelithiasis 36.4%, pleural effusion 18.2%, collections 18.2% and dilated bile duct 9%. Conclusion: Unlike other studies, the most common cause of AP in this series is lithiasic, consistent with the high rate of cholelithiasis in the adult population of our country. In this context it is relevant to study the etiology of AP by imaging studies to determine the adequate treatment.

Características de pacientes con colelitiasis en la edad pediátrica: hallazgos ecográficos, experiencia de diez años / Characteristics in Pediatric Patients with Cholelithiasis: Sonographic Findings, 10 years' Experience

Introducción: Las enfermedades de la vía biliar y la litiasis vesicular son una causa poco frecuente de dolor abdominal agudo en niños, a diferencia de lo que ocurre en adultos. Con la masificación del ultrasonido es posible detectar litiasis biliar en pacientes asintomáticos, lo que podría explicar el aumento de su incidencia. Objetivos: Describir los hallazgos ecográficos y las características epidemiológicas de los pacientes pediátricos con diagnóstico de colelitiasis. Metodología: Análisis retrospectivo de las características clínicas y ecográficas de pacientes pediátricos con colelitiasis en el Hospital Padre Hurtado (Santiago de Chile), entre 2002 y 2012. Resultados: 33 casos (13 hombres y 20 mujeres), de 21 días de vida hasta 15 años, todos evaluados con ecografía abdominal. El diagnóstico se realizó como hallazgo incidental en 3 pacientes; en 13 pacientes se indicó el estudio por cólico biliar recurrente; a 4 pacientes, por sospecha de apendicitis aguda; en 9 casos, como dolor abdominal asociado a vómitos; en 2 casos, como hallazgo en estudio renal, y en 2 pacientes, dentro del estudio de una pancreatitis. En la ecografía, la litiasis múltiple se presentó en el 93% de los casos. En 2 casos se observó coledocolitiasis asociada. Un 93% presentó vía biliar normal. El tratamiento de elección fue la colecistectomía laparoscópica. Conclusión: La litiasis biliar en nuestra población pediátrica es más frecuente de lo informado en la literatura. Como principales factores de riesgo se identificaron el sobrepeso y la obesidad. El principal motivo de realización del examen es el dolor abdominal.

Introduction: Biliary tract and gallstone diseases are a rare cause of acute abdominal pain in children, which is not the case in adults. With the widespread use of ultrasound examination, now we can detect gallstones in asymptomatic patients, which could explain the increased incidence. Objective: To describe the sonographic findings and epidemiological characteristics of pediatric patients diagnosed with cholelithiasis. Methodology: We performed a retrospective analysis of the clinical and sonographic characteristics of the pediatric patients with cholelithiasis in the Hospital Padre Hurtado (Santiago de Chile) during the period 2002-2012. Results: There were a total of 33 cases, 13 males and 20 females with an age range from 21 days old up to 15 years old, all of them were evaluated with abdominal ultrasound. In 3 patients the diagnosis was an incidental finding, 13 patients were studied for recurrent biliary colic, 4 patients as suspected acute appendicitis, 9 cases as abdominal pain associated with vomiting, 2 cases as a finding in renal study and 2 patients in the context of pancreatitis study. Ultrasound showed multiple lithiasis in 93%. In 2 cases there was also a choledocholithiasis. Normal biliary duct was seen in 93% of the cases. The treatment of choice was laparoscopic cholecystectomy. Conclusion: Cholecystolithiasis is more in children than is suggested in literature, and ultrasound is an appropriate imaging study for its detection. The main risk factors identified were excess weight and obesity. The main objective of this test is abdominal pain.

Effect of garlic-derived organosulfur compounds on mitochondrial function and integrity in isolated mouse liver mitochondria.

The objectives of this work were to evaluate the direct effects of diallysulfide (DAS) and diallyldisulfide (DADS), two major organosulfur compounds of garlic oil, on mitochondrial function and integrity, by using isolated mouse liver mitochondria in a cell-free system. DADS produced concentration-dependent mitochondrial swelling over the range 125-1000µM, while DAS was ineffective. Swelling experiments performed with de-energized or energized mitochondria showed similar maximal swelling amplitudes. Cyclosporin A (1µM), or ethylene glycol-bis(2-aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA, 1mM) were ineffective in inhibiting DADS-induced mitochondrial swelling. DADS produced a minor (12%) decrease in mitochondrial membrane protein thiols, but did not induce clustering of mitochondrial membrane proteins. Incubation of mitochondria with DADS (but not DAS) produced an increase in the oxidation rate of 2',7' dichlorofluorescein diacetate (DCFH-DA), together with depletion of reduced glutathione (GSH) and increased lipid peroxidation. DADS (but not DAS) produced a concentration-dependent dissipation of the mitochondrial membrane potential, but did not induce cytochrome c release. DADS-dependent effects, including mitochondrial swelling, DCFH-DA oxidation, lipid peroxidation and loss of mitochondrial membrane potential, were inhibited by antioxidants and iron chelators. These results suggest that DADS causes direct impairment of mitochondrial function as the result of oxidation of the membrane lipid phase initiated by the GSH- and iron-dependent generation of oxidants.

Increased oxidative stress and cytotoxicity by hydrogen sulfide in HepG2 cells overexpressing cytochrome P450 2E1.

The main objectives of this work were to evaluate the effects of hydrogen sulfide on oxidative stress and cytotoxicity parameters in HepG2 cells and to assess the extent to which cytochrome P450 2E1 (CYP2E1) activity modulates the effects of hydrogen sulfide on oxidative stress and cytotoxicity. Sodium hydrosulfide (NaHS) caused time- and concentration-dependent cytotoxicity in both non-P450-expressing HepG2 cells (C34 cells) and CYP2E1-overexpressing HepG2 cells (E47 cells); however, NaHS-dependent cytotoxicity was higher in E47 than C34 cells. Cytotoxicity by NaHS in C34 and E47 cells was mainly necrotic in nature and associated with an early decrease in mitochondrial membrane potential. NaHS caused increased oxidation of lipophilic (C11-BODIPY(581/591)) and hydrophilic (DCFH-DA) probes only in E47 cells, at a time point prior to overt cytotoxicity. Trolox, an amphipathic antioxidant, partially inhibited both the cytotoxicity and the increased oxidative stress detected in E47 cells exposed to NaHS. Cell-permeable iron chelators and CYP2E1 inhibitors significantly inhibited the oxidation of C11-BODIPY(581/591) in E47 cells in the presence of NaHS. NaHS produced lipid peroxidation and cytotoxicity in E47 cells supplemented with a representative polyunsaturated fatty acid (docosahexaenoic acid) but not in C34 cells; these effects were inhibited by α-tocopherol, a lipophilic antioxidant. These data suggest that CYP2E1 enhances H(2)S-dependent cytotoxicity in HepG2 cells through the generation of iron-dependent oxidative stress and lipid peroxidation.

Ecological convergence in a rocky intertidal shore metacommunity despite high spatial variability in recruitment regimes.

In open ecological systems, community structure can be determined by physically modulated processes such as the arrival of individuals from a regional pool and by local biological interactions. There is debate centering on whether niche differentiation and local interactions among species are necessary to explain macroscopic community patterns or whether the patterns can be generated by the neutral interplay of dispersal and stochastic demography among ecologically identical species. Here we evaluate how much of the observed spatial variation within a rocky intertidal metacommunity along 800 km of coastline can be explained by drift in the structure of recruits across 15 local sites. Our results show that large spatial changes in recruitment do not explain the observed spatial variation in adult local structure and that, in comparison with the large drift in structure of recruits, local adult communities converged to a common, although not unique, structure across the region. Although there is no unique adult community structure in the entire region, the observed variation represents only a small subset of the possible structures that would be expected from passive recruitment drift. Thus, in this diverse system our results do not support the idea that rocky intertidal metacommunities are structured by neutral mechanisms.