Simulation of the electrical stimulation of the rat brain using sleep frequencies: A finite element modeling approach.

A realistic rat brain model was used to simulate current density and electric field distributions under frequencies characteristic of sleeping states (0.8, 5, and 12 Hz). Two anode-electrode setups were simulated: plate vs. screws-anode, both with a cephalic cathode. Our simulations showed that these frequencies have limited impact on electric field and current density; however, the highest frequency evidenced higher values for both variables. The type of electrode setup had a greater effect on current distribution and induced fields. In that sense, the screws setup resulted in higher values of the modeled variables. The numeric results obtained are within the range of available data for rodent models using the finite elements method. These modeled effects should be analyzed regarding anatomical consequences (depth of penetration of the currents) and purpose of the experiment (i.e., entrainment of brain oscillations) in the context of sleep research.

Insertions of antihypertensive peptides and their applications in pharmacy and functional foods.

Hypertension is a worldwide health problem. It is the main cardiovascular risk factor and affects about 31% of the world's adult population. The drugs used to control hypertension may cause side effects; for this reason, there are many investigations focused on searching for alternatives to control or prevent this disease through diet. For example, many peptides have demonstrated antihypertensive effects. The insertion of bioactive peptides is a biotechnological implement used to improve the nutraceutical properties of proteins. This work reviews the current data on the insertion of antihypertensive peptides (AHPs) into food proteins, the systems used to produce the AHPs, the advantages and disadvantages between them, the parameters to produce them at major scales, and their potential applications in pharmacy and functional foods.

Behavioral effects of environmental enrichment on male and female wistar rats with early life stress experiences.

Exposure to adverse childhood experiences or early life stress experiences (ELSs) increase the risk of non-adaptive behaviors and psychopathology in adulthood. Environmental enrichment (EE) has been proposed to minimize these effects. The vast number of methodological variations in animal studies underscores the lack of systematicity in the studies and the need for a detailed understanding of how enrichment interacts with other variables. Here we evaluate the effects of environmental enrichment in male and female Wistar rats exposed to adverse early life experiences (prenatal, postnatal, and combined) on emotional (elevated plus maze), social (social interaction chamber), memory (Morris water maze) and flexibility tasks. Our results-collected from PND 51 to 64-confirmed: 1) the positive effect of environmental enrichment (PND 28-49) on anxiety-like behaviors in animals submitted to ELSs. These effects depended on type of experience and type of enrichment: foraging enrichment reduced anxiety-like behaviors in animals with prenatal and postnatal stress but increased them in animals without ELSs. This effect was sex-dependent: females showed lower anxiety compared to males. Our data also indicated that females exposed to prenatal and postnatal stress had lower anxious responses than males in the same conditions; 2) no differences were found for social interactions; 3) concerning memory, there was a significant interaction between the three factors: A significant interaction for males with prenatal stress was observed for foraging enrichment, while physical enrichment was positive for males with postnatal stress; d) regarding cognitive flexibility, a positive effect of EE was found in animals exposed to adverse ELSs: animals with combined stress and exposed to physical enrichment showed a higher index of cognitive flexibility than those not exposed to enrichment. Yet, within animals with no EE, those exposed to combined stress showed lower flexibility than those exposed to both prenatal stress and no stress. On the other hand, animals with prenatal stress and exposed to foraging-type enrichment showed lower cognitive flexibility than those with no EE. The prenatal stress-inducing conditions used here 5) did not induced fetal or maternal problems and 6) did not induced changes in the volume of the dentate gyrus of the hippocampus.

Feasibility of whole genome and transcriptome profiling in pediatric and young adult cancers.

The utility of cancer whole genome and transcriptome sequencing (cWGTS) in oncology is increasingly recognized. However, implementation of cWGTS is challenged by the need to deliver results within clinically relevant timeframes, concerns about assay sensitivity, reporting and prioritization of findings. In a prospective research study we develop a workflow that reports comprehensive cWGTS results in 9 days. Comparison of cWGTS to diagnostic panel assays demonstrates the potential of cWGTS to capture all clinically reported mutations with comparable sensitivity in a single workflow. Benchmarking identifies a minimum of 80× as optimal depth for clinical WGS sequencing. Integration of germline, somatic DNA and RNA-seq data enable data-driven variant prioritization and reporting, with oncogenic findings reported in 54% more patients than standard of care. These results establish key technical considerations for the implementation of cWGTS as an integrated test in clinical oncology.

Improvements in planning lacrimal surgery using DICOM Horos® viewer 3D images.

INTRODUCTION AND OBJECTIVE: The individual anatomic variation of the course of the lacrimal duct and surrounding structures requires the thorough knowledge of its three-dimensional configuration in order to perform the surgery in the safest and most efficient way. The aim of this study was to consider virtual surgical planning in order to improve dacryocystorhinostomies. METHODS: Horos® was used as a viewer and manager of DICOM-format images for multiplanar, three-dimensional (3D) reconstruction when planning 148 first-time lacrimal operations and 26 reoperations by laser endonasal and endocanalicular DCRs. RESULTS: The 3D images of the CT dacryocystography were much better identified than the 2D ones, Horos® showing a statistically significant correlation (P < .0001). Over 98.27% of the images match the programme reconstruction. Less than 1.73% of them showed some discordance due to study distortion. These cases were related to trauma. The intraopearative location of the lacrimal system was very accurate, avoiding complications. CONCLUSIONS: Viewing and studying 3D images, Horos® is a very useful tool for diagnosis and preoperative planning. It is very helpful in complex conditions by marking surgical references, locating the lacrimal sac and controlling the post-operative permeability of the lacrimal system. The information loss produced by the image selection is also avoided. Another great advantage is that the programme is free.

Improvements in planning lacrimal surgery using DICOM Horos® viewer 3D images. / Mejora de la planificación de las cirugías lagrimales a partir de imágenes tridimensionales con el visualizador DICOM Horos®.

INTRODUCTION AND OBJECTIVE: The individual anatomic variation of the course of the lacrimal duct and surrounding structures requires the thorough knowledge of its three-dimensional configuration in order to perform the surgery in the safest and most efficient way. The aim of this study was to consider virtual surgical planning in order to improve dacryocystorhinostomies. METHODS: Horos® was used as a viewer and manager of DICOM-format images for multiplanar, three-dimensional (3D) reconstruction when planning 148 first-time lacrimal operations and 26 reoperations by laser endonasal and endocanalicular DCRs. RESULTS: The 3D images of the CT dacryocystography were much better identified than the 2D ones, Horos® showing a statistically significant correlation (P<.0001). Over 98.27% of the images match the programme reconstruction. Less than 1.73% of them showed some discordance due to study distortion. These cases were related to trauma. The intraopearative location of the lacrimal system was very accurate, avoiding complications. CONCLUSIONS: Viewing and studying 3D images, Horos® is a very useful tool for diagnosis and preoperative planning. It is very helpful in complex conditions by marking surgical references, locating the lacrimal sac and controlling the post-operative permeability of the lacrimal system. The information loss produced by the image selection is also avoided. Another great advantage is that the programme is free.

Mathematical modelling of microbial growth in ground beef from Argentina. Effect of lactic acid addition, temperature and packaging film.

The effects of: (i) storage temperature (0, 4 and 10°C), (ii) gaseous permeability of the packaging film (polyethylene and EVA SARAN EVA for vacuum packaging), and (iii) natural beef pH (5.6, 5.8 and 6.1) on the growth of different bacteria isolated from beef muscle were examined. The bacteria were Klebsiella, Pseudomonas sp. and Escherichia coli. Microbial growth was modelled using Gompertz and linear equations. The effects of temperature on microbial growth rate (µ) and on lag phase duration were modelled using an Arrhenius type equation. In polyethylene, E. coli was the microorganism, that showed the highest µ values and also the greatest effect of pH on µ, especially in samples stored at 4 and 10°C. In the case of Klebsiella sp., neither pH nor temperature had marked effects on µ and on LPD. In ESE film, µ of all the microorganisms were less affected by pH and temperature than in polyethylene. In ESE film E. coli showed the highest effect of pH on µ, at 4 and 10°C. LPD increased significantly with respect to the values in polyethylene, with Klebsiella sp., showing the highest values of LPD, followed by E. coli. Experiments in ground beef with added lactic acid producing a decrease of the original muscle pH from 6.1 to 5.6 showed that the kinetic parameters of the microbial flora did not differ significantly from those of beef samples in which the original pH was 5.6.

Reference genes for RT-qPCR normalisation in different tissues, developmental stages and stress conditions of amaranth.

Studies of gene expression are very important for the identification of genes that participate in different biological processes. Currently, reverse transcription quantitative real-time PCR (RT-qPCR) is a high-throughput, sensitive and widely used method for gene expression analysis. Nevertheless, RT-qPCR requires precise normalisation of data to avoid the misinterpretation of experimental data. In this sense, the selection of reference genes is critical for gene expression analysis. At this time, several studies focus on the selection of reference genes in several species. However, the identification and validation of reference genes for the normalisation of RT-qPCR have not been described in amaranth. A set of seven housekeeping genes were analysed using RT-qPCR, to determine the most stable reference genes in amaranth for normalisation of gene expression analysis. Transcript stability and gene expression level of candidate reference genes were analysed in different tissues, at different developmental stages and under different types of stress. The data were compared using the geNorm, NormFinder and Bestkeeper statistical methods. The reference genes optimum for normalisation of data varied with respect to treatment. The results indicate that AhyMDH, AhyGAPDH, AhyEF-1α and AhyACT would be optimum for accurate normalisation of experimental data, when all treatment are analysed in the same experiment. This study presents the most stable reference genes for normalisation of gene expression analysis in amaranth, which will contribute significantly to future gene studies of this species.

[Complications of the direct endonasal transsphenoidal approach in the management of pituitary adenomas]. / Complicaciones del abordaje endonasal directo transesfenoidal en el manejo de adenomas de hipófisis.

OBJECTIVE: To describe the frequency of complications and complaints caused by direct endonasal transsphenoidal approach used in the resection of pituitary adenomas. PATIENTS AND METHODS: In a retrospective way, we review patients' records with pituitary adenomas, operated by means of direct endonasal transsphenoidal approach, between August 2003 and December 2004. We recollected information about operative and postoperative complications, besides complaints registered in patients' records. RESULTS: 41 patients were included, 23 (56.1%) males and 18 (43.9%) females, with a mean age of 47.7 -/+16.8 years. Operative complications were intrasellar hemorrhage in three patients (7.3%), hypertension in two (4.9%) and cerebrospinal fluid fistula in one (2.4%). On the other hand, postoperative complications were diabetes insipidus (24.4%) in ten cases, anterior pituitary insufficiency (4.9%) in two and sinusitis (2.4%) in one. Nasal congestion was the most common complaint (31.7%) in thirteen patients. CONCLUSIONS: Supported in our results, the direct endonasal transsphenoidal approach tends to present mainly fewer nasal complications and complaints, and in the future it could be considered like the preferred approach for resection of pituitary adenomas.

Comparing the Expression of Genes Related to Serotonin (5-HT) in C57BL/6J Mice and Humans Based on Data Available at the Allen Mouse Brain Atlas and Allen Human Brain Atlas.

Brain atlases are tools based on comprehensive studies used to locate biological characteristics (structures, connections, proteins, and gene expression) in different regions of the brain. These atlases have been disseminated to the point where tools have been created to store, manage, and share the information they contain. This study used the data published by the Allen Mouse Brain Atlas (2004) for mice (C57BL/6J) and Allen Human Brain Atlas (2010) for humans (6 donors) to compare the expression of serotonin-related genes. Genes of interest were searched for manually in each case (in situ hybridization for mice and microarrays for humans), normalized expression data (z-scores) were extracted, and the results were graphed. Despite the differences in methodology, quantification, and subjects used in the process, a high degree of similarity was found between expression data. Here we compare expression in a way that allows the use of translational research methods to infer and validate knowledge. This type of study allows part of the relationship between structures and functions to be identified, by examining expression patterns and comparing levels of expression in different states, anatomical correlations, and phenotypes between different species. The study concludes by discussing the importance of knowing, managing, and disseminating comprehensive, open-access studies in neuroscience.

General characterization of noncommercial microbial lipases in hydrolytic and synthetic reactions.

Fourteen noncommercial preparations of microbial lipases were investigated with respect to their catalytic activity for hydrolysis and synthesis of ester bonds. Six of the lipases were derived from microorganisms that have not previously been described as lipase producers, and another four were characterized for the first time. The synthetic reactions were carried out in two solvents of different polarities (n-heptane and acetone) using a series of fatty acids and primary and secondary alcohols with different chain lengths. Under the culture conditions employed, Pseudomonas cepacia produced more active enzyme than the other microorganisms. The lipase preparations produced using Ovadendron sulphureo-ochraceum, Monascus mucoroides, Monascus sp., Fusarium oxysporum, Penicillium chrysogenum, Rhodotorula araucariae, Pseudomonas cepacia, Streptomyces halstedii, and Streptomyces sp.were the most efficient catalysts for hydrolysis at lipid-water interfaces. Enzyme preparations from P. cepacia, Streptomyces sp., S. halstedii, and R. araucariae were good biocatalysts for esterification in the polar medium (acetone). When the lipase preparations with the greatest activity for hydrolytic reactions were excluded, regression analysis of the data for the hydrolytic and synthetic activities of the remaining lipase preparations yielded high multiple correlation coefficients for these reactions in both n-heptane and acetone (R = 0.82 and 0.91, respectively).

Cytokine and immunoglobulin concentrations in cervical secretions: reproducibility of the Weck-cel collection instrument and correlates of immune measures.

Elucidation of local immune response at the cervix is important for understanding and evaluating STD vaccine approaches currently being proposed. However, no well-validated method exists for the collection of cervical secretions for evaluation of cervical immune response. The purpose of this study was to determine the reproducibility of the Weck-cel sponge used to collect cervical secretions for immunological assessment. Additionally, it was possible to examine correlates of immunity as part of our investigation. Two cervical secretion specimens were collected sequentially from each of 120 women using Weck-cel sponges. Cervical secretions were collected prior to Pap smear sampling to avoid blood contamination. At the laboratory, the duplicate specimens were weighed and tested in replicate wells to determine the concentration of two cytokines (IL-10 and IL-12) and two immunoglobulin isotypes (IgG and IgA). IL-12, total IgG, and total IgA showed a strong correlation between samples from the same woman ranging from 0.78 to 0.84. Kappa coefficients obtained after categorizing assay results ranged from 0.62 to 0.67. Variance components analysis suggested that 69% to 85% of the variance observed was accounted for by between-women variance, with the remaining variability attributed to variation between samples collected from the same woman. IL-10 results were less reproducible than those obtained from the other assays examined, suggesting problems with the assay used to measure this cytokine rather than with the Weck-cel sampling instrument. Various factors were found to significantly correlate with cytokine and immunoglobulin measures at the cervix. Age and reproductive status were associated with all four immune measures; women over 50 years of age and those who were postmenopausal had increased concentrations of IL-10, IL-12, IgG, and IgA. Hemoglobin concentrations were positively correlated with IgG and IL-10 concentrations, but not with IgA or IL-12 concentrations, suggesting local production of IgA and IL-12. The concentration of all immune measures decreased with increasing volume of collection. No significant association was observed between time from collection to freezing of specimens and concentrations of cytokines or immunoglobulins. Overall, our data suggest that measurement of immunological parameters in cervical secretions collected using Weck-cel sponges are reproducible. In addition, various correlates of cytokine and immunoglobulin concentrations were identified.

Synthesis and antitumor evaluation of new thiazolo[5,4-b]quinoline derivatives.

A new synthesis of 9-hydroxy- and 9-(alkylamino)thiazolo[5,4-b]quinolines by cyclization of 4-(ethoxycarbonyl)-5-(arylamino)thiazoles and 5-(arylamino)-4-carbamoylthiazoles, respectively, is described. In vitro cytotoxicity of a large number of derivatives of these compounds has been tested against several cell lines. The highest activities observed are associated with the presence of a 2-[[(N,N-diethylamino)ethyl]amino] substituent at C-2 and a fluorine atom at the C-7 position of the tricyclic planar heteroaromatic framework. Three structural features seem to be essential for antitumor activities: a positive charge density at carbon C-7, a side chain at position C-2 or C-9 of the thiazoloquinoline skeleton with two basic nitrogens and a pKa value of 7.5-10 in the most basic center, and a conformational flexibility of this basic side chain. These structural requirements must be simultaneously satisfied in order to ensure a significant antitumor activity.

Vibrissal sense is not the main sensory modality in rat exploratory behavior in the elevated plus-maze.

Four groups of male Wistar rats were submitted to acute bilateral removal of mystacial vibrissae at different lengths from the follicle. Each group was divided into two subgroups, tested under high (150 Lux) and low environmental illumination (2 Lux). All the subjects were allowed to freely explore an elevated plus-maze for 5 min. Results indicated that rats tested under low illumination tended to explore the open arms more frequently and longer then rats tested under high illumination. When tested under low illumination, rats in the group that suffered whole vibrissa removal stayed longer in the open arms than those in the other groups but did not differ in the number of entries. The average increase in the length of open arm entries, rather than a decrease in aversion to the open arms, may be due to the need of more time to obtain information about the environment since there is no light and the vibrissae were removed. This effect was not seen with rats tested under high illumination, possibly because vision could be used to obtain relevant information.

Dissociation of memory and anxiety in a repeated elevated plus maze paradigm: forebrain cholinergic mechanisms.

The effect of intraseptal injection of the cholinergic immunotoxin 192-IgG-saporin on behavior in the elevated plus maze was investigated. A 5-min test-retest paradigm, with minute-by-minute analysis of the first session, was used to evaluate both anxiety and memory in this task. Biochemical analyses revealed a decrease in acetylcholinesterase (AChE) activity in the hippocampus (HPC), septum, and frontal cortex of animals injected with IgG-192 saporin (237.5 ng) when compared with controls. No statistical differences were found between groups in terms of behaviors associated with locomotor activity, conventional measures of anxiety, or ethological behaviors during either session 1 or 2. During test session 2 the controls exhibited decreased exploratory activity and increased indices of anxiety. In contrast, the saporin-treated rats did not exhibit these experience-dependent behavioral changes from session 1 to 2. The minute-by-minute analysis showed a significant decrease in exploratory as well in anxiety associated behaviors during the first session for the control group, but not for the saporin-treated group. These results suggest that the cholinergic innervation of the HPC, the frontal cortex, or both forebrain structures, modulate the initiation of exploratory activity which, results in the acquisition and retention of spatial information, but does not affect the expression of anxiety in the elevated plus-maze.

Electrocardiographic alterations during treatment of mucocutaneous leishmaniasis with meglumine antimoniate and allopurinol.

The electrocardiographic (ECG) changes in Bolivian patients with mucocutaneous leishmaniasis, treated with meglumine antimoniate and allopurinol, were evaluated. Electric changes due to the antimonial compound appeared in 45% of the patients, and consisted of repolarization alteration, principally affecting the T wave and the S-T segment. The changes disappeared within 2 months following the end of the antimonial treatment. In patients with associated Chagas disease and leishmaniasis, antimonial therapy did not aggravate the ECG changes characteristic of Chagasic cardiopathy.

Effects of septal cholinergic lesion on rat exploratory behavior in an open-field.

The medial septum participates in the modulation of exploratory behavior triggered by novelty. Also, selective lesions of the cholinergic component of the septohippocampal system alter the habituation of rats to an elevated plus-maze without modifying anxiety indices. We investigated the effects of the intraseptal injection of the cholinergic immunotoxin 192 IgG-saporin (SAP) on the behavior of rats in an open-field. Thirty-nine male Wistar rats (weight: 194-230 g) were divided into three groups, non-injected controls and rats injected with either saline (0.5 microl) or SAP (237.5 ng/0.5 microl). Twelve days after surgery, the animals were placed in a square open-field (120 cm) and allowed to freely explore for 5 min. After the test, the rats were killed by decapitation and the septum, hippocampus and frontal cortex were removed and assayed for acetylcholinesterase activity. SAP increased acetylcholinesterase activity in the septum, hippocampus and frontal cortex and decreased the total distance run (9.15 +/- 1.51 m) in comparison to controls (13.49 +/- 0.91 m). The time spent in the center and at the periphery was not altered by SAP but the distance run was reduced during the first and second minutes (2.43 +/- 0.36 and 1.75 +/- 0.34 m) compared to controls (4.18 +/- 0.26 and 3.14 +/- 0.25 m). SAP-treated rats showed decreased but persistent exploration throughout the session. These results suggest that septohippocampal cholinergic mechanisms contribute to at least two critical processes, one related to the motivation to explore new environments and the other to the acquisition and storage of spatial information (i.e., spatial memory).

Vascular trauma: late sequelae and treatment.

58 patients presenting with late manifestations of vascular trauma underwent operative correction at an average of 37.2 months from the date of injury. False aneurysms alone were seen in 23 patients, arteriovenous fistulae in another 35, and both lesions concurrently in 6 patients. Excellent results were achieved in 54 patients, fair results in 4 patients, and only 3 patients required later reoperation despite the chronic nature of these lesions.

[Cystic lymphangioma of the colon: endoscopic treatment and diagnosis]. / Linfangioma quístico de colon: diagnóstico y tratamiento endoscópico.

We present a case of cavernomatous cystic lymphangioma in the hepatic angle of the colon, a extremely rare benign tumor developed in a patient under continued radiologic and endoscopic surveillance because of multiple polyps and colon carcinoma. The lesion was asymptomatic and was diagnosed in a routine follow-up colonoscopy. The endoscopic appearance was similar to that of an adenomatous polyp and was safely resected by polypectomy without evidence of relapse to the present time. Trends in the treatment of lymphangioma have been changing since the development of snare polypectomy; thus before 1980 it was treated mainly by surgery, while at present lymphangiomas less than 2 cm have been removed more frequently by polypectomy.

[Cutaneous and muucocutaneous leishmaniasis. New findings on the subject]. / Leishmaniasis cutánea y cutáneo-mucosa. Nuevos aportes sobre el tema.

The authors have carried a work in which they studied the Leishmaniasis of the skin and their cutaneo-mucosal manifestations, marking on the fact that both are caused by the same agent. They considered also that the visceral Leishmaniasis would be occasioned by the same parasite but in this latter case, it can occur only in anergic people. Finally, they made a clinical and pathologic classification of the cutaneous Leishmania and cutaneo-mucosal Leishmania in: 1. A primary period with 3 histologic manifestations very well known. 2. A period of latency which is variable in time of duration; some times is permanently with parasites in quiescent state in the cells of the reticulous endothelial system. 3. A period of reactivation with cutaneo-mucosal lesions, which shows 3 anatomic and clinic periods: erythematous edematous, granulomatous-proliferative and granulose-necrotic with very important destructions in oropharynx.