Aplicación de la topología molecular en la predicción de la inhibición de Trypanosoma cruzi Hexokinasa y un grupo de derivados bifosfonatos

A topological-mathematical model has been arranged to search for new derivatives of bisphosphonate compounds actingas inhibitors against Trypanosoma cruzi hexokinase. By using linear discriminant analysis, a four-variable function wasachieved allowing an accurate prediction of the IC50 for each compound of the training and test series. After carryingout a virtual screening based upon such a model, new structures potentially actives against T. cruzi are proposedSe ha desarrollado un modelo topológico-matemático para la búsqueda de nuevos derivados bisfosfonatos activosfrente a la hexokinasa de Trypanosoma cruzi. Utilizando el análisis lineal discriminante se ha seleccionado una funcióncon cuatro variables capaz de predecir adecuadamente la CI50 para cada compuesto de las series de entrenamientoy test. El modelo propuesto se ha aplicado a una librería molecular y se han propuesto nuevas estructuraspotencialmente activas frente a T. cruzi

Characterization of steel billet scales generated during the continuous casting process in SIDERPERU steel plant

AbstractTons of waste is produced during iron steel’s industrial production, creating environmental pollution. This work aims to characterize the steel scale formed on the billet surface during the last step of steel production in the SIDERPERU steel plant. Scanning Electron Microscopy (SEM) shows stacked layers one above the other on steel billets scales surface. Energy Dispersive X-ray (EDX) and X-ray Fluorescence (XRF) reveal the high content of Fe and O, with Ca, Si, Mn, and Cr as minority elemental compounds. X-ray Diffraction (XRD) shows FeO, α-Fe2O3 and Fe3O4 as crystallographic phases. Magnetometry reveals Verwey transition and paramagnetic signals that screen the Morin transition. Mössbauer Spectroscopy at room temperature displays magnetic and non-magnetic parts. The non-magnetic part has the hyperfine parameters corresponding to predominant nonstoichiometric wustite. Octahedral (Fe+2/Fe3+) and tetrahedral Fe+3 hyperfine fields of 46.0 and 49.4 T values respectively are associated to nonstoichiometric magnetite and another sextet with a hyperfine field of 52.0 T is related to hematite.</jats:p

Characterization of steel billet scales generated during the continuous casting process in SIDERPERU steel plant

AbstractTons of waste is produced during iron steel’s industrial production, creating environmental pollution. This work aims to characterize the steel scale formed on the billet surface during the last step of steel production in the SIDERPERU steel plant. Scanning Electron Microscopy (SEM) shows stacked layers one above the other on steel billets scales surface. Energy Dispersive X-ray (EDX) and X-ray Fluorescence (XRF) reveal the high content of Fe and O, with Ca, Si, Mn, and Cr as minority elemental compounds. X-ray Diffraction (XRD) shows FeO, α-Fe2O3 and Fe3O4 as crystallographic phases. Magnetometry reveals Verwey transition and paramagnetic signals that screen the Morin transition. Mössbauer Spectroscopy at room temperature displays magnetic and non-magnetic parts. The non-magnetic part has the hyperfine parameters corresponding to predominant nonstoichiometric wustite. Octahedral (Fe+2/Fe3+) and tetrahedral Fe+3 hyperfine fields of 46.0 and 49.4 T values respectively are associated to nonstoichiometric magnetite and another sextet with a hyperfine field of 52.0 T is related to hematite.</jats:p

Somatic evolution and global expansion of an ancient transmissible cancer lineage

The canine transmissible venereal tumour (CTVT) is a cancer lineage that arose several millennia ago and survives by ‘metastasising’ between hosts via cell transfer. The somatic mutations in this cancer record its phylogeography and evolutionary history. We constructed a time-resolved phylogeny from 546 CTVT exomes and describe the lineage’s worldwide expansion. Examining variation in mutational exposure, we identify a highly context-specific mutational process that operated early but subsequently vanished, correlate ultraviolet-light mutagenesis with tumour latitude, and describe tumours with heritable hyperactivity of an endogenous mutational process. CTVT displays little evidence of ongoing positive selection, and negative selection is detectable only in essential genes. We illustrate how long-lived clonal organisms capture changing mutagenic environments, and reveal that neutral drift is the dominant feature of long-term cancer evolution

A fluorogenic cyclic peptide for imaging and quantification of drug-induced apoptosis

Programmed cell death or apoptosis is a central biological process that is dysregulated in many diseases, including inflammatory conditions and cancer. The detection and quantification of apoptotic cells in vivo is hampered by the need for fixatives or washing steps for non-fluorogenic reagents, and by the low levels of free calcium in diseased tissues that restrict the use of annexins. In this manuscript, we report the rational design of a highly stable fluorogenic peptide (termed Apo-15) that selectively stains apoptotic cells in vitro and in vivo in a calcium-independent manner and under wash-free conditions. Furthermore, using a combination of chemical and biophysical methods, we identify phosphatidylserine as a molecular target of Apo-15. We demonstrate that Apo-15 can be used for the quantification and imaging of drug-induced apoptosis in preclinical mouse models, thus creating opportunities for assessing the in vivo efficacy of anti-inflammatory and anti-cancer therapeutics

Adaptación cultural al español del instrumento de evaluación de funcionalidad física en Unidad de Paciente Crítico: “The Chelsea Critical Care Physical Assessment Tool (CPAx)”

Las Unidades de Cuidados Intensivos (UCI), presentan una sobrevida cada vez mayor de los pacientes que ingresan a ellas, donde se ven enfrentados a una nueva entidad fisiopatológica llamada Debilidad Muscular Adquirida en UCI (DAUCI). Algunos test desarrollados para la evaluación de función motriz, que permiten objetivar la progresión del paciente, son la escala de fuerza muscular del Medical Research Council (MRC), el Functional status score for the intensive care unit (FSS-ICU) y el “Chelsea Critical Care Physical Assessment Tool (CPAx). La ventaja del CPAx radica en que este test incluye mayor información asociada al funcionamiento humano como recomienda la OMS, incorporando tanto el componente ventilatorio (que también se ve deteriorado por DAUCI) como neuromuscular lo que permite al profesional kinesiólogo tener una herramienta objetiva más completa del nivel funcional del paciente. Para que sea confiable, todo test debe ser validado en el país donde quiere aplicarse, pero antes de esto debe ser adaptado culturalmente. El objetivo de este trabajo fue efectuar la adaptación transcultural (AT) al español del test de funcionalidad física de aplicación kinésica CPAx. Se utilizó el proceso establecido por Beaton y cols que incluye la formación de un comité de expertos multidisciplinario que da una visión integral a la adaptación y una prueba piloto en que kinesiólogos de UCI sin capacitación previa del test lo lean, posteriormente lo apliquen y entreguen sus observaciones. Conclusiones: Realizar la AT permite dimensionar la importancia que tiene cada una de las etapas de este proceso. El test es el mismo, equivalente al original, pero contiene nuestras características culturales y condiciones técnicas, que lo hace ser comprensible y aplicable en nuestro país. Esta adaptación transcultural también es útil a nivel latinoamericano; para los países de habla hispana que quieran validarlo tenerlo adaptado al español, hace el proceso menos complejo. Palabras clave: Evaluación funcional, Unidad de cuidados intensivos, CPAx, adaptación transcultural

Membrane-mediated interactions

Interactions mediated by the cell membrane between inclusions, such as membrane proteins or antimicrobial peptides, play important roles in their biological activity. They also constitute a fascinating challenge for physicists, since they test the boundaries of our understanding of self-assembled lipid membranes, which are remarkable examples of two-dimensional complex fluids. Inclusions can couple to various degrees of freedom of the membrane, resulting in different types of interactions. In this chapter, we review the membrane-mediated interactions that arise from direct constraints imposed by inclusions on the shape of the membrane. These effects are generic and do not depend on specific chemical interactions. Hence, they can be studied using coarse-grained soft matter descriptions. We deal with long-range membrane-mediated interactions due to the constraints imposed by inclusions on membrane curvature and on its fluctuations. We also discuss the shorter-range interactions that arise from the constraints on membrane thickness imposed by inclusions presenting a hydrophobic mismatch with the membrane.Comment: 38 pages, 10 figures, pre-submission version. In: Bassereau P., Sens P. (eds) Physics of Biological Membranes. Springer, Cha

ELISA versus PCR for diagnosis of chronic Chagas disease: systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Most current guidelines recommend two serological tests to diagnose chronic Chagas disease. When serological tests are persistently inconclusive, some guidelines recommend molecular tests. The aim of this investigation was to review chronic Chagas disease diagnosis literature and to summarize results of ELISA and PCR performance.</p> <p>Methods</p> <p>A systematic review was conducted searching remote databases (MEDLINE, LILACS, EMBASE, SCOPUS and ISIWeb) and full texts bibliography for relevant abstracts. In addition, manufacturers of commercial tests were contacted. Original investigations were eligible if they estimated sensitivity and specificity, or reliability -or if their calculation was possible - of ELISA or PCR tests, for chronic Chagas disease.</p> <p>Results</p> <p>Heterogeneity was high within each test (ELISA and PCR) and threshold effect was detected only in a particular subgroup. Reference standard blinding partially explained heterogeneity in ELISA studies, and pooled sensitivity and specificity were 97.7% [96.7%-98.5%] and 96.3% [94.6%-97.6%] respectively. Commercial ELISA with recombinant antigens studied in phase three investigations partially explained heterogeneity, and pooled sensitivity and specificity were 99.3% [97.9%-99.9%] and 97.5% [88.5%-99.5%] respectively. ELISA's reliability was seldom studied but was considered acceptable. PCR heterogeneity was not explained, but a threshold effect was detected in three groups created by using guanidine and boiling the sample before DNA extraction. PCR sensitivity is likely to be between 50% and 90%, while its specificity is close to 100%. PCR reliability was never studied.</p> <p>Conclusions</p> <p>Both conventional and recombinant based ELISA give useful information, however there are commercial tests without technical reports and therefore were not included in this review. Physicians need to have access to technical reports to understand if these serological tests are similar to those included in this review and therefore correctly order and interpret test results. Currently, PCR should not be used in clinical practice for chronic Chagas disease diagnosis and there is no PCR test commercially available for this purpose. Tests limitations and directions for future research are discussed.</p

Pooled analysis of who surgical safety checklist use and mortality after emergency laparotomy

Background: The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods: In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results: Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89⋅6 per cent) compared with that in countries with a middle (753 of 1242, 60⋅6 per cent; odds ratio (OR) 0⋅17, 95 per cent c.i. 0⋅14 to 0⋅21, P &lt; 0⋅001) or low (363 of 860, 42⋅2 percent; OR 0⋅08, 0⋅07 to 0⋅10, P &lt; 0⋅001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference −9⋅4 (95 per cent c.i. −11⋅9 to −6⋅9) per cent; P &lt; 0⋅001), but the relationship was reversed in low-HDI countries (+12⋅1 (+7⋅0 to +17⋅3) per cent; P &lt; 0⋅001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0⋅60, 0⋅50 to 0⋅73; P &lt; 0⋅001). The greatest absolute benefit was seen for emergency surgery in low-and middle-HDI countries. Conclusion: Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries