Automated FerryBox monitoring reveals the first recorded river induced crude oil seep transport to the Strait of Magellan in southern Patagonia.

This study presents the first documented occurrence of a natural crude oil seep plume associated with river discharge along the Strait of Magellan in southern Patagonia in modern times. Between September and December 2022, hydrocarbon signals were detected using a crude oil sensor integrated into a FerryBox system that traversed the Strait of Magellan and several channels of southern Patagonia, covering approximately 510 km. The highest levels of crude oil signals were observed in the mid-basin of the Strait of Magellan. These signals exhibited a strong negative correlation with sea surface salinity, coinciding with the water discharge from the San Juan River. Notably, during periods of high river discharge, typically exceeding 15 m3 s-1, a distinct crude oil plume was detected moving towards the Magellan Strait. Conversely, when river discharge fell below this threshold, no noticeable crude oil signal was observed. As river discharge decreased and winds intensified during the austral summer, the crude oil signal gradually dissipated. This observation suggests that the dispersion of crude oil becomes limited during periods of low river discharge, as buoyant currents remain confined close to the coast. Historical records indicate that this seep has been releasing hydrocarbons into the Strait of Magellan for at least the past 120 years, implying a long history of chronic crude oil input into this relatively isolated region of the world. This finding shows the potential contribution to the understanding of marine ecosystems dynamics and potential pollutants in poorly studied regions through the use of automated monitoring FerryBox system, enabling both spatial and temporal high-resolution surveys.

Política industrial farmacéutica, un requisito clave para la autonomía sanitaria de Colombia / Pharmaceutical industrial policy, a key requirement for health autonomy in Colombia

Colombia depende de la importación de medicamentos, así como de gran parte de los materiales (principios activos y excipientes) requeridos para su elaboración; problemática que genera consecuencias sanitarias y macroeconómicas, las cuales se agudizan en el contexto de desindustrialización nacional y de disrupción tecnológica. De esta manera, se acepta que la disponibilidad y acceso a medicamentos y otras tecnologías sanitarias esenciales son un requisito fundamental para alcanzar la autonomía sanitaria de un país. Por lo tanto, resulta imprescindible coordinar esfuerzos entre diversos sectores sociales para desarrollar una agenda pública enfocada a la creación de condiciones que fortalezcan las capacidades científicas y tecnológicas de la industria farmacéutica local, y con ello, mejorar el suministro farmacéutico del país. En el presente documento se presentan conceptos teóricos y prácticos que deberían ser considerados en la definición y materialización de una política pública encaminada a fortalecer la industria farmacéutica y favorecer la autonomía sanitaria de Colombia.

Colombia has a notorious dependency on the importation of medicines, as well as a large part of the materials (active ingredients and excipients) required for their manufacture. This problem generates health and macroeconomic consequences, which are exacerbated in the context of national deindustrialization and technological disruption. In this way, it is accepted that the availability and access to medicines and other essential health technologies are a fundamental requirement to achieve the health autonomy of a country. Therefore, it is crucial to coordinate efforts between several social sectors to develop a public agenda focused on creating conditions that allow strengthening the scientific and technological capabilities of the local pharmaceutical industry, thereby, improving the country's pharmaceutical supply. This document presents conceptual and practical topics that should be considered to defining and materializing a public policy aimed at strengthening the local pharmaceutical industry and favoring Colombia's sanitary autonomy.

Lymphovascular Space Invasion in Early-Stage Endometrial Cancer (LySEC): Patterns of Recurrence and Predictors. A Multicentre Retrospective Cohort Study of the Spain Gynecologic Oncology Group.

The main aim is to compare oncological outcomes and patterns of recurrence of patients with early-stage endometrioid endometrial cancer according to lymphovascular space invasion (LVSI) status. The secondary objective is to determine preoperative predictors of LVSI. We performed a multicenter retrospective cohort study. A total of 3546 women diagnosed with postoperative early-stage (FIGO I-II, 2009) endometrioid endometrial cancer were included. Co-primary endpoints were disease-free survival (DFS), overall survival (OS), and pattern of recurrence. Cox proportional hazard models were used for time-to-event analysis. Univariate and multivariate logistical regression models were employed. Positive LVSI was identified in 528 patients (14.6%) and was an independent prognostic factor for DFS (HR 1.8), OS (HR 2.1) and distant recurrences (HR 2.37). Distant recurrences were more frequent in patients with positive LVSI (78.2% vs. 61.3%, p < 0.01). Deep myometrial invasion (OR 3.04), high-grade tumors (OR 2.54), cervical stroma invasion (OR 2.01), and tumor diameter ≥ 2 cm (OR 2.03) were independent predictors of LVSI. In conclusion, in these patients, LVSI is an independent risk factor for shorter DFS and OS, and distant recurrence, but not for local recurrence. Deep myometrial invasion, cervical stroma invasion, high-grade tumors, and a tumor diameter ≥ 2 cm are independent predictors of LVSI.

Estudio comparativo lesional en judocas de élite / Lessional Comparative Study in Elite Judocas

El Judo es un deporte estático alto y dinánimo bajo, con alto riesgo de colisión corporal y lesional. El objetivo de este trabajo es determinar la incidencia lesional y comparar los distintos factores de riesgo que pudieran estar implicados. Se estudió a un total de 86 judocas del Equipo Nacional de Judo español (ENJE) durante dos períodos olímpicos: Beijing-Río. Se produjeron 2028 lesiones con mayor frecuencia en miembro inferior, sin diferencias significativas por sexo. Se objetivó mayor incidencia lesional cuando el judoca era tori y durante el momento del entrenamiento. No existen trabajos previos que comparen estos parámetros, por lo que este estudio aporta datos que pueden ser utilizados para prevenir los riesgos de lesión en el judo de alta competición. (AU)

Judo is a high static and low dynamic sport, with a high risk of bodily and injury collision. The objective of this work is to determine the incidence of injury and to compare the different risk factors that may be involved. A total of 86 judokas from the Spanish National Judo Team (ENJE) were studied during two Olympic periods: Beijing-Rio. 2028 injuries occurred more frequently in the lower limb, without significant differences by sex. A higher incidence was observed in tori judoka and during training. No existing work has examined these parameters. The present study provides data that can be used to reduce the risk of injury in elite judokas. (AU)

Pathology findings and clinical outcomes after risk reduction salpingo-oophorectomy in BRCA mutation carriers: a multicenter Spanish study.

OBJECTIVE: To determine the incidence of serous tubal intraepithelial carcinoma (STIC) after risk reduction salpingo-oophorectomy(RRSO), and to describe oncological outcomes after RRSO. MATERIALS AND METHODS: BRCA pathogenic mutation carriers who had undergone an RRSO were evaluated in this retrospective multicenter observational study. Patients were only included when fallopian tubes were analyzed following the protocol for Sectioning and Extensively Examining the FIMbria (SEE-FIM). Surgeries were performed between June 2010 and April 2017 at eight Spanish hospitals. RESULTS: A total of 359 patients met the inclusion criteria. STIC was diagnosed in 3 (0.8%) patients; one of them underwent surgical staging due to positive peritoneal washing, with absence of disease at the final pathology report. None of the three patients received adjuvant chemotherapy and were free of disease at last follow-up. Fallopian tube and ovarian carcinoma were diagnosed in 5 (1.4%) and 1 (0.3%), respectively. At a median (range) follow-up time of 29 (3-92) months, five patients had a newly diagnosed breast cancer. Other types of cancer, which were diagnosed during the follow-up time, included: serous primary peritoneal carcinoma (n = 1), serous endometrial carcinoma (n = 1), colon (n = 1), pancreas (n = 1), jaw (n = 1), and lymphoma (n = 1). Seven patients died due to different types of cancer: breast (n = 4), pancreas (n = 1), jaw (n = 1), and colon (n = 1). CONCLUSION: The incidence of STIC after RRSO in BRCA mutation carriers is low (0.8%) and it presents an excellent oncological outcome. Patients after RRSO, however, run the risk to develop other types of cancer during follow-up and should be properly advised before the prophylactic surgery.

Modelo pedagógico predominante en un grupo de profesores de una escuela de enfermería: estudio exploratorio / Pedagogical predominant model in a group of teachers in a school of Nursing: exploratory study

Introducción. En los últimos años se ha propuesto un modelo enseñanza-aprendizaje centrado en el estudiante. Objetivo. Elaborar un diagnóstico del modelo pedagógico predominante en los profesores y las metodologías educativas más relevantes en términos de aprendizaje desde la perspectiva de los estudiantes. Sujetos y métodos. Se recogió información de características demográficas y académicas y formación pedagógica de los profesores y se les aplicó el instrumento Approaches to Teaching Inventory (ATI). Los estudiantes respondieron una encuesta para identificar las metodologías más relevantes en términos de su aprendizaje y la frecuencia con que los profesores las utilizaban. Resultados. La muestra estuvo constituida por 35 profesores (68,6%), que en promedio tienen 13,6 ± 10,5 años de experiencia en docencia universitaria y han realizado 3,86 ± 3,19 actividades de formación pedagógica. De acuerdo al ATI, la mayoría enfoca su enseñanza en los estudiantes, lo que se refuerza en la intención y estrategias que refieren. Con respecto a los estudiantes, la muestra quedó constituida por 444 alumnos de pregrado (82,6%), los cuales identifican claramente las metodologías más favorables para su aprendizaje y la frecuencia con que los docentes las utilizan. Conclusiones. La mayoría de los profesores refiere que se centra en el estudiante y su aprendizaje, y se enfoca en la adquisición de conceptos. Los alumnos reconocen claramente algunas metodologías como muy favorables para su aprendizaje y la frecuencia con que se practican

Introduction. In the last years there has been proposed a model teaching focused on the student and his learning. Aim. To develop a diagnostic about the predominant teaching model in teachers and relevant educational methodologies in terms of learning from the perspective of students. Subjects and methods. Demographic, academic information and pedagogical training of teachers were collected and were applied the Approaches to Teaching Inventory (ATI) instrument. Students answered a survey to identify the most relevant methodologies in terms of their learning and how often teachers used them. Results. The sample consisted of 35 teachers (68.6%) on average have 13.6 ± 10.5 years in university teaching experience and have made 3.86 ± 3.19 teacher training activities. According to the ATI the majority report that your teaching focusing on student learning. Regarding students, the sample was composed of 444 undergraduate students (82.6%), which clearly identifies the most favorable methodologies for your learning and teachers often use them. Conclusions. Most of the teachers focuses on the student and learning and in the acquisition of concepts. Students clearly recognize some methodologies as very favorable for learning and the frequency with which these are used

Diurnal preference, mood and the response to morning light in relation to polymorphisms in the human clock gene PER3.

PER3 gene polymorphisms have been associated with differences in human sleep-wake phenotypes, and sensitivity to light. The aims of this study were to assess: i) the frequency of allelic variants at two PER3 polymorphic sites (rs57875989 length polymorphism: PER3 4, PER3 5; rs228697 SNP: PER3 C, PER3 G) in relation to sleep-wake timing; ii) the effect of morning light on behavioural/circadian variables in PER3 4 /PER3 4 and PER3 5 /PER3 5 homozygotes. 786 Caucasian subjects living in Northern Italy donated buccal DNA and completed diurnal preference, sleep quality/timing and sleepiness/mood questionnaires. 19 PER3 4 /PER3 4 and 11 PER3 5 /PER3 5 homozygotes underwent morning light administration, whilst monitoring sleep-wake patterns and the urinary 6-sulphatoxymelatonin (aMT6s) rhythm. No significant relationship was observed between the length polymorphism and diurnal preference. By contrast, a significant association was observed between the PER3 G variant and morningness (OR = 2.10), and between the PER3 G-PER3 4 haplotype and morningness (OR = 2.19), for which a mechanistic hypothesis is suggested. No significant differences were observed in sleep timing/aMT6s rhythms between PER3 5 /PER3 5 and PER3 4 /PER3 4 subjects at baseline. After light administration, PER3 4 /PER3 4 subjects advanced their aMT6s acrophase (p < 0.05), and showed a trend of advanced sleep-wake timing. In conclusion, significant associations were observed between PER3 polymorphic variants/their combinations and both diurnal preference and the response to light.

Removal naturally occurring radionuclides from drinking water using a filter specifically designed for Drinking Water Treatment Plants.

The occurrence of naturally occurring radionuclides in drinking water can pose health hazards in some populations, especially taking into account that routine procedures in Drinking Water Treatment Plants (DWTPs) are normally unable to remove them efficiently from drinking water. In fact, these procedures are practically transparent to them, and in particular to radium. In this paper, the characterization and capabilities of a patented filter designed to remove radium from drinking water with high efficiency is described. This filter is based on a sandwich structure of silica and green sand, with a natural high content manganese oxide. Both sands are authorized by Spanish authorities to be used in Drinking Water Treatment Plants. The Mn distribution in the green sand was found to be homogenous, thus providing a great number of adsorption sites for radium. Kinetic studies showed that the 226Ra adsorption on green sand was influenced by the content of major cations solved in the treated water, but the saturation level, about 96-99%, was not affected by it. The physico-chemical parameters of the treated water were unaltered by the filter. The efficiency of the filter for the removal of 226Ra remained unchanged with large water volumes passed through it, proving its potential use in DWTP. This filter was also able to remove initially the uranium content due to the presence of Fe2O3 particles in it, although it is saturated faster than radium.

SURGICAL CORRECTION OF TRAUMATIC PATELLAR LUXATION IN AN EURASIAN LYNX (LYNX LYNX).

The aim of this report is to describe the successful surgical repair of a traumatic medial patellar luxation in a 4-yr-old female Eurasian lynx ( Lynx lynx ). The animal presented with hind limb lameness. Physical and radiographic examinations were performed under sedation. After diagnosing a medial patellar luxation, surgical repair was recommended. A combination of soft tissue reconstructive techniques was used to repair the medial patellar luxation. The limb was not immobilized postoperatively, but the animal was confined to a cage for 1 mo. The recovery was uneventful and return to normal activity was observed within 1 mo. Soft tissue reconstructive techniques can be used as the only surgical treatment for the repair of a traumatic patellar luxation in both domestic and wild animals.

Is the step-wise tiered approach for ERA of pharmaceuticals useful for the assessment of cancer therapeutic drugs present in marine environment?

Methotrexate (MTX) and tamoxifen (TMX) cancer therapeutic drugs have been detected within the aquatic environment. Nevertheless, MTX and TMX research is essentially bio-medically orientated, with few studies addressing the question of its toxicity in fresh water organisms, and none to its' effect in the marine environment. To the authors' knowledge, Environmental Risk Assessments (ERA) for pharmaceuticals has mainly been designed for freshwater and terrestrial environments (European Medicines Agency-EMEA guideline, 2006). Therefore, the purpose of this research was (1) to assess effect of MTX and TMX in marine organism using the EMEA guideline, (2) to develop an ERA methodology for marine environment, and (3) to evaluate the suitability of including a biomarker approach in Phase III. To reach these aims, a risk assessment of MTX and TMX was performed following EMEA guideline, including a 2-tier approach during Phase III, applying lysosomal membrane stability (LMS) as a screening biomarker in tier-1 and a battery of biochemical biomarkers in tier-2. Results from Phase II indicated that MTX was not toxic for bacteria, microalgae and sea urchin at the concentrations tested, thus no further assessment was required, while TMX indicated a possible risk. Therefore, Phase III was performed for only TMX. Ruditapes philippinarum were exposed during 14 days to TMX (0.1, 1, 10, 50 µg L(-1)). At the end of the experiment, clams exposed to environmental concentration indicated significant changes in LMS compared to the control (p<0.01); thus a second tier was applied. A significant induction of biomarkers (activity of Ethoxyresorufin O-deethylase [EROD], glutathione S-transferase [GST], glutathione peroxidase [GPX], and lipid peroxidation [LPO] levels) was observed in digestive gland tissues of clams compared with control (p<0.01). Finally, this study indicated that MTX was not toxic at an environmental concentration, whilst TMX was potentially toxic for marine biota. This study has shown the necessity to create specific guidelines in order to evaluate effects of pharmaceuticals in marine environment which includes sensitive endpoints. The inadequacy of current EMEA guideline to predict chemotherapy agents toxicity in Phase II was displayed whilst the usefulness of other tests were demonstrated. The 2-tier approach, applied in Phase III, appears to be suitable for an ERA of cancer therapeutic drugs in the marine environment.

The self-morningness/eveningness (Self-ME): An extremely concise and totally subjective assessment of diurnal preference.

The assessment of diurnal preference, or the preferred timing of sleep and activity, is generally based on comprehensive questionnaires such as the Horne-Östberg (HÖ). The aim of the present study was to assess the reliability of a subject's self-classification as extremely morning (Self-MM), more morning than evening (Self-M), more evening than morning (Self-E) or extremely evening (Self-EE) type, based on the last question of the HÖ (Self-ME). A convenience sample of 461 subjects [23.8 ± 4.7 years; 322 females] completed a full sleep-wake assessment, including diurnal preference (HÖ), night sleep quality (Pittsburgh Sleep Quality Index, PSQI), daytime sleepiness (Karolinska Sleepiness Scale, KSS), and habitual sleep-wake timing (12 d sleep diaries; n = 296). Significant differences in HÖ total score were observed between Self-ME classes, with each class being significantly different from neighboring classes (p < 0.0001). Significant differences in sleep-wake timing (bed time, try to sleep and sleep onset, wake up, and get up time) were observed between Self-ME classes. Such differences were maintained when sleep-wake habits were analysed separately on work and free days, and also in a smaller group of 67 subjects who completed the Self-ME as a stand-alone rather than as part of the original questionnaire. Significant differences were observed in the time-course of subjective sleepiness by Self-ME class in both the large and the small group, with Self-MM and Self-M subjects being significantly more alert in the morning and sleepier in the evening hours compared with their Self-E and Self-EE counterparts. Finally, significant differences were observed in night sleep quality between Self-ME classes, with Self-EE/Self-E subjects sleeping worse than their Self-MM/Self-M counterparts, and averaging just over the abnormality PSQI threshold of 5. In conclusion, young, healthy adults can define their diurnal preference based on a single question (Self-ME) in a way that reflects their sleep-wake timing, their sleepiness levels over the daytime hours, and their night sleep quality. Validation of the Self-ME across the decades and in diseased populations seems worthy.

Gestación a término tras cesárea y B-Lynch / Term pregnancy after cesarean section and B-Lynch suture

La sutura hemostática uterina de B-Lynch es una alternativa quirúrgica indicada para el tratamiento de la hemorragia posparto secundaria a atonía uterina que no responde a tratamiento médico. Presentamos el caso de una aplicación de sutura de B-Lynch durante el puerperio inmediato de una paciente a la que se le realizó una cesárea por fracaso de inducción tras rotura prematura de membranas a término, que presentaba hemorragia puerperal no controlada con tratamiento médico. Su evolución posterior fue favorable. Tras 5 años, presentó nueva gestación. El curso del embarazo fue normal. En la semana 39 + 5 se le realizó una cesárea electiva por historia obstétrica + ligadura tubárica bilateral, sin incidencias. El puerperio transcurrió sin complicaciones importantes. Concluimos que, en nuestra experiencia, la B-Lynch es una técnica quirúrgica sencilla, con baja morbilidad y con ventajas claras para la preservación de la fertilidad posterior

The B-Lynch hemostatic suture is a surgical alternative indicated for the treatment of postpartum haemorrhage due to uterine atony unresponsive to medical treatment. We describe the application of B-Lynch suture during the early postpartum period in a patient who had a cesarean section for induction failure after premature rupture of membranes complicated by postpartum haemorrhage not controlled by medical treatment. Outcome was favorable. The patient became pregnant again 5 years later and there were no complications during the gestation. At week 39 + 5, an elective cesarean section with bilateral tubal ligation was performed due to the obstetric history. There were no major complications during the postpartum period. We conclude that B-Lynch suture is a simple technique with low morbility that allows fertility to be preserved in women with uncontrolled postpartum haemorrhage

Are standard tests sensitive enough to evaluate effects of human pharmaceuticals in aquatic biota? Facing changes in research approaches when performing risk assessment of drugs.

Nowadays, the presence of pharmaceutical products in aquatic environments is not only common, but is also of significant concern regarding the adverse effect they may produce to aquatic biota. In order to determine the adverse effects of caffeine (CAF), ibuprofen (IBU), carbamazepine (CBZ) and novobiocin (NOV), at environmental occurring concentrations, standardized endpoints applied in current guidelines were evaluated in four organisms including bioluminescence response in Vibrio fischeri, growth inhibition in Isochrysis galbana (marine water) and Pseudokirchneriella subcapitata (fresh water) and fertilization and embryo-larval development in Paracentrotus lividus. To reach this aim bioassays were implemented by exposing organisms to water spiked with drugs dissolved in DMSO (0.001% v/v). Risk characterization was performed, calculating the environmental impact of drugs by calculating environmental concentration and predicted no effect concentration ratio (MEC/PNEC). Results indicate that acute toxicity was found above environmental concentrations in the order of mg L(-1) for bacteria bioluminescence, microalgae growth inhibition and sea urchin fertilization. However, teratogenicity was observed on sea urchin after exposure to environmental concentrations of drugs at 0.00001 mg L(-1); at this concentration CBZ and IBU were found to reduce significantly the embryo-larval development compared to controls (p<0.01). The risk calculated for selected drugs suggested they are harmless for aquatic environment except when applying the embryo-larval development endpoint. Endpoints applied in this study showed the necessity of using more sensitive responses, when assessing risk of pharmaceuticals in aquatic environments, since endpoints applied in current guidelines may not be suitable.

Proposed improvements to existing water monitoring systems in automatic radiological warning networks.

The main objective of automatic environmental radiation warning networks is to quantify a set of radiological parameters corresponding to the medium being monitored (water, air, etc) in the shortest possible time so as to be able to provide rapid and precise information on the medium's radiological status, and on any alterations that may occur and their severity. Specifically, in this paper we present the substantial improvements that have been carried out in an automatic near-real-time radiation monitoring of a water system belonging to Radiation Alert Network of Extremadura (RARE) in southwest Spain. These improvements are based on the incorporation of (i) a gamma spectrometry system with solid scintillation detectors and compact digital electronics, (ii) continuous measurement of the water flow that is being monitored, (iii) improvements in the maintenance tasks required to optimise the operation of this type of equipment and (iv) the controlled and automated collection of water samples so that, in the case of a possible radiological anomaly, it will be possible to perform ulterior specific complementary determinations in a low-background laboratory.

Calibration of an air monitor prototype for a radiation surveillance network based on gamma spectrometry.

The objective of this work is to present the improvements that have been made in quasi-real-time air radioactivity concentration monitors which were initially based on overall activity determinations, by incorporating gamma spectrometry into the current prototype. To this end it was necessary to develop a careful efficiency calibration procedure for both the particulate and the gaseous fractions of the air being sampled. The work also reports the values of the minimum detectable activity calculated for different isotopes and acquisition times.

Comparative performances of eggs and embryos of sea urchin (Paracentrotus lividus) in toxicity bioassays used for assessment of marine sediment quality.

The potential toxicity of sediments from various ports was assessed by means of two different liquid-phase toxicity bioassays (acute and chronic) with embryos and eggs of sea urchin Paracentrotus lividus. Performances of embryos and eggs of P. lividus in these bioassays were compared for their interchangeable applicability in integrated sediment quality assessment. The obtained endpoints (percentages of normally developed plutei and fertilized eggs) were linked to physical and chemical properties of sediments and demonstrated dependence on sediment contamination. The endpoints in the two bioassays were strongly correlated and generally exhibited similar tendency throughout the samples. Therein, embryos demonstrated higher sensitivity to elutriate exposure, compared to eggs. It was concluded that these tests could be used interchangeably for testing toxicity of marine sediments. Preferential use of any of the bioassays can be determined by the discriminatory capacity of the test or vulnerability consideration of the test subject to the surrounding conditions.

HLA in Jaidukama: an Amerindian secluded Colombian population with new haplotypes and Asian and Pacific-shared alleles.

America first inhabitants and peopling are still debated. In order to increase knowledge about these questions, we have aimed to detect HLA genes of an Amerindian secluded community: Jaidukama, who lives in North Colombia Equatorial forest. HLA genotyping and extended haplotype calculations were carried out in 39 healthy individuals belonging to 13 families. HLA frequencies were compared to other Amerindians and worldwide populations by calculating genetic distances, relatedness dendrograms and correspondence analyses. Only four DRB1 alleles were found (*0404, *0407, *1402 and *1602); however a total of 17 Amerindian different extended class I-class II HLA haplotypes were directly counted from the family studies, nine of them were specific of Jaidukamas. Some of the alleles or group of alleles within an extended haplotype (i.e. DQB1-DRB1) were also found in Asians and Pacific Islanders, further supporting existence of Asian and Pacific gene flow with Amerindians or a common founder effect. It is further supported that HLA extended haplotypes vary faster than alleles in populations. It is concluded that this unique model of Amerindian secluded families study suggests that rapid HLA haplotype variation may be more important than allele variation for survival (starting immune responses). This work may also be useful for future transplant programs in the area.

Estudio experimental y teórico de la síntesis de n-alquil-nitroimidazoles / Experimental and theoretical study of shyntesis of n-alkyl-nitroimidazoles

En este trabajo se realizó un estudio experimental y teórico sobre la N-alquilación de nitroimidazoles. Los N-alquil-2-metil-nitroimidazoles corresponden a moléculas con actividad biológica, que se obtienen por la reacción del 2-metil-5-nitroimidazol y diferentes halogenuros de alquilo. En esta reacción se observó la formación de una mezcla de productos isoméricos en diferente proporción, denominados como N-alquil-2-metil-4-nitroimidazol y N-alquil-2-metil-5-nitroimidazol, respectivamente. La reacción sugiere la formación de un equilibrio tautomérico, que genera dos sitios nucleofílicos susceptibles a un ataque electrofílico por parte del halogenuro de alquilo. La reactividad local nucleofílica del anillo nitroimidazólico se determinó utilizando índices de reactividad local, como la función de Fukui y el potencial electrostático, además de la función de localización electrónica (ELF). La función de Fukui se integra en los átomos utilizando los esquemas de partición basados en el análisis de cargas de Mulliken y orbitales naturales de enlace (NBO). Por último, se evaluaron los perfiles de reacción. Los resultados mostraron una leve diferencia en la reactividad local, sin embargo, se observan diferencias significativas en las barreras energéticas, que explican la formación de un producto isomérico sobre el otro, encontrándo así, concordancia entre los resultados experimentales y los teóricos.

In this work we realized and experimental and theoretical study of the N-alkylation of nitroimidazoles. The N-alkyl-2-methyl-nitroimidazoles correspond to biologically active molecules, obtained by reaction of 2-methyl-5-nitroimidazole and different alkyl halides. This reaction showed the formation of a mixture of isomeric products in different proportions, denominated like N-alkyl-2-methyl-4-nitroimidazole and N-alkyl-2-methyl-5-nitroimidazole, respectively. The reaction suggestes the formation of a tautomeric equilibrium, which generates two nucleophilic sites susceptible to electrophilic attack by the alkyl halide. The local nucleophilic reactivity of the nitroimidazole ring is determined using local reactivity indices such as the Fukui function and the electrostatic potential, besides the electronic localization function (ELF). The Fukui function was integrated for each atom using partition schemes based on analysis of Mulliken charges and natural bond orbital (NBO). Finally the reaction profiles were assessed. The results show a minor difference in the local reactivity. Nevertheless a significant difference in energy barriers is observed explaining the formation of an isomeric product over another. These results agree quite well with the experimental data.