Determining the safety of the tobacco cembranoid (1S,2E,4R,6R,7E,11E)-Cembratriene-4,6-diol (4R): A translational study in nonhuman primates.

The tobacco cembranoid known as (1S,2E,4R,6R,7E,11E)-2,7,11-cembratriene-4,6-diol (4R) has been shown to offer neuroprotection against conditions such as brain ischemia, systemic inflammation, Parkinson's disease, and organophosphate toxicity in rodents. Previous safety studies conducted on male and female Sprague Dawley rats revealed no significant side effects following a single injection of 4R at varying concentrations (6, 24, or 98 mg/kg of body weight). This study aimed to assess the potential of 4R for clinical trials in neurotherapy in male nonhuman primates. Ten macaques (Macacca mulatta) were randomly separated into two groups of 5 and then intravenously injected with 4R or vehicle for 11 consecutive days at a dose of 1.4 mg/kg. Throughout the study, we monitored brain activity by electroencephalogram, somatosensory evoked potentials, and transcranial motor evoked potentials on days 0, 4, 8, and 12 and found no significant changes. The spontaneous behavior of the primates remained unaffected by the treatment. Minor hematological and blood composition variations were also detected in the experimental animals but lacked clinical significance. In conclusion, our results reinforce the notion that 4R is non-toxic in nonhuman primates under the conditions of this study.

Proof of concept of the Universal Baby video innovation for early child development in Lima, Peru.

OBJECTIVE: Community-based video interventions offer an effective and potentially scalable early interaction coaching tool for caregivers living in low resource settings. We tested the Universal Baby (UB) video innovation; an early interaction coaching tool using video sourced and produced locally with early child development (ECD) expert supervision. METHODS: This proof-of-concept study enrolled 40 caregivers of children ages 10-18 months assigned to intervention and control groups by health establishments in Carabayllo, Lima, Peru. Mother/child dyads received 12 weekly group health education sessions with social support. Of those, 16 caregivers also received 6 UB videos featuring brain science education and local clips of responsive, reciprocal interaction, also known as "serve and return" interaction. Survey data assessed feasibility and acceptability of the intervention. We assessed improved quality of mother/child interaction using the Parenting Interactions with Children: Checklist of Observations Linked to Outcomes (PICCOLO). RESULTS: We found the program feasible. We successfully trained the local team to produce UB videos using locally-sourced footage and delivered the videos as part of a community-based intervention. We also found it to be acceptable in that participants enthusiastically received the UB videos, reporting they enjoyed being videotaped, and learned how to recognize and appropriately respond to their child's nuanced sounds and gestures. The median change in total PICCOLO scores favored the intervention group compared to the control group. CONCLUSIONS: UB offers great potential as a sustainable, potentially scalable, and culturally appropriate tool to promote equity for child development among young children living in low resource homes globally.

Metal-chloroquine derivatives as possible anti-malarial drugs: evaluation of anti-malarial activity and mode of action.

BACKGROUND: Malaria still has significant impacts on the world; particularly in Africa, South America and Asia where spread over several millions of people and is one of the major causes of death. When chloroquine diphosphate (CQDP) lost its efficiency as a first-line anti-malarial drug, this was a major setback in the effective control of malaria. Currently, malaria is treated with a combination of two or more drugs with different modes of action to provide an adequate cure rate and delay the development of resistance. Clearly, a new effective and non-toxic anti-malarial drug is urgently needed. METHODS: All metal-chloroquine (CQ) and metal-CQDP complexes were synthesized under N(2) using Schlenk techniques. Their interactions with haematin and the inhibition of ß-haematin formation were examined, in both aqueous medium and near water/n-octanol interfaces at pH 5. The anti-malarial activities of these metal- CQ and metal-CQDP complexes were evaluated in vitro against two strains, the CQ-susceptible strain (CQS) 3D7 and the CQ-resistant strain (CQR) W2. RESULTS: The previously synthesized Au(CQ)(Cl) (1), Au(CQ)(TaTg) (2), Pt(CQDP)(2)Cl(2) (3), Pt(CQDP)(2)I(2) (4), Pd(CQ)(2)Cl(2) (5) and the new one Pd(CQDP)(2)I(2) (6) showed better anti-malarial activity than CQ, against the CQS strain; moreover, complexes 2, 3 and 4 were very active against CQR strain. These complexes (1-6) interacted with haem and inhibited ß-haematin formation both in aqueous medium and near water/n-octanol interfaces at pH 5 to a greater extent than chloroquine diphosphate (CQDP) and other known metal-based anti-malarial agents. CONCLUSIONS: The high anti-malarial activity displayed for these metal-CQ and metal-CQDP complexes (1-6) could be attributable to their effective interaction with haem and the inhibition of ß-haematin formation in both aqueous medium and near water/n-octanol interfaces at pH 5.

Copper (I)-Chloroquine Complexes: Interactions with DNA and Ferriprotoporphyrin, Inhibition of ß-Hematin Formation and Relation to Antimalarial Activity.

A new Cu(I)-chloroquine (CQ) complex [Cu(CQ)(PPh3)2]NO3 (1) was synthesized and characterized, and its mechanism of action studied concomitant with the previously reported complex [Cu(CQ)2]Cl (2). These copper (I) coordination compounds can be considered as potential antimalarial agents because they show better inhibition of the CQ-resistant strain in in vitro studies than CQ alone. In comparison with other metal-CQ complexes, only the gold complex was similar to (1), i.e., more active than CQ against both CQ-susceptible (3D7) and CQ-resistant strains (W2). These two copper (I)-compounds also demonstrated higher antiplasmodial activity against W2 than other copper complexes reported to date. This suggests that the incorporation of the copper metal center enhanced the biological activity of CQ. To better understand their significant growth inhibition of the Plasmodium falciparum parasite, the interaction with two essential molecular targets for the survival and proliferation of the malarial parasite were studied. These were the ferriprotoporphyrin group and the DNA, both important targets for current antimalarial drugs at the asexual erythrocytic stages. Both compounds (1,2) exhibited significant interactions with these targets. In particular, interactions with the DNA were dominated by the intercalator properties of the CQ ligand but may have also been affected by the presence of copper. Overall, these compounds were better parasitic inhibitors than chloroquine diphosphate (CQDP) alone or other previously reported metal-CQ complexes such as platinum, ruthenium and gold.

A Novel Hybrid of Chloroquine and Primaquine Linked by Gold(I): Multitarget and Multiphase Antiplasmodial Agent.

Plasmodium parasites kill 435 000 people around the world every year due to unavailable vaccines, a limited arsenal of antimalarial drugs, delayed treatment, and the reduced clinical effectiveness of current practices caused by drug resistance. Therefore, there is an urgent need to discover and develop new antiplasmodial candidates. In this work, we present a novel strategy to develop a multitarget metallic hybrid antimalarial agent with possible dual efficacy in both sexual and asexual erythrocytic stages. A hybrid of antimalarial drugs (chloroquine and primaquine) linked by gold(I) was synthesized and characterized by spectroscopic and analytical techniques. The CQPQ-gold(I) hybrid molecule affects essential parasite targets, it inhibits ß-hematin formation and interacts moderately with the DNA minor groove. Its interaction with PfTrxR was also examined in computational modeling studies. The CQPQ-gold(I) hybrid displayed an excellent in vitro antimalarial activity against the blood-stage of Plasmodium falciparum and liver-stage of Plasmodium berghei and efficacy in vivo against P. berghei, thereby demonstrating its multiple-stage antiplasmodial activity. This metallic hybrid is a promising chemotherapeutic agent that could act in the treatment, prevention, and transmission of malaria.

Neck muscle responses of driver and front seat passenger during frontal-oblique collisions.

BACKGROUND: Low-velocity motor vehicle crashes often lead to severe and chronic neck disorders also referred to as whiplash-associated disorders (WAD). The etiology of WAD is still not fully understood. Many studies using a real or simulated collision scenario have focused on rear-end collisions, whereas the kinematics and muscular responses during frontal-oblique collisions have hardly been investigated. In particular for rear-end collisions, drivers were shown to have a higher WAD risk than front seat passengers. Yet, independently from the impact direction, neither the muscular nor the kinematic responses of drivers and front seat passengers have been compared to date, although some findings indicate that the neck muscles have the potential to alter the head and neck kinematics, and that the level of neck muscle activity during impact may be relevant for the emergence of WAD. OBJECTIVE: In this study, we quantitatively examined the subjects' neck muscle activity during low-velocity left-frontal-oblique impacts to gain further insights into the neuromuscular mechanism underlying whiplash-like perturbations that may lead to WAD. METHODS: In a within-subject study design, we varied several impact parameters to investigate their effect on neck muscle response amplitude and delay. Fifty-two subjects experienced at least ten collisions while controlling for the following parameters: change in velocity Δv (3 / 6 km/h), seating position (driver / front seat passenger), and deliberate pre-tension of the musculature (tense / relaxed) to account for a potential difference between an expected and an unexpected crash. Ten of the 52 subjects additionally ran the same experimental conditions as above, but without wearing a safety belt. FINDINGS: There were significant main effects of Δv and muscle pre-tension on the reflex amplitude but not of seating position. As for the reflex delay, there was a significant main effect of muscle pre-tension, but neither of Δv nor of seating position. Moreover, neither the safety belt nor its asymmetrical orientation had an influence on the reflexive responses of the occupants. CONCLUSION: In summary, we did not find any significant differences in the reflex amplitude and delay of the neck musculature between drivers and front seat passengers. We therefore concluded that an increased risk of the driver sustaining WAD in frontal-oblique collisions, if it exists, cannot be due to differences in the reflexive responses.

Extensively drug-resistant (XDR) Pseudomonas aeruginosa identified in Lima, Peru co-expressing a VIM-2 metallo-ß-lactamase, OXA-1 ß-lactamase and GES-1 extended-spectrum ß-lactamase.

INTRODUCTION: Pseudomonas aeruginosa has the ability to acquire plasmids and other mobile genetic elements that confer resistance to antibiotics. Bacterial genes encoding different ß-lactamases (bla), such as metallo-ß-lactamases (MBLs) and extended-spectrum ß-lactamases (ESBL), can confer resistance to multiple classes of ß-lactam antibiotics. CASE PRESENTATION: An 83 year old female was admitted in 2012 to the Peruvian Naval Hospital, Centro Médico Naval 'Cirujano Mayor Santiago Távara' (CEMENA), in Lima, Peru. A midstream urine sample was collected and sent to the local CEMENA laboratory for routine urine culture. P. aeruginosa was isolated and initial antibiotic susceptibility testing showed it to be sensitive to imipenem. The clinicians started a course of meropenem, but the patient did not improve. After 5 days, a second urine culture was performed and a P. aeruginosa was isolated again, but this time the strain showed resistance to imipenem. The treatment course was changed to fosfomycin and the patient improved. Phenotypic and molecular laboratory testing to characterize the antibiotic resistance were performed, demonstrating the presence of both MBL and ESBL genes. CONCLUSION: To our knowledge, this is the first report of a P. aeruginosa XDR clinical isolate that co-expresses an MBL (VIM-2), OXA-1 beta-lactamase and the ESBL (GES-1) in Peru. It is also the first report of a VIM carbapenemase in Peru.

Use, knowledge, and perception of the scientific contribution of Sci-Hub in medical students: Study in six countries in Latin America.

INTRODUCTION: Sci-Hub is a useful web portal for people working in science as it provides access to millions of free scientific articles. Satisfaction and usage should be explored in the Latino student population. The objective of this study was to evaluate the use, knowledge, and perception of the scientific contribution of Sci-Hub in medical students from Latin America. METHODOLOGY: A multicenter, observational, analytical study was conducted in 6632 medical students from 6 countries in Latin America. We surveyed from a previously validated instrument, delving into knowledge, monthly average usage, satisfaction level, and perception of the scientific contributions provided by Sci-Hub. Frequencies and percentages are described, and generalized linear models were used to establish statistical associations. RESULTS: Only 19.2% of study participants knew of Sci-Hub and its function, while the median use was twice a month. 29.9% of Sci-Hub-aware participants claimed they always find the desired scientific information in their Sci-Hub search; 62.5% of participants affirmed that Sci-Hub contributes to scientific investigation; only 2.2% reported that Sci-Hub does not contribute to science. CONCLUSION: The majority of Latino students are not aware of Sci-Hub.

Violencia simbólica en Instituciones de Educación Superior. Experiencia de docentes de una Universidad Pública colombiana / Symbolic violence in higher education institutions. Experience of teachers from a public university

En las Instituciones de Educación Superior (IES) se presentan algunas formas de violencia directa, aunque poco se han estudiado otras formas de violencia como la simbólica. Objetivo: señalar, a partir de las experiencias de algunos docentes de educación superior, las manifestaciones de violencia simbólica presentes en su lugar de trabajo. Método: investigación de corte mixto enmarcada en el paradigma empírico analítico. Se utilizaron como instrumentos una encuesta estructurada aplicada a 200 docentes y una entrevista en profundidad en la que participaron cinco docentes de una IES pública en Colombia. Resultados: los hallazgos develan la presencia de ciertas formas de violencia simbólica en la IES que se traducen, principalmente, en limitaciones al ejercicio del libre desarrollo de cátedra, restricciones para opinar o presentar los puntos de vista, dificultades para el reconocimiento de la pluralidad ideológica, tratamiento diferencial por sexo y escasa importancia otorgada a algunas disciplinas. Conclusión: las universidades son estructuras jerárquicas de poder sobre las cuales pueden anidar formas particulares de violencia simbólica que exigen estrategias y líneas de acción particulares desde la gestión humana.

In Higher Education Institutions there are some forms of direct violence, although seldom nobody has been studied other forms of violence such as symbolic violence. Objective: to point out, based on the experiences of some higher education professors, the manifestations of symbolic violence present in their workplace. Method: research of mixed focus framed in the analytical empirical paradigm. The instruments used were a structured survey applied to 200 professors and an in-depth interview in which five professors from a public higher education institution in Colombia participated. Results: The findings reveal the presence of certain forms of symbolic violence in the HEI that are translated, mainly, in limitations to the exercise of the free development of the chair, restrictions to express their opinions or own points of view, difficulties in the recognition of ideological plurality, differential treatment by sex and not more importance given to some disciplines. Conclusion: universities are hierarchical structures of power on which special forms of symbolic violence can nest that require strategies and particular lines of action from human management.

Efectos de la aplicación del Programa de Enriquecimiento Instrumental sobre un grupo de jóvenes infractores / The Effects of Applying the Instrumental Enrichment Program to a Group of Juvenile Offenders / Efeitos da implementai em um grupo de jovens infratores

Resumen Esta investigación tuvo como objetivo analizar los efectos de la aplicación del Programa de Enriquecimiento Instrumental (PEI) de Reuven Feuerstein sobre un grupo de jóvenes infractores en proceso de resocialización de la Fundación El Faro del municipio de San José de Cúcuta, Colombia. Corresponde a un estudio cualitativo de nivel descriptivo enmarcado en la orientación epistemológica del paradigma interpretativo. En el estudio participaron diez jóvenes en proceso de resocialización con diversas características y limitaciones; para la intervención y recolección de información se utilizaron los instrumentos de relaciones virtuales, comparaciones y relaciones espaciales del PEI junto al diario de campo. Los resultados presentados desde la perspectiva cualitativa muestran un conjunto de cambios en las estructuras cognitivas de los jóvenes sujetos a intervención, es decir, sobre las funciones cognitivas y las operaciones mentales, aunque algunos factores limitaron la mediación como el consumo de sustancias psicoactivas y el ambiente del centro de rehabilitación. La evidencia permite concluir que son significativas las potencialidades del programa cognitivo y la Experiencia de Aprendizaje Mediado -EAM- como se señalan en otros estudios sobre los diferentes ámbitos de aplicación de la teoría de la Modificabilidad Estructural Cognitiva.

Abstract The objective of this research was to analyze the effects of applying Reuven Feuerstein's Instrumental Enrichment (FIE) Program to a group of juvenile offenders during a resocialization process by Fundación El Faro in the municipality of San José of Cucuta, Colombia. It corresponds to a qualitative, descriptive study framed within the epistemological orientation of the interpretative paradigm. Ten young people with various characteristics and limitations participated in the resocialization process. Virtual relationship instruments, comparisons and FIE spatial relationships were used in the intervention and for information collection, along with the field log. The results presented from a qualitative perspective show a set of changes in the cognitive structures of young people subject to intervention. That is, cognitive functions and mental operations changed, although some factors limited mediation, such as psychoactive substance consumption and the environment within the rehabilitation center. The evidence allows concluding that the Mediated Learning Experience (MLE) and the program's cognitive potentials are significant, as indicated in other studies on the different environments in which the Structural Cognitive Modifiability Theory is applied.

Resumo Esta pesquisa teve como objetivo analisar os efeitos da aplicação do Programa de Enriquecimento Instrumental (PEI) de Reuven Feuerstein num grupo de jovens infratores em processo de ressocialização da Fundação El Faro do município de San José de Cúcuta, Colômbia. Trata-se de um estudo qualitativo de nível descritivo enquadrado na orientação epistemológica do paradigma interpretativo. Participaram do estudo dez jovens em processo de ressocialização, com diversas características e limitações. Para a intervenção e coleta de informações, foram utilizados os instrumentos de relações virtuais, comparações e relações espaciais do PEI, juntamente com o diário de campo. Os resultados apresentados na perspectiva qualitativa mostram um conjunto de mudanças nas estruturas cognitivas dos jovens sujeitos à intervenção, ou seja, nas funções cognitivas e nas operações mentais, embora alguns fatores tenham limitado a mediação, como o consumo de substâncias psicoativas e o ambiente do centro de reabilitação. As evidências permitem concluir que as potencialidades do programa cognitivo e da Experiência de Aprendizagem Mediada -EAM- são significativas, conforme apontado em outros estudos nas diferentes áreas de aplicação da teoria da Modificabilidade Estrutural Cognitiva.

La política colombiana de emprendimiento en educación y su impacto en el acceso al empleo de jóvenes / Colombia's Education Entrepreneurship Policy and its Impact on Access to Employment for the Young People

Resumen La política colombiana de emprendimiento en educación sobre el acceso al empleo de los jóvenes egresados de educación media, traducida en la denominada forma ción técnica en el ámbito de la educación, cumple su propósito de adiestrar a los es tudiantes en determinadas competencias laborales específicas, pero no su objetivo de mejorar la calidad de vida y ampliar las potencialidades de los estudiantes frente a su proyecto de vida y no ha tenido un impacto favorable sobre las posibilidades de acceso al empleo de los jóvenes.

Abstract Colombia's education entrepreneurship policy on access to employment for young middle-educated graduates, translated into so-called technical training in the field of education, fulfils its purpose of training students in certain specific job competen cies. However, it does not fulfill their objective of improving life quality and expan ding students' potentials regarding their life project, and it has not had a favorable impact on the possibilities of access to employment of young people.

Sources of indoor air pollution in New York City residences of asthmatic children.

Individuals spend ∼90% of their time indoors in proximity to sources of particulate and gaseous air pollutants. The sulfur tracer method was used to separate indoor concentrations of particulate matter (PM) PM2.5 mass, elements and thermally resolved carbon fractions by origin in New York City residences of asthmatic children. Enrichment factors relative to sulfur concentrations were used to rank species according to the importance of their indoor sources. Mixed effects models were used to identify building characteristics and resident activities that contributed to observed concentrations. Significant indoor sources were detected for OC1, Cl, K and most remaining OC fractions. We attributed 46% of indoor PM2.5 mass to indoor sources related to OC generation indoors. These sources include cooking (NO2, Si, Cl, K, OC4 and OP), cleaning (most OC fractions), candle/incense burning (black carbon, BC) and smoking (K, OC1, OC3 and EC1). Outdoor sources accounted for 28% of indoor PM2.5 mass, mainly photochemical reaction products, metals and combustion products (EC, EC2, Br, Mn, Pb, Ni, Ti, V and S). Other indoor sources accounted for 26% and included re-suspension of crustal elements (Al, Zn, Fe, Si and Ca). Indoor sources accounted for ∼72% of PM2.5 mass and likely contributed to differences in the composition of indoor and outdoor PM2.5 exposures.

The effects of PM2.5 and its components from indoor and outdoor sources on cough and wheeze symptoms in asthmatic children.

Particulate matter with aerodynamic diameter <2.5 µm (PM2.5) is associated with asthma exacerbation. In the Children's Air Pollution Asthma Study, we investigated the longitudinal association of PM2.5 and its components from indoor and outdoor sources with cough and wheeze symptoms in 36 asthmatic children. The sulfur tracer method was used to estimate infiltration factors. Mixed proportional odds models for an ordinal response were used to relate daily cough and wheeze scores to PM2.5 exposures. The odds ratio associated with being above a given symptom score for a SD increase in PM2.5 from indoor sources (PMIS) was 1.24 (95% confidence interval: 0.92-1.68) for cough and 1.63 (1.11-2.39) for wheeze. Ozone was associated with wheeze (1.82, 1.19-2.80), and cough was associated with indoor PM2.5 components from outdoor sources (denoted with subscript "OS") bromine (BrOS: 1.32, 1.05-1.67), chlorine (ClOS: 1.27, 1.02-1.59) and pyrolyzed organic carbon (OPOS: 1.49, 1.12-1.99). The highest effects were seen in the winter for cough with sulfur (SOS: 2.28, 1.01-5.16) and wheeze with organic carbon fraction 2 (OC2OS: 7.46, 1.19-46.60). Our results indicate that exposure to components originating from outdoor sources of photochemistry, diesel and fuel oil combustion is associated with symptom's exacerbation, especially in the winter. PM2.5 mass of indoor origin was more strongly associated with wheeze than with cough.

Medicinal potential of ciprofloxacin and its derivatives.

Ciprofloxacin (CP) is a fluoroquinolone that is highly active against diverse microorganisms. At concentrations less than 1 µg/ml it is active against a diverse types of bacteria, including Staphylococcus aureus, Staphylococcus epidermidis, Bacillius subtilius, Escherichia coli and Mycobacterium tuberculosis. In addition, it has shown to be effective against other diseases such as malaria, cancer and AIDS. The extended antimicrobial activity, lack of plasmid-mediated resistance, large volume of distribution and minimal adverse effects of CP are therapeutically advantageous. In the pursuit of increasing their effectiveness against these diseases and prevent unwanted resistance, researchers have begun to synthesize a class of organic, inorganic and organometallic derivatives, which have displayed interesting activities. This review describes the development and recent advances on the evaluation of CP and its derivatives as a new class of drugs with potential for clinical development.

Factores académicos asociados a la procrastinación / Academic factors associated to procrastination

Introducción: La procrastinación es el dejar las cosas para última hora, esto puede tener repercusiones en la esfera académica. Objetivo: Determinar los factores académicos asociados a la procrastinación general. Métodos: Se realizó un estudio transversal analítico en estudiantes de una universidad particular en la serranía peruana, como resultados preliminares tomados en todas las facultades de una universidad en la ciudad de Huancayo-Perú. Los procrastinadores fueron los estudiantes que estuvieron en el tercio superior del puntaje total de un test validado, luego se asoció a factores educativos. Se obtuvieron estadísticos de asociación. Resultados: De los 5 812 estudiantes encuestados, el 48 por ciento (2 776) fueron hombres, con una mediana de edad de 20 años. En el análisis multivariado, la mayor frecuencia de procrastinación se dio en los estudiantes varones (p: 0,005), entre los que tenían menor edad (p: 0,003), menos horas diarias de estudio (p< 0,001) y menores promedios ponderados en el ciclo anterior (p< 0,001); así mismo, las facultades de ciencias de la salud (p: 0,005) y derecho (p: 0,006) tenían menores frecuencias de procrastinación; ajustado por cuatro variables. Conclusiones: Aquellas carreras con mayor exigencia y los estudiantes que realizan una mayor actividad académica son los que procrastinan menos, esto puede ayudar para la generación de estrategias y apoyo a los estudiantes que tienen estos hábitos inadecuados de estudio(AU)

Introduction: Procrastination is leaving things for the last minute, this can have repercussions in the academic domain. Objective: To determine the academic factors associated with general procrastination. Methods: An analytical cross-sectional study was carried out in students of a particular university in the Peruvian highlands, as preliminary results from all faculties of a university in the city of Huancayo-Peru. The procrastinators were the students who were in the upper third of the total score of a validated test, then associated with educational factors. Association statistics were obtained. Results: 5 812 students were surveyed. 48 percent (2 776) were men, with a median age of 20 years. In the multivariate analysis, the highest frequency of procrastination occurred in male students (p: 0.005), among those who were younger (p: 0.003), less daily hours of study (p< 0.001) and lower weighted averages in the previous cycle (p< 0.001). Likewise, the faculties of health sciences (p: 0.005) and law (p: 0.006) had lower frequencies of procrastination; adjusted by four variables. Conclusions: Those with more demanding studies and the students who carry out the most academic activities are those who procrastinate the least, this can help to generate strategies and support students who have these inadequate study habits(AU)

The therapeutic potential of metal-based antimalarial agents: implications for the mechanism of action.

Despite recent encouraging advances against the disease, malaria remains a major public health problem affecting almost half a billion people and killing almost a million per annum. Due to a short arsenal of efficient antimalarial agents and the frequent appearance of resistance to the drugs in current use, which consequently reduce our means to treat patients, there is a very urgent and continuous need to develop new compounds. This perspective outlines a unique strategy for that purpose through the development of metal-based antimalarial agents. The examples presented here illustrate an attractive alternative to classical drugs.

The mechanism of antimalarial action of [Au(CQ)(PPh(3))]PF(6): structural effects and increased drug lipophilicity enhance heme aggregation inhibition at lipid/water interfaces.

The mechanism of antimalarial action of [Au(CQ)(PPh(3))]PF(6) (1), which is active in vitro against CQ-resistant P. falciparum and in vivo against P. berghei, has been investigated in relation to hemozoin formation and DNA as possible important targets. Complex 1 interacts with heme and inhibits ß-hematin formation both in aqueous medium and near water/n-octanol interfaces at pH ~5 to a greater extent than chloroquine diphosphate (CQDP) or other known metal-based antimalarial agents; the higher inhibition activity is probably related to the higher lipophilicity observed for 1 through partition coefficient measurements at low pH, with respect to CQDP. The interactions of complex 1 with DNA were explored using spectrophotometric and fluorimetric titrations, circular dichroism spectroscopy, viscosity and melting point studies, as well as electrophoresis and covalent binding assays. The experimental data indicate that complex 1 interacts with DNA predominantly by intercalation and electrostatic association of the CQ moiety, similarly to free CQDP, while no covalent metal-DNA binding seems to take place. The most likely antimalarial mechanism for complex 1 is thus heme aggregation inhibition; the high activities observed against resistant parasites are probably due to the structural modification of CQ introduced by the presence of the gold-triphenylphosphine fragment, together with the enhanced lipophilic character.

Construcción de ciudadanía: un modelo para su desarrollo en la escuela / The construction of citizenship: a model for its development in the school

Se analiza las relaciones entre ciudadanía, política y educación, y a partir de ello, se propone un modelo para la formación de ciudadanos en la escuela, para la formación de la ciudadanía que incluye: propósitos de la enseñanza, papel de los contenidos en este proceso, formas para llevar a cabo enseñanza - aprendizaje y evaluación del aprendizaje.

The relationship among citizens, politics, and education is discussed, and based on that, a model for the training of citizens in the school, for the formation of citizenship is proposed, which includes purposes of education, the role of the contents in this process, ways to carry out the teaching - learning process, and learning assessment.

Synthesis, characterization and biological activity of trans-platinum(II) complexes with chloroquine.

Three platinum-chloroquine complexes, trans-Pt(CQDP)(2)(I)(2) [1], trans-Pt(CQDP)(2)(Cl)(2) [2] and trans-Pt(CQ)(2)(Cl)(2) [3], were prepared and their most probable structure was established through a combination of spectroscopic analysis and density functional theory (DFT) calculations. Their interaction with DNA was studied and their activity against 6 tumor cell lines was evaluated. Compounds 1 and 2 interact with DNA primarily through electrostatic contacts and hydrogen bonding, with a minor contribution of a covalent interaction, while compound 3 binds to DNA predominantly in a covalent fashion, with weaker secondary electrostatic interactions and possibly hydrogen bonding, this complex also exerted greater cytotoxic activity against the tumor cell lines.