QSAR analysis of five generations of cephalosporins to establish the structural basis of activity against methicillin-resistant and methicillin-sensitive Staphylococcus aureus.

Solving the worldwide problem of growing bacterial drug resistance will require a short-run and medium-term strategy. Structure-activity relationship (SAR) and quantitative SAR (QSAR) analyses have recently been utilized to reveal the molecular basis of the antibacterial activity and antibacterial spectrum of penicillins, the use of which is no longer solely empirical. Likewise, a more rational drug design can be achieved with cephalosporins, the largest group of ß-lactam antibiotics. The current contribution aimed to establish the molecular and physicochemical basis of the antibacterial activity of five generations of cephalosporins on methicillin-sensitive (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA). With SAR and QSAR analyses, the molecular portions that provide essential and additional antibacterial activity were identified. The substitutions with greater volume and polarity on the R2 side chain of the cephem nucleus increase potency on MSSA. The best effect is produced by substitutions with polar nitrogen atoms at the alpha-carbon (Cα). Substitutions with greater volume and polarity on the R1 side chain further enhance antibacterial activity. In contrast, the effect against MRSA seems to be independent of any substitution on R2 or at the Cα, while depending on the accessory portions with greater volume and polarity on R1.

Spanish translation, retranslation, and content validation of the Quality of Life in Alzheimer's Disease scale in patients with Alzheimer's dementia. / Traducción al español, retraducción y validación de contenido de la escala Quality of Life in Alzheimer's Disease en pacientes con demencia Alzheimer.

Introduction: It is estimated that by the year 2050, persons over 60 will account for 22% of the world population. Consequently, the incidence and prevalence of Alzheimer's disease will increase correspondingly. One of the pillars of the treatment of this condition is to improve the quality of life. In this sense, questionnaires such as the Quality of Life in Alzheimer's Disease allow us to measure the quality of life in patients and caregivers. Objective: To translate into Chilean Spanish and carry out the content validation of the Quality of Life in Alzheimer's Disease scale in patients with Alzheimer's dementia at the Guillermo Grant Benavente Hospital in Concepción, Chile. Methods: Translation, back-translation and content validity were carried out by expert judgment, using Lawshe analysis, pre-test and semantic validation using the respondent debriefing strategy. Results: The translated and retranslated versions were compared with each other and with the original version. Lawshe indicates that a Content Validity Ratio equal 0.49 is adequate to consider the item valid when 15 experts participated in the content validation process, as in our study. The analysis yielded a content validity ratio greater than 0.49 in 11 of the 13 items on the scale. Of these, 8 obtained a value greater than 0.8 and 3 between 0.49 and 0.79. In semantic validation using the respondent debriefing strategy, the scale was applied to five people with Alzheimer's and their respective caregivers. With the data obtained, modifications were generated in those items that obtained a content validity ratio of less than 0.49. Conclusions: The version obtained in Spanish of the Quality of Life in Alzheimer's Disease scale is valid from the point of view of its content and equivalent to its original version.

Introducción: Se estima que para el año 2050 los mayores de 60 años corresponderán al 22% de la población mundial y con ello aumente la incidencia y prevalencia de enfermedad de Alzheimer. Uno de los pilares del tratamiento de esta condición es mejorar la calidad de vida, en este sentido surgen herramientas como la Quality of Life in Alzheimer's Disease Scale que permite medir calidad de vida en pacientes y sus cuidadores. Objetivo: Realizar la traducción al español chileno y validación de contenido de la Quality of Life in Alzheimer's Disease Scale en pacientes con demencia por Alzheimer del Hospital Guillermo Grant Benavente de Concepción, Chile. Métodos: Se llevó a cabo la traducción, retraducción y validez de contenido por juicio experto, utilizando el análisis Lawshe, pre-test y validación semántica usando la estrategia de respondent debriefing. Resultados: Las versiones traducidas y retraducidas fueron comparadas entre ellas y con la versión original. Lawshe indica que una razón de validez de contenido de 0,49 es adecuado para considerar aceptable el ítem cuando en el proceso de validación de contenido han participado 15 expertos como en este estudio. El análisis arrojó una razón de validez de contenido mayor a 0,49 en 11 de los 13 ítems de la escala. De estos, ocho obtuvieron un valor superior a 0,8 y tres entre 0,49 y 0,79. En la validación semántica mediante la estrategia de se aplicó la escala a cinco personas con enfermedad de Alzheimer y a sus respectivos cuidadores. Con los datos obtenidos, se generaron modificaciones en aquellos ítems que obtuvieron una razón de validez de contenido menor a 0,49. Conclusión: La versión obtenida en español de la resulta ser válida desde el punto de vista de su contenido y equivalente a su versión original.

Traducción al español, retraducción y validación de contenido de la escala Quality of Life in Alzheimer's Disease en pacientes con demencia Alzheimer / Spanish translation, retranslation, and content validation of the Quality of Life in Alzheimer's Disease scale in patients with Alzheimer's dementia

Introducción Se estima que para el año 2050 los mayores de 60 años corresponderán al 22% de la población mundial y con ello aumente la incidencia y prevalencia de enfermedad de Alzheimer. Uno de los pilares del tratamiento de esta condición es mejorar la calidad de vida, en este sentido surgen herramientas como la Quality of Life in Alzheimer's Disease Scale que permite medir calidad de vida en pacientes y sus cuidadores. Objetivo Realizar la traducción al español chileno y validación de contenido de la Quality of Life in Alzheimer's Disease Scale en pacientes con demencia por Alzheimer del Hospital Guillermo Grant Benavente de Concepción, Chile. Métodos Se llevó a cabo la traducción, retraducción y validez de contenido por juicio experto, utilizando el análisis Lawshe, pre-test y validación semántica usando la estrategia de respondent debriefing. Resultados Las versiones traducidas y retraducidas fueron comparadas entre ellas y con la versión original. Lawshe indica que una razón de validez de contenido de 0,49 es adecuado para considerar aceptable el ítem cuando en el proceso de validación de contenido han participado 15 expertos como en este estudio. El análisis arrojó una razón de validez de contenido mayor a 0,49 en 11 de los 13 ítems de la escala. De estos, ocho obtuvieron un valor superior a 0,8 y tres entre 0,49 y 0,79. En la validación semántica mediante la estrategia de se aplicó la escala a cinco personas con enfermedad de Alzheimer y a sus respectivos cuidadores. Con los datos obtenidos, se generaron modificaciones en aquellos ítems que obtuvieron una razón de validez de contenido menor a 0,49. Conclusión La versión obtenida en español de la resulta ser válida desde el punto de vista de su contenido y equivalente a su versión original.

Introduction It is estimated that by the year 2050, persons over 60 will account for 22% of the world population. Consequently, the incidence and prevalence of Alzheimer's disease will increase correspondingly. One of the pillars of the treatment of this condition is to improve the quality of life. In this sense, questionnaires such as the Quality of Life in Alzheimer's Disease allow us to measure the quality of life in patients and caregivers. Objective To translate into Chilean Spanish and carry out the content validation of the Quality of Life in Alzheimer's Disease scale in patients with Alzheimer's dementia at the Guillermo Grant Benavente Hospital in Concepción, Chile. Methods Translation, back-translation and content validity were carried out by expert judgment, using Lawshe analysis, pre-test and semantic validation using the respondent debriefing strategy. Results The translated and retranslated versions were compared with each other and with the original version. Lawshe indicates that a Content Validity Ratio equal 0.49 is adequate to consider the item valid when 15 experts participated in the content validation process, as in our study. The analysis yielded a content validity ratio greater than 0.49 in 11 of the 13 items on the scale. Of these, 8 obtained a value greater than 0.8 and 3 between 0.49 and 0.79. In semantic validation using the respondent debriefing strategy, the scale was applied to five people with Alzheimer's and their respective caregivers. With the data obtained, modifications were generated in those items that obtained a content validity ratio of less than 0.49. Conclusions The version obtained in Spanish of the Quality of Life in Alzheimer's Disease scale is valid from the point of view of its content and equivalent to its original version.

La reducción voluntaria del consumo como oportunidad de desarrollo a escala humana / Voluntary Consumption Reduction as an Opportunity for Human Scale Development

Resumen Se plantea hoy, la posibilidad de ampliar espacios de intercambio de mercancías que rebasen la visión estrecha del consumismo inspirado en el capitalismo salvaje; entre ellas, la posibilidad del No Consumo como opción válida para establecer procesos alternativos de crecimiento y desarrollo económico, sobre todo en los países latinoamericanos, que incorpore otros saberes y lógicas para el intercambio de bienes y servicios, por ejemplo, el concepto quechua del Buen Vivir. Aspectos centrales de la propuesta alternativa de reducción del consumo voluntario ("No Consumo"), desde la bioética global, se presentan además como estrategia para que el ser humano pueda construir escenarios que propendan por la satisfacción de necesidades, la equidad en el bienestar y el empleo; para reconvertir a las empresas, adaptando sus líneas de producción a esquemas que mitiguen el impacto sobre el medio ambiente y para promover mercados regionales latinoamericanos que fomenten la recuperación, la reutilización, el reciclaje y la reparación.

Abstract: The possibility of expanding spaces for the exchange of goods, which go beyond the narrow vision of consumerism inspired by savage capitalism, is being considered today. Among them, the possibility of Non-Consumption as a valid option to establish alternative processes of economic growth and development, especially, in Latin American countries, by incorporating other knowledge and logics for the exchange of goods and services, for example, the Quechua concept of Buen Vivir.. Central aspects of the alternative proposal for the reduction of voluntary consumption ("Non-Consumption") from a global bioethics perspective, the following are presented are also presented as a strategy for human beings to build scenarios, which promote the satisfaction of needs, equity in welfare and employment to reconvert companies, by adapting their production lines to schemes, which mitigate the impact on the environment and to promote Latin American regional markets, which encourage recovery, reuse, recycling, and repair.

Resistencia cruzada entre isoniacida y etionamida y su alta correlación con la mutación C-15T en aislamientos de Mycobacterium tuberculosis de Perú / Cross-resistance between isoniazid and ethionamide and its strong association with mutation C-15T in Mycobacterium tuberculosis isolates from Peru

Resumen Diversos estudios han evidenciado una resistencia cruzada entre isoniacida y etionamida, 2 de los fármacos utilizados en el tratamiento de la tuberculosis multirresistente.El objetivo del presente estudio fue determinar la resistencia cruzada entre ambos fármacos en aislados de Mycobacterium tuberculosis obtenidos en un hospital de Lima (Perú), conalta proporción de pacientes con tuberculosis. Se calculó la frecuencia de mutaciones asociadas con la resistencia a la isoniacida (INH) evaluando el gen katG y la región promotorainhA mediante la prueba molecular Genotype MTBDRplus v2.0. El método gold standard conocido como agar proporciones en placa (APP) permitió la identificación de resistencia a INH yetionamida. De 107 aislamientos resistentes a INH, 54 fueron multirresistentes (identificadosmediante la prueba Genotype MTBDRplus) y 49 (es decir, el 45,8% del total) también fueronresistentes a etionamida por el método APP. En los aislamientos resistentes a INH, se encontraron mutaciones en el gen katG en el 50,5% (54/107); en la región promotora inhA en el23,3% (25/107), y un 14,0% (15/107) presentaron mutaciones en ambos. Un 12,1% (13/107)fueron resistentes a INH por ausencia de banda wild type y banda de mutación. La mutaciónC-15T en la región promotora inhA presentó una fuerte asociación con la resistencia a etionamida y alcanzó el 73,4% (36/49) de los aislamientos resistentes a dicho fármaco. Los resultadosdel presente estudio sugieren que la identificación de mutaciones relacionadas con resistenciaa INH, sobre todo en la región promotora inhA, podría ser de gran utilidad para identificarla resistencia cruzada a etionamida y mejorar el tratamiento de las personas afectadas portuberculosis.© 2019 Asociacion Argentina de Microbiolog´ía. Publicado por Elsevier Espana, S.L.U. Este es unart´ículo Open Access bajo la licencia CC BY-NC-ND (https://creativecommons.org/licenses/by-nc-nd/4.0/).

Abstract Several studies have shown cross-resistance between isoniazid and ethionamide, 2of the drugs used in the treatment of multidrug-resistant tuberculosis. The objective of this study was to determine the cross-resistance between both drugs in Mycobacterium tuberculosis isolates from a hospital with high incidence of tuberculosis in Lima, Peru. The frequency of mutations to isoniazid in the katG gene and the inhA promoter region was identified by the Genotype MTBDRplus v2.0 molecular test. The gold standard Agar Proportion method (APM) allowed todetect resistance to isoniazid and ethionamide. Of 107 isoniazid-resistant isolates (54 multidrug-resistant isolates identified by the Genotype MTBDRplus test, 45.8% (49/107) were also resistant to ethionamide by the APM. Mutations were found in the katG gene in 50.5% (54/107), in the promoter region inhA in 23.3% (25/107) and 14.0% (15/107) that share both mutations in the resistant isolates to INH. The absence of the wild type and mutation bands indicated that 12.1% (13/107) of the isolates were resistant to INH. The mutation C-15T in the inhA promoter region showed a strong association with resistance to ethionamide in 73.4% (36/49) of the isolates analyzed. The results of the present study suggest that the identification of mutations related to resistance to isoniazid, especially in the inhA promoter region, could be very useful to identify cross-resistance to ethionamide and improve the treatment of individuals suffering from this disease.

[Cross-resistance between isoniazid and ethionamide and its strong association with mutation C-15T in Mycobacterium tuberculosis isolates from Peru]. / Resistencia cruzada entre isoniacida y etionamida y su alta correlación con la mutación C-15T en aislamientos de Mycobacterium tuberculosis de Perú.

Several studies have shown cross-resistance between isoniazid and ethionamide, 2of the drugs used in the treatment of multidrug-resistant tuberculosis. The objective of this study was to determine the cross-resistance between both drugs in Mycobacterium tuberculosis isolates from a hospital with high incidence of tuberculosis in Lima, Peru. The frequency of mutations to isoniazid in the katG gene and the inhA promoter region was identified by the Genotype MTBDRplus v2.0 molecular test. The gold standard Agar Proportion method (APM) allowed todetect resistance to isoniazid and ethionamide. Of 107 isoniazid-resistant isolates (54 multidrug-resistant isolates identified by the Genotype MTBDRplus test, 45.8% (49/107) were also resistant to ethionamide by the APM. Mutations were found in the katG gene in 50.5% (54/107), in the promoter region inhA in 23.3% (25/107) and 14.0% (15/107) that share both mutations in the resistant isolates to INH. The absence of the wild type and mutation bands indicated that 12.1% (13/107) of the isolates were resistant to INH. The mutation C-15T in the inhA promoter region showed a strong association with resistance to ethionamide in 73.4% (36/49) of the isolates analyzed. The results of the present study suggest that the identification of mutations related to resistance to isoniazid, especially in the inhA promoter region, could be very useful to identify cross-resistance to ethionamide and improve the treatment of individuals suffering from this disease.

Índice de sospecha: manifestaciones psiquiátricas de la encefalitis por anticuerpos anti-NMDAR en pacientes pediátricos / Suspicion Index: Psychiatric Manifestations of NMDAR Encephalitis in Paediatric Patients

Resumen Las encefalitis inmunitarias son un grupo particular de trastornos que se distinguen por su aproximación diagnostica única y manejo específico. Algunas de las manifestaciones iniciales son inespecíficas y difíciles de distinguir de encefalitis de otros orígenes, e incluso con los tests diagnósticos modernos aún hay cierto número de casos en que no se logra aclarar la causa específica. Entre ellas, las encefalitis anti-NMDAR son una particular forma de encefalitis inmunitaria que tiene manifestaciones clínicas distintivas, algunas de las cuales permiten al evaluador médico apuntar a un diagnóstico más preciso e iniciar tratamientos aun sin tener los reportes específicos de laboratorio. En este artículo se presentan 3 casos de pacientes pediátricos tratados como encefalitis anti-NMDAR, y después de comparar su presentación clínica, se revisa este trastorno específico y algunos de los datos más relevantes en su fisiopatología, como una forma de explicar las manifestaciones psiquiátricas iniciales, de cuyo reconocimiento inicial van a depender los apropiados diagnóstico y tratamiento.

Abstract Immune encephalitis is a diverse group of disorders that share some unique diagnostic approaches and specific treatments. Some of the initial manifestations are non-specific and difficult to distinguish from encephalitis of other aetiologies, and even with modern diagnostic tools there are still a number of cases for which definitive causes cannot be clarified. Among these, N-methyl-D-aspartate receptor (NMDAR) encephalitis is a particular form of immune encephalitis that has some distinctive clinical manifestations, which allows the clinical evaluator to suggest a more accurate diagnosis and start treatments even in the absence of specific laboratory tests. Three paediatric patients, who were treated for NMDAR encephalitis are described in this article, as well as comparing their clinical presentation. This specific disorder and some of the more relevant features of its physiopathology are reviewed in order to explain the initial psychiatric manifestations, for which early recognition is critical for an appropriate diagnosis and treatment.

[Suspicion Index: Psychiatric Manifestations of NMDAR Encephalitis in Paediatric Patients]. / Índice de sospecha: manifestaciones psiquiátricas de la encefalitis por anticuerpos anti-NMDAR en pacientes pediátricos.

Immune encephalitis is a diverse group of disorders that share some unique diagnostic approaches and specific treatments. Some of the initial manifestations are non-specific and difficult to distinguish from encephalitis of other aetiologies, and even with modern diagnostic tools there are still a number of cases for which definitive causes cannot be clarified. Among these, N-methyl-D-aspartate receptor (NMDAR) encephalitis is a particular form of immune encephalitis that has some distinctive clinical manifestations, which allows the clinical evaluator to suggest a more accurate diagnosis and start treatments even in the absence of specific laboratory tests. Three paediatric patients, who were treated for NMDAR encephalitis are described in this article, as well as comparing their clinical presentation. This specific disorder and some of the more relevant features of its physiopathology are reviewed in order to explain the initial psychiatric manifestations, for which early recognition is critical for an appropriate diagnosis and treatment.

Dose escalation of once weekly oral vinorelbine concurrent with weekly split dose hypofractionated chest radiation for palliation of advanced non-small cell lung cancer: a phase I/II study.

INTRODUCTION: Daily chest radiation schedules can be cumbersome for some patients and could also delay the administration of higher, systemic doses of chemotherapy. METHODS: Thirty-six patients with advanced non-small cell lung cancer (stages IIIB and IV) were treated using a once weekly hypofractionated chest irradiation schedule (5 Gy divided in 2 fractions 6 hours apart × 12 weeks), concurrently with escalating doses of oral vinorelbine. RESULTS: The maximum tolerated dose of vinorelbine was 80 mg/m; 28 patients were treated at 70 mg/m(2). Dose-limiting toxicity was hematopoietic. A mean of 8.5 cycles per patient was administered, with 53% receiving all 12 cycles. Median overall survival was 9.9 months (95% confidence interval, 5.6-14.2 months). Within the radiation field, 1 patient (4%) had a complete response, 13 (54%) a partial response, and 10 (42%) had stable disease. Nine patients could be assessed for disease outside the radiation field, of whom 7 had stable disease and 2 progressed. CONCLUSIONS: Weekly, hypofractionated chest radiation is well tolerated and can be administered safely concurrently with vinorelbine at systemic doses. This simplified, convenient regimen could benefit patients in need for both local and systemic palliation.

Once-weekly, high-dose stereotactic body radiotherapy for lung cancer: 6-year analysis of 60 early-stage, 42 locally advanced, and 7 metastatic lung cancers.

PURPOSE: To explore once-weekly stereotactic body radiotherapy (SBRT) in nonoperable patients with localized, locally advanced, or metastatic lung cancer. METHODS AND MATERIALS: A total of 102 primary (89 untreated plus 13 recurrent) and 7 metastatic tumors were studied. The median follow-up was 38 months, the average patient age was 75 years. Of the 109 tumors studied, 60 were Stage I (45 IA and 15 IB), 9 were Stage II, 30 were Stage III, 3 were Stage IV, and 7 were metastases. SBRT only was given in 73% (40 Gy in four fractions to the planning target volume to a total dose of 53 Gy to the isocenter for a biologically effective dose of 120 Gy(10)). SBRT was given as a boost in 27% (22.5 Gy in three fractions once weekly for a dose of 32 Gy at the isocenter) after 45 Gy in 25 fractions to the primary plus the mediastinum. The total biologically effective dose was 120 Gy(10). Respiration gating was used in 46%. RESULTS: The overall response rate was 75%; 33% had a complete response. The overall response rate was 89% for Stage IA patients (40% had a complete response). The local control rate was 82%; it was 100% and 93% for Stage IA and IB patients, respectively. The failure rate was 37%, with 17% within the planning target volume. No Grade 3-4 acute toxicities developed in any patient; 12% and 7% of patients developed Grade 1 and 2 toxicities, respectively. Late toxicity, all Grade 2, developed in 3% of patients. The 5-year cause-specific survival rate for Stage I was 70% and was 74% and 64% for Stage IA and IB patients, respectively. The 3-year Stage III cause-specific survival rate was 30%. The patients with metastatic lung cancer had a 57% response rate, a 27% complete response rate, an 86% local control rate, a median survival time of 19 months, and 23% 3-year survival rate. CONCLUSIONS: SBRT is noninvasive, convenient, fast, and economically attractive; it achieves results similar to surgery for early or metastatic lung cancer patients who are older, debilitated, and with comorbidities. Elderly patients and/or patients medically unfit for combined modality therapy with locally advanced disease can find an effective palliative alternative in SBRT.

Atención psicosocial integral en enfermedad catastrófica (Atinar) / Integrative Psychosocial Care in Catastrophic Illness

La enfermedad médico-quirúrgica catastrófica (EMQ-C) se define como una enfermedad aguda o prolongada, usualmente considerada como amenazante para la vida o con el riesgo de dejar discapacidad residual importante. La EMQ-C , a menudo, conlleva trastornos psicosociales que afectan de manera importante su evolución, porque alteran el proceso de rehabilitación, los hábitos saludables y la calidad de vida y, además, limitan la adherencia al tratamiento. Por lo tanto, para ofrecer un tratamiento a la persona quien la padece, es necesario desarrollar modelos que permitan identificar y tratar integralmente todos los aspectos médicos, psicológicos y sociales. La legislación colombiana, desde la aprobación de la Ley 100 de 1993, reglamentó la atención integral de la EMQ-C. No obstante, el desarrollo de programas de atención integral que incluyan lo psicosocial ha sido lento. Se presenta un modelo teórico de atención psicosocial integral en EMQ-C, que sigue los lineamientos de la medicina biopsicosocial de Ángel, junto a un modelo denominado medicina cognitiva , desarrollado previamente por uno de los autores (HR). El modelo incluye aspectos y procedimientos necesarios para su funcionamiento ajustado a la ley colombiana.

Medical Surgical Catastrophic Illness (MSIC) is defined as an acute or chronic lifethreatening disease or with risk of important disability. MSI-C is frequently associated with Psychosocial Disorders influencing the outcome due to effects on the rehabilitation process, quality of life and compliance. The development of integrative models of care that cover medical, psychological and social aspects is necessary in order to offer treatment to the person with MSI-C. Since Law 100 of 1993 was passed, Colombia ruled an integrative model of care for catastrophic illness. Noteworthy, implementation of these programs has been slow. In this article a theoretical model of integrative psychosocial care that follows recommendations of Engel's Biopsychosocial Model and the Cognitive Medicine model developed by one of the authors (HR). The model includes necessary aspects and procedures for its implementation according to Colombian Law.

Preparation and characterization of a monoclonal antibody specific to Plasmodium falciparum TATA binding protein.

PfTBP is a transcriptional factor required by all three types of RNA polymerases in eukaryotic cells. In order to obtain a specific monoclonal antibody (MAb) against PfTBP, a DNA fragment of 684 base pairs (bp) that contained the complete PfTBP gene was amplified by polymerase chain reaction (PCR) and inserted into the pGEX prokaryotic expression vector. The recombinant protein (GST-PfTBP) was expressed in Escherichia coli, purified, and used as antigen to immunize mice. MAbs against PfTBP were obtained and hybridomas were screened by enzyme-linked immunosorbent assay (ELISA). Western blotting and immunofluorescence assays showed that MAb Pf.r1 recognized the PfTBP protein in nuclear extracts from Plasmodium falciparum as well as a native protein in the nuclei of this parasite. This MAb will be a helpful tool for the identification of the TBP associated factors (TAFs), which are apparently highly divergent with other eukaryotes. This information could help to identify new candidate gene products to develop novel drugs or vaccines.

Telomeric heterochromatin propagation and histone acetylation control mutually exclusive expression of antigenic variation genes in malaria parasites.

Malaria parasites use antigenic variation to avoid immune clearance and increase the duration of infection in the human host. Variation at the surface of P. falciparum-infected erythrocytes is mediated by the differential control of a family of surface antigens encoded by var genes. Switching of var gene expression occurs in situ, mostly from telomere-associated loci, without detectable DNA alterations, suggesting that it is controlled by chromatin structure. We have identified chromatin modifications at telomeres that spread far into telomere-proximal regions, including var gene loci (>50 kb). One type of modification is mediated by a protein homologous to yeast Sir2 called PfSir2, which forms a chromosomal gradient of heterochromatin structure and histone hypoacetylation. Upon activation of a specific telomere-associated var gene, PfSir2 is removed from the promoter region and acetylation of histone occurs. Our data demonstrate that mutually exclusive transcription of var genes is linked to the dynamic remodeling of chromatin.

Recombinant and native Plasmodium falciparum TATA-binding-protein binds to a specific TATA box element in promoter regions.

RNA polymerase II promoters in Plasmodium spp., like in most eukaryotes, have a bipartite structure. However, the identification of a functional TATA box located within the Plasmodium spp. core promoters has been difficult, mainly because of its high A+T content. Only few putative trans-acting elements have been identified in the malaria parasite genome such as a gene orthologous to the TATA box binding protein (PfTBP). In this study, we demonstrate that PfTBP is part of the DNA-protein complexes formed in the kahrp and gbp-130 gene promoter regions. Supershift and footprinting assays performed with a GST-PfTBP fusion protein showed that PfTBP associates with a consensus TATA box sequence located 81 base pairs upstream of the transcription start site in the kahrp promoter region and with a TATA box-like (TGTAA) sequence at position -186 of the gbp-130 gene promoter region. Chromatin immunoprecipitation assays confirmed that native PfTBP is able to associate in vivo with both TATA box elements. This is the first study that reports the identification of cis-acting sequences (TATAA and TGTAA) and their corresponding trans-acting (PfTBP) factor in P. falciparum.

Dose escalation of docetaxel concomitant with hypofractionated, once weekly chest radiotherapy for non-small-cell lung cancer: a phase I study.

Hypofractionated chest radiotherapy has been used as an alternative when standard fractionated schedules are neither practical nor feasible. To explore docetaxel as radiosensitizer in a hypofractionated chest irradiation schedule, a docetaxel dose escalation study was conducted in which 26 patients with advanced non-small-cell lung cancer (NSCLC) (stages III and IV) were enrolled. Docetaxel was administered 24 hours prior to irradiation (starting dose 10mg/m2; escalating in 5mg/m2 increments). Radiation was administered at 500 cGy (one fraction) once/wk for 10 consecutive weeks (5000 cGy total). The docetaxel dose was escalated up to 45 mg/m2/wk. The treatment was well tolerated over 10 consecutive weeks without requiring dose reductions or interruptions. Toxicities were mainly docetaxel related. One of 19 evaluable patients had a complete radiographic response within the radiation treatment port, 13 had a partial response, and 5 had stable disease. No patient recurred within the radiation field. Three patients who underwent surgical resection following treatment were pathologically down staged to stage I. This trial of a small group of patients supports, in selected patients, synchronous administration of effective hypofractionated, radiosensitized radiation therapy and optimized systemic chemotherapy.

Intento de suicidio en niños menores de 14 años atendidos en el Hospital Universitario del Valle, Cali / Attempted suicide in children lower 14 years old in Hospital University from Valle del Cauca

Objetivos. Describir las características biopsicosociales de los menores de 14 años con intento de suicidio, los métodos utilizados, las características psicológicas y la estructura y dinámica de las familias de origen. Materiales y métodos. Estudio clínico descriptivo de menores de 14 años que consulta al Hospital Universitario del Valle por intento suicida en el período octubre 1 de 2001 a septiembre 30 de 2002; cada menor se evaluó con la aplicación de la historia toxicológica o de trauma, historia clínica psiquiátrica, el Child Behavior Checklists (CBCL), prueba de la figura humana y de la familia, la Escala Revisada de Inteligencia de Wechsler para Niños (WISC-R), y una entrevista semi-estructurada de evaluación familiar. Resultados. Consultaron 18 menores de edad; 2 mujeres menores fallecieron y de los restantes, sólo 8 menores (7 mujeres y 1 hombre) aceptaron participar. El envenenamiento autoinfringido por ingestión de sustancias es el método suicida más utilizado y además más frecuente en mujeres; todos tienen enfermedad mental asociada; la mitad un retardo mental. La mayoría presenta compromiso de la atención, comportamientos violentos, disociales, delictivos, aislamiento, etc. Como características psicológicas predominantes está perturbación en el ámbito sexual, represión emocional, negación de la situación penosa y agresividad, además de disfunción familiar severa en todos los casos. Conclusiones. Las características biopsicosociales encontradas coinciden con las descritas previamente en la literatura pero se requieren investigaciones adicionales que validen los hallazgos

Uso de drogas entre estudiantes de Cali, Colombia / Drug use among students in Cali, Colombia

The use of alcohol, tobacco, marihuana, cocaine, and bazuco was examined in a cross-sectional study or a random sample of 512 secondary-school students enrolled in public and private schools in Cali, Colombia. The overall prevalence of use for any of these substances was 59.38 percent in the public schools and 36.96 percent in the private schools (z = 4.6, P 0.05). The probability of finding an alcohol user was about 55.26 percent. The frequency of use for all the substances was 18.9 percent in the public schools and 7.46 percent in the private ones. Experience with marihuana, cocaine and bazuco was more frequent in the public schools. The average ages of users (19.91 years) was higher than that of non-users, (16.25 years): t = 8.34, P 0.05. Students in the public schools with a family history of mental illness had almost a ninefold greater risk of being substance users (RR = 8.84, IC 95 percent = 1.22-3.37); among students in the private schools, having personal conflicts with authority figures (teachers and the police) was a significant risk factor (RR = 2.03, IC 95 percent = 1.22-3.37)

Uso de drogas entre estudiantes de Cali, Colombia / Drug use among students in Cali, Colombia

The use of alcohol, tobacco, marihuana, cocaine, and bazuco was examined in a cross-sectional study or a random sample of 512 secondary-school students enrolled in public and private schools in Cali, Colombia. The overall prevalence of use for any of these substances was 59.38 percent in the public schools and 36.96 percent in the private schools (z = 4.6, P 0.05). The probability of finding an alcohol user was about 55.26 percent. The frequency of use for all the substances was 18.9 percent in the public schools and 7.46 percent in the private ones. Experience with marihuana, cocaine and bazuco was more frequent in the public schools. The average ages of users (19.91 years) was higher than that of non-users, (16.25 years): t = 8.34, P 0.05. Students in the public schools with a family history of mental illness had almost a ninefold greater risk of being substance users (RR = 8.84, IC 95 percent = 1.22-3.37); among students in the private schools, having personal conflicts with authority figures (teachers and the police) was a significant risk factor (RR = 2.03, IC 95 percent = 1.22-3.37)

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