Molecular mechanisms of cell death induced in glioblastoma by experimental and antineoplastic drugs: New and old drugs induce apoptosis in glioblastoma.

Glioblastoma multiforme (GBM) is one of the most aggressive astrocytic tumors; it is resistant to most chemotherapeutic agents currently available and is associated with a poor patient survival. Thus, the development of new anticancer compounds is urgently required. Herein, we studied the molecular mechanisms of cell death induced by the experimental drugs resveratrol and MG132 or the antineoplastic drugs cisplatin and etoposide on a human GBM cell line (D54) and on primary cultured mouse astrocytes (PCMAs). Caspases, Bcl-2, inhibitors of apoptosis proteins (IAP) family members, and p53 were identified as potential molecular targets for these drugs. All drugs had a cytotoxic effect on D54 cells and PCMAs, with a similar inhibitory concentration (IC50) after 24 h. However, MG132 and cisplatin were more effective to induce apoptosis and autophagy than resveratrol and etoposide. Cell death by apoptosis involved the activation of caspases-3/7, -8, and -9, increased lysosomal permeability, LC3 lipidation, poly-(ADP-ribose) polymerase (PARP)-1 fragmentation, and a differential expression of genes related with apoptosis and autophagy like Mcl-1, Survivin, Noxa, LC3, and Beclin. In addition, apoptosis activation was partially dependent on p53 activation. Since experimental and antineoplastic drugs yielded similar results, further work is required to justify their use in clinical protocols.

Acceptability and experience of supportive companionship during childbirth in Malawi.

OBJECTIVE: To study the acceptability and experience of supportive companionship during childbirth by mothers, health professionals and supportive companions. DESIGN: Cross-sectional surveys before and after introducing supportive companionship. SETTING: Maternity facilities in Blantyre City, Malawi. POPULATION: Mothers who had normal deliveries before discharge from hospital, health professionals in health facilities and women from the community, who had given birth before and had interest in providing or had provided support to fellow women during childbirth. METHODS: Combined qualitative and quantitative methods. MAIN OUTCOME MEASURE: Perceptions on labour companionship among participants. RESULTS: The majority of supported women (99.5%), companions (96.6%) and health professionals (96%) found the intervention beneficial, mainly for psychological and physical support to the labouring woman and for providing assistance to healthcare providers. Some companions (39.3%) unwillingly accompanied the women they were supporting and 3.5% of companions mentioned that their presence in the labour ward was an opportunity for them to learn how to conduct deliveries. CONCLUSION: Supportive companionship for women during childbirth is highly acceptable among mothers and health professionals, and the community in Malawi, but should be governed by clear guidelines to avoid potential harm to labouring women. Women require information regarding the need for a supportive companion and their expected role before they present at a health facility in labour. Such notification will provide an opportunity for the pregnant woman to identify someone of their choice who is ready and capable of safely taking up the role of a companion.

[Attention deficit disorder and hyperactivity: a pattern of evolution?]. / Trastorno por déficit de atención/hiperactividad: un patrón evolutivo?

INTRODUCTION: When the frequency of a gene in the general population exceeds 1%, is not considered a random mutation but a mutation that has been positively selected during evolution. The high prevalence of attention deficit/hyperactivity disorder (ADHD) from 5-10% and its association with the seven-repeat allele of DRD4, which is positively selected in evolution, raising the possibility that ADHD increases the reproductive fitness of the individual and/or group. One of the main characteristics of ADHD is its diversity and is a well recognized fact that diversity confers many benefits to a population (eg. immunity). DEVELOPMENT: This article discusses the various studies that support this hypothesis and offers further explanations on the prevalence, age distribution and sex distribution of the severity and heterogeneity of ADHD. CONCLUSION: It is possible that the presence of altered gene combinations, as in ADHD, can bring concrete benefits to society but are detrimental to the individual.

Maternal exposure to floricultural work during pregnancy, PON1 Q192R polymorphisms and the risk of low birth weight.

BACKGROUND: Although there is evidence from animal studies of impaired reproductive function by exposure to organophosphates (OP), the effects on birth weight have not been sufficiently evaluated in epidemiological studies. Paraoxonase (PON1) detoxifies organophosphates by cleavage of active oxons. Some PON1 gene polymorphisms could reduce the enzyme activity and increase susceptibility to OP toxicity. OBJECTIVE: To assess the association between maternal exposure to floriculture during pregnancy and the risk of low birth weight (<2500 g) in their offspring, as well as to evaluate the interaction between this exposure and maternal genotype for PON1 Q192R polymorphisms. MATERIALS AND METHODS: A cross sectional study was carried out in two Mexican states (States of Mexico and Morelos) with high frequencies of greenhouse activity. We interviewed and collected blood samples from 264 females (floriculturists or partners of floricultural workers) who became pregnant during the 10 years prior to the interview. The questionnaire measured socioeconomic characteristics, tobacco and alcohol consumption, diseases and occupational and reproductive history. We also applied a food frequency questionnaire. Information was obtained pertaining to 467 pregnancies. DNA was extracted from white cells, and PON1 genotype was determined by Restriction Fragment Length Polymorphism for Q192R polymorphisms. Results were analyzed with generalized estimating equations models. RESULTS: After adjusting for potential confounders, we detected a statistically significant interaction between maternal exposure to flower growing work during pregnancy and PON1 Q192R polymorphisms on risk of low birth weight. The risk of having a baby with LBW is nearly six times higher if a mother is a floriculture worker during pregnancy and has PON1 192RR genotype (OR 5.93, 95% CI 1.28, 27.5). CONCLUSION: These results suggest that the interaction between maternal floriculture work during pregnancy and 192RR PON1 genotype increases the probability of having children with LBW.

¿Cuál es la combinación de síntomas según padres y maestros más fiable para el diagnóstico de TDAH? / What combination of symptoms according to parents and teachers would be more reliable for the diagnosis of ADHD?

Introducción: El método politético, recogido en el Manual Diagnóstico y Estadístico de los Trastornos Mentales-IV, es el que se plantea tradicionalmente para el diagnóstico de los trastornos por déficit de atención e hiperactividad (TDAH). Sin embargo, es probable que este procedimiento, que conlleva establecer cualquier combinación de 6 ítems, no sea el más adecuado para establecer un diagnóstico de TDAH y que las diferentes combinaciones de ítems tengan desigual peso. Objetivo: Determinar qué combinaciones de ítems de las escalas de inatención e hiperactividad-impulsividad de DuPaul, para padres y maestros, son las más efectivas a la hora de diagnosticar o descartar un TDAH. Resultados: No todas las combinaciones de ítems de padres y maestros obtuvieron el mismo valor predictivo. Todas ellas ofrecieron altos grados de especificidad, pero bajos grados de sensibilidad; es decir, las combinaciones resultaron más efectivas y confiables para descartar este tipo de trastornos que a la hora de diagnosticarlos. Discusión: El método que implica establecer combinaciones de los ítems mejores predictores del TDAH ofreció superiores resultados que los del método politético. No obstante, se requieren futuros estudios con muestras que posean tasas base más elevadas para obtener datos más fiables. Asimismo, sería conveniente emplear un método alternativo para la selección de los sujetos participantes que permita comprobar, posteriormente, la eficacia diagnóstica pura de los diferentes ítems de las escalas de clasificación de los TDAH (AU)

Introduction: The polythetic method used in the DSM is the one proposed traditionally for the diagnosis of Attention Disorders with or without Hyperactivity (ADHD). However, it is possible that the approach which aggregates any combination of 6 items won’t be the optimal method to establish a diagnosis of ADHD, and that the different combinations may not be the same as regards to their ability to predict ADHD. Aim: Determine which combinations of items of DuPaul's inattention and hyperactivity-impulsivity scales (from parent and teacher versions), are the most effective to predict or rule out a diagnosis of ADHD. Results: Not every combination of items from parents and teachers obtained the same predictive value. All of them offered high levels of specificity, but had low sensivity; that is to say, the combinations were more effective and reliable for ruling out the disorder than predicting it. Conclusions: Data show that not every combination of ADHD items has the same predictive value and, therefore, the well-known polythetic method is disputable. The highest predictive value combinations, limitations of the study, and future lines of investigation are analyzed (AU)

[What combination of symptoms according to parents and teachers would be more reliable for the diagnosis of ADHD?]. / ¿Cuál es la combinación de síntomas según padres y maestros más fiable para el diagnóstico de TDAH?

INTRODUCTION: The polythetic method used in the DSM is the one proposed traditionally for the diagnosis of Attention Disorders with or without Hyperactivity (ADHD). However, it is possible that the approach which aggregates any combination of 6 items won't be the optimal method to establish a diagnosis of ADHD, and that the different combinations may not be the same as regards to their ability to predict ADHD. AIM: Determine which combinations of items of DuPaul's inattention and hyperactivity-impulsivity scales (from parent and teacher versions), are the most effective to predict or rule out a diagnosis of ADHD. RESULTS: Not every combination of items from parents and teachers obtained the same predictive value. All of them offered high levels of specificity, but had low sensivity; that is to say, the combinations were more effective and reliable for ruling out the disorder than predicting it. CONCLUSIONS: Data show that not every combination of ADHD items has the same predictive value and, therefore, the well-known polythetic method is disputable. The highest predictive value combinations, limitations of the study, and future lines of investigation are analyzed.

[Oppositional defiant disorder: aspects related to sex differences and informant]. / Trastorno negativista desafiante: aspectos relacionados con el sexo y el evaluador.

INTRODUCTION: Oppositional defiant disorder (ODD) is one of the most common externalizing disorders in childhood. ODD prevalence global rates vary from 2% to 16%. Along with conduct disorder and attention deficit disorder, ODD is one of the leading reasons for referral to neuropediatric and psychiatric services. Even though ODD has recognized clinical importance, key aspects of its conceptualization and prevalence in childhood and adolescence remain uncertain. DEVELOPMENT: We examine previous research findings of ODD prevalence and analyze sex differences and differences according to informants. CONCLUSIONS: ODD prevalence rates present high variability. A number of studies suggest that ODD is more common in boys than in girls. Nevertheless, some authors point that this sex differences may be due to methodological bias. We recommend the validation of an ODD scale that has into consideration the following aspects: level of the subject's development (age), gender and environment.

Trastorno negativista desafiante: aspectos relacionados con el sexo y el evaluador / Oppositional deflant disorder: aspects related to sex differences and informant

Introducción. El trastorno negativista desafiante (TND) es uno de los trastornos externalizantes más prevalentes, con una tasa global del 2-16%. El TND, junto con el déficit de atención/hiperactividad y el trastorno de conducta, es una de las causas principales de derivación a los servicios especializados de neuropediatría y psiquiatría infantil. Aunque el trastorno tiene una relevancia clínica considerable, existe cierta incertidumbre con relación a los aspectos clave de su conceptualización y prevalencia tanto en la niñez como en la adolescencia. Desarrollo. Se revisan los estudios realizados sobre la prevalencia del TND y se analizan los aspectos relacionados con las diferencias según el sexo y en función del evaluador, debido a que en la actualidad los datos disponibles con relación a estos factores son escasos e inconsistentes. Conclusiones. Los índices de prevalencia del TND presentan una gran variabilidad dependiendo de la metodología utilizada y del evaluador (padres frente a maestros). La mayoría de estudios sugieren que el TND es más común en niños que en niñas, aunque algunos autores señalan que esto puede deberse a ciertos sesgos metodológicos. Se propone validar una escala de TND que tenga en cuenta el nivel de desarrollo del sujeto (edad), sexo y ambiente (AU)

Introduction. Oppositional defiant disorder (ODD) is one of the most common externalizing disorders in childhood. ODD prevalence global rates vary from 2% to 16%. Along with conduct disorder and attention deficit disorder, ODD is one of the leading reasons for referral to neuropediatric and psychiatric services. Even though ODD has recognized clinical importance, key aspects of its conceptualization and prevalence in childhood and adolescence remain uncertain. Development. We examine previous research findings of ODD prevalence and analyze sex differences and differences according to informants. Conclusions. ODD prevalence rates present high variability. A number of studies suggest that ODD is more common in boys than in girls. Nevertheless, some authors point that this sex differences may be due to methodological bias. We recommend the validation of an ODD scale that has into consideration the following aspects: level of the subject’s development (age), gender and environment. (AU)

[Soft neurological signs: are they of any value in the assessment and diagnosis of attention deficit hyperactivity disorder?]. / Signos neurológicos blandos:¿tienen alguna utilidad en la evaluación y diagnósticodel trastorno por déficit de atención/hiperactividad?

INTRODUCTION: The association between difficulties on motor skills, visual-hand coordination and excess motor activity was described previously of being established the attention-deficit/hyperactivity disorder (ADHD) as a diagnostic category. These disorders have been grouped under different terminologies, being one of them the soft neurological signs (SNS). Traditionally, the European scientific community has put more attention on the SNS than the American one. However, nowadays there are a lot of neuropediatrician and community pediatrician that continue to think that those deficits, together with inattention and hyperactivity, form part of the same disorder. DEVELOPMENT: In this article we have tried to do a neurobiological revision of the movement and the possible relationship between motor problems and cognitive processes from different points of view: neuroanatomical, findings on different clinical examination tests and neuropsychological experimental models. CONCLUSION: Most of the revised articles conclude that the SNS prevalence is greater in ADHD children compared with control. Therefore we recommend to include the SNS in the evaluation and diagnosis protocols of these disorders in order to improve the sensitivity and specificity of the diagnosis and to be able to evaluate the real needs of the ADHD patients.

Signos neurológicos blandos: ¿tienen alguna utilidad en la evaluación y diagnóstico del trastorno por déficit de atención/hiperactividad? / Soft neurological signs: are they of any value in the assessment and diagnosis of attention déficit hyperactivity disorder?

Introducción. La asociación entre dificultades en las habilidades motoras, la coordinación visuomanual y el comportamiento sobreactivo fue descrita mucho antes de que se estableciera como categoría diagnóstica el trastorno por déficit de atención/hiperactividad (TDAH). Estas alteraciones se han intentado agrupar bajo diferentes terminologías, siendo una de ellas los signos neurológicos blandos (SNB). Tradicionalmente se ha prestado más atención a los llamados SNB entre la comunidad científica europea que en la americana. En la actualidad, muchos neuropediatras y pediatras del desarrollo continúan considerando que estos déficit, junto con la inatención y la hiperactividad, forman parte de un mismo trastorno. Desarrollo. En este artículo se intenta realizar una revisión neurobiológica del movimiento, de la posible relación entre las alteraciones motoras y los procesos cognitivos desde diferentes perspectivas: neuroanatómica, hallazgos en diferentes test de exploración clínica y modelos experimentales neuropsicológicos. Conclusión. La mayoría de los artículos revisados concluyen que la prevalencia de los SNB es muy superior en los niños con TDAH respecto a los controles, por lo que se recomienda su inclusión en los protocolos de evaluación y diagnóstico de estos trastornos, no sólo para mejorar la sensibilidad y especificidad en el diagnóstico, sino también para poder evaluar cuáles son las necesidades reales de los pacientes con TDAH (AU)

Introduction. The association between difficulties on motor skills, visual-hand coordination and excess motor activity was described previously of being established the attention-deficit/hyperactivity disorder (ADHD) as a diagnostic category. These disorders have been grouped under different terminologies, being one of them the soft neurological signs (SNS). Traditionally, the European scientific community has put more attention on the SNS than the American one. However, nowadays there are a lot of neuropediatrician and community pediatrician that continue to think that those deficits, together with inattention and hyperactivity, form part of the same disorder. Development. In this article we have tried to do a neurobiological revision of the movement and the possible relationship between motor problems and cognitive processes from different points of view: neuroanatomical, findings on different clinical examination tests and neuropsychological experimental models. Conclusion. Most of the revised articles conclude that the SNS prevalence is greater in ADHD children compared with control. Therefore we recommend to include the SNS in the evaluation and diagnosis protocols of these disorders in order to improve the sensitivity and specificity of the diagnosis and to be able to evaluate the real needs of the ADHD patients (AU)

Acute acalculous cholecystitis in patients with acute traumatic spinal cord injury.

Acute acalculous cholecystitis (AAC) is a very serious complication which can be found in patients with multiple serious traumatic lesions ('polytrauma'). Very few patients have been reported in the literature with an acute spinal injury and associated AAC. We report seven patients with polytrauma and acute spinal cord injury who developed AAC. All had no complaint of the principal warning symptom: right upper quadrant abdominal pain. All presented with a palpable mass in this site and the laboratory results were compatible with cholestasis. The diagnosis of AAC was confirmed both by ultra sound and CT scanning. We discuss the possible precipitating factors and the treatment. One hundred and ninety one patients were admitted to the Intensive Care Unit in our Hospital with SCI over a period of 2 years, all of these in the acute stage. AAC was diagnosed in seven patients among them. Our purpose is to call attention to this clinical condition which can complicate the outcome of patients with multiple trauma and acute spinal cord injury. To date AAC in this group of patients has been infrequently described in the available literature.

Karonga lakeshore integrated rural groundwater supply project: village level operation and maintenance; first sociological and technical monitotring report

In 1986 the Government of Malawi; with assistance from the Danish International Development Agency [DANIDA] commenced an integrated rural groundwater supply project in the southern lakeshore part of Karonga District. The project handed over 295 boreholes to communities on 31 March 1991. From that date operation and maintenance will be achieved at village level. This report presents and discusses the findings from sociological and technical monitoring during the first four months of the system's existence