Intra-dialytic intracranial pressure monitoring in a patient with lumbo-peritoneal shunt for idiopathic intracranial hypertension.

We present the case of a 25-year-old female with End-Stage Renal Disease (ESRD) and Idiopathic Intracranial Hypertension (IIH) who developed severe headaches during haemodialysis (HD). The headaches resolved several hours after each HD session. We were able to diagnose dialysis disequilibrium syndrome (DDS) following intracranial pressure (ICP) monitoring and use a novel strategy to treat her symptoms.

Variation in training requirements within general surgery: comparison of 23 countries.

Background: Many differences exist in postgraduate surgical training programmes worldwide. The aim of this study was to provide an overview of the training requirements in general surgery across 23 different countries. Methods: A collaborator affiliated with each country collected data from the country's official training body website, where possible. The information collected included: management, teaching, academic and operative competencies, mandatory courses, years of postgraduate training (inclusive of intern years), working-hours regulations, selection process into training and formal examination. Results: Countries included were Australia, Belgium, Canada, Colombia, Denmark, Germany, Greece, Guatemala, India, Ireland, Italy, Kuwait, the Netherlands, New Zealand, Russia, Saudi Arabia, South Africa, South Korea, Sweden, Switzerland, UK, USA and Zambia. Frameworks for defining the outcomes of surgical training have been defined nationally in some countries, with some similarities to those in the UK and Ireland. However, some training programmes remain heterogeneous with regional variation, including those in many European countries. Some countries outline minimum operative case requirement (range 60-1600), mandatory courses, or operative, academic or management competencies. The length of postgraduate training ranges from 4 to 10 years. The maximum hours worked per week ranges from 38 to 88 h, but with no limit in some countries. Conclusion: Countries have specific and often differing requirements of their medical profession. Equivalence in training is granted on political agreements, not healthcare need or competencies acquired during training.

Antecedentes: Existen muchas diferencias entre los programas de formación quirúrgica de posgrado del mundo. El objetivo de este estudio fue proporcionar una visión general de los requisitos formativos en cirugía general en 23 países diferentes. Métodos: En cada uno de los países participantes, un colaborador recopiló datos de la página web del organismo oficial encargado de la formación, si era posible. La información incluyó: gestión, formación, competencias académicas y operatorias, cursos obligatorios, años de formación de postgrado (que incluía el período de internado), regulaciones sobre las horas de trabajo, proceso de selección para la formación y existencia de un examen final. Resultados: Se incluyeron los datos de Australia, Bélgica, Canadá, Colombia, Dinamarca, Alemania, Grecia, Guatemala, India, Irlanda, Italia, Kuwait, Países Bajos, Nueva Zelanda, Rusia, Arabia Saudita, Sudáfrica, Corea del Sur, Suecia, Suiza, Reino Unido, Estados Unidos de América y Zambia. En algunos países existen los marcos normativos para definir los resultados del programa de formación, con ciertas semejanzas a los del Reino Unido e Irlanda. Sin embargo, algunos programas de formación, incluso en muchos países europeos, son muy heterogéneos con variaciones regionales. Pocos países describen el número mínimo de procedimientos quirúrgicos (rango 60 a 1.600), los cursos obligatorios o competencias quirúrgicas, académicos o de gestión exigidos. La duración de la formación postgraduada osciló de los 4 a los 10 años. El número de horas trabajadas máximas por semana oscilaron entre 38 y 88, sin límite en algunos países. Conclusión: Cada país tiene unos requisitos específicos, a menudo diferentes, para la formación de sus médicos. La convalidación se otorga por acuerdos políticos, más que por las necesidades médicas o por las competencias adquiridas durante la formación.

Defective positioning in granulomas but not lung-homing limits CD4 T-cell interactions with Mycobacterium tuberculosis-infected macrophages in rhesus macaques.

Protection against Mycobacterium tuberculosis (Mtb) infection requires CD4 T cells to migrate into the lung and interact with infected macrophages. In mice, less-differentiated CXCR3+ CD4 T cells migrate into the lung and suppress growth of Mtb, whereas CX3CR1+ terminally differentiated Th1 cells accumulate in the blood vasculature and do not control pulmonary infection. Here we examine CD4 T-cell differentiation and lung homing during primary Mtb infection of rhesus macaques. Mtb-specific CD4 T cells simultaneously appeared in the airways and blood ∼21-28 days post exposure, indicating that recently primed effectors are quickly recruited into the lungs after entering circulation. Mtb-specific CD4 T cells in granulomas display a tissue-parenchymal CXCR3+CX3CR1-PD-1hiCTLA-4+ phenotype. However, most granuloma CD4 T cells are found within the outer lymphocyte cuff and few localize to the myeloid cell core containing the bacilli. Using the intravascular stain approach, we find essentially all Mtb-specific CD4 T cells in granulomas have extravasated across the vascular endothelium into the parenchyma. Therefore, it is unlikely to be that lung-homing defects introduced by terminal differentiation limit the migration of CD4 T cells into granulomas following primary Mtb infection of macaques. However, intralesional positioning defects within the granuloma may pose a major barrier to T-cell-mediated immunity during tuberculosis.

Towards high-resolution laser ionization spectroscopy of the heaviest elements in supersonic gas jet expansion.

Resonant laser ionization and spectroscopy are widely used techniques at radioactive ion beam facilities to produce pure beams of exotic nuclei and measure the shape, size, spin and electromagnetic multipole moments of these nuclei. However, in such measurements it is difficult to combine a high efficiency with a high spectral resolution. Here we demonstrate the on-line application of atomic laser ionization spectroscopy in a supersonic gas jet, a technique suited for high-precision studies of the ground- and isomeric-state properties of nuclei located at the extremes of stability. The technique is characterized in a measurement on actinium isotopes around the N=126 neutron shell closure. A significant improvement in the spectral resolution by more than one order of magnitude is achieved in these experiments without loss in efficiency.

Significados y vivencias en pacientes adultos sometidos a cirugía bariátrica / Meanings and experiences in adult patients under going bariatric surgery

Introduction: Obesity is a public health problem and Chile prevalence has increased in recent years, showing a higher percentage of overweight in adult men and of obesity in adult women. In this context, bariatric surgery appears to be a feasible, alternative. Objective: To describe meanings and experiences of adult patients who have undergone bariatric surgery in private clinics. Method: A qualitative approach based on Grounded Theory was used. The sample selection was made trough key informants and snowball, and was composed of 8 women and 3 men. To collect data semi-structured in depth interviews were used, and data analysis was performed trough open coding. Results: Three categories emerge from descriptive analysis: 1) Motivations and expectations regarding bariatric surgery; 2) Experiences in relation to overweight, and 3) Experiences in relation to food. Conclusions: Further investigation is needed from the subjectivity of the patients themselves, given the impact that obesity and bariatric surgery hason people’s lives.

Introducción: La obesidad es un problema de salud pública y en Chile ha ido en aumento en los últimos años, observándose mayor porcentaje de sobrepeso en adultos hombres y de obesidad en adultas mujeres. En este contexto, la cirugía bariátrica surge como posible alternativa. Objetivo: Describir los significados y vivencias de pacientes adultos que han sido sometidos a cirugía bariátrica en clínicas privadas. Método: Se usó un enfoque cualitativo, basado en la Teoría Fundamentada. La selección de la muestra se realizó a través de informantes clave y bola de nieve, y quedó conformada por 8 mujeres y 3 hombres. Para recoger los datos se utilizaron entrevistas en profundidad semi-estructuradas, y para el análisis se usó la codificación abierta. Resultados: Del análisis descriptivo se obtuvieron tres categorías: 1) Motivaciones y expectativas en relación a la cirugía bariátrica; 2) Vivencias en relación al sobrepeso, y 3) Vivencias en relación a la comida. Conclusiones: Es necesario continuar investigando desde la subjetividad de los propios pacientes dado el impacto que la obesidad y la cirugía bariátrica tienen en la vida de las personas.

Patrón adaptativo obesogénico cerebral: una propuesta para comprender y evaluar la obesidad en la práctica clínica / Adaptative obesogenic brain pattern: a proposal for understanding and assessing obesity in clinical practice

Obesity appears to be a complex condition. Current treatments are based on simple models of input and output power with regular short-term results. It is possible that changing the model of understanding long-term, better results are achieved. Neurobiological research proposes to consider the existence of an Adaptative Obesogenic Pattern (AOP) where the functioning of the nervous system is organized to increase intake. AOP is proposed as an early and maladaptive response establishing that the reward systems can modulate the axis HPA (hypothalamic pituitary adrenal axis) in the absence of sufficient social regulation. This would facilitate the reverberation of the reward system by exposing it to addictions. Based on the failure of integration between axis HPA a model is presented. Child and adolescent observational grid is proposed to evaluate AOP during the current clinical interview.

La obesidad parece ser una condición compleja. Los tratamientos actuales se basan en modelos simples de entrada y salida de energía con regulares resultados a corto plazo. Es posible que cambiando el modelo de comprensión se logren resultados a más estables en el tiempo. A través de la neurobiología se propone considerar la posible existencia de un patrón adaptativo obesogénico (PAO) donde el funcionamiento del Sistema Nervioso se organizaría tempranamente aumentando la ingesta como principal regulador del estrés. Se propone el PAO como un modelo de comprensión basado en la falla de integración precoz entre los diversos sistemas que regulan el eje HPA. Sería una respuesta maladaptativa establecida tempranamente que liga preferentemente los sistemas de recompensa a la modulación del eje HPA (hipotálamo-pituitaria-adrenal) en ausencia de suficiente regulación social y que podría explicar la obesidad temprana infantil. Se propone una forma para evaluarlo basada en la observación de la relación madre-hijo en la consulta clínica habitual.

Endocrine differentiation of fetal ovaries and testes of the spotted hyena (Crocuta crocuta): timing of androgen-independent versus androgen-driven genital development.

Female spotted hyenas (Crocuta crocuta) have an erectile peniform clitoris and a pseudoscrotum but no external vagina, all established by day 35 of a 110-day gestation. Recent studies indicate that these events are androgen-independent, although androgen secretion by fetal ovaries and testis was hypothesized previously to induce phallic development in both sexes. We present the first data relating to the capacity of the ovaries and testes of the spotted hyena to synthesize androgens at different stages of fetal life. Specifically, spotted hyena fetal gonads were examined by immunohistochemistry at GD 30, 45, 48, 65, and 95 for androgen-synthesizing enzymes, as related to the morphological development. Enzymes included 17alpha-hydroxylase/17,20-lyase cytochrome P450 (P450c17), cytochrome b5, 3beta-hydroxysteroid dehydrogenase (3betaHSD), and cholesterol side-chain cleavage cytochrome P450 (P450scc). Anti-Müllerian-hormone (AMH) expression was also examined. AMH was strongly expressed in fetal Sertoli cells from GD 30 and after. P450c17 expression was detected in Leydig cells of developing testes and surprisingly in Müllerian duct epithelium. Fetal ovaries began to organize and differentiate by GD 45, and medullary cells expressed P450c17, cytochrome b5, 3betaHSD, and P450scc. The findings support the hypothesis that external genital morphology is probably androgen-independent initially, but that fetal testicular androgens modify the secondary, male-specific phallic form and accessory organs. Fetal ovaries appear to develop substantial androgen-synthesizing capacity but not until phallic differentiation is complete, i.e. after GD 45 based on circulating androstenedione concentrations. During late gestation, fetal ovaries and testes synthesize androgens, possibly organizing the neural substrates of aggressive behaviors observed at birth in spotted hyenas. These data provide an endocrine rationale for sexual dimorphisms in phallic structure and reveal a potential source of androgenic support for neonatal aggression in female and male C. crocuta.

Gonadotropin-inhibitory hormone in Gambel's white-crowned sparrow (Zonotrichia leucophrys gambelii): cDNA identification, transcript localization and functional effects in laboratory and field experiments.

The neuropeptide control of gonadotropin secretion is primarily through the stimulatory action of the hypothalamic decapeptide, GnRH. We recently identified a novel hypothalamic dodecapeptide with a C-terminal LeuPro-Leu-Arg-Phe-NH2 sequence in the domestic bird, Japanese quail (Coturnix japonica). This novel peptide inhibited gonadotropin release in vitro from the quail anterior pituitary; thus it was named gonadotropin-inhibitory hormone (GnIH). GnIH may be an important factor regulating reproductive activity not only in domesticated birds but also in wild, seasonally breeding birds. Thus, we tested synthetic quail GnIH in seasonally breeding wild bird species. In an in vivo experiment, chicken gonadotropin-releasing hormone-I (cGnRH-I) alone or a cGnRH-I/quail GnIH cocktail was injected i.v. into non-breeding song sparrows (Melospiza melodia). Quail GnIH rapidly (within 2 min) attenuated the GnRH-induced rise in plasma LH. Furthermore, we tested the effects of quail GnIH in castrated, photostimulated Gambel's white-crowned sparrows (Zonotrichia leucophrys gambelii), using quail GnIH or saline for injection. Again, quail GnIH rapidly reduced plasma LH (within 3 min) compared with controls. To characterize fully the action of GnIH in wild birds, the identification of their endogenous GnIH is essential. Therefore, in the present study a cDNA encoding GnIH in the brain of Gambel's white-crowned sparrow was cloned by a combination of 3' and 5' rapid amplification of cDNA ends and compared with the quail GnIH cDNA previously identified. The deduced sparrow GnIH precursor consisted of 173 amino acid residues, encoding one sparrow GnIH and two sparrow GnIH-related peptides (sparrow GnIH-RP-1 and GnIH-RP-2) that included Leu-Pro-Xaa-Arg-Phe-NH2 (Xaa=Leu or Gln) at their C-termini. All these peptide sequences were flanked by a glycine C-terminal amidation signal and a single basic amino acid on each end as an endoproteolytic site. Although the homology of sparrow and quail GnIH precursors was approximately 66%, the C-terminal structures of GnIH, GnIH-RP-1 and GnIH-RP-2 were all identical in two species. In situ hybridization revealed the cellular localization of sparrow GnIH mRNA in the paraventricular nucleus (PVN) of the hypothalamus. Immunohistochemical analysis also showed that sparrow GnIH-like immunoreactive cell bodies and terminals were localized in the PVN and median eminence respectively. Thus, only the sparrow PVN expresses GnIH, which appears to be a hypothalamic inhibitory factor for LH release, as evident from our field injections of GnIH into free-living breeding white-crowned sparrows. Sparrow GnIH rapidly (within 2 min) reduced plasma LH when injected into free-living Gambel's white-crowned sparrows on their breeding grounds in northern Alaska. Taken together, our results indicate that, despite amino acid sequence differences, quail GnIH and sparrow GnIH have similar inhibitory effects on the reproductive axis in wild sparrow species. Thus, GnIH appears to be a modulator of gonadotropin release.

Differential mechanisms for regulation of the stress response across latitudinal gradients.

We examined plasticity of the stress response among three populations of the white-crowned sparrow (Zonotrichia leucophrys). These populations breed at different elevations and latitudes and thus have breeding seasons that differ markedly in length. We hypothesize that in populations where birds raise only one or rarely two broods in a season, the fitness costs of abandoning a nest are substantially larger than in closely related populations that raise up to three broods per season. Thus individuals with short breeding seasons should be less responsive to stressors and therefore less likely to abandon their young. In our study, baseline and handling-induced corticosterone levels were similar among populations, but corticosteroid-binding globulins differed, leading to a direct relationship between stress-induced free corticosteroid levels and length of breeding season. There were also population-specific differences in intracellular low-affinity (glucocorticoid-like) receptors in both liver and brain tissue. Although investigations of population-based differences in glucocorticoid secretion are common, this is the first study to demonstrate population-level differences in binding globulins. These differences could lead to dramatically different physiological and behavioral responses to stress.

Case of interstitial 12q deletion in association with Wilms tumor.

A 14-month-old boy presenting with Wilms tumor (WT) was found to have a small de novo deletion of the long arm of chromosome 12 (12q11-12q13.11). Microsatellite analysis of this region from constitutional DNA showed that the paternal allele was absent between the markers D12S331 and D12S1713 (inclusive). In the WT there was no evidence of loss of the maternal chromosome. Constitutional chromosome abnormalities can often point to the presence of genes that are important in disease, and the deletion of chromosome 12 in this patient may indicate a gene involved in WT. To determine whether a WT predisposition locus exists at 12q we examined the region in two familial Wilms tumor (FWT) pedigrees unlinked to the known FWT genes on chromosomes 17q (FWT1), 19q (FWT2), and 11p (WT1). In both families WT did not segregate with chromosome 12q markers located within the deletion boundaries.

In vivo platelet activation in atherothrombotic stroke is not determined by polymorphisms of human platelet glycoprotein IIIa or Ib.

Platelet membrane glycoprotein polymorphisms are candidate risk factors for thrombosis, but epidemiological data are conflicting. Thus, demonstration of a genotype-dependent alteration in function is desirable to resolve these inconsistencies. We investigated in vivo platelet activation in acute thrombosis and related this to platelet genotype. Frequencies of the 1b and 2b alleles of the HPA 1a/1b and HPA 2a/2b platelet glycoprotein polymorphisms were determined in 150 (52 men/98 women, mean age 58.3 years) patients with atherothrombotic stroke, and the influence of genotype on markers of platelet activation was assessed. Platelet P-selectin (CD62P) expression and fibrinogen binding was measured using whole blood flow cytometry within 24 h of stroke and 3 months later in 77 patients who provided a repeat blood sample. Results were compared with matched controls. Neither the 1b allele [allele frequency 0.11 vs. 0.13, odds ratio (OR) confidence interval (CI) 0.8 (0.5-1.3)] nor the 2b allele [0.09 vs. 0.07, OR (CI) 1.4 (0.8-2.4)] was significantly over-represented in patients. Increased numbers of activated platelets were found following stroke (acute mean P-selectin expression 0.64% vs. control 0.35%, P < 0.001; acute mean fibrinogen binding 1.6% vs. control 0.9%, P < 0.001). Activation persisted in the convalescent phase (P < 0.001 and P = 0.005 vs. controls for P-selectin and fibrinogen respectively). Expression of P-selectin and fibrinogen was not influenced by either the HPA 1a/1b genotype (P > 0.95 for each marker, Scheffe's test) or the 2a/2b genotype (P > 0.95 for each). Although persisting platelet activation is seen in atherothrombotic stroke, it is independent of HPA 1a/1b and 2a/2b genotypes. These data suggest an underlying prothrombotic state, but do not support the polymorphisms studied as risk factors for thrombotic stroke in this population.

Gastric tube graft interposition as an oesophageal substitute.

BACKGROUND: Use and techniques of oesophageal replacement for long gap oesophageal atresia are still evolving. Gastric tube graft interposition as an oesophageal substitute was evaluated on an animal model. METHODS: Twenty-three postweaned, 28-day-old-piglets were used as the experimental animals. Isoperistaltic gastric tube interposition based on the right gastroepiploic vessels was performed at 28 days of life. Postoperative evaluation included weekly measurement of weight, clinical assessment for gastrointestinal and respiratory complications and deglutition difficulties. Haemoglobin, serum ferritin, albumin, globulins, total proteins and red cell folate were assayed. Pigs were killed and analysed histopathologically following a maximum observation period of 149 days. RESULTS: Growth of the pigs was normal. Deglutition was not impaired in 16 pigs (89%). Minor leak was diagnosed in three pigs (17%), which was successfully managed conservatively. Anastomotic stricture was seen in two pigs (11%). Graft necrosis was not seen. Gross histology showed the absence of hypertrophy, redundancy and kinking of the interposed gastric tube graft. Microscopically non-erosive oesophagitis was seen in three pigs (17%), ulcerative oesophagitis was seen in two pigs (11%) and submucosal fibrosis was seen in seven pigs (39%). Dysplasia or Barrett's oesophagitis was not observed at the end of animal growth. CONCLUSIONS: Gastric tube graft interposition is an immediate ideal oesophageal substitute due to fewer complications, probable absence of gastro-oesophageal reflux in the majority by histology, and absence of dilatation and redundancy of the interpose tube. The oesophageal substitute adequately met the nutritional needs for growth and development in the animal model.

Chemotherapeutic CNS prophylaxis and neuropsychologic change in children with acute lymphoblastic leukemia: a prospective study.

OBJECTIVE: To determine whether prophylactic CNS chemotherapy for childhood acute lymphoblastic leukemia is associated with declines in neuropsychological abilities. METHODS: Growth curve analysis was used to examine neuropsychological outcome and treatment-related change in children (N = 30) who were treated at two childhood cancer centers. A comprehensive test battery was administered at baseline (8 months), 2, 3, and 4 years postdiagnosis (age at diagnosis M = 5.90 years, SD = 4.2C). RESULTS: Results indicated modest declines in arithmetic, visual motor integration, and verbal fluency. Intrathecal and systemic treatment was related to poorer visual motor integration at 4 years postdiagnosis and a faster rate of decline in visual motor integration skills across the observation period than intrathecal treatment alone. Arithmetic proficiency at 4 years after diagnosis was related to maternal education, but the rate of decline was not. Verbal fluency was unrelated to demographic or treatment variables. CONCLUSIONS: These findings suggest that neuropsychological outcome and declines are related to both demographic and treatment characteristics depending on the cognitive domain examined.

Cognitive consequences and central nervous system injury following treatment for childhood leukemia.

OBJECTIVES: To determine the relationship between membrane damage and intellectual and academic abilities in children with acute lymphoblastic leukemia (ALL) and pilot test a math intervention for children with ALL who were affected. DATA SOURCES: Research studies and review articles. CONCLUSIONS: Despite the prophylactic central nervous system (CNS) treatment for long-term disease-free survival, many children with ALL subsequently experience declines in intellectual and academic skills. IMPLICATIONS FOR NURSING PRACTICE: Improving academic abilities in children who have received CNS treatment is of high priority and may have longlasting implications on quality of life.

A rab1 GTPase is required for transport between the endoplasmic reticulum and golgi apparatus and for normal golgi movement in plants.

We describe a green fluorescent protein (GFP)-based assay for investigating membrane traffic on the secretory pathway in plants. Expression of AtRab1b(N121I), predicted to be a dominant inhibitory mutant of the Arabidopsis Rab GTPase AtRab1b, resulted in accumulation of a secreted GFP marker in an intracellular reticulate compartment reminiscent of the endoplasmic reticulum. This accumulation was alleviated by coexpressing wild-type AtRab1b but not AtRab8c. When a Golgi-targeted and N-glycosylated variant of GFP was coexpressed with AtRab1b(N121I), the variant also accumulated in a reticulate network and an endoglycosidase H-sensitive population appeared. Unexpectedly, expression of AtRab1b(N121I), but not of the wild-type AtRab1b, resulted in a reduction or cessation of vectorial Golgi movement, an effect that was reversed by coexpression of the wild type. We conclude that AtRab1b function is required for transport from the endoplasmic reticulum to the Golgi apparatus and suggest that this process may be coupled to the control of Golgi movement.

Telomere sequences at the novel joints of four independent amplifications in Saccharomyces cerevisiae.

Primary gene amplification, the mutation from one copy of a gene per genome to two or more genes per genome is a major mechanism of oncogene overexpression. We previously developed a system in the yeast Saccharomyces cerevisiae to phenotypically detect primary amplifications of a reporter cassette, ADH4:CUP1. We present here the sequence analysis of novel joints from four independent, spontaneous circular amplifications identified by the ADH4:CUP1 system. All four novel joints consist of C(1-3) A telomeric repeats joined to short (14- to 16-bp) CA-rich tracts between ADH4 and the telomere of chromosome VII. In three of the four amplifications, the telomeric sequence and the CA-rich tract that are joined in the amplification are normally located in inverted orientation to each other on chromosome VII. In the fourth amplification, the CA-rich tract on chromosome VII is joined to telomere sequences from another chromosome. We suggest that formation of these amplifications was initiated by recombination between these CA-rich tracts and a telomere. The resulting dicentric chromosome could start a breakage-fusion-bridge cycle that could be resolved by the formation of a circular amplification structure.

Formation of circular amplifications in Saccharomyces cerevisiae by a breakage-fusion-bridge mechanism.

Primary gene amplification, the mutation from one gene copy per genome to two or more copies per genome, is a major mechanism of oncogene overexpression in human cancers. Analysis of the structures of amplifications can provide important evidence about the mechanism of amplification formation. We report here the analysis of the structures of four independent spontaneous circular amplifications of ADH4:CUP1 in the yeast Saccharomyces cerevisiae. The structures of all four amplifications are consistent with their formation by a breakage-fusion-bridge (BFB) mechanism. All four of these amplifications include a centromere as predicted by the BFB model. All four of the amplifications have a novel joint located between the amplified DNA and the telomere, which results in a dicentric chromosome, and is adjacent to all the copies of the amplified DNA as predicted by the BFB model. In addition we demonstrated that two of the amplifications contain most of chromosome VII in an unrearranged form in a 1:1 ratio with the normal copy of chromosome VII, again consistent with the predictions of the BFB model. Finally, all four amplifications are circular, one stable endpoint for molecules after breakage- fusion-bridge.

Technical advance: the DNA-binding activity of gal4 is inhibited by methylation of the gal4 binding site in plant chromatin.

Derivatives of the Saccharomyces cerevisiae transcription factor Gal4 which act as effective transcription activators in yeast, Drosophila, mammalian cells and plant protoplasts are shown to direct expression from a GUS reporter construct when expressed in transgenic tobacco. However, in comparison to 35S-GUS controls, Gal4-mediated expression of the reporter gene was relatively weak and extremely variable. GUS expression was lost as plants matured and it was almost undetectable in most of their progeny. Gal4-mediated gene expression could be restored by treating tissues with 5-aza-cytidine, implicating cytosine methylation in the loss of Gal4-mediated expression. Restoration of reporter expression was not accompanied by an increase in steady-state levels of the activator transcript. We propose that the DNA-binding activity of Gal4 is sensitive to methylation of its binding site in plant chromatin. The Gal4-DNA co-crystal predicts that 5-methylcytosine at either of the outer two positions of the binding site will effectively prevent Gal4 binding. We show that these positions become extensively methylated in transgenic plants and that methylation of Gal4-binding sites interferes with Gal4 binding in vitro. These observations suggest that the Gal4 DNA-binding domain is intrinsically sensitive to cytosine methylation and that, despite the success of Gal4-based expression systems in yeast and Drosophila, Gal4 is not ideal for use in plant gene expression technology.

Review of research studies that evaluated the impact of treatment for childhood cancers on neurocognition and behavioral and social competence: nursing implications.

ISSUES AND PURPOSE: Given the increasing incidence of childhood cancer, increasing survivor rates, and documented incidence of sequelae, nurses need evidence on which to base interventions for families at risk. The authors review and critique research studies that evaluated the impact of treatment for childhood cancers. Implications for nursing practice are discussed. CONCLUSIONS: Research to evaluate the effects of treatment on neurocognition and behavioral and social competency of children with cancer has produced conflicting results. Most studies found deleterious effects on all three areas associated with childhood cancer treatment. Some studies, however, found no differences between childhood cancer survivors and children on therapy compared to normative data or healthy controls. PRACTICE IMPLICATIONS: Knowledge of the short- and long-term impact of treatment for childhood cancer on neurocognition and behavioral and social competence allows nurses to design interventions that mitigate neurocognitive effects, decrease behavioral problems, and improve social competence.