Mutations in the John Cunningham virus VP1 gene could predispose to the development of progressive multifocal leukoencephalopathy in multiple sclerosis patients undergoing treatment with natalizumab.

BACKGROUND: Patients with Multiple Sclerosis (MS) undergoing treatment with natalizumab (NTZ) are at risk of developing progressive multifocal leukoencephalopathy (PML) due to the reactivation of John Cunningham (JC) virus. A relevant characteristic among PML cases is the development of single nucleotide mutations in the VP1 gene of the causal JC virus. The identification of such mutations in timely manner can provide valuable information for MS management. OBJECTIVE: To identify mutations along the JC virus VP1 gene in MS patients undergoing treatment with NTZ, and correlate them with anti-JC virus antibody index. METHODS: Eighty-eight MS patients, one hundred twenty controls, and six patients with diagnosis of Human Immunodeficiency Virus (HIV) with and without secondary PML were included. JC virus was identified in peripheral blood mononuclear cells and cerebrospinal fluid by PCR. Amplification and sequencing of the entire length of the VP1 gene were performed in all positive clinical samples. RESULTS: In MS cases no mutations were observed in the JC virus VP1 gene, but it was positive in HIV controls with PML. Interestingly, the JC virus VP1 gene sequence derived from the HIV patients exhibited a non-silent substitution in position 186 (G â†’ C), leading to an amino acid change (Lys â†’ Asp). We did not find correlation between anti-JC virus antibody index and DNA viral detection. CONCLUSIONS: . The identification of single nucleotide mutants in the JC virus VP1 gene might be an early predictive marker to PML for efficient patient treatment and follow-up.

Mre11 complex and DNA replication: linkage to E2F and sites of DNA synthesis.

We show that the Mre11 complex associates with E2F family members via the Nbs1 N terminus. This association and Nbs1 phosphorylation are correlated with S-phase checkpoint proficiency, whereas neither is sufficient individually for checkpoint activation. The Nbs1 E2F interaction occurred near the Epstein-Barr virus origin of replication as well as near a chromosomal replication origin in the c-myc promoter region and was restricted to S-phase cells. The Mre11 complex colocalized with PCNA at replication forks throughout S phase, both prior to and coincident with the appearance of nascent DNA. These data suggest that the Mre11 complex suppresses genomic instability through its influence on both the regulation and progression of DNA replication.

Respiratory sinus arrhythmia in growth restricted fetuses with normal Doppler hemodynamic indices.

BACKGROUND: The autonomic behavior of growth-restricted fetuses at different evolving hemodynamic stages has not been fully elicited. AIM: To analyze the respiratory sinus arrhythmia (RSA) of growth-restricted fetuses that despite this severe condition show normal Doppler hemodynamics. SUBJECTS: 10 growth-restricted fetuses (FGR group) with normal arterial pulsatility indices (umbilical, uterine, middle cerebral, ductus venosus and aortic isthmus), and 10 healthy fetuses (Control group), 32-37weeks of gestation. METHOD: B-mode ultrasound images for visualizing fetal breathing movements (FBM) or breathing akinesis (FBA), and the simultaneous RR-interval time series from maternal abdominal ECG recordings were obtained. The root-mean-square of successive differences of RR-intervals (RMSSD) was considered as a RSA-related parameter among the instantaneous amplitude of the high-frequency component (AMPHF) and its corresponding instantaneous frequency (IFHF), both computed by using empirical mode decomposition. Mean fetal heart-periods and RSA-related parameters were assessed during episodes of FBM and FBA in 30s length windows. RESULTS: FGR and Control groups presented RSA-related fluctuations during FBM and FBA. Also, both groups showed significant higher (p<0.001) values for the mean heart-period, RMSSD and AMPHF during FBM. No-significant differences (p>0.05) were found for the IFHF regardless of breathing activity (FBM vs. FBA). CONCLUSION: Growth-restricted fetuses without evident hemodynamic compromise exhibit a preserved autonomic cardiovascular regulation, characterized by higher values of RSA and mean heart-period in the presence of FBM. This physiological response reflects a compensatory strategy that may contribute to preserve blood flow redistribution to vital organs.

Alteration of N-terminal phosphoesterase signature motifs inactivates Saccharomyces cerevisiae Mre11.

Saccharomyces cerevisiae Mre11, Rad50, and Xrs2 function in a protein complex that is important for nonhomologous recombination. Null mutants of MRE11, RAD50, and XRS2 are characterized by ionizing radiation sensitivity and mitotic interhomologue hyperrecombination. We mutagenized the four highly conserved phosphoesterase signature motifs of Mre11 to create mre11-11, mre11-2, mre11-3, and mre11-4 and assessed the functional consequences of these mutant alleles with respect to mitotic interhomologue recombination, chromosome loss, ionizing radiation sensitivity, double-strand break repair, and protein interaction. We found that mre11 mutants that behaved as the null were sensitive to ionizing radiation and deficient in double-strand break repair. We also observed that these null mutants exhibited a hyperrecombination phenotype in mitotic cells, consistent with previous reports, but did not exhibit an increased frequency of chromosome loss. Differential ionizing radiation sensitivities among the hypomorphic mre11 alleles correlated with the trends observed in the other phenotypes examined. Two-hybrid interaction testing showed that all but one of the mre11 mutations disrupted the Mre11-Rad50 interaction. Mutagenesis of the phosphoesterase signatures in Mre11 thus demonstrated the importance of these conserved motifs for recombinational DNA repair.

[The quality of the discharge reports from the internal medicine services of Castilla-La Mancha (a structural evaluation)]. / Calidad de los informes de alta de los Servicios de Medicina Interna de Castilla-La Mancha (valoración de la estructura).

UNLABELLED: The discharge report is one of the final outputs of the health care activity. We have tried to analyze several aspects related to its quality. For this purpose, we conducted a cross-sectional study analyzing 800 reports of patients admitted in the services of Internal Medicine at 6 hospitals of Castilla-La Mancha during the year 1991. We must stress the absence of discharge reports for death patients and the failure to record drug allergies (69.9%), medical history (10.4%) and time of evolution of the disease (16.9%), as well as treatment in 17 reports out of 781 and follow-up review after discharge in 12.8%. CONCLUSIONS: Discharge reports have a low scientific content and the production of this type of records is not a routine practice in the case of death patients.

[Quality of discharge reports prepared by the services of internal medicine in Castilla-La Mancha (assessment of clinical data)]. / Calidad de los informes de alta de Castilla-La Mancha en los servicios de medicina interna (valoración de la información clínica).

We analyzed several aspects of the quality (at the level of clinical data) of discharge reports prepared by the Services of Internal Medicine in the hospitals of Castilla-La Mancha, taking into account that these are the end written products of the health care activity. We analyzed 800 reports and we found terms such as "probably, not discarded" in the clinical judgment in 150 reports out of 794 and abbreviations in 370 out of 792. 10.8% of the reports written at discharge (86 out of 794) were waiting for the results, reflecting thus severe shortcomings in the clinical data of these reports, that must be corrected in our area.

Automatic Segmentation of the Cerebellum in Ultrasound Volumes of the Fetal Brain / Segmentación automática del cerebelo en volúmenes de ultrasonido del cerebro fetal

The size of the cerebellum in ultrasound volumes of the fetal brain has shown a high correlation with gestational age, which makes it a valuable feature to detect fetal growth restrictions. Manual annotation of the 3D surface of the cerebellum in an ultrasound volume is a time consuming task, which needs to be performed by a highly trained expert. In order to assist the experts in the evaluation of cerebellar dimensions, we developed an automatic scheme for the segmentation of the 3D surface of the cerebellum in ultrasound volumes, using a spherical harmonics model. In this work we present our validation results on 10 ultrasound volumes in which we have obtained an adequate accuracy in the segmentation of the cerebellum (mean Dice coefficient of 0.689). The method reported shows potential to effectively assist the experts in the assessment of fetal growth in ultrasound volumes.

El tamaño del cerebelo, en un volumen de ultrasonido del cerebro fetal, ha mostrado una alta correlación con la edad gestacional, lo que hace importante a esta medición para la detección de restricciones del crecimiento del feto. La anotación manual de la superficie 3D del cerebelo en un volumen de ultrasonido es una tarea demandante, que debe ser realizada por un experto. Con el propósito de apoyar a los expertos en la evaluación de las dimensiones del cerebelo fetal, hemos desarrollado un método automático para la segmentación de la superficie 3D del cerebelo en volúmenes de ultrasonido, utilizando un modelo de harmónicos esféricos (spherical harmonics). En este trabajo presentamos los resultados de una evaluación del método automático en 10 volúmenes de ultrasonido con los que hemos obtenido un valor adecuado de exactitud (coeficiente promedio de Dice de 0.689). El método reportado tiene potencial para asistir de manera efectiva a los expertos en la evaluación del crecimiento fetal, utilizando volúmenes de ultrasonido.

Autopercepción de la imagen corporal en estudiantes universitarios de Chile y Panamá / Body image perception in university students from Chile and Panama

Objetivo: Determinar la concordancia entre el estado nutricional y la percepción de la imagen corporal en universitarios chilenos y panameños. Métodos: Estudio observacional transversal en 792 estudiantes de ambos sexos, de 18 a 30 años de edad de la Universidad Santo Tomás de Vina del Mar en Chile, la Universidad Autónoma de Chile y la Universidad Latinoamericana de Ciencia y Tecnología (ULACIT) de Panamá. Se determinó el IMC real y el IMC percibido y luego éstos fueron comparados. Resultados: De 792 estudiantes evaluados, 480 eran de Chile (51,4% mujeres) y 312 de Panamá (56,7% mujeres). El IMC percibido por los chilenos fue mayor al real, en hombres y mujeres (60%); en cambio, los panameños presentan una sobreestimación menor al 50% en ambos sexos. En ambos países y para ambos sexos el porcentaje de estudiantes que se perciben igual es similar (20%). Hay concordancia diagnóstica entre el IMC y la imagen corporal en la mitad de los alumnos chilenos y en un tercio de las alumnas, pero la mejor concordancia se observó en personas con sobrepeso (69% y 90,5% respectivamente). En los panameños se observó concordancia diagnóstica de 40% en varones y 19,2% en mujeres; la mejor concordancia se observó en hombres con sobrepeso (83%). Conclusión: En los estudiantes con normopeso de ambos países existe una tendencia a sobreestimar el peso, mientras que por el contrario los obesos tienden a subestimarlo.

Objective: To determine the association between nutritional status and body image perception among university students from Chile and Panamá. Methods: An observational cross-sectional study was conducted among 792 students of both sexes, ages 18 to 30 years, from University Santo Tomás of Viña del Mar, Chile, University Autónoma of Chile and University Latinoamericana de Ciencia y Tecnología (ULACIT) of Panama. We determined the real BMI and the perceived BMI. Afterward, the two were compared to each other. Results: In a sample of 792 students, 480 from Chile (51,4% females) and 312 from Panamá (56,7% females), the perceived BMI is higher than the real one in the Chileans, men and women (60%). Instead, in Panamá the over-estimation is less than 50% in both sexes. The percentage is the same in both countries and both sexes that perceive themselves as they really are (20%). There is concordance between BMI and body image in half of Chilean men and a third of Chilean women. However, a better concordance is observed in overweight students (69% in men, 90,5% in women). In Panamanians, there is a concordance observed of40% in men and 19,9% in women. Conclusion: There is a tendency for overestimation in normal weight students of both countries. However the obese students tended to underestimate their weight.

[Training and use of dental manpower resources in Mexico]. / Formación y utilización de recursos humanos odontológicos en México.

The introductory section describes the general situation of dental care in Mexico, analyzes the prevailing service model (including the kind of work done by the dental professional and the technology he employs), and briefly reviews the evolution of dentistry in the country. There follows an account of a series of new approaches to service and manpower training in experimental implementation since 1972 in the stomatology curriculum at the Xochimilco campus of the Metropolitan Autonomous University, at the National School of Professional Studies at Zaragoza, in the School of Dentistry of Nuevo León Autonomous University, Monterrey, and in the Dental Services at Ciudad Netzahualcóyotl. In each case, the background, characteristics, and objectives of the programs, and their evolution and prospects are described.

Assembly of RecA-like recombinases: distinct roles for mediator proteins in mitosis and meiosis.

Members of the RecA family of recombinases from bacteriophage T4, Escherichia coli, yeast, and higher eukaryotes function in recombination as higher-order oligomers assembled on tracts of single-strand DNA (ssDNA). Biochemical studies have shown that assembly of recombinase involves accessory factors. These studies have identified a class of proteins, called recombination mediator proteins, that act by promoting assembly of recombinase on ssDNA tracts that are bound by ssDNA-binding protein (ssb). In the absence of mediators, ssb inhibits recombination reactions by competing with recombinase for DNA-binding sites. Here we briefly review mediated recombinase assembly and present results of new in vivo experiments. Immuno-double-staining experiments in Saccharomyces cerevisiae suggest that Rad51, the eukaryotic recombinase, can assemble at or near sites containing ssb (replication protein A, RPA) during the response to DNA damage, consistent with a need for mediator activity. Correspondingly, mediator gene mutants display defects in Rad51 assembly after DNA damage and during meiosis, although the requirements for assembly are distinct in the two cases. In meiosis, both Rad52 and Rad55/57 are required, whereas either Rad52 or Rad55/57 is sufficient to promote assembly of Rad51 in irradiated mitotic cells. Rad52 promotes normal amounts of Rad51 assembly in the absence of Rad55 at 30 degrees C but not 20 degrees C, accounting for the cold sensitivity of rad55 null mutants. Finally, we show that assembly of Rad51 is induced by radiation during S phase but not during G(1), consistent with the role of Rad51 in repairing the spontaneous damage that occurs during DNA replication.

The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response.

Nijmegen breakage syndrome (NBS) is an autosomal recessive disorder characterized by increased cancer incidence, cell cycle checkpoint defects, and ionizing radiation sensitivity. We have isolated the gene encoding p95, a member of the hMre11/hRad50 double-strand break repair complex. The p95 gene mapped to 8q21.3, the region that contains the NBS locus, and p95 was absent from NBS cells established from NBS patients. p95 deficiency in these cells completely abrogates the formation of hMre11/hRad50 ionizing radiation-induced foci. Comparison of the p95 cDNA to the NBS1 cDNA indicated that the p95 gene and NBS1 are identical. The implication of hMre11/hRad50/p95 protein complex in NBS reveals a direct molecular link between DSB repair and cell cycle checkpoint functions.

4-Ethoxycarbonyl-3-hydroxy-3-phenylcyclohexanone.

The title compound, ethyl 2-hydroxy-4-oxo-2-phenylcyclohexanecarboxylate, C(15)H(18)O(4), was obtained by a Michael-Aldol condensation and has the cyclohexanone in a chair conformation. The attached hydroxy, ethoxycarbonyl and phenyl groups are disposed in beta-axial, beta-equatorial and alpha-equatorial configurations, respectively. An intermolecular hydrogen bond, with an O.O distance of 2.874 (2) A, links the OH group and the ring carbonyl. Weak intermolecular C-H.O=C (ester and ketone), O-H.O=C (ketone) and C-H.OH hydrogen bonds exist.

2,9-bis(3-nitrophenyl)-1-azaadamantan-4-one.

The title compound, 2,9-bis(3-nitrophenyl)-1-azatricyclo[3.3.1.1(3,7)]decan-4-one, C21H19N3O5, has a tricyclic structure. The torsion angles may be used to describe the relationship of the carbonyl group to the adjacent faces, whereby it is seen that the angles on the face of the arylpiperidinone side [122.0 (3) and -122.0 (3) degrees ] are greater than those on the cyclohexanone side [-119.8 (4) and 119.9 (4) degrees ]. Although these differences may explain a facial selectivity during nucleophilic addition to the carbonyl group, the presence of the aryl rings is probably also important.