The Structure of Mammalian Prions and Their Aggregates.

Prion diseases, such as Creutzfeldt-Jakob disease in humans, bovine spongiform encephalopathy in cattle, chronic wasting disease in cervids (i.e., deer, elk, moose, and reindeer), and sheep scrapie, are caused by the misfolding of the cellular prion protein (PrPC) into a disease-causing conformer (PrPSc). PrPC is a normal, GPI-anchored protein that is expressed on the surface of neurons and other cell types. The structure of PrPC is well understood, based on studies of recombinant PrP, which closely mimics the structure of native PrPC. In contrast, PrPSc is prone to aggregate into a variety of quaternary structures, such as oligomers, amorphous aggregates, and amyloid fibrils. The propensity of PrPSc to assemble into these diverse forms of aggregates is also responsible for our limited knowledge about its structure. Then again, the repeating nature of certain regular PrPSc aggregates has allowed (lower resolution) insights into the structure of the infectious conformer, establishing a four-rung ß-solenoid structure as a key element of its architecture.

Aneurismas incidentales en el contexto de hemorragias subaracnoideas perimesencefálicas / Incidental aneurysms and perimesencephalic subarachnoid haemorrhages

La hemorragia subaracnoidea perimesencefálica se refiere a la presencia de sangre alrededor del mesencéfalo y angiografía normal, cumpliendo con criterios clínicos y radiológicos bien establecidos. A diferencia de la hemorragia subaracnoidea de causa aneurismática, presenta un buen pronóstico, siendo la recuperación, en la mayoría de los casos, completa y satisfactoria. Por otra parte, entre el 2 y el 5% de la población desarrollará un aneurisma intracraneal en el curso de la vida, la mayoría de ellos asintomáticos, siendo posible encontrar un aneurisma incidental en pacientes que han sufrido una hemorragia perimesencefálica. La importancia de un diagnóstico adecuado regirá la conducta a seguir planteando un reto para los equipos de tratamiento vascular, debiendo analizar pormenorizadamente los hallazgos e individualizando las decisiones terapéuticas (AU)

A perimesencephalic subarachnoid hemorrhage refers to the presence of bleeding around the midbrain with a normal angiography, meeting the well established clinical criteria and radiological criteria. Unlike the aneurysmal subarachnoid hemorrhage, it has a good prognosis, the recovery in most cases being complete and satisfactory. On the other hand, between 2 and 5% of the population will develop an intracranial aneurysm in the course of their life, most of them asymptomatic, with the likelihood of finding an incidental aneurysm in patients who have suffered a perimesencephalic hemorrhage. The importance of a proper diagnosis governs the course to follow, being a challenge for vascular treatment teams who must analyse the findings in detail and individualize treatment decisions (AU)

[Incidental aneurysms and perimesencephalic subarachnoid haemorrhages]. / Aneurismas incidentales en el contexto de hemorragias subaracnoideas perimesencefálicas.

A perimesencephalic subarachnoid hemorrhage refers to the presence of bleeding around the midbrain with a normal angiography, meeting the well established clinical criteria and radiological criteria. Unlike the aneurysmal subarachnoid hemorrhage, it has a good prognosis, the recovery in most cases being complete and satisfactory. On the other hand, between 2 and 5% of the population will develop an intracranial aneurysm in the course of their life, most of them asymptomatic, with the likelihood of finding an incidental aneurysm in patients who have suffered a perimesencephalic hemorrhage. The importance of a proper diagnosis governs the course to follow, being a challenge for vascular treatment teams who must analyse the findings in detail and individualize treatment decisions.

An evaluation of spatio-temporal models for the estimation of the mortality relative risk from breast cancer in Galicia, Spain.

BACKGROUND: Disease mapping is now a big focus of interest in the area of Public Health, and the geographical distribution of a disease has an important role in understanding its origin or its causes. The purpose of this work is to review and evaluate different techniques to map the mortality risk of a disease in small geographical areas. METHODS: Three different methods have been studied. The first one is a classical approach consisting of mapping SMRs, which are maximum likelihood estimates of the relative risk under a Poisson model of death counts. In a second step we consider Poisson and negative binomial regression to fit the rates and finally we use a Bayesian approach that assumes a hierarchical model where the death counts follow a Poisson distribution conditioned by the prior information. These methods have been applied to the study of geographical variation in female breast cancer mortality from 1976 to 1999 in the districts of Galicia, Spain. RESULTS: Mapping the SMRs using the first method has important drawbacks and there are difficulties to distinguish the mortality pattern. With the second method we achieved some improvements. The Bayesian methodology produces smoother maps with a clear mortality pattern. DISCUSSION: These methods are powerful tools for identifying areas with elevated risk. The Bayesian methodology has many advantages over the other methods that had been analysed in this work.

Survival to oral cancer. A study of clinical risk markers with independent prognostic value.

BACKGROUND: The aims of this study have been to describe survival to oral cancer and to identify clinical variables with independent influence on its prognosis before treatment. METHODS: 94 oral cancer patients treated during 1991-99 entered the study. The variables considered were: age, sex, location of the lesion, clinical presentation, symptoms, TNM classification, months elapsed since treatment and ploidy pattern. A descriptive study of the data was performed, along with a survival analysis using Kaplan-Meier curves (log rank test for comparison among curves) and single and multivariate Cox regression. RESULTS: Multivariate analysis recognized a prognostic value for the age of the patient (OR = 1.06; CI95%: 1.02-1.09) and also for tumour size. Tumour stage resulted also selected, but its predictive value was lower than size's, so it was excluded from the predictive model. No statistically significant differences in terms of survival were identified on the rest of variables considered in the study. CONCLUSIONS: This study suggests the need for considering age and tumour size as the most relevant clinical variables for predicting survival to oral cancer at the time of diagnosis.

[Space-time distribution of suicide in Galicia, Spain [1976-1998]]. / Distribución geográfica y temporal del suicidio en Galicia (1976-1998).

OBJECTIVE: To study the space-time distribution of suicide in Galicia from 1976 to 1998, taking into account gender, age, season and method of suicide. METHODS: For each sex crude and age-adjusted rates per province and age-specific rates per period (1978-84, 1985-91, 1992-98) were calculated. To estimate mortality risk and time trends in the municipalities, a Bayesian hierarchical model was used. RESULTS: In the last few years mortality from suicide has increase considerably. Age-adjusted rates of 6 per 105 at the beginning of the study rose to 10 per 105 at the end. The increase was greatest among men. The higher rates were observed in the elderly, although in terms of time trends the highest increase occurred among adolescents and young adults. In both sexes the main method of suicide was hanging. Less common methods were jumping from a height and shooting. The greatest number of suicides took place during the spring and summer months. In terms of spatial distribution, a high number of suicides were committed in the province of Lugo; in the municipalities, mortality risk decreased from North to South and an inverse temporal trend was observed in both sexes. This differed from the space-time patterns of suicides committed using methods other than hanging. CONCLUSIONS: Suicide is an important health problem in Galicia not only because to its magnitude but also because of the increasing rates, especially among young people. Geographical and temporal analysis can identify priority areas where preventive policies should be implemented.

Distribución geográfica y temporal del suicidio en Galicia (1976-1998) / Space-time distribution of suicide in Galicia, Spain [1976-1998]

Objetivo: Estudiar la distribución geográfica y temporal de la mortalidad por suicidio en Galicia desde 1976 a 1998, teniendo en cuenta el sexo, la edad, la estacionalidad y el método empleado. Métodos: Para cada sexo se calcularon las tasas provinciales, brutas y ajustadas por edad y las tasas específicas por edad y período (1978-1984, 1985-1991, 1992-1998). Para la estimación del riesgo y la tendencia temporal en el ámbito municipal se utilizó un modelo jerárquico bayesiano. Resultados: La mortalidad por suicidio aumentó considerablemente en los últimos años, pasando de tasas ajustadas en torno al 6 por 105 en los primeros años de estudio a tasas del 10 por 105 en los últimos, siendo este aumento más acentuado en los varones. Las tasas más elevadas se observan en edades avanzadas, aunque al valorar la tendencia temporal, los mayores incrementos se presentan en adolescentes y adultos jóvenes. El principal método de suicidio, tanto en varones como en mujeres, ha sido el ahorcamiento, seguido a gran distancia por la caída de lugar elevado y el uso de armas de fuego. Los meses con mayor número de suicidios corresponden a la primavera y el verano. En cuanto a la (..) (AU)

Objective: To study the space-time distribution of suicide in Galicia from 1976 to 1998, taking into account gender, age, season and method of suicide. Methods: For each sex crude and age-adjusted rates per province and age-specific rates per period (1978-84, 1985-91,1992-98) were calculated. To estimate mortality risk and time trends in the municipalities, a Bayesian hierarchical model was used. Results: In the last few years mortality from suicide has increase considerably. Age-adjusted rates of 6 per 105 at the beginning of the study rose to 10 per 105 at the end. The increase was greatest among men. The higher rates were observed in the elderly, although in terms of time trends the highest increase occurred among adolescents and young adults. In both sexes the main method of suicide was hanging. Less common methods were jumping from a height and shooting. The greatest number of suicides took place during the spring (..) (AU)

Reporting delay: a review with a simulation study and application to Spanish AIDS data.

To correct for the effect of reporting delay on incidence data relating to AIDS, three methods of estimation have been analysed: Poisson log-linear; log-linear logistic mixed regression (log-logit), and truncation. The first two methods transform the data in a contingency table. The difference between them is the hypothesis of delay stationarity, which is only assumed by the former. A correction is proposed for the first method to improve its asymptotic properties. The truncation method is based on the product-limit estimator. A simulation study was carried out to examine the behaviour (means, variances and mean squared errors) of the three methods. All were applied to data from the National Commission on AIDS (Spain), showing an improvement in reporting efficiency.

[Descriptive study of suicide in Galicia, 1987]. / Estudio descriptivo do suicidio en Galicia, 1987.

Deaths caused by suicide in Galicia during 1987 are studied, in order to identify high incidence areas where further studies could be designed to define specific factors for suicide. Three hundred and three death certificates and their corresponding judicial reports in the subgroup E950-959 of the International Classification of Diseases (ICD-9) were processed. Suicide rate in Galicia was found to be 10.65 per 100,000 inhabitants, with 5,313 Years of Potential Life Lost. The suicide rate in the province of Coruña was the highest (12.79 per 100,000 inhabitants) and, within it, the Narón area reached the highest rate (35.40 deaths per 100,000 inhabitants). Male to female ratio was 3.7. Mean age at suicide was 52.8 (sigma = 18.8), the range being 14-90 years. The age distribution was concentrated at older ages, especially among women, who contributed to a higher number of deaths by suicide on sundays and first days of the week. Hanging was the method chosen in 66% of deaths. We conclude that Galicia has a high mortality due to suicide, especially in the industrial area where the economic crisis is more pronounced.

[The quality of mortality statistics. Galicia 1987]. / Aproximación a calidade das estadísticas de mortalidade. Galicia 1987.

We intend to study the reliability of the mortality statistics in Galicia (1987), comparing the basic cause of death, with that we obtain by the Autopsy Report (AR). After independently studying 90 AR, three physicians selected the basic cause of death, subsequently coded by the same team. All this persons were blind in relation with the previous certification. 41.1% of the causes of death agreed in 4 digit, 45.6% agreed in 3 digit and the 63.3% remained in the same ICD-9 group. Taking into account all the mistakes found, the 13.3% took place due to an incomplete definition, but the classification remained correct. The 10.0% due to an error in the logic sequence, the 15.6% by an error in the selection of the cause of death and, in the 20.0% there was no relationship between causes. For cardiovascular diseases, the Predictive Positive Value (PPV) was 76.9%, the Sensibility (S) was 83.0% and the Specificity (Sp) 90.9%. For the tumors, the value of the PPV and the S was 73.7% and the Sp was 92.9%. In spite of selection bias because of the method used, we think that the information produced is useful for evaluating the quality of mortality statistics in Galicia. When comparing our results with similar studies, we find an acceptable level.

[Morbidity, vaccine coverage and immunity against measles, mumps and rubella in a Gallician population from 2 to 5 years old]. / Morbilidad, cobertura vacunal e immunidad frente a sarampión, parotiditis y rubéola en una población gallega de dos a cinco años.

Vaccine coverage, morbidity prevalence, and immunity to measles, rubella, and mumps, were estimated in 1985-1986 among a sample of 2 to 5 years old Galician children, studied through questionnaires and immunoenzymatic determinations of antibodies. According to the mothers, measles vaccine and measles-mumps-rubella vaccine were administered to 22.1% and 45.7%, respectively, of their children, whereas measles were reported in 17.9, mumps in 14.3%, and rubella in 2.9%. The seroconversion to rubella (50.7%) resulted significantly lower (p less than 0.001) than that to measles (75%) or mumps (68.6%). The three types of antibodies were found altogether in 32.1% of the subjects, and 5% of them showed none of these antibodies. The analysis of the serologic data stresses the need for reaching rapidly higher vaccination rates.