Mapping cumulative compound hydrometeorological and marine-induced risks on the NW Mediterranean coast.

Coastal risks in the Mediterranean are a result of the complex interplay between hydrometeorological and marine hazards. The region encompasses areas with varying degrees of vulnerability to these hazards, as well as spatial variations in exposure values, making it essential to adopt a comprehensive and nuanced approach to risk assessment and management. It is worth noting that hydrometeorological hazards, such as flash floods, can often have a greater impact than strictly coastal hazards, highlighting the need to consider the full range of potential risks. Therefore, coastal managers must adopt a multi-hazard approach to make sound risk management decisions. This study addresses this need using an index-based framework that assesses the integrated risk in time and space (hereafter referred to as cumulative compound risk) in coastal zones by aggregating the main hydrometeorological and marine hazards, the vulnerability of the territory to both types of hazards, and values at exposure. The framework is designed for use at large spatial scales (applied to a 1100 km coastline in this study), with the basic spatial unit being relevant for management (here set as the municipality in this study). Its application enables the assessment of spatial variations in integrated risk as well as individual hydrometeorological and marine contributions. The combined use of the indices and cluster analysis helps identify similarities and differences in the risk profile of spatial units, and thus, define homogeneous areas from a risk management perspective. In this study, the framework was applied to the Spanish Mediterranean coastline, an area representative of the climatic, geomorphological, and socioeconomic conditions of the Mediterranean coast.

Relationship between glucose control, glycemic variability, and oxidative stress in children with type 1 diabetes / Relación entre control metabólico, variabilidad glucémica y estrés oxidativo en niños con diabetes tipo 1

Introduction: Few studies assessing the relationship between oxidative stress and glycemic variability in children with type 1 diabetes mellitus (T1DM) are available, and most of them reported no significant results. Objective: To assess the relationship between glucose control, glycemic variability, and oxidative stress as measured by urinary excretion of 8-iso-prostanglandin F2-alpha (8-iso-PGF2alfa) in children with T1DM. Materials and methods: A cross-sectional study including 25 children with T1DM. Participants were evaluated during five days in two different situations: 1st phase during a summer camp, and 2nd phase in their everyday life at home. The following data were collected in each study phase:. Six capillary blood glucose measurements per day. Mean blood glucose (MBG) levels and glucose variability parameters, including standard deviation, coefficient of variation, and mean amplitude of glycemic excursions (MAGE), were calculated. - Capillary HbA1c level. - 24-h urine sample to measure 8-iso-PGF2alfa. Results: There were no statistically significant differences in urinary 8-iso-PGF2alfa levels (142 ± 37 vs. 172 ± 61 pg/mg creatinine) and glucose control and glycemic variability parameters between both phases. In the 2nd phase, statistically significant correlations were found between urinary 8-iso-PGF2alfa and HbA1c levels (r = 0.53), MBG (r = 0.72), standard deviation (r = 0.49), and MAGE (r = 0.42). No significant correlations between glucose control, glycemic variability and urinary 8-iso-PGF2alfa excretion were found in the 1st phase. Conclusions: A significant correlation was found between glycemic variability and HbA1c level and urinary 8-iso-PGF2α excretion in a group of children with T1DM during their daily lives. Additional studies are needed to confirm this finding and to explore its long-term impact on health

Introducción: En niños con diabetes tipo 1 (DM1) hay pocos estudios que evalúen la relación entre estrés oxidativo y variabilidad glucémica, y la mayoría de ellos no encuentran resultados significativos. Objetivo: Evaluar la relación entre control metabólico, variabilidad glucémica y estrés oxidativo medido por la excreción urinaria de 8-iso-prostaglandina F2 alfa (8-iso-PGF2alfa) en niños con DM1. Material y método: Estudio transversal que incluyó 25 niños con DM1. Los participantes fueron evaluados durante 5 días en 2 situaciones diferentes: 1.a fase durante un campamento de verano y 2.a fase durante su actividad habitual en domicilio. En cada fase se recogieron:- Seis determinaciones de glucemia capilar diarias. Se calcularon glucemia media y parámetros de variabilidad glucémica: desviación estándar, coeficiente de variación y «mean amplitude of glycemic excursions» (MAGE). - HbA1c capilar. - Muestra de orina de 24h para la determinación de 8-iso-PGF2alfa. Resultados: No se encontraron diferencias estadísticamente significativas en excreción urinaria de 8-iso-PGF2alfa (142 ± 37 vs. 172 ± 61 pg/mg creatinina) y parámetros de control y variabilidad glucémicos entre las fases. En la 2.a fase se observaron correlaciones estadísticamente significativas entre 8-iso-PGF2alfa urinario con HbA1c (r = 0,53), glucemia media (r = 0,72), desviación estándar (r = 0,49) y MAGE (r = 0,42). En la 1.a fase del estudio no se han detectado correlaciones significativas. Conclusiones: Se ha encontrado una correlación significativa entre parámetros de variabilidad glucémica y HbA1c con la excreción urinaria de 8-iso-PGF2alfa en un grupo de niños con DM1 evaluados durante su vida diaria. Son necesarios más estudios para confirmar estos resultados y evaluar el impacto a largo plazo sobre la salud

Relationship between glucose control, glycemic variability, and oxidative stress in children with type 1 diabetes.

INTRODUCTION: Few studies assessing the relationship between oxidative stress and glycemic variability in children with type 1 diabetes mellitus (T1DM) are available, and most of them reported no significant results. OBJECTIVE: To assess the relationship between glucose control, glycemic variability, and oxidative stress as measured by urinary excretion of 8-iso-prostanglandin F2-alpha (8-iso-PGF2α) in children with T1DM. MATERIALS AND METHODS: A cross-sectional study including 25 children with T1DM. Participants were evaluated during five days in two different situations: 1st phase during a summer camp, and 2nd phase in their everyday life at home. The following data were collected in each study phase:. - Six capillary blood glucose measurements per day. Mean blood glucose (MBG) levels and glucose variability parameters, including standard deviation, coefficient of variation, and mean amplitude of glycemic excursions (MAGE), were calculated. - Capillary HbA1c level. - 24-h urine sample to measure 8-iso-PGF2α. RESULTS: There were no statistically significant differences in urinary 8-iso-PGF2α levels (142±37 vs. 172±61pg/mg creatinine) and glucose control and glycemic variability parameters between both phases. In the 2nd phase, statistically significant correlations were found between urinary 8-iso-PGF2α and HbA1c levels (r=0.53), MBG (r=0.72), standard deviation (r=0.49), and MAGE (r=0.42). No significant correlations between glucose control, glycemic variability and urinary 8-iso-PGF2α excretion were found in the 1st phase. CONCLUSIONS: A significant correlation was found between glycemic variability and HbA1c level and urinary 8-iso-PGF2α excretion in a group of children with T1DM during their daily lives. Additional studies are needed to confirm this finding and to explore its long-term impact on health.

[Clinical learning strategies among medical students]. / Evaluación de aproximaciones al aprendizaje clínico a través de CEACLIN: Resultados en estudiantes de medicina en una universidad chilena.

BACKGROUND: Throughout medical education, students are gradually incorporated into authentic clinical practice scenarios. AIM: To describe the use of clinical learning strategies by Chilean students and compare them according to sex and year of training. MATERIAL AND METHODS: The Clinical Learning Strategies Questionnaire (CEACLIN) was applied to 336 students from the 4th to 6th year of medicine at a Chilean university. RESULTS: The most frequently reported strategies were related to the search for autonomy, reliable environments for learning, observation of others and attention to emotions. The less frequent was the handling of academic burden. Gender accounted for significant differences in eight of the 11 strategies identified by CEACLIN, while years of training accounted for five of the 11. The cluster analysis identified two groups: the first group comprised nine CEACLIN strategies, with a slightly higher proportion of women and 5th and 6th year students. The second group consisted mainly of men in the 4th year. CONCLUSIONS: Reported strategies include a set of actions oriented to the development of autonomy and confidence through the search for valid information and learning from and with others. These findings are associated with sex and year of training.

[Undergraduate student's perception of clinical simulation workshops: assessment of an instrument]. / Percepción de estudiantes de pregrado de Medicina de talleres de simulación de procedimientos médico-quirúrgicos.

BACKGROUND: Simulation is a useful training tool for undergraduate medical students. A valid instrument is needed to assess students' perception of simulation workshops. AIM: To adapt and validate an instrument to assess the undergraduate medical student's perception of simulation workshops of clinical procedures. MATERIAL AND METHODS: Delphi Methodology was used to adapt the instrument. Exploratory and confirmatory analyses were performed to determine the construct validity and Cronbach's Alpha (0 to 1) for internal consistency of the instrument. RESULTS: A Delphi panel of 10 experts adapted a seven-item questionnaire (Likert scale 1-5; ranging from 7 to 35) and four open-questions. After 3-delphi-rounds, the instrument was administered to 210 students in six simulation training programs (Paracentesis, Cardiopulmonary Resuscitation, Airway management, Sutures, Thoracentesis and Nursing Procedures). The instrument was considered unidimensional in the factorial analysis. The overall median (Q1-Q3) score was 34 ranging from 32 to 35 and the Cronbach Alpha coefficient was 0.72, indicating a good reliability. CONCLUSIONS: The perception questionnaire is a useful and reliable instrument to assess students' perceptions of clinical simulations.

Evaluación de aproximaciones al aprendizaje clínico a través de CEACLIN: Resultados en estudiantes de medicina en una universidad chilena / Clinical learning strategies among medical students

Background: Throughout medical education, students are gradually incorporated into authentic clinical practice scenarios. Aim: To describe the use of clinical learning strategies by Chilean students and compare them according to sex and year of training. Material and Methods: The Clinical Learning Strategies Questionnaire (CEACLIN) was applied to 336 students from the 4th to 6th year of medicine at a Chilean university. Results: The most frequently reported strategies were related to the search for autonomy, reliable environments for learning, observation of others and attention to emotions. The less frequent was the handling of academic burden. Gender accounted for significant differences in eight of the 11 strategies identified by CEACLIN, while years of training accounted for five of the 11. The cluster analysis identified two groups: the first group comprised nine CEACLIN strategies, with a slightly higher proportion of women and 5th and 6th year students. The second group consisted mainly of men in the 4th year. Conclusions: Reported strategies include a set of actions oriented to the development of autonomy and confidence through the search for valid information and learning from and with others. These findings are associated with sex and year of training.

Percepción de estudiantes de pregrado de Medicina de talleres de simulación de procedimientos médico-quirúrgicos / Undergraduate student's perception of clinical simulation workshops: assessment of an instrument

Background: Simulation is a useful training tool for undergraduate medical students. A valid instrument is needed to assess students' perception of simulation workshops. Aim: To adapt and validate an instrument to assess the undergraduate medical student's perception of simulation workshops of clinical procedures. Material and Methods: Delphi Methodology was used to adapt the instrument. Exploratory and confirmatory analyses were performed to determine the construct validity and Cronbach's Alpha (0 to 1) for internal consistency of the instrument. Results: A Delphi panel of 10 experts adapted a seven-item questionnaire (Likert scale 1-5; ranging from 7 to 35) and four open-questions. After 3-delphi-rounds, the instrument was administered to 210 students in six simulation training programs (Paracentesis, Cardiopulmonary Resuscitation, Airway management, Sutures, Thoracentesis and Nursing Procedures). The instrument was considered unidimensional in the factorial analysis. The overall median (Q1-Q3) score was 34 ranging from 32 to 35 and the Cronbach Alpha coefficient was 0.72, indicating a good reliability. Conclusions: The perception questionnaire is a useful and reliable instrument to assess students' perceptions of clinical simulations.

[CEACLIN, an instrument suited to identify medical students' strategies to learn in pre-clerkship years]. / CEACLIN, un instrumento en español para identificar estrategias para el aprendizaje de la clínica de estudiantes de medicina: Desarrollo y validación.

BACKGROUND: Upon the beginning of pre-clerkship years, medical students must develop strategies to learn from experience and to improve their relational skills to communicate with patients. AIM: To develop an instrument to identify the strategies used by medical students to learn in clinical contexts. MATERIAL AND METHODS: Using a Delfi technique to reach consensus, a national panel of students and clinical teachers from 15 Chilean medical schools analyzed an 80-item questionnaire built from perceptions of Chilean students and teachers from one medical school. After two Delfi rounds and a pilot application, a 48-item questionnaire was obtained. Its reliability and construct validity were assessed by Cronbach alpha coefficient and factor analysis, respectively, on the base of an application to 336 medical students. RESULTS: The questionnaire developed, named CEACLIN, is highly reliable (α= 0.84). Its inner structure is made of eleven factors: Autonomy, Solving doubts and problems, Searching and organizing information, Proactivity, Reaching to others, Paying attention and emotions, Searching for trust, Evading burden, Coping with burden, Motivation and Postponing the personal life. All together, these factors account for 47.4 % of the variance. CONCLUSIONS: CEACLIN is a valid, reliable and easy to use instrument suited to identify students' strategies to learn in pre-clerkship years. Many of its items allude to concepts of theories of experiential learning and motivation. We hope that CEACLIN will be of value to medical students and clinical teachers to improve the learning and teaching of clinical reasoning and communication skills.

Estrategias del aprendizaje inicial de la clínica: más allá de los hábitos de estudio. Percepciones de estudiantes y docentes clínicos / Learning during the early clinical years takes more than good study habits: Perceptions of students and teachers

Background: Teaching methods of the undergraduate medical curriculum change considerably from the first years to clinical training. Clinical learning occurs in complex and varied scenarios while caring for patients. Students have to adapt their learning approaches and strategies to be able to integrate theory and clinical practice and become experiential learners. Aim: To identify the strategies used by medical students to learn during the initial clinical years, as reported by students themselves and by their clinical tutors. Material and Methods: We performed eight focus group discussions with 54 students enrolled in years three to six and we interviewed eight clinical tutors. Both focus group discussions and interviews were audio recorded, transcribed and analyzed according to Grounded Theory. Results: Four main themes were identified in the discourse of both students and tutors: Strategies oriented to theoretical learning, strategies oriented to experiential learning, strategies for integrating theory and practice and strategies oriented to evaluation. The mentioning of individual differences was present across the reports of both students and tutors. Conclusions: Students use a rich variety of strategies to face the challenges of clinical learning. Both students and tutors recognize that the learning approaches and strategies vary according the nature of the task and individual differences. The responses of students bring particular knowledge of the approaches used for the theoretical and practical integration and delve into the social dimension of learning.

CEACLIN, un instrumento en español para identificar estrategias para el aprendizaje de la clínica de estudiantes de medicina: Desarrollo y validación / CEACLIN, an instrument suited to identify medical students´ strategies to learn in pre-clerkship years

Background: Upon the beginning of pre-clerkship years, medical students must develop strategies to learn from experience and to improve their relational skills to communicate with patients. Aim: To develop an instrument to identify the strategies used by medical students to learn in clinical contexts. Material and Methods: Using a Delfi technique to reach consensus, a national panel of students and clinical teachers from 15 Chilean medical schools analyzed an 80-item questionnaire built from perceptions of Chilean students and teachers from one medical school. After two Delfi rounds and a pilot application, a 48-item questionnaire was obtained. Its reliability and construct validity were assessed by Cronbach alpha coefficient and factor analysis, respectively, on the base of an application to 336 medical students. Results: The questionnaire developed, named CEACLIN, is highly reliable (α= 0.84). Its inner structure is made of eleven factors: Autonomy, Solving doubts and problems, Searching and organizing information, Proactivity, Reaching to others, Paying attention and emotions, Searching for trust, Evading burden, Coping with burden, Motivation and Postponing the personal life. All together, these factors account for 47.4 % of the variance. Conclusions: CEACLIN is a valid, reliable and easy to use instrument suited to identify students´ strategies to learn in pre-clerkship years. Many of its items allude to concepts of theories of experiential learning and motivation. We hope that CEACLIN will be of value to medical students and clinical teachers to improve the learning and teaching of clinical reasoning and communication skills.

[Learning during the early clinical years takes more than good study habits: Perceptions of students and teachers]. / Estrategias del aprendizaje inicial de la clínica: más allá de los hábitos de estudio. Percepciones de estudiantes y docentes clínicos.

BACKGROUND: Teaching methods of the undergraduate medical curriculum change considerably from the first years to clinical training. Clinical learning occurs in complex and varied scenarios while caring for patients. Students have to adapt their learning approaches and strategies to be able to integrate theory and clinical practice and become experiential learners. AIM: To identify the strategies used by medical students to learn during the initial clinical years, as reported by students themselves and by their clinical tutors. MATERIAL AND METHODS: We performed eight focus group discussions with 54 students enrolled in years three to six and we interviewed eight clinical tutors. Both focus group discussions and interviews were audio recorded, transcribed and analyzed according to Grounded Theory. RESULTS: Four main themes were identified in the discourse of both students and tutors: Strategies oriented to theoretical learning, strategies oriented to experiential learning, strategies for integrating theory and practice and strategies oriented to evaluation. The mentioning of individual differences was present across the reports of both students and tutors. CONCLUSIONS: Students use a rich variety of strategies to face the challenges of clinical learning. Both students and tutors recognize that the learning approaches and strategies vary according the nature of the task and individual differences. The responses of students bring particular knowledge of the approaches used for the theoretical and practical integration and delve into the social dimension of learning.

[Perceptions of students and teachers about clinical medicine learning]. / ¿Cómo aprenden los estudiantes de medicina en la transición hacia el ciclo clínico? Estudio cualitativo de las percepciones de estudiantes y docentes acerca del aprendizaje inicial de la clínica.

BACKGROUND: The transition to the clinical courses represents a major challenge for medical students who are expected to become experiential learners, able to integrate theory and practice in the context of patient care. There are questions about how students face this challenge. AIM: To understand and compare the perceptions of students and clinical tutors on how medical students learn during the transition to the clinical levels of the curriculum. MATERIAL AND METHODS: We performed eight focus group discussions with 54 students enrolled in years three to seven and we interviewed eight clinical tutors. Both students' focus group discussions and tutors' interviews were audio recorded, transcribed and analyzed according to the Grounded Theory. RESULTS: Nine main themes emerged from the analysis of students' opinions and six from the tutors' views. The following themes were common to both students and educators: educational activities, actors, clinical settings, learning strategies, transition markers and tutor's role. Educators emphasized the importance of curricular courses' design and students, that of emotions, adaptation and self-care strategies, and threats to learning. CONCLUSIONS: There is a common core of students' and clinical tutors' perceptions about the relevance of practical activities, social interactions and context in the development of students' learning and adaptation strategies during the transition to the clinical levels of the curriculum. These results are related to social and cultural theories of learning. Thus we propose a model for early clinical learning that might help to stimulate the reflection of students and medical educators regarding clinical learning and contribute to the development of interventions that improve the clinical learning and teaching practices.

]]¿Cómo aprenden los estudiantes de medicina en la transición hacia el ciclo clínico?: Estudio cualitativo de las percepciones de estudiantes y docentes acerca del aprendizaje inicial de la clínica / Perceptions of students and teachers about clinical medicine learning

Background: The transition to the clinical courses represents a major challenge for medical students who are expected to become experiential learners, able to integrate theory and practice in the context of patient care. There are questions about how students face this challenge. Aim: To understand and compare the perceptions of students and clinical tutors on how medical students learn during the transition to the clinical levels of the curriculum. Material and Methods: We performed eight focus group discussions with 54 students enrolled in years three to seven and we interviewed eight clinical tutors. Both students' focus group discussions and tutors' interviews were audio recorded, transcribed and analyzed according to the Grounded Theory. Results: Nine main themes emerged from the analysis of students' opinions and six from the tutors' views. The following themes were common to both students and educators: educational activities, actors, clinical settings, learning strategies, transition markers and tutor's role. Educators emphasized the importance of curricular courses' design and students, that of emotions, adaptation and self-care strategies, and threats to learning. Conclusions: There is a common core of students' and clinical tutors' perceptions about the relevance of practical activities, social interactions and context in the development of students' learning and adaptation strategies during the transition to the clinical levels of the curriculum. These results are related to social and cultural theories of learning. Thus we propose a model for early clinical learning that might help to stimulate the reflection of students and medical educators regarding clinical learning and contribute to the development of interventions that improve the clinical learning and teaching practices.

Gut microbiota in children with type 1 diabetes differs from that in healthy children: a case-control study.

BACKGROUND: A recent study using a rat model found significant differences at the time of diabetes onset in the bacterial communities responsible for type 1 diabetes modulation. We hypothesized that type 1 diabetes in humans could also be linked to a specific gut microbiota. Our aim was to quantify and evaluate the difference in the composition of gut microbiota between children with type 1 diabetes and healthy children and to determine the possible relationship of the gut microbiota of children with type 1 diabetes with the glycemic level. METHODS: A case-control study was carried out with 16 children with type 1 diabetes and 16 healthy children. The fecal bacteria composition was investigated by polymerase chain reaction-denaturing gradient gel electrophoresis and real-time quantitative polymerase chain reaction. RESULTS: The mean similarity index was 47.39% for the healthy children and 37.56% for the children with diabetes, whereas the intergroup similarity index was 26.69%. In the children with diabetes, the bacterial number of Actinobacteria and Firmicutes, and the Firmicutes to Bacteroidetes ratio were all significantly decreased, with the quantity of Bacteroidetes significantly increased with respect to healthy children. At the genus level, we found a significant increase in the number of Clostridium, Bacteroides and Veillonella and a significant decrease in the number of Lactobacillus, Bifidobacterium, Blautia coccoides/Eubacterium rectale group and Prevotella in the children with diabetes. We also found that the number of Bifidobacterium and Lactobacillus, and the Firmicutes to Bacteroidetes ratio correlated negatively and significantly with the plasma glucose level while the quantity of Clostridium correlated positively and significantly with the plasma glucose level in the diabetes group. CONCLUSIONS: This is the first study showing that type 1 diabetes is associated with compositional changes in gut microbiota. The significant differences in the number of Bifidobacterium, Lactobacillus and Clostridium and in the Firmicutes to Bacteroidetes ratio observed between the two groups could be related to the glycemic level in the group with diabetes. Moreover, the quantity of bacteria essential to maintain gut integrity was significantly lower in the children with diabetes than the healthy children. These findings could be useful for developing strategies to control the development of type 1 diabetes by modifying the gut microbiota.

Proliferaciones linforreticulares del pulmón / Pulmonary lymphoproliferative lesions

The present review describes the current classification of the pulmonary lymphoproliferative lesions as proposed by the WHO in 2004 with emphasis in the clinical picture and histopathological features. The definition of these entities includes the clinical picture, histopathology, immunohistochemistry and molecular features. The differential diagnosis of the most important entities is also briefly discussed

En el presente trabajo de revisión se describe la clasificación actual de las lesiones linfoproliferativas del pulmón propuesta por la OMS el año 2004 con énfasis en el cuadro clínico y los aspectos histopatológicos. La definición de estas entidades incluye cuadro clínico, histopatología, inmunohistoquímica y características moleculares. Se discute brevemente el diagnóstico diferencial de las formas más importantes

Handling of clinical tissue specimens for molecular profiling studies.

The relationship between gene expression profiles and cellular phenotypes is an important aspect of functional genomics. Clinical tissue specimens will play a vital role in this effort. The usefulness of tissue for molecular profiling is significantly influenced by the manner of specimen handling. Crucial components of this process include the optimization of the methods of tissue fixation and embedding, not only to obtain excellent histological detail, but also to promote the elucidation of the gene and protein expression profiles. In this article, we describe handling of clinical specimens using whole-mount prostate as an example, the use of new high-throughput techniques that allow molecular profiling analysis and the use of a web-based 3-dimensional model to combine these data to make it available to clinicians and the research community. Complete protocols and additional discussion are available on the website, http://cgap-mf.nih.gov.

Molecular differentiation of high- and moderate-grade human prostate cancer by cDNA microarray analysis.

The prognosis of men with moderate-grade prostate cancer is uncertain. At present, there are few if any reliable molecular markers that can distinguish moderate-grade tumors from those that behave more aggressively. To better understand the molecular basis of human prostate cancer and potentially provide information toward more accurate prognosis, we measured and analyzed gene expression profiles of 13 high- and moderate-grade human prostate tumors using cDNA microarrays. The expression of 136 genes was observed to differ significantly (P < 0.001) between normal prostate and tumors using one-sample t testing and Wilcoxon ranking. Hierarchical clustering of genes demonstrated a relatively similar pattern of differential expression across the tumors. However, importantly, permutation t tests (two-tailed P < 0.001) revealed 21 genes whose expression profiles segregated moderate- and high-grade tumors from each other, which was significantly (P < 0.03) greater than what was expected by chance. These results were compared in silico with prostate cancer profiling efforts performed by other groups, including a meta-analysis of four data sets, which validated many of the dysregulated genes. We suggest that these data provide insight into the molecular nature of clinically aggressive prostate cancer.

Alterations in gene expression profiles during prostate cancer progression: functional correlations to tumorigenicity and down-regulation of selenoprotein-P in mouse and human tumors.

To identify molecular changes that occur during prostate tumor progression, we have characterized a series of prostate cancer cell lines isolated at different stages of tumorigenesis from C3(1)/Tag transgenic mice. Cell lines derived from low- and high-grade prostatic intraepithelial neoplasia, invasive carcinoma, and a lung metastasis exhibited significant differences in cell growth, tumorigenicity, invasiveness, and angiogenesis. cDNA microarray analysis of 8700 features revealed correlations between the tumorigenicity of the C3(1)/Tag-Pr cells and changes in the expression levels of genes regulating cell growth, angiogenesis, and invasion. Many changes observed in transcriptional regulation in this in vitro system are similar to those reported for human prostate cancer, as well as other types of human tumors. This analysis of expression patterns has also identified novel genes that may be involved in mechanisms of prostate oncogenesis or serve as potential biomarkers or therapeutic targets for prostate cancer. Examples include the L1-cell adhesion molecule, metastasis-associated gene (MTA-2), Rab-25, tumor-associated signal transducer-2 (Trop-2), and Selenoprotein-P, a gene that binds selenium and prevents oxidative stress. Many genes identified in the Pr-cell line model have been shown to be altered in human prostate cancer. The comprehensive microarray data provides a rational basis for using this model system for studies where alterations of specific genes or pathways are of particular interest. Quantitative real-time reverse transcription-PCR for Selenoprotein-P demonstrated a similar down-regulation of the transcript of this gene in a subset of human prostate tumors, mouse tumors, and prostate carcinoma cell lines. This work demonstrates that expression profiling in animal models may lead to the identification of novel genes involved in human prostate cancer biology.

Proteomic analysis of human prostate cancer.

Proteomics is a promising approach in the identification of proteins and biochemical pathways involved in tumorigenesis. In an effort to discover such proteins and pathways that are deregulated in prostate tumorigenesis, cellular proteomes of matched normal prostate epithelial cells and high-grade prostate cancer cells were analyzed by tissue microdissection, two-dimensional electrophoresis, and mass spectrometry. Forty protein alterations were detected in the tumors; however, the majority of these changes were not shared among the 12 neoplasms. In contrast, parallel cDNA microarray analysis identified a number of common gene expression changes. The marked heterogeneity of the observed protein alterations may have significance with regard to tumor biology and research strategies for molecular profiling analyses of human prostate cancer.

Evaluación y terapéutica inmunológica en la otitis media supurativa crónica no colesteatomatosa / Evaluation and immunological therapeutics in chronic suppurative otitis media without cholesteatoma

Se estudiaron 40 pacientes con otitis media supurativa crónica no colesteatomatosa a los que se les realizó tratamiento quirúrgico (técnica cerrada). Se analizaron los resultados de las pruebas inmunológicas y la evolución clínica de 20 pacientes con tratamiento inmunológico preoperatorio por un período de 6 a 12 meses y se compararon con la de 20 pacientes operados sin dicho tratamiento. El seguimiento evolutivo se realizó durante un año posterior a la intervención quirúrgica. La alteración inmunológica más frecuente fue un déficit de la inmunidad celular (65 porciento), con defecto humoral asociado o sin él. Tuvo evolución no satisfactoria sólo 1 paciente que recibió tratamiento inmunológico previo, a diferencia de 11 (55 porciento) de los 20 pacientes operados sin dicho tratamiento. La deficiencia inmunológica contribuye a la evolución desfavorable de la otitis media supurativa crónica no colesteatomatosa y el tratamiento inmunológico previo puede ayudar al éxito del tratamiento quirúgico