IMP3 Immunohistochemical Expression Is Related with Progression and Metastases in Xenografted and Cutaneous Melanomas.

INTRODUCTION: Insulin-like growth factor-II messenger RNA-binding protein-3 (IMP3) over-expression is a predictor of tumor recurrence and metastases in some types of human melanoma. Our objective was to evaluate the immunohistochemical expression of IMP3 and other molecules related to tumor prognosis in melanoma-xeno-tumors undergoing treatment. We test the effect of radiotherapy (RT) and mesenchymal stromal cells (MSCs) treatment, analyzing the tumorigenic and metastatsizing capacity in a mice melanoma xenograft model. MATERIALS AND METHODS: We inoculated A375 and G361 human melanoma cell lines into NOD/SCID gamma mice (n = 64). We established a control group, a group treated with MSCs, a group treated with MSCs plus RT, and a group treated with RT. We assessed the immunohistochemical expression of IMP3, E-cadherin, N-cadherin, PARP1, HIF-1α, and the proliferation marker Ki-67. Additionally, we performed a retrospective study including 114 histological samples of patients diagnosed with malignant cutaneous superficial spreading melanoma (n = 104) and nodular melanoma (n = 10) with at least 5 years of follow-up. RESULTS: Most morphological and immunohistochemical features show statistically significant differences between the 2 cell lines. The A375 cell line induced the formation of metastases, while the G361 cell line provoked tumor formation but not metastases. All three treatments reduced the cell proliferation evaluated by the Ki-67 nuclear antigen (p = 0.000, one-way ANOVA test) and reduced the number of metastases (p = 0.004, one-way ANOVA test). In addition, the tumor volumes reduced in comparison with the control groups, 31.74% for RT + MSCs in the A357 tumor cell line, and 89.84% RT + MSCs in the G361 tumor cell line. We also found that IMP3 expression is associated with greater tumor aggressiveness and was significantly correlated with cell proliferation (measured by the expression of Ki-67), the number of metastases, and reduced expression of adhesion molecules. CONCLUSIONS: The combined treatment of RT and MSCs on xenografted melanomas reduces tumor size, metastases frequency, and the epithelial to mesenchymal transition/PARP1 metastatic phenotype. This treatment also reduces the expression of molecules related to cellular proliferation (Ki-67), molecules that facilitate the metastatic process (E-cadherin), and molecules related with prognosis (IMP3).

Lifting COVID-19 mitigation measures in Spain (May-June 2020).

Introduction: The state of alarm was declared in Spain due to the COVID-19 epidemic on March 14, 2020, and established population confinement measures. The objective is to describe the process of lifting these mitigation measures. Methods: The Plan for the Transition to a New Normality, approved on April 28, contained four sequential phases with progressive increase in socio-economic activities and population mobility. In parallel, a new strategy for early diagnosis, surveillance and control was implemented. A bilateral decision mechanism was established between the Spanish Government and the autonomous communities (AC), guided by a set of qualitative and quantitative indicators capturing the epidemiological situation and core capacities. The territorial units were established ad-hoc and could be from Basic Health Zones to entire AC. Results: The process run from May 4 to June 21, 2020. AC implemented plans for reinforcement of core capacities. Incidence decreased from a median (50% of territories) of 7.4 per 100,000 in 7 days at the beginning to 2.5 at the end. Median PCR testing increased from 53% to 89% of suspected cases and PCR total capacity from 4.5 to 9.8 per 1000 inhabitants weekly; positivity rate decreased from 3.5% to 1.8%. Median proportion of cases with traced contacts increased from 82% to 100%. Conclusion: Systematic data collection, analysis, and interterritorial dialogue allowed adequate process control. The epidemiological situation improved but, mostly, the process entailed a great reinforcement of core response capacities nation-wide, under common criteria. Maintaining and further reinforcing capacities remained crucial for responding to future waves.

Introducción: El 14 de marzo de 2020 España declaró el estado de alarma por la pandemia por COVID-19 incluyendo medidas de confinamiento. El objetivo es describir el proceso de desescalada de estas medidas. Métodos: Un plan de transición hacia una nueva normalidad, del 28 de abril, incluía 4 fases secuenciales incrementando progresivamente las actividades socioeconómicas y la movilidad. Concomitantemente, se implementó una nueva estrategia de diagnóstico precoz, vigilancia y control. Se estableció un mecanismo de decisión bilateral entre Gobierno central y comunidades autónomas (CCAA), guiado por un panel de indicadores cualitativos y cuantitativos de la situación epidemiológica y las capacidades básicas. Las unidades territoriales evaluadas comprendían desde zonas básicas de salud hasta CCAA. Resultados: El proceso se extendió del 4 de mayo al 21 de junio y se asoció a planes de refuerzo de las capacidades en las CCAA. La incidencia disminuyó de una mediana inicial de 7,4 por 100.000 en 7 días a 2,5 al final del proceso. La mediana de pruebas PCR aumentó del 53% al 89% de los casos sospechosos, y la capacidad total de 4,5 a 9,8 pruebas semanales por 1.000 habitantes; la positividad disminuyó del 3,5% al 1,8%. La mediana de casos con contactos trazados aumentó del 82% al 100%. Conclusión: La recogida y análisis sistemático de información y el diálogo interterritorial logaron un adecuado control del proceso. La situación epidemiológica mejoró, pero sobre todo, se aumentaron las capacidades, en todo el país y con criterios comunes, cuyo mantenimiento y refuerzo fue clave en olas sucesivas.

Heme Iron Concentrate and Iron Sulfate Added to Chocolate Biscuits: Effects on Hematological Indices of Mexican Schoolchildren.

OBJECTIVE: Food fortification is one of the most effective strategies for increasing iron intake in the population. A simple blind trial was conducted to compare the effect of 2 forms of iron fortification and assess the changes in hemoglobin and iron status indices among preschool children from rural communities. METHODS: Hemoglobin was evaluated in 47 children aged 3-6 years old. For 72 days (10-week period), children ate Nito biscuits. Thirteen pupils with elevated hemoglobin levels were assigned to the biscuit control group, and pupils with hemoglobin equal to 13.5 mg/dL or less were randomly allocated to consume fortified biscuits with a heme iron concentrate (n = 15) or iron sulfate (n = 19). Changes in hemoglobin, plasma ferritin, and other hematological indices were evaluated with analysis of variance (ANOVA) for repeated measurements. RESULTS: Except mean corpuscular hemoglobin concentrations (+1.27 ± 2.25 g/dL), hematological indices increased significantly across the study: Mean corpuscular volume (+2.2 ± 1.0 f/dL), red blood cells (+0.30 ± 0.37 M/µL), mean corpuscular hemoglobin (+1.8 ± 1.74 pg), hemoglobin (+1.68 ± 0.91 g/dL), hematocrit (+3.43% ± 3.03%), and plasma ferritin (+18.38 ± 22.1 µg/L) were all p < 0.05. After 10 weeks, the adjusted effect of the iron-fortified chocolate biscuits in the hemoglobin levels was higher than the control group (+1.1 ± 0.2 g/dL) but no difference was found between consumers of fortified biscuits with heme iron concentrate or iron sulfate (+1.9 ± 0.2 g/dL and +2.0 ± 0.2 g/dL, respectively). CONCLUSION: Heme iron concentrate and iron sulfate were equally effective in increasing Hb levels and hematological indices. Processed foods were shown to be an effective, valuable, and admissible intervention to prevent anemia in preschool children.

Advanced Imaging Methodology in Bacterial Biofilms with a Fluorescent Enzymatic Sensor for pepN Activity.

This research explores the use of the pepN activity fluorescent sensor DCM-Ala in bacterial biofilms, emphasizing its significance due to the critical role of biofilms in various biological processes. Advanced imaging techniques were employed to visualize pepN activity, introducing a novel approach to examining biofilm maturity. We found that the overexpression of pepN increases the ability of E. coli to form biofilm. The findings demonstrate varying levels of pepN activity throughout biofilm development, suggesting potential applications in biofilm research and management. The results indicate that the fluorescent emission from this sensor could serve as a reliable indicator of biofilm maturity, and the imaging techniques developed could enhance our understanding and control of biofilm-related processes. This work highlights the importance of innovative methods in biofilm study and opens new avenues for utilizing chemical emissions in biofilm management.

Ratiometric Two-Photon Near-Infrared Probe to Detect DPP IV in Human Plasma, Living Cells, Human Tissues, and Whole Organisms Using Zebrafish.

DPP IV, otherwise known as CD26 lymphocyte T surface antigen, is a transmembrane glycoprotein also found in circulation in the blood. It plays an important role in several processes like glucose metabolism and T-cell stimulation. Moreover, it is overexpressed in renal, colon, prostate, and thyroid human carcinoma tissues. It can also serve as a diagnostic in patients with lysosomal storage diseases. The biological and clinical importance of having readouts for the activity of this enzyme, in physiological and disease conditions, has led us to design a near-infrared (NIR) fluorimetric probe that also has the characteristics of being ratiometric and excitable by two simultaneous NIR photons. The probe consists of assembling an enzyme recognition group (Gly-Pro) (Mentlein, 1999; Klemann et al., 2016) on the two-photon (TP) fluorophore (derivative of dicyanomethylene-4H-pyran, DCM-NH2) disturbing its NIR characteristic internal charge transfer (ICT) emission spectrum. When the dipeptide group is released by the DPP IV-specific enzymatic action, the donor-acceptor DCM-NH2 is restored, forming a system that shows high ratiometric fluorescence output. With this new probe, we have been able to detect, quickly and efficiently, the enzymatic activity of DPP IV in living cells, human tissues, and whole organisms, using zebrafish. In addition, due to the possibility of being excited by two photons, we can avoid the autofluorescence and subsequent photobleaching that the raw plasma has when it is excited by visible light, achieving detection of the activity of DPP IV in that medium without interference.

New bioisosteric sulphur-containing choline kinase inhibitors with a tracked mode of action.

Since the identification of human choline kinase as a protein target against cancer progression, many compounds have been designed to inhibit its function and reduce the biosynthesis of phosphatidylcholine. Herein, we propose a series of bioisosteric inhibitors that are based on the introduction of sulphur and feature improved activity and lipophilic/hydrophilic balance. The evaluation of the inhibitory and of the antiproliferative properties of the PL (dithioethane) and FP (disulphide) libraries led to the identification of PL 48, PL 55 and PL 69 as the most active compounds of the series. Docking analysis using FLAP suggests that for hits to leads, binding mostly involves an interaction with the Mg2+ cofactor, or its destabilization. The most active compounds of the two series are capable of inducing apoptosis following the mitochondrial pathway and to significantly reduce the expression of anti-apoptotic proteins such as the Mcl-1. The fluorescence properties of the compounds of the PL library allowed the tracking of their mode of action, while PAINS (Pan Assays Interference Structures) filtration databases suggest the lack of any unspecific biological response.

Lifting COVID-19 mitigation measures in Spain (May-June 2020).

INTRODUCTION: The state of alarm was declared in Spain due to the COVID-19 epidemic on March 14, 2020, and established population confinement measures. The objective is to describe the process of lifting these mitigation measures. METHODS: The Plan for the Transition to a New Normality, approved on April 28, contained four sequential phases with progressive increase in socio-economic activities and population mobility. In parallel, a new strategy for early diagnosis, surveillance and control was implemented. A bilateral decision mechanism was established between the Spanish Government and the autonomous communities (AC), guided by a set of qualitative and quantitative indicators capturing the epidemiological situation and core capacities. The territorial units were established ad-hoc and could be from Basic Health Zones to entire AC. RESULTS: The process run from May 4 to June 21, 2020. AC implemented plans for reinforcement of core capacities. Incidence decreased from a median (50% of territories) of 7.4 per 100,000 in 7 days at the beginning to 2.5 at the end. Median PCR testing increased from 53% to 89% of suspected cases and PCR total capacity from 4.5 to 9.8 per 1000 inhabitants weekly; positivity rate decreased from 3.5% to 1.8%. Median proportion of cases with traced contacts increased from 82% to 100%. CONCLUSION: Systematic data collection, analysis, and interterritorial dialogue allowed adequate process control. The epidemiological situation improved but, mostly, the process entailed a great reinforcement of core response capacities nation-wide, under common criteria. Maintaining and further reinforcing capacities remained crucial for responding to future waves.

Hypothalamic orexinergic neuron changes during the hibernation of the Syrian hamster.

Hibernation in small mammals is a highly regulated process with periods of torpor involving drops in body temperature and metabolic rate, as well as a general decrease in neural activity, all of which proceed alongside complex brain adaptive changes that appear to protect the brain from extreme hypoxia and low temperatures. All these changes are rapidly reversed, with no apparent brain damage occurring, during the short periods of arousal, interspersed during torpor-characterized by transitory and partial rewarming and activity, including sleep activation, and feeding in some species. The orexins are neuropeptides synthesized in hypothalamic neurons that project to multiple brain regions and are known to participate in the regulation of a variety of processes including feeding behavior, the sleep-wake cycle, and autonomic functions such as brown adipose tissue thermogenesis. Using multiple immunohistochemical techniques and quantitative analysis, we have characterized the orexinergic system in the brain of the Syrian hamster-a facultative hibernator. Our results revealed that orexinergic neurons in this species consisted of a neuronal population restricted to the lateral hypothalamic area, whereas orexinergic fibers distribute throughout the rostrocaudal extent of the brain, particularly innervating catecholaminergic and serotonergic neuronal populations. We characterized the changes of orexinergic cells in the different phases of hibernation based on the intensity of immunostaining for the neuronal activity marker C-Fos and orexin A (OXA). During torpor, we found an increase in C-Fos immunostaining intensity in orexinergic neurons, accompanied by a decrease in OXA immunostaining. These changes were accompanied by a volume reduction and a fragmentation of the Golgi apparatus (GA) as well as a decrease in the colocalization of OXA and the GA marker GM-130. Importantly, during arousal, C-Fos and OXA expression in orexinergic neurons was highest and the structural appearance and the volume of the GA along with the colocalization of OXA/GM-130 reverted to euthermic levels. We discuss the involvement of orexinergic cells in the regulation of mammalian hibernation and, in particular, the possibility that the high activation of orexinergic cells during the arousal stage guides the rewarming as well as the feeding and sleep behaviors characteristic of this phase.

Thermal and Rheological Properties of Hydrophobic Nanosilica in Sunflower Oil Suspensions at High Pressures.

Nowadays, the reduction of the environmental impact associated with the operation of the oil industry is a primary concern. A growing trend is to develop low-toxicity formulations based on biodegradable components. In this sense, vegetable oils structured with nanomaterials could be an alternative to mineral or synthetic oils for sustainable fluid formulations. Hydrophobic fumed silica nanoparticles have the capability to change the rheological behavior of oil in suspensions, providing a large variety of non-Newtonian behaviors over a wide range of temperatures, from shear-thinning to gel-like, depending on the concentration and the nanosilica's hydrophobicity, that permits the design of fluids with selected characteristic and applications. This work explores the microstructure and the rheological behavior of hydrophobic fumed silica dispersed in a sunflower oil as a function of temperature and pressure. The results suggest that the suspensions of hydrophobic silica in sunflower oil reveals appropriate rheological and thermal properties over a wide range of temperatures and pressures to serve as components of sustainable drilling fluids.

New Red-Emitting Chloride-Sensitive Fluorescent Protein with Biological Uses.

A new chloride-sensitive red fluorescent protein derived from Entacmaea quadricolor is described. We found that mBeRFP exhibited moderate sensitivity to chloride and, via site-directed mutagenesis (S94V and R205Y), we increased the chloride affinity by more than an order of magnitude (kd = 106 ± 6 mM) at physiological pH. In addition, cis-trans isomerization of the chromophore produces a dual emission band with different chloride sensitivities, which allowed us to develop a ratiometric methodology to measure intracellular chloride concentrations.

Lifting COVID-19 mitigation measures in Spain (May-June 2020).

INTRODUCTION: The state of alarm was declared in Spain due to the COVID-19 epidemic on March 14, 2020, and established population confinement measures. The objective is to describe the process of lifting these mitigation measures. METHODS: The Plan for the Transition to a New Normality, approved on April 28, contained four sequential phases with progressive increase in socio-economic activities and population mobility. In parallel, a new strategy for early diagnosis, surveillance and control was implemented. A bilateral decision mechanism was established between the Spanish Government and the autonomous communities (AC), guided by a set of qualitative and quantitative indicators capturing the epidemiological situation and core capacities. The territorial units were established ad-hoc and could be from Basic Health Zones to entire AC. RESULTS: The process run from May 4 to June 21, 2020. AC implemented plans for reinforcement of core capacities. Incidence decreased from a median (50% of territories) of 7.4 per 100,000 in 7 days at the beginning to 2.5 at the end. Median PCR testing increased from 53% to 89% of suspected cases and PCR total capacity from 4.5 to 9.8 per 1000 inhabitants weekly; positivity rate decreased from 3.5% to 1.8%. Median proportion of cases with traced contacts increased from 82% to 100%. CONCLUSION: Systematic data collection, analysis, and interterritorial dialogue allowed adequate process control. The epidemiological situation improved but, mostly, the process entailed a great reinforcement of core response capacities nation-wide, under common criteria. Maintaining and further reinforcing capacities remained crucial for responding to future waves.

Trends in the consumption of antidepressants in Castilla y León (Spain). Association between suicide rates and antidepressant drug consumption.

OBJECTIVE: To learn the evolution of antidepressant and lithium use in Castilla y León (Central Spain) and its relationship with suicide rates. METHODS: A search in the ECOM (Especialidades Consumo de Medicamentos) database of the Spanish Ministry of Health for antidepressants and lithium was carried out for the period 1992-2005. Defined daily doses (DDD) per 1000 inhabitants per day were obtained as consumption data. Population and suicide rates data come from the Spanish National Statistics Institute. RESULTS: Antidepressant consumption increased 7-fold, from 6.9 DDD per 1000 inhabitants per day in 1992 to 47.3 in 2005; the corresponding increase in cost was more than 10-fold. Selective serotonin reuptake inhibitors (SSRIs) comprised 77% of the total consumption. Venlafaxine consumption multiplied by 2.2. The consumption of monoamine oxidase inhibitors (MAOIs) decreased after venlafaxine and mirtazapine were marketed. Lithium consumption increased by 76% during the period studied, but it plateaued in 2000. CONCLUSIONS: The consumption of antidepressants in Castilla y León has increased remarkably and the pattern has changed; there is an increase in the consumption of the new and more expensive antidepressants such as venlafaxine and escitalopram. No association was observed between suicide rates and antidepressant consumption.

[Municipalism and community health: transforming through local government. SESPAS Report 2018]. / Municipalismo y salud comunitaria: transformar desde los ayuntamientos. Informe SESPAS 2018.

Municipalities and local government are an essential element to promote public policies that improve people's health, and impact the social determinants of health, through developing approaches which incorporate equity, community engagement and intersectoral partnership at their core. The objective of this article is to analyze the barriers and opportunities that can be encountered within local governments when interventions aimed at improving people's health are developed and implemented. The evolution of the city councils, their competence frameworks and the current socio-political context are described, and three key tools for local action are proposed: intersectorality, community engagement and working in partnership with other administrations. Global strategies such as the implementation of the "community health" and "health in all policies" approach through cross-sectoral networks/partnerships are described, emphasizing the importance of developing formal and informal structures or processes of community engagement and designing local health action plans in cooperation with other administrations, such as regional and national governing bodies. To continue supporting these forms of local governance, we propose adapting the local administrations to the new social realities, with more horizontal and flexible organization models and resource allocation, integrating efficiency and evaluation processes, reclaiming local autonomy, and building local governance through networks and alliances.

Intersectorality and social participation as coping policies for health inequities-worldwide.

OBJECTIVE: To determine the impact that intersectoral policies and social participation, implemented worldwide, have had on the modification of the social determinants for health and on the reduction of social health inequities. METHOD: A scoping review of the literature published in the period 2005-2015 was performed. The literature search was conducted on PubMed and Scielo databases. Two researchers reviewed each document. Data were analysed according to the intersectoral action and social participation variables and according to the theoretical frameworks of the Social Determinants Model of the Commission on Social Determinants of Health (CSDH) and the theoretical constructs of Social Capital (SC) and Life Course (LC). RESULTS: Out of 45 documents likely to be selected for final review, all of them based on title and abstract, 20 documents were eventually picked out and analysed; most them (n = 8) were conducted in all Latin America and Latin America's countries. Twelve documents reported intersectoral action associated with social participation in partnership with different institutions. Regarding theoretical frameworks, most of studies (n = 8) used CSDH and SC. In relation to health outcomes, the studies showed mainly: increased access to health and education, follow-up of pregnant women, increasing in prenatal examinations, reduction in malnutrition/child mortality, reduction in extreme poverty/hunger; reduction in epidemics/tuberculosis, control of alcohol/drug consumption, promotion of health/mental as well as basic sanitation improvements. CONCLUSIONS: Intersectoral and social participation experiences studied yielded positive outcomes regarding health status and quality of life in the communities in which such experiences were implemented.

Extracellular Phosphorylation of TIMP-2 by Secreted c-Src Tyrosine Kinase Controls MMP-2 Activity.

The tissue inhibitor of metalloproteinases 2 (TIMP-2) is a specific endogenous inhibitor of matrix metalloproteinase 2 (MMP-2), which is a key enzyme that degrades the extracellular matrix and promotes tumor cell invasion. Although the TIMP-2:MMP-2 complex controls proteolysis, the signaling mechanism by which the two proteins associate in the extracellular space remains unidentified. Here we report that TIMP-2 is phosphorylated outside the cell by secreted c-Src tyrosine kinase. As a consequence, phosphorylation at Y90 significantly enhances TIMP-2 potency as an MMP-2 inhibitor and weakens the catalytic action of the active enzyme. TIMP-2 phosphorylation also appears to be essential for its interaction with the latent enzyme proMMP-2 in vivo. Absence of the kinase or non-phosphorylatable Y90 abolishes TIMP-2 binding to the latent enzyme, ultimately hampering proMMP-2 activation. Together, TIMP-2 phosphorylation by secreted c-Src represents a critical extracellular regulatory mechanism that controls the proteolytic function of MMP-2.

A pharmacoepidemiological study of the consumption of antiparkinson drugs in the Basque Autonomous Community (Spain) (1992-2004).

PURPOSE: To monitor the rise in consumption of antiparkinson drugs as well as the prevalence of this illness in the Basque Autonomous Community (Spain) over a period of 13 years (1992-2004). METHODS: A retrospective population-based study where consumption of antiparkinson drugs was conducted using data obtained from the ECOM (Especialidades Consumo de Medicamentos) database of the Spanish Ministry of Health, which contains the number of prescriptions filled in community pharmacies and charged to the National Health System. The results are expressed as DID, Defined daily doses per 1000 inhabitants per day. CONCLUSIONS: Consumption of antiparkinson drugs has increased in the Basque Autonomous Community.

Non-steroidal anti-inflammatory drug-related hepatic damage in France and Spain: analysis from national spontaneous reporting systems.

Several non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with liver damage. The aim of this study was to compare proportions of hepatic adverse drug reaction reports associated with NSAIDs in France and Spain. Information from the Spanish and French pharmacovigilance databases were used from 1982 to 2001. To assess the risk of liver injury, the case/non-case methodology was applied, 'cases' being reports of liver damage and 'non-cases' or controls, all other reports. Exposure was considered as the presence of at least one NSAID. Liver injury risk was estimated for each drug in the two databases by calculation of reporting odds ratio in cases and non-cases, with its 95% confidence interval. Out of 62 456 reports from the Spanish database, 2114 (3.38%) were identified as liver injuries, whereas there were 27 372 liver injuries out of 200 046 (13.68%) in the French database. In Spain, there was a significant association between liver injuries and droxicam, sulindac, and nimesulide. The risk was also slightly above 1 for aceclofenac. In France, the risk was very high with clometacin, followed by sulindac, and was slightly above 1 for naproxen, diclofenac, piroxicam, and tenoxicam. This study shows that some NSAIDs are associated with reports of hepatic injuries when compared with other drugs, and most of those have been withdrawn from the market for this reason. However, the frequency of drug-related hepatic injuries reported differed in the French and Spanish databases, and some drugs did not show the same risk level in the two countries. These discrepancies could be explained in part not only by reporting rates, but also by difference in drug use patterns and/or by genetic or environmental factors.

[Quality of observational post-authorization studies registered in Spain before their regulation]. / Calidad de los estudios postautorización de tipo observacional registrados en España antes de su regulación.

BACKGROUND AND OBJECTIVE: In July, 2002, observational post-authorization studies were subjected to regulation in Spain, giving rise to an uproar among sponsors and investigators. The aim of the present report was to assess the scientific and ethical quality of the studies presented during the year before the regulation came into force. In addition, we explored how many of them reached publication. MATERIAL AND METHOD: We extracted information relative to administrative procedures, methods, follow-up and ethical issues from the protocol of the studies presented to the Spanish Agency for Medicines and Healthcare Products (AEMPS) during 2001. RESULTS: A total of 162 studies intended to recruit 306,539 patients were registered as post-authorization studies in 2001. The most widely used design was the <> (122 studies; 75%). Physicians were the only source of information in 99% of the studies. In 43% of them, the sample size was neither specified nor justified. In 83% of the studies the observation period per patient was less than 12 months. An ethical review was requested for only 13% of the studies while a procedure to inform patients was planned in 44%. Eleven studies (10% of those finalized) had been published in scientific journals (1 of them international) and 13 (12% of those finalized) were reported as a communication to a national (11) or international (2) congress. CONCLUSIONS: Most post-authorization studies presented to the AEMPS in 2001 had poor methodological and ethical quality. Only a few became published, raising doubts about their scientific aims. These results give empirical support to the regulation adopted.

[Field epidemiology and social epidemiology]. / Epidemiología de campo y epidemiología social.

Comparing field epidemiology and social epidemiology, we pretend to think about the no explicit images and meanings operating in both necessary convergent fields, about the obstacles present in epidemiological practice to fulfil its social function and about the necessity of changing epistemological, methodological and practice grounds, beginning with field epidemiologists teaching programmes. Field epidemiology would tend to act in an absent theoretical frame. On the other hand, social epidemiology would tend to prioritize theoretical developments (thinking and research about social determinants) without correspondent action, because of the limits to change public policies. Other differences are found at intervention level (micro-macrospace), its aim (outbreak control vs. inequalities control) and the way to communicate with society. They are similar in the methodological concern, the predominance of orientation based on positivism and framed through statistic methods, but in process of epistemological opening, the stress experienced between the alternative relationship to a virtual world of data bases or to the real society, their peripherical situation in relation of the political, social, institutional and professional system and the tendency to professional frustration. Finally, we ask ten questions to the field epidemiologists related with their present practice, in order to consider if they are developing social epidemiology, and propose some changes in epidemiologist teaching and practice.