The RICA-2 registry: design and baseline characteristics of the first 1,000 patients.

BACKGROUND AND OBJECTIVE: Heart failure (HF) is a syndrome of epidemic proportions and one of the main reasons for hospital admission. Patient registries provide real-world clinical practice information which is complementary to clinical trials. RICA-2 is a registry of the Spanish Society of Internal Medicine. Its main goal is to know the clinical and epidemiological characteristics and prognostic factors of patients with HF treated in Internal Medicine Departments. The objective of this study is to present the design of the RICA-2, the baseline characteristics of the first 1000 patients included and their comparison with those of the historical cohort of the RICA registry. METHODS: Observational, multicentre and prospective study of patients with HF with the following inclusion criteria: age equal to or greater than 18 years old, diagnosis of HF according to the European Guidelines, indistinct inclusion in decompensation or stable phase, of patients with de novo HF or chronic HF, regardless of left ventricular ejection fraction, aetiology and comorbidities. RESULTS: RICA-2 patients have advanced age (83 years old) and 51% are women. The comorbidity burden is higher than in the RICA registry (5 points in the Charlson comorbidity index), with predominating chronic decompensated HF (74%), hypertensive aetiology (39%) and preserved ejection fraction (52%). Most patients are pre-frail or vulnerable and are at risk of malnutrition. CONCLUSION: The RICA-2 represents a contemporary cohort of patients that will provide us with clinical, epidemiological and prognostic information on patients with acute and chronic HF treated in Internal Medicine.

Influencia del grado de anemia en el pronóstico de los pacientes de edad avanzada con insuficiencia cardíaca (Estudio SPAN-HF) / Influence of the degree of anaemia on the prognosis of older adults with heart failure (SPAN-HF study)

Objetivo:Evaluar si un valor óptimo de hemoglobina sostenido en los 3 meses posteriores al ingreso por descompensación de insuficiencia cardíaca (IC) reduce la morbimortalidad durante los 12 meses posteriores a un ingreso por IC aguda.Pacientes y método:Estudio retrospectivo de los 1408 pacientes mayores de 65 años incluidos en el registro RICA divididos en 3 grupos: sin anemia (grupo A), anemia recuperada (grupo B) y anemia persistente (grupo C), según los niveles de hemoglobina en el ingreso y a los 3 meses tras el alta. Se construyeron curvas de Kaplan-Meier, comparando los grupos mediante la prueba de log-rank y se realizó un modelo de regresión de Cox para analizar la supervivencia.Resultados:Se incluyeron 578 (41,1%), 299 (21,2%) y 531 (37,7%) en los grupos A, B y C, respectivamente. Registramos un total de 768 muertes y reingresos. Hubo 23 (4%), 12 (4%) y 49 (9,2%) (p=0,001) individuos que fallecieron debido a la IC, y 154 (27%), 73 (24%) y 193 (36%) (p<0,001) reingresaron por esta patología, respectivamente. Los pacientes con anemia persistente tuvieron un riesgo superior de fallecimiento (RR: 1,29; IC95% de 1,04-1,61; p=0,024) o reingreso (1,92; IC95% de 1,16-3,19; p=0,012) por IC.Conclusiones:La anemia persistente en los meses posteriores a un ingreso por IC aumenta la morbimortalidad en el año posterior.

Objective:To assess whether a sustained optimal haemoglobin value in the 3 months after admission for heart failure (HF) decompensation reduces morbidity and mortality during the 12 months after admission for acute HF.Patients and method:Retrospective study of the 1408 patients older than 65 years included in the RICA registry divided into 3 groups: no anaemia (group A), recovered anaemia (group B), and persistent anaemia (group C), according to haemoglobin levels on admission, and 3 months after discharge. Kaplan-Meier curves were constructed, comparing the groups using the log-rank test and a Cox regression model was performed to analyse survival.Results:578 (41.1%), 299 (21.2%) and 531 (37.7%) were included in groups A, B and C, respectively. We recorded a total of 768 deaths and readmissions. There were 23 (4%), 12 (4%) and 49 (9.2%), (p=.001) individuals who died due to HF and 154 (27%), 73 (24%) and 193 (36%) (P<.001) admissions for this pathology, respectively. Patients with persistent anaemia had a higher risk of death (RR 1.29, 95% CI 1.04-1.61, P=.024) or readmission (1.92, 95% CI 1.16-3, 19; P=.012) due to HF.Conclusions:Persistent anaemia in the months after admission for HF increases morbidity and mortality in the subsequent year. (AU)

[Influence of the degree of anaemia on the prognosis of older adults with heart failure (SPAN-HF study)]. / Influencia del grado de anemia en el pronóstico de los pacientes de edad avanzada con insuficiencia cardíaca (Estudio SPAN-HF).

OBJECTIVE: To assess whether a sustained optimal haemoglobin value in the 3 months after admission for heart failure (HF) decompensation reduces morbidity and mortality during the 12 months after admission for acute HF. PATIENTS AND METHOD: Retrospective study of the 1408 patients older than 65 years included in the RICA registry divided into 3 groups: no anaemia (group A), recovered anaemia (group B), and persistent anaemia (group C), according to haemoglobin levels on admission, and 3 months after discharge. Kaplan-Meier curves were constructed, comparing the groups using the log-rank test and a Cox regression model was performed to analyse survival. RESULTS: 578 (41.1%), 299 (21.2%) and 531 (37.7%) were included in groups A, B and C, respectively. We recorded a total of 768 deaths and readmissions. There were 23 (4%), 12 (4%) and 49 (9.2%), (p=.001) individuals who died due to HF and 154 (27%), 73 (24%) and 193 (36%) (P<.001) admissions for this pathology, respectively. Patients with persistent anaemia had a higher risk of death (RR 1.29, 95% CI 1.04-1.61, P=.024) or readmission (1.92, 95% CI 1.16-3, 19; P=.012) due to HF. CONCLUSIONS: Persistent anaemia in the months after admission for HF increases morbidity and mortality in the subsequent year.

Biallelic variants in genes previously associated with dominant inheritance: CACNA1A, RET and SLC20A2.

A subset of families with co-dominant or recessive inheritance has been described in several genes previously associated with dominant inheritance. Those recessive families displayed similar, more severe, or even completely different phenotypes to their dominant counterparts. We report the first patients harboring homozygous disease-related variants in three genes that were previously associated with dominant inheritance: a loss-of-function variant in the CACNA1A gene and two missense variants in the RET and SLC20A2 genes, respectively. All patients presented with a more severe clinical phenotype than the corresponding typical dominant form. We suggest that co-dominant or recessive inheritance for these three genes could explain the phenotypic differences from those documented in their cognate dominant phenotypes. Our results reinforce that geneticists should be aware of the possible different forms of inheritance in genes when WES variant interpretation is performed. We also evidence the need to refine phenotypes and inheritance patterns associated with genes in order to avoid failures during WES analysis and thus, raising the WES diagnostic capacity in the benefit of patients.

Impact of COVID-19 outbreak in reperfusion therapies of acute ischaemic stroke in northwest Spain.

BACKGROUND AND PURPOSE: Spain has been one of the countries more heavily stricken by SARS-CoV-2, which has had huge implications for stroke care. The aim was to analyse the impact of the COVID-19 epidemic outbreak on reperfusion therapies for acute ischaemic stroke in the northwest of Spain. METHODS: This was a Spanish multicentre retrospective observational study based on data from tertiary hospitals of the NORDICTUS network. All patients receiving reperfusion therapy for ischaemic stroke between 30 December 2019 and 3 May 2020 were recorded, and their baseline, clinical and radiological characteristics, extra- and intra-hospital times of action, Code Stroke activation pathway, COVID-19 status, reperfusion rate, and short-term outcome before and after the setting of the emergency state were analysed. RESULTS: A total of 796 patients received reperfusion therapies for ischaemic stroke. There was a decrease in the number of patients treated per week (46.5 patients per week vs. 39.0 patients per week, P = 0.043) and a delay in out-of-hospital (95.0 vs. 110.0 min, P = 0.001) and door-to-needle times (51.0 vs. 55.0, P = 0.038). Patients receiving endovascular therapy obtained less successful reperfusion rates (92.9% vs. 86.6%, P = 0.016). COVID-19 patients had more in-hospital mortality. CONCLUSION: A decrease in the number of patients benefiting from reperfusion therapies was found, with a delay in out-of-hospital and door-to-needle times and worse reperfusion rates in northwest Spain. COVID-19 patients had more in-hospital mortality.

Estimating Barcelona's metropolitan daytime hot and cold poles using Landsat-8 Land Surface Temperature.

The Barcelona Metropolitan Area (BMA) is located in Catalonia, northeastern Spain. With a population of over 3 billion people, the BMA is one of the most populous metropolitan areas on the Mediterranean coast. A local climatic modification known as the urban heat island (UHI) occurs in the urban areas. The UHI is usually quantified by means of air temperature, although remote sensing can be used to extract a thermal image of the earth's surface to provide temperature values throughout the study area. Estimation of the land surface temperature (LST) for the BMA enabled us to establish the spatial patterns of LST and to detect the poles of heat and cold within the BMA on 24 dates during the 2013-2018 period, distributed among the 4 seasons of the year. To this end we performed a principal component analysis (PCA) and a cluster analysis (CA). Moreover, we employed the Random Forest (RF) regression method to quantify the influence and variation of diverse geographic covariates according to season and location in the study area. Finally, to determine the influence of land covers on temperature, the thermal values of the 4 land covers included in the Corine Land Cover dataset were analyzed: industrial units, continuous urban fabric, green urban areas, and forest areas. Results show that the heat poles are concentrated in industrial areas primarily, followed by urban fabric areas. On the contrary, the cold pole is found in green urban areas, as well as forested areas. The maximum temperature range between land covers was detected in spring and summer, while in winter this difference was negligible. Our study showed that green urban areas presented temperatures up to 2.5 °C lower than in urban areas. The results of the present research are intended to serve as a roadmap for enhancing thermal comfort in the BMA.

[Infantile epileptic encephalopathy: a good genetic study should be a priority]. / Encefalopatia epileptica del lactante: lo prioritario es un buen estudio genetico.

TITLE: Encefalopatia epileptica del lactante: lo prioritario es un buen estudio genetico.

Insecticide susceptibility status in Mexican populations of Stegomyia aegypti (= Aedes aegypti): a nationwide assessment.

In Mexico, mosquito vector-borne diseases are of public health concern as a result of their impact on human morbidity and mortality. The use of insecticides against adult mosquitoes is one of the most common ways of controlling mosquito population densities. However, the use of these compounds has resulted in the development of insecticide resistance. The aim of this study was to estimate susceptibility to six pyrethroids, two carbamates and two organophosphates in Mexican populations of Stegomyia aegypti (Linnaeus, 1762) (= Aedes aegypti) (Diptera: Culicidae) mosquitoes. Bottle insecticide susceptibility tests, with 1 h exposure, were performed on adult mosquitoes from 75 localities across 28 states. At 30 min of exposure, the proportion of fallen mosquitoes was recorded. After 60 min of exposure, mosquitoes were recovered in non-treated containers and mortality was determined at 24 h after the set-up of the experiment. In general, the carbamate insecticides represented the most effective group in terms of the proportion of mosquitoes fallen at 30 min (72-100%) and 24-h mortality (97-100%). High and widespread resistance to pyrethroids Types I and II and, to a lesser extent, to organophosphates was observed. Insecticide susceptibility among and within states was highly variable.

Resiniferatoxin modulates the Th1 immune response and protects the host during intestinal nematode infection.

In the early stage of the intestinal phase of Trichinella spiralis infection, the host triggers a Th1-type immune response with the aim of eliminating the parasite. However, this response damages the host which favours the survival of the parasite. In the search for novel pharmacological strategies that inhibit the Th1 immune response and assist the host against T. spiralis infection, a recent study showed that resiniferatoxin had anti-inflammatory activity contributed to the host in T. spiralis infection. In this study, we evaluated whether RTX modulates the host immune response through the inhibition of Th1 cytokines in the intestinal phase. In addition, it was determined whether the treatment with RTX affects the infectivity of T. spiralis-L1 and the development of the T. spiralis life cycle. Our results show that RTX decreased serum levels of IL-12, INF-γ, IL-1ß, TNF-α and parasite burden on muscle tissue. It was observed that T. spiralis-L1 treated with RTX decreased their infectivity affecting the development of the T. spiralis life cycle in mouse. These results demonstrate that RTX is able to inhibit the production of Th1 cytokines, contributing to the defence against T. spiralis, which places it as a potential drug modulator of the immune response.

El sentido de la vida en universitarios españoles / The meaning of life in Spanish university students

Presentamos un estudio en el que se propone un perfil del Sentido de la Vida en jóvenes universitarios. En el estudio participaron 1172 estudiantes de diferentes universidades españolas (888 mujeres, 284 hombres). Con una edad comprendida entre los 17 y más de 23 años. Se aplicaron el instrumento PIL (Purpose in Life) para la medición del Sentido de la Vida y un cuestionario complementario

We present a study in which proposed a profile of Meaning in Life in universities students. In this study participated 1172 students from different Spanish universities (888 women, 284 men). With an age between 17 and 23 years. Were applied the PIL (Purpose in Life) instrument for measuring the Meaning of Life and an additional questionnaire

First report of Stegomyia aegypti (= Aedes aegypti) in Mexico City, Mexico.

Stegomyia aegypti (= Aedes aegypti) (Diptera: Culicidae) is a species of mosquito that is currently widespread in Mexico. Historically, the mosquito has been distributed across most tropical and subtropical areas lower than 1700 m a.s.l. Currently, populations that are found at higher altitudes in regions with cold and dry climates suggest that these conditions do not limit the colonization and population growth of S. aegypti. During a survey of mosquitoes in September 2015, larvae of S. aegypti mosquitoes were found in two different localities in Mexico City, which is located at about 2250 m a.s.l. Mexico City is the most populous city in Mexico and has inefficient drainage and water supply systems. These factors may result in the provision of numerous larval breeding sites. Mosquito monitoring and surveillance are now priorities for the city.

Resiniferatoxin lowers TNF-α, NO and PGE2 in the intestinal phase and the parasite burden in the muscular phase of Trichinella spiralis infection.

During the course of infection with Trichinella spiralis, an inflammatory response is triggered at the intestinal level in the host, playing a crucial role in the expulsion and elimination of the parasite. However, several studies have demonstrated that this inflammatory response is harmful to the host; hence, the importance of studying molecules with therapeutic potential like resiniferatoxin, which is known to have an anti-inflammatory effect both in vitro and in vivo. In this article, we evaluated the anti-inflammatory activity of resiniferatoxin during the intestinal phase of T. spiralis infection by quantitatively determining the levels of TNF-α, NO and PGE2 as well as the percentage of eosinophils in the blood and intestinal pathology. In addition, parasite burden was determined during the muscle infection. Our results show that resiniferatoxin lowered the serum levels of TNF-α, NO and PGE2 , as well as the percentage of eosinophils in the blood and intestinal pathology during the intestinal infection. Moreover, resiniferatoxin also lowered the parasite burden in muscle, resulting in a reduction of the humoral response (IgG) associated to treatment with resiniferatoxin. These findings suggest a potential therapeutic use of the anti-inflammatory effect of resiniferatoxin, which also contributes to host defence against the challenge of T. spiralis infection.

Effectiveness and predictors of failure of noninvasive mechanical ventilation in acute respiratory failure.

OBJECTIVE: To assess the effectiveness and identify predictors of failure of noninvasive ventilation. DESIGN: A retrospective, longitudinal descriptive study was made. SETTING: Adult patients with acute respiratory failure. PATIENTS: A total of 410 consecutive patients with noninvasive ventilation treated in an Intensive Care Unit of a tertiary university hospital from 2006 to 2011. PROCEDURES: Noninvasive ventilation. MAIN VARIABLES OF INTEREST: Demographic variables and clinical and laboratory test parameters at the start and two hours after the start of noninvasive ventilation. Evolution during admission to the Unit and until hospital discharge. RESULTS: The failure rate was 50%, with an overall mortality rate of 33%. A total of 156 patients had hypoxemic respiratory failure, 87 postextubation respiratory failure, 78 exacerbation of chronic obstructive pulmonary disease, 61 hypercapnic respiratory failure without chronic obstructive pulmonary disease, and 28 had acute pulmonary edema. The failure rates were 74%, 54%, 27%, 31% and 21%, respectively. The etiology of respiratory failure, serum bilirubin at the start, APACHEII score, radiological findings, the need for sedation to tolerate noninvasive ventilation, changes in level of consciousness, PaO2/FIO2 ratio, respiratory rate and heart rate from the start and two hours after the start of noninvasive ventilation were independently associated to failure. CONCLUSIONS: The effectiveness of noninvasive ventilation varies according to the etiology of respiratory failure. Its use in hypoxemic respiratory failure and postextubation respiratory failure should be assessed individually. Predictors of failure could be useful to prevent delayed intubation.

Factores pronósticos relacionados con la mortalidad del paciente con trauma grave: desde la atención prehospitalaria hasta la Unidad de Cuidados Intensivos / Prognostic factors associated with mortality in patients with severe trauma: From prehospital care to the Intensive Care Unit

OBJETIVO: Identificar los factores relacionados con la mortalidad de los pacientes adultos politraumatizados, analizar las características clínicas, epidemiológicas y terapéuticas en los niveles prehospitalario, Servicio de Urgencias y Cuidados Intensivos. DISEÑO: Estudio retrospectivo, longitudinal y descriptivo. Análisis estadístico a través del programa SPSS, MultBiplot y la metodología de minería de datos. ÁMBITO: Pacientes adultos politraumatizados ingresados en el Complejo Hospitalario de Salamanca entre los años 2006 y 2011. VARIABLES DE INTERÉS PRINCIPALES: Variables demográficas, clínicas, terapéuticas y analíticas desde el lugar del accidente hasta el ingreso en la UCI. Variables evolutivas durante el ingreso en la UCI y hasta el alta hospitalaria. RESULTADOS: Se incluyó a 497 pacientes, con una mediana de edad 45,5 años. Predominio de varones (76,7%). La causa principal del traumatismo fueron los accidentes de tráfico (56,1%), precipitaciones (18,4%) y caídas (11%). Los factores con mayor asociación a un incremento del riesgo de mortalidad (p<0,05) fueron la edad > 65 años (OR 3,15), el traumatismo craneoencefálico (OR 3,1), las alteraciones pupilares (OR 113,88), el nivel de consciencia según la escala de Glasgow ≤ 8 (OR 12,97) y las cifras de lactato > 4 mmol/L (OR 9,7). CONCLUSIONES: Los principales factores de riesgo identificados en relación con el pronóstico de los pacientes politraumatizados son los relacionados con la presencia de traumatismo craneoencefálico. Mediante la utilización de distintas técnicas estadísticas menos conocidas como la minería de datos o el MultBiplot también se destaca la importancia de otros factores como el lactato. Los registros de traumatismos ayudan a conocer la asistencia sanitaria realizada para poder establecer medidas de mejora

OBJECTIVE: To identify factors related to mortality in adult trauma patients, analyzing the clinical, epidemiological and therapeutic characteristics at the pre-hospital levels, in the Emergency Care Department and in Intensive Care. DESIGN: A retrospective, longitudinal descriptive study was carried out. Statistical analysis was performed using SPSS, MultBiplot and data mining methodology. SETTING: Adult multiple trauma patients admitted to the Salamanca Hospital Complex (Spain) from 2006 to 2011. MAIN VARIABLES OF INTEREST: Demographic variables, clinical, therapeutic and analytical data from the injury site to ICU admission. Evolution from ICU admission to hospital discharge. RESULTS: A total of 497 patients with a median age of 45.5 years were included. Males predominated (76.7%). The main causes of injury were traffic accidents (56.1%), precipitation (18.4%) and falls (11%). The factors with the strongest association to increased mortality risk (P < .05) were age > 65 years (OR 3.15), head injuries (OR 3.1), pupillary abnormalities (OR 113.88), level of consciousness according to the Glasgow Coma Scale ≤ 8 (OR 12.97), and serum lactate levels > 4 mmol/L (OR 9.7). CONCLUSIONS: The main risk factors identified in relation to the prognosis of trauma patients are referred to the presence of head injuries. Less widely known statistical techniques such as data mining or MultBiplot also underscore the importance of other factors such as lactate concentration. Trauma registries help assess the healthcare provided, with a view to adopting measures for improvement

Prognostic factors associated with mortality in patients with severe trauma: from prehospital care to the Intensive Care Unit.

OBJECTIVE: To identify factors related to mortality in adult trauma patients, analyzing the clinical, epidemiological and therapeutic characteristics at the pre-hospital levels, in the Emergency Care Department and in Intensive Care. DESIGN: A retrospective, longitudinal descriptive study was carried out. Statistical analysis was performed using SPSS, MultBiplot and data mining methodology. SETTING: Adult multiple trauma patients admitted to the Salamanca Hospital Complex (Spain) from 2006 to 2011. MAIN VARIABLES OF INTEREST: Demographic variables, clinical, therapeutic and analytical data from the injury site to ICU admission. Evolution from ICU admission to hospital discharge. RESULTS: A total of 497 patients with a median age of 45.5 years were included. Males predominated (76.7%). The main causes of injury were traffic accidents (56.1%), precipitation (18.4%) and falls (11%). The factors with the strongest association to increased mortality risk (P<.05) were age > 65 years (OR 3.15), head injuries (OR 3.1), pupillary abnormalities (OR 113.88), level of consciousness according to the Glasgow Coma Scale ≤ 8 (OR 12.97), and serum lactate levels > 4 mmol/L (OR 9.7). CONCLUSIONS: The main risk factors identified in relation to the prognosis of trauma patients are referred to the presence of head injuries. Less widely known statistical techniques such as data mining or MultBiplot also underscore the importance of other factors such as lactate concentration. Trauma registries help assess the healthcare provided, with a view to adopting measures for improvement.

Hiperalgesia asociada al tratamiento con opioides / Opioid-induced hyperalgesia

La hiperalgesia inducida por opioides es una reacción paradójica caracterizada por una percepción intensificada de dolor relacionada con el uso de estos medicamentos en ausencia de progresión de la enfermedad o de síndrome de retirada. A diferencia de los casos de tolerancia, definida como pérdida de potencia analgésica durante el uso prolongado de opioides, no se produce mejoría con el escalado de dosis. La hiperalgesia inducida por opioides se ha manifestado en pacientes con dosis de mantenimiento y retirada, pacientes con dosis elevadas o escalado de dosis y pacientes con dosis ultra bajas. Para establecer un diagnóstico diferencial es importante tener en cuenta que un incremento de dosis puede producir una mejoría temporal en pacientes con tolerancia pero no en los que han desarrollado hiperalgesia. La prevalencia de dicho fenómeno es desconocida, pero puede ser más frecuente de lo esperado y muchas veces no reconocido. El mecanismo subyacente no está bien definido, pero existen diversos estudios experimentales tanto en modelos animales como en humanos en los que se observa que la hiperalgesia no está desencadenada por un único factor, sino que son muchos los implicados. Entre los mecanismos propuestos destacan: la mediación del receptor NMDA (N-metil-D-aspartato) activado por la liberación presináptica de glutamato, la modulación por la proteína-kinasa de calcio/calmodulina, el aumento en el número de nociceptores o la liberación de neurotransmisores excitadores. Se han realizado diversos estudios para describir la expresión y la relevancia de la hiperalgesia inducida por opioides en distintos grupos de pacientes: ex-adictos a opioides en tratamiento de mantenimiento con metadona, en exposición perioperatoria, en voluntarios sanos o en dolor crónico. Existen diferentes estrategias de tratamiento disponibles; entre las más aceptadas se encuentra la reducción en la dosis del opioide utilizado, la rotación del opioide o la asociación al tratamiento de otro tipo de analgésico. Otras opciones son los antagonistas del receptor NMDA o la terapia combinada con los inhibidores de la COX-2. En el presente trabajo se revisan los avances recientes en el conocimiento de los mecanismos subyacentes que la producen, los estudios clínicos realizados así como las diferentes estrategias de tratamiento disponibles (AU)

Opioid induced hyperalgesia is a paradoxical reaction characterized by an enhanced perception of pain related to the use of these drugs in the absence of disease progression or withdrawal syndrome. In contrast to cases of tolerance, defined as the loss of analgesic potency during prolonged use of opioids, no improvement is seen with dose escalation. Opioid induced hyperalgesia could be manifested in the context of maintenance dosing and withdrawal, at very high or escalating doses, and at ultra-low doses. To establish a differential diagnosis is important to consider that increasing the dose may produce a temporary improvement in patients with tolerance but not in those who develop hyperalgesia. Pathogenesis of this phenomenon is not well defined, but there are several experimental studies in animal models and in humans that have shown that hyperalgesia is not triggered by a single factor. Proposed mechanisms include: NMDA receptor mediation, modulation by the calcium/calmodulin protein kinase, the increase in the number of nociceptors or excitatory neurotransmitters release. There are different treatment strategies available, such as the reduction in the dose of opioid used, opioid rotation or association of other analgesic. Other options are NMDA receptor antagonists or combination therapy with COX-2 inhibitors. In this paper we review recent advances in the understanding of the underlying mechanisms, clinical studies and available treatment strategies (AU)

Homocysteine predicts increased NT-pro-BNP through impaired fatty acid oxidation.

BACKGROUND: The deficiency in methyl donors, folate and vitamin B12, increases homocysteine and produces myocardium hypertrophy with impaired mitochondrial fatty acid oxidation and increased BNP, through hypomethylation of peroxisome-proliferator-activated-receptor gamma co-activator-1α, in rat. This may help to understand better the elusive link previously reported between hyperhomocysteinemia and BNP, in human. We investigated therefore the influence of methyl donors on heart mitochondrial fatty acid oxidation and brain natriuretic peptide, in two contrasted populations. METHODS: Biomarkers of heart disease, of one carbon metabolism and of mitochondrial fatty acid oxidation were assessed in 1020 subjects, including patients undergoing coronarography and ambulatory elderly subjects from OASI cohort. RESULTS: Folate deficit was more frequent in the coronarography population than in the elderly ambulatory volunteers and produced a higher concentration of homocysteine (19.3 ± 6.8 vs. 15.3 ± 5.6, P<0.001). Subjects with homocysteine in the upper quartile (≥ 18 µmol/L) had higher concentrations of NT-pro-BNP (or BNP in ambulatory subjects) and of short chain-, medium chain-, and long chain-acylcarnitines, compared to those in the lower quartile (≤ 12 µmol/L), in both populations (P<0.001). Homocysteine and NT-pro-BNP were positively correlated with short chain-, medium chain-, long chain-acylcarnitines and with acylcarnitine ratios indicative of decreased mitochondrial acyldehydrogenase activities (P<0.001). In multivariate analysis, homocysteine and long chain acylcarnitines were two interacting determinants of NT-pro-BNP, in addition to left ventricular ejection fraction, body mass index, creatinine and folate. CONCLUSIONS: This study showed that homocysteine predicts increased NT-pro-BNP (or BNP) through a link with impaired mitochondrial fatty oxidation, in two contrasted populations.

Current immunity markers in insect ecological immunology: assumed trade-offs and methodological issues.

The field of ecological immunology currently relies on using a number of immune effectors or markers. These markers are usually used to infer ecological trade-offs (via conflicts in resource allocation), though physiological nature of these markers remains elusive. Here, we review markers frequently used in insect evolutionary ecology research: cuticle darkening, haemocyte density, nodule/capsule formation, phagocytosis and encapsulation/melanization via use of nylon filaments and beads, phenoloxidase activity, nitric oxide production, lysozyme and antimicrobial peptide production. We also provide physiologically based information that may shed light on the probable trade-offs inferred when these markers are used. In addition, we provide a number of methodological suggestions to improve immune marker assessment.