Capillary malformation-arteriovenous malformation syndrome: a multicentre study.

BACKGROUND: Capillary malformation-arteriovenous malformation (CM-AVM) syndrome is a rare syndrome with characteristic skin lesions that are associated with fast-flow vascular malformations (FFVMs) in one-third of patients. Few case series have been described, and none in Spain. AIM: To identify the prevalence of dermatological parameters, FFVMs and associated features in a large series of patients with CM-AVM. METHODS: We conducted an observational study of patients with CM-AVM syndrome diagnosed in 15 Spanish hospitals over 3 years. The main clinical, radiological, genetic findings and associated diseases were analysed. RESULTS: In total, 64 patients were assessed. In 26.5% of cases, the diagnosis was incidental. In 75% of patients, there was one significantly larger macule, which we termed the 'herald patch'. FFVMs were detected in 34% of the patients, with 30% located on the skin, 7.8% in the brain and in 1.5% in the spine. There was a positive family history in 65% of the 64 patients. Genetic analysis was performed for RASA1 mutations in 57 patients, of whom 42 (73%) had a positive result. All 4 patients tested for EPHB4 mutations had a positive result. No tumour lesions were detected in the series, except for five infantile haemangiomas. CONCLUSIONS: Our data on clinical lesions, associated FFVM, family history and genetics are similar to those previously published in the literature. An extensive data analysis failed to demonstrate any statistically significant association between the presence of an FFVM and any clinical, familial or genetic parameter that could predict its onset, although a link between the presence of a herald patch on the midline face and the presence of a brain FFVM was observed. We did not detect any genotype-phenotype correlation.

Ecological drivers of body size evolution and sexual size dimorphism in short-horned grasshoppers (Orthoptera: Acrididae).

Sexual size dimorphism (SSD) is widespread and variable in nature. Although female-biased SSD predominates among insects, the proximate ecological and evolutionary factors promoting this phenomenon remain largely unstudied. Here, we employ modern phylogenetic comparative methods on eight subfamilies of Iberian grasshoppers (85 species) to examine the validity of different models of evolution of body size and SSD and explore how they are shaped by a suite of ecological variables (habitat specialization, substrate use, altitude) and/or constrained by different evolutionary pressures (female fecundity, strength of sexual selection, length of the breeding season). Body size disparity primarily accumulated late in the history of the group and did not follow a Brownian motion pattern, indicating the existence of directional evolution for this trait. We found support for the converse of Rensch's rule (i.e. females are proportionally bigger than males in large species) across all taxa but not within the two most speciose subfamilies (Gomphocerinae and Oedipodinae), which showed an isometric pattern. Our results do not provide support for the fecundity or sexual selection hypotheses, and we did not find evidence for significant effects of habitat use. Contrary to that expected, we found that species with narrower reproductive window are less dimorphic in size than those that exhibit a longer breeding cycle, suggesting that male protandry cannot solely account for the evolution of female-biased SSD in Orthoptera. Our study highlights the need to consider alternatives to the classical evolutionary hypotheses when trying to explain why in certain insect groups males remain small.

The role of environment and core-margin effects on range-wide phenotypic variation in a montane grasshopper.

The integration of genetic information with ecological and phenotypic data constitutes an effective approach to gain insight into the mechanisms determining interpopulation variability and the evolutionary processes underlying local adaptation and incipient speciation. Here, we use the Pyrenean Morales grasshopper (Chorthippus saulcyi moralesi) as study system to (i) analyse the relative role of genetic drift and selection in range-wide patterns of phenotypic differentiation and (ii) identify the potential selective agents (environment, elevation) responsible for variation. We also test the hypothesis that (iii) the development of dispersal-related traits is associated with different parameters related to population persistence/turnover, including habitat suitability stability over the last 120 000 years, distance to the species distribution core and population genetic variability. Our results indicate that selection shaped phenotypic differentiation across all the studied morphological traits (body size, forewing length and shape). Subsequent analyses revealed that among-population differentiation in forewing length was significantly explained by a temperature gradient, suggesting an adaptive response to thermoregulation or flight performance under contrasting temperature regimes. We found support for our hypothesis predicting a positive association between the distance to the species distribution core and the development of dispersal-related morphology, which suggests an increased dispersal capability in populations located at range edges that, in turn, exhibit lower levels of genetic variability. Overall, our results indicate that range-wide patterns of phenotypic variation are partially explained by adaptation in response to local environmental conditions and differences in habitat persistence between core and peripheral populations.

Dispersion of the invasive common carp Cyprinus carpio in southern South America: changes and expectations, westward and southward.

Common carp Cyprinus carpio possess multiple traits that contribute to their success as an invasive species. They have been introduced across the globe, and abundant populations can have numerous negative effects. Although ecological niche-based modelling techniques have been used to predict the potential range of C. carpio invasion in U.S.A., occurrence and abundance patterns have not yet been considered on a regional scale. In the present review new locations are documented, the status of the southernmost population has been studied and the probability of new lakes and reservoirs being colonized by C. carpio has been obtained and related to environmental conditions. The new localities for C. carpio have expanded its distribution westward, into the Andean Region, and present results from the South American southernmost population have shown a well-established population. Analysis of presence data provided two principal results: (1) the probability of a site being with C. carpio can be inferred using environmental variables and (2) the probability of a site being with C. carpio is a useful tool for the prediction of future invasions. Selective fishing on the Negro basin could constitute a potential mitigation measure, decreasing the abundance of the species and thus reducing the species' potential for southward expansion. These results reinforce the idea that artisanal fisheries, food production and conservation interests should be taken into account by local government management agencies in any discussion regarding the southern distribution of C. carpio in the near future.

Maternal obesity programs offspring non-alcoholic fatty liver disease through disruption of 24-h rhythms in mice.

BACKGROUND: Maternal obesity increases offspring propensity to metabolic dysfunctions and to non-alcoholic fatty liver disease (NAFLD), which may lead to cirrhosis or liver cancer. The circadian clock is a transcriptional/epigenetic molecular machinery synchronising physiological processes to coordinate energy utilisation within a 24-h light/dark period. Alterations in rhythmicity have profound effects on metabolic pathways, which we sought to investigate in offspring with programmed NAFLD. METHODS: Mice were fed a standard or an obesogenic diet (OD), before and throughout pregnancy, and during lactation. Offspring were weaned onto standard or an OD at 3 weeks postpartum and housed in 12:12 light/dark conditions. Biochemical and histological indicators of NAFLD and fibrosis, analysis of canonical clock genes with methylation status and locomotor activity were investigated at 6 months. RESULTS: We show that maternal obesity interacts with an obesogenic post-weaning diet to promote the development of NAFLD with disruption of canonical metabolic rhythmicity gene expression in the liver. We demonstrate hypermethylation of BMAL-1 (brain and muscle Arnt like-1) and Per2 promoter regions and altered 24-h rhythmicity of hepatic pro-inflammatory and fibrogenic mediators. CONCLUSIONS: These data implicate disordered circadian rhythms in NAFLD and suggest that disruption of this system during critical developmental periods may be responsible for the onset of chronic liver disease in adulthood.

Perinatal maternal feeding with an energy dense diet and/or micronutrient mixture drives offspring fat distribution depending on the sex and growth stage.

Maternal nutrition during pregnancy and lactation influences offspring development and health. Novel studies have described the effects on next generation obesity-related features depending on maternal macro- and micro-nutrient perinatal feeding. We hypothesized that the maternal obesogenic diet during pregnancy and lactation programs an obese phenotype, while maternal micronutrient supplementation at these stages could partially prevent these features. Thus, the aim was to assess the influence of a perinatal maternal feeding with an obesogenic diet enriched in fat and sucrose and a micronutrient supplementation during pregnancy and lactation on offspring growth and obese phenotypical features during life course. Female Wistar rats were assigned to four dietary groups during pregnancy and lactation: control, control supplemented with micronutrients (choline, betaine, folic acid and vitamin B12 ), high-fat sucrose (HFS) and HFS supplemented. At weaning, the offspring were transferred to a chow diet, and weight and fat mass were measured at weeks 3, 12 and 20. At birth, both male and female offspring from mothers fed the obesogenic diet showed lower body weight (-5 and -6%, respectively), while only female offspring weight decreased by maternal micronutrient supplementation (-5%). During lactation, maternal HFS diet was associated with increased body weight, while micronutrient supplementation protected against body weight gain. Whole body fat mass content increased at weeks 3, 12 and 20 (from 16 to 65%) due to maternal HFS diet. Maternal micronutrient supplementation decreased offspring fat mass content at week 3 (-8%). Male offspring showed higher adiposity than females at weeks 12 and 20. In conclusion, maternal HFS feeding during pregnancy and lactation was associated with a low offspring weight at birth and obese phenotypical features during adult life in a sex- and time-dependent manner. Furthermore, maternal methyl donor supplementation protected against body weight gain in male offspring during lactation and in female offspring also during juvenile period.

Previous outpatient antibiotic use in patients admitted to hospital for COPD exacerbations: room for improvement.

PURPOSE: Several studies have analyzed factors associated to hospitalization in chronic obstructive pulmonary disease (COPD) patients. However, data are lacking on the quality of treatment received by patients prior to hospital admission. The present study analyzed how often patients requiring hospitalization for a COPD exacerbation had received previous treatment for the exacerbation, particularly antibiotics. METHODS: This was a multicenter, cross-sectional, observational study conducted in 30 Spanish hospitals among COPD patients aged >40 years who were hospitalized for an acute exacerbation. Patients were grouped according to whether or not they had received treatment prior to admission and, subsequently, according to whether or not they had received antibiotics. Patient eligibility for antibiotic therapy was assessed using both national and European guidelines. RESULTS: The study population consisted of 298 patients, of which 277 (93 %) were men, with a mean [standard deviation (SD)] age of 69.1 (9.5) years. One hundred and thirty-three patients (45 %) had received treatment prior to admission; among these, 76/133 (57 %) had received antibiotic therapy. However, 81-91 % of these patients fulfilled criteria for this therapy. Antibiotic use was significantly associated with yellow or green-yellow sputum prior to the exacerbation, a higher number of exacerbations in the previous year, more visits to emergency departments, and bronchiectasis. On the other hand, 10-20 % of patients who did receive antibiotics were not eligible for this therapy according to guidelines. CONCLUSIONS: This study demonstrates a low rate of previous outpatient treatment and antibiotic use among patients with a COPD exacerbation requiring hospital admission.

Tradeoffs and synergies in wetland multifunctionality: A scaling issue.

Wetland area in agricultural landscapes has been heavily reduced to gain land for crop production, but in recent years there is increased societal recognition of the negative consequences from wetland loss on nutrient retention, biodiversity and a range of other benefits to humans. The current trend is therefore to re-establish wetlands, often with an aim to achieve the simultaneous delivery of multiple ecosystem services, i.e., multifunctionality. Here we review the literature on key objectives used to motivate wetland re-establishment in temperate agricultural landscapes (provision of flow regulation, nutrient retention, climate mitigation, biodiversity conservation and cultural ecosystem services), and their relationships to environmental properties, in order to identify potential for tradeoffs and synergies concerning the development of multifunctional wetlands. Through this process, we find that there is a need for a change in scale from a focus on single wetlands to wetlandscapes (multiple neighboring wetlands including their catchments and surrounding landscape features) if multiple societal and environmental goals are to be achieved. Finally, we discuss the key factors to be considered when planning for re-establishment of wetlands that can support achievement of a wide range of objectives at the landscape scale.

Maternal weight gain induced by an obesogenic diet affects adipose accumulation, liver weight, and insulin homeostasis in the rat offspring depending on the sex.

BACKGROUND: The aim of this research was to analyze the influence of the maternal dietary intake before pregnancy, as well as the parental impact on the response to a transgenerational high-fat-diet in rats. METHODS: Ten female Wistar rats were fed a standard or a high-fat-sucrose (HFS) diet in the 8 weeks prior to pregnancy. Adult offsprings were assigned to a control or obesogenic diet for 8 weeks. Then, rat tissues and plasma samples were collected for analyzing tissue weight, liver triglycerides, and biochemical parameters such as triglycerides, HDL cholesterol, glucose, and insulin levels. RESULTS: The offspring of rats fed a HFS diet gained less weight when they were fed the same diet than those fed a HFS diet combined with maternal control diet. Insulin levels were higher in rats fed a HFS diet (p<0.05) in both sexes; however, maternal HFS diet reversed, partially in males and total- ly in females, this hormonal imbalance. In male newborns, diet-induced maternal weight gain before pregnancy significantly influenced visceral (R 2 =0.373) and subcutaneous (R 2 =0.239) adipose deposition as well as liver weight (R 2 =0.130). Paternal genetic make-up was also a relevant factor affecting adiposity in both sexes (R 2 =0.333 in visceral fat; R 2 =0.183 in subcutaneous fat in males, and 0.292 and 0.282, respectively in females) as well as plasma triglycerides (R 2 =0.193 in males and R 2 =0.251 in females). CONCLUSIONS: The genetic parental background and pre-natal maternal diet are important factors in the response to a hypercaloric diet and affect body composition and glucose homeostasis traits, including insulin secretion and homeostatic model assessment index.

Evidence of subtle departures from Mendelian segregation in a wild lesser kestrel (Falco naumanni) population.

Some alleles are inherited more frequently than expected from Mendel's rule. This phenomenon, known as transmission ratio distortion (TRD), is found in a broad variety of taxa, but it is thought to be unusual and occurs at a low frequency in any particular population. Here, we used seven microsatellite markers to search for possible TRD in a wild lesser kestrel (Falco naumanni) population. Among the nine alleles analysed with at least 200 known meioses for each sex, we found that two of them (156-AG5 in males and 362-FN1.11 in females) presented subtle (k=0.6) but significant departures from Mendelian segregation. Moreover, in a sample of 53 alleles with at least 15 known meioses, we found a positive correlation between their transmission rates and their frequencies in the population. To estimate the transmission scores for the loci and individuals, we developed a method that allowed us to discover that another locus, FP-46, showed significant TRD, despite the lack of a significant deviation from parity for the alleles considered individually. Finally, we found a consistent transmission bias both within loci and within individuals across loci. Inter-individual differences in TRD support the idea that distorters act over several loci that are evenly distributed across the whole genome, particularly in individuals bearing the distorter alleles. Overall, these findings suggest that TRD might be a more widespread phenomenon than previously revealed by analyses at the allele level.

The situation of infection in the elderly in Spain: a multidisciplinary opinion document.

Infection in the elderly is a huge issue whose treatment usually has partial and specific approaches. It is, moreover, one of the areas where intervention can have the most success in improving the quality of life of older patients. In an attempt to give the widest possible focus to this issue, the Health Sciences Foundation has convened experts from different areas to produce this position paper on Infection in the Elderly, so as to compare the opinions of expert doctors and nurses, pharmacists, journalists, representatives of elderly associations and concluding with the ethical aspects raised by the issue. The format is that of discussion of a series of pre-formulated questions that were discussed by all those present. We begin by discussing the concept of the elderly, the reasons for their predisposition to infection, the most frequent infections and their causes, and the workload and economic burden they place on society. We also considered whether we had the data to estimate the proportion of these infections that could be reduced by specific programmes, including vaccination programmes. In this context, the limited presence of this issue in the media, the position of scientific societies and patient associations on the issue and the ethical aspects raised by all this were discussed.

Temporal variation of heterozygosity-based assortative mating and related benefits in a lesser kestrel population.

Heterozygosity as a target of mate choice has received much attention in recent years and there is growing evidence supporting its role in the evolution of mate preferences. In this study we analyse mating patterns in relation to heterozygosity in a lesser kestrel (Falco naumanni) population intensively monitored over six study years (2002-2007). The magnitude of heterozygosity-based assortative mating varied over time, being particularly patent in the last study years (2006, 2007). We have found evidence that this mating pattern entails both direct and indirect-genetic benefits. Clutch size increased with female heterozygosity and more heterozygous males raised a higher number of fledglings particularly in those years when the strength of the heterozygosity-based assortative mating was markedly higher. In the last study year, parent-offspring correlation of heterozygosity was stronger and higher than the expected if individuals would have randomly mated with respect to heterozygosity. Overall, our results offer empirical support to the heterozygous mate hypothesis of sexual selection but suggest that genetic diversity may act as a temporally variable target for mate choice.

Fat-to-glucose interconversion by hydrodynamic transfer of two glyoxylate cycle enzyme genes.

The glyoxylate cycle, which is well characterized in higher plants and some microorganisms but not in vertebrates, is able to bypass the citric acid cycle to achieve fat-to-carbohydrate interconversion. In this context, the hydrodynamic transfer of two glyoxylate cycle enzymes, such as isocytrate lyase (ICL) and malate synthase (MS), could accomplish the shift of using fat for the synthesis of glucose. Therefore, 20 mice weighing 23.37 +/- 0.96 g were hydrodinamically gene transferred by administering into the tail vein a bolus with ICL and MS. After 36 hours, body weight, plasma glucose, respiratory quotient and energy expenditure were measured. The respiratory quotient was increased by gene transfer, which suggests that a higher carbohydrate/lipid ratio is oxidized in such animals. This application could help, if adequate protocols are designed, to induce fat utilization for glucose synthesis, which might be eventually useful to reduce body fat depots in situations of obesity and diabetes.

Characterization of the cytotoxic effects of the combination of cisplatin and flavanol (-)-epicatechin on human lung cancer cell line A549. An isobolographic approach.

BACKGROUND: Among malignancies, lung cancer is a leading cause of death. Platinum-based therapeutic compounds used to treat lung cancer have not been able to increase the survival of patients and such compounds have a high incidence of adverse and toxic effects. It has been proposed that flavonoids such as catechins may significantly reduce the risk of developing cancer, alongside with other health benefits. The aim of this work was to determine the effect of (-)-epicatechin, the main flavanol found in cocoa, on the proliferation of the lung non-small cell adenocarcinoma cancer cell line A549, and to determine its effects when added simultaneously with cisplatin. MATERIALS AND METHODS: Concentration-response curves for cisplatin and epicatechin were obtained, inhibitory concentrations calculated and an isobolographic analysis was then performed. RESULTS: We found that epicatechin has a concentration-dependent inhibitory effect on proliferation of tumor cells and the isobolographic analysis reveals that the effect of its combination with cisplatin is synergistic. It was also observed that epicatechin promotes cell death by apoptosis. CONCLUSIONS: Epicatechin might be considered for future studies to explore its possible use as coadjuvant in cisplatin-based treatments.

[Efficiency and mitochondrial metabolism: an etiological axis for obesity?]. / Eficiencia y metabolismo mitocondrial: un eje etiológico de la obesidad?

Obesity, an increasing prevalent disease, appears as a consequence of an energetic umbalance that might be related to the efficiency of the cellular energetic machinery involving the mitochondria. In this organelle takes place the oxidative phosphorylation, that ends with the transformation of the nutrients to energy and the ATP production. During this process, free radicals of high oxidative power maybe blocked by endogenous antioxidants like the glutathion, in collaboration with the contribution of antioxidants supplied by the diet. The discovery of mitochondrial uncoupling proteins (UCPs) opened a new field of investigation, emphasizing the role of UCP1 or thermogenin, which generates an energy dissipation as heat and diminishing the amount of formed ATP and ROS and forcing the cell that expresses the UCP1 to oxidize more nutrients to obtain energy. Also, genetic studies have been carried out about UCP2 and UCP3 polymorphisms that relate them to obesity.

Bariatric surgery as a treatment for metabolic syndrome.

Obesity is the pandemic of the 21st century. Obesity comorbidities, including hypertension, dyslipidaemia and glucose intolerance define metabolic syndrome, which increases mortality risk and decreases the quality of life. Compared with lifestyles (diet and physical activity) and pharmacological interventions, bariatric surgery is by far the most effective treatment for obesity and its comorbidities. This minimally invasive surgical treatment is based on an increase of satiety (by hormonal regulation and decreasing stomach volume) or a decrease in nutrient retention (gastric and/or intestinal resection). Bariatric surgery has widely demonstrated a beneficial effect on excess body weight loss, cardiovascular risk, dyslipidaemia, non-alcoholic fatty liver disease or glucose homeostasis, among other obesity-related metabolic diseases. This review describes current efforts for the implementation of bariatric surgery in metabolic syndrome, which are mainly focused on the formulation of key definition criteria for targeting the most suitable population for this therapeutic approach. Patients should undergo appropriate nutritional and psychological follow up in order to achieve and maintain weight loss milestones and a healthy metabolic status.

BAHNG score: predictive model for detection of subjects with the oropharynx colonized by uncommon microorganisms.

OBJECTIVE: Pneumonia is most frequently produced by the microaspiration of flora that colonizes the oropharynx. Etiological diagnosis of pneumonia is infrequent in clinical practise and empirical treatment should be prescribed. The aims of the present study were to determine the factors associated with oropharynx colonization by uncommon microorganisms (UM) and to develop a predictive model. METHODS: A cross-sectional study that included all pa-tients living in one long-term care facilities was developed. Demographic, comorbidities, basal functional status and clinical data were collected. To determinate the oropharyngeal colonization, a single sample of pharynx was obtained for each subject using a cotton swab. RESULTS: A total of 221 subjects were included, mean age 86.27 (SD 8.05) years and 157 (71%) were female. In 32 (14.5%) subjects UM flora was isolated, Gram-negative bacilli in 16 (7.2%) residents, and Staphylococcus aureus in 16 (7.2%). The predictive model included the presence of hypertension, neuromuscular disease, Barthel <90 and use of PEG. The BAHNG score (BArthel, Hypertension, Neuromuscular, Gastrostomy), showed an area under the curve of 0.731 (CI 95% 0.643-0.820; p<0.001). We have classified patients according to this score in low (0-2 points), intermediate (3-5 points) and high risk (≥ 6). The probability of UM colonization in the oropharyngeal based on this classification is 4.1%, 15.8% and 57.1% for low, intermediate and high risk, respectively. CONCLUSIONS: The BAHNG score could help in the identifications of elderly patients with high risk of colonization by UM. In case of pneumonia the evaluation of the subject through this score could help in the initial decisions concerning antibiotic treatment.

Role of assessing liver fibrosis in management of chronic hepatitis C virus infection.

Fibrosis progression is common in hepatitis C. Both host and viral factors influence its natural history. Liver fibrosis is a key predictive factor for advanced disease including endpoints such as liver failure, cirrhosis and hepatocellular carcinoma (HCC). METAVIR fibrosis stages F3-F4 have been considered as the threshold for antiviral therapy. However, this aspect is controversial after the advent of new direct-acting antivirals (DAAs) because they show an excellent efficacy and safety profile. Moreover, in the DAA era, fibrosis stage seems not to be a predictive factor of a sustained virological response (SVR). Viral eradication decreases liver damage by improving the inflammation, as well as by regressing fibrosis irrespective of the treatment regimen. Non-invasive methods are useful in the assessment of liver fibrosis, replacing liver biopsy in clinical practice; but their usefulness for monitoring fibrosis after SVR needs to be demonstrated. Fibrosis regression has been demonstrated after the eradication of hepatitis C virus infection and is associated with a lower risk of hepatic cirrhosis and liver cancer. However, patients showing advanced fibrosis and cirrhosis must be followed-up after SVR, as risks of portal hypertension and HCC remain.

[About microbiological methods for detection of oxacillin resistance in coagulase-negative staphylococci]. / Sobre los métodos microbiológicos para la detección de la resistencia a oxacilina en Staphylococcus coagulasa negativos.

OBJECTIVE: Coagulase-negative staphylococci (CoNS) take part of the human skin and mucous membranes, but they are also involving in infections with the increasing use of prosthetic, indwelling devices or intravascular catheter-related bacteraemia. They are more resistance than Staphylococcus aureus against a wide range of antimicrobial agents, and it have been observed an increase in morbidity and mortality of patients with incorrect treatment. METHODS: To analyze the results obtained by different commercial techniques: two automatic microdilution systems (MicroScan and Vitek2 Compact), PBP2a agglutiation test, with and without 1 µg oxacillin disk induction, and detection of mecA gene by nucleic acids amplification techniques, for the diagnosis of methicillin resistance staphylococci in 170 strains of CoNS isolated from blood cultures. RESULTS: One hundred and seventy methicillin resistance staphylococci were detected by MicroScan, 167 strains by Vitek 2 Compact, 115 strains were PBP2a positive without oxacillin induction and 168 after oxacillin induction. Finally, 167 strains were mecA gene positive detected by nucleic acids amplification techniques. CONCLUSIONS: It is necessary to do oxacillin induction before PBP2a test to avoid false negatives. There are a great variability in the phenotypic expression of methicillin resistance in CoNS.