Genetic architecture of ADHD and overlap with other psychiatric disorders and cognition-related phenotypes.

Attention-deficit/hyperactivity disorder (ADHD) co-occurs with many other psychiatric disorders and traits. In this review, we summarize and interpret the existing literature on the genetic architecture of these comorbidities based on hypothesis-generating approaches. Quantitative genetic studies indicate that genetic factors play a substantial role in the observed co-occurrence of ADHD with many different disorders and traits. Molecular genetic correlations derived from genome-wide association studies and results of studies based on polygenic risk scores confirm the general pattern but provide effect estimates that are smaller than those from twin studies. The identification of the specific genetic variants and biological pathways underlying co-occurrence using genome-wide approaches is still in its infancy. The first analyses of causal inference using genetic data support causal relationships between ADHD and comorbid disorders, although bidirectional effects identified in some instances point to complex relationships. While several issues in the methodology and inferences from the results are still to be overcome, this review shows that the co-occurrence of ADHD with many psychiatric disorders and traits is genetically interpretable.

Effectiveness of nanoemulsions of clove and lemongrass essential oils and their major components against Escherichia coli and Botrytis cinerea.

Nanoemulsions exhibit a number of advantages to carry and deliver lipophilic compounds such as essential oils (EOs) due to their good stability and high surface area per volume unit. The purpose of this work was to assess the long-term stability of nanoemulsions of clove and lemongrass (LG) EOs and their principal components eugenol and citral (CI), respectively, at 3 different concentrations (2, 5 or 10 times their respective minimum inhibitory concentrations) and at two storage temperatures (1 °C and 21 °C). The initial droplet size of LG and CI-loaded nanoemulsions was below 100 nm and most of them kept droplet sizes in the nano-range until the end of storage at both temperatures. The ζ-potential was lower than - 40 mV, but it increased through storage, indicating a weaker alginate adsorption at the oil surface at both temperatures. The antimicrobial activity increased with the EOs concentration and was negatively affected by the highest storage temperature. Nanoemulsions containing CI and LG were able to significantly decrease Escherichia coli counts during storage, particularly at 1 °C. Nanoemulsions containing 1.0 and 2.0% w/w CI and 2.5% w/w LG were the most efficient in reducing Botrytis cinerea growth through storage, mainly at 1 °C. The nanoemulsions containing 1.0 and 2.0% w/w CI, as well as, 1.25 and 2.5% w/w LG better maintained their stability and antimicrobial effect along 6-months storage mainly when at 1 °C, making those nanoemulsions suitable as edible coatings for food preservation. Future studies should be oriented to evaluate the impact of these nanoemulsions on the organoleptic properties of coated foods and their potential toxicity.

Shock hipovolémico en paciente cirrótico secundario a hematoma del psoas / Hypovolemic shock in a patients with cirrhosis secondary to hematoma of the psoas

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What can genetics tell us about the cause of fixed airflow obstruction?

Chronic obstructive pulmonary disease (COPD) is a major cause of chronic morbidity and mortality worldwide with smoking being the most important risk factor of the disease. However, lung function and COPD are known to also have a genetic component and a deeper knowledge of the genetic architecture of the disease could lead to further understanding of predisposition to COPD and also to development of new therapeutic interventions. Genetic linkage studies and candidate gene association studies have not provided evidence to convincingly identify the genes underlying lung function or COPD. However, recent large genome-wide association studies (GWAS) including tens of thousands of individuals have identified 26 variants at different loci in the human genome that show robust association with quantitative lung function measures in the general population. A growing number of these variants are being shown to be associated with COPD. Following the identification of these new lung function loci, the challenge now lies in refining the signals to identify the causative variants underlying the association signals and relating these signals to the molecular pathways that underlie lung function.

Genome-wide association study to identify genetic determinants of severe asthma.

BACKGROUND: The genetic basis for developing asthma has been extensively studied. However, association studies to date have mostly focused on mild to moderate disease and genetic risk factors for severe asthma remain unclear. OBJECTIVE: To identify common genetic variants affecting susceptibility to severe asthma. METHODS: A genome-wide association study was undertaken in 933 European ancestry individuals with severe asthma based on Global Initiative for Asthma (GINA) criteria 3 or above and 3346 clean controls. After standard quality control measures, the association of 480 889 genotyped single nucleotide polymorphisms (SNPs) was tested. To improve the resolution of the association signals identified, non-genotyped SNPs were imputed in these regions using a dense reference panel of SNP genotypes from the 1000 Genomes Project. Then replication of SNPs of interest was undertaken in a further 231 cases and 1345 controls and a meta-analysis was performed to combine the results across studies. RESULTS: An association was confirmed in subjects with severe asthma of loci previously identified for association with mild to moderate asthma. The strongest evidence was seen for the ORMDL3/GSDMB locus on chromosome 17q12-21 (rs4794820, p=1.03×10((-8)) following meta-analysis) meeting genome-wide significance. Strong evidence was also found for the IL1RL1/IL18R1 locus on 2q12 (rs9807989, p=5.59×10((-8)) following meta-analysis) just below this threshold. No novel loci for susceptibility to severe asthma met strict criteria for genome-wide significance. CONCLUSIONS: The largest genome-wide association study of severe asthma to date was carried out and strong evidence found for the association of two previously identified asthma susceptibility loci in patients with severe disease. A number of novel regions with suggestive evidence were also identified warranting further study.

Clinical, molecular and biochemical characterization of nine Spanish families with Conradi-Hünermann-Happle syndrome: new insights into X-linked dominant chondrodysplasia punctata with a comprehensive review of the literature.

BACKGROUND: Conradi-Hünermann-Happle syndrome (CDPX2, OMIM 302960) is an inherited X-linked dominant variant of chondrodysplasia punctata which primarily affects the skin, bones and eyes. CDPX2 results from mutations in EBP (emopamil binding protein), and presents with increased levels of sterol precursors 8(9)-cholesterol and 8-dehydrocholesterol. OBJECTIVES: To expand the understanding of CDPX2, clinically, biochemically and genetically. METHODS: We present one of the largest series reported to date, including 13 female patients belonging to nine Spanish families. Patients were studied biochemically using gas chromatography-mass spectrometry, genetically using polymerase chain reaction and in their methylation status using the HUMARA assay. RESULTS: In our cases, there was a clear relationship between abnormal sterol profile and the EBP gene mutation. We describe three novel mutations in the EBP gene. EBP mutations were inherited in three out of nine families and were sporadic in the remaining cases. CONCLUSIONS: No clear genotype-phenotype correlation was found. Patients' biochemical profiles did not reveal a relationship between sterol profiles and severity of disease. A skewed X-chromosome inactivation may explain the clinical phenotype in CDPX2 in some familial cases.

[Therapeutic hypothermia in neurocritical patients]. / Hipotermia terapéutica en pacientes neurocríticos.

Induced hypothermia in neurocritical patients is one of the most promising neuroprotective therapies in the last decade. Unfortunately, the promising results obtained in experimental studies have had an unequal reflection in the different diseases that affect the neurocritical patient. The use of therapeutic hypothermia is clearly established in patients with neurological deterioration after cardiac arrest. On the contrary, its use in patients with traumatic brain injury is highly controversial. There is not enough evidence in stroke and hemorrhagic patients to support its use except in clinical trials. Nowadays, the greater understanding of the pathophysiology of secondary brain damage, the go od clinical results obtained in randomized clinical trials in patients with cerebral anoxia after ventricular fibrillation and the new cooling methods that have appeared have improved the interest of hypothermia in neurocritical patients. Induced hypothermia has a role in the intensive care unit. Critical care physicians should be familiar with the physiologic effects, current indications, techniques, and complications of induced hypothermia. This review elaborates on the clinical implications of hypothermia research in traumatic brain injury, anoxic, brain injury, stroke and intracerebral hemorrhage.

[Genetic mechanisms in the hereditary predisposition to colorectal cancer]. / Mecanismos genéticos en la predisposición hereditaria al cáncer colorrectal.

A proportion of colorectal cancers shows some type of genetic predisposition that can be recognised in clinical practice. From the classical dominant inheritance pattern of familial adenomatous polyposis or hereditary non-polyposis colorectal cancer, through the recessive transmission of the MYH associated polyposis, to the new syndromes of the "serrated pathway" or low-penetrance alleles, the discovery of new genes and a deeper understanding of the mechanisms of action of already-known ones are enabling us to understand new aspects of the colorectal carcinogenesis. This is throwing a new light on some of the observed familial aggregation patterns which had remained unexplained.

Mecanismos genéticos en la predisposición hereditaria al cáncer colorrectal / Genetic mechanisms in the hereditary predisposition to colorectal cancer

Una proporción de los cánceres colorrectales presentan algún tipo de predisposición genética que es posible reconocer en la práctica clínica. Desde los clásicos patrones hereditarios dominantes de la poliposis adenomatosa familiar o el cáncer de colon hereditario no asociado a poliposis, pasando por la transmisión recesiva mostrada por la poliposis asociada al gen MYH, hasta llegar a los novedosos síndromes de la “vía serrada” o los alelos de baja penetrancia, el descubrimiento de nuevos genes y el mejor conocimiento de los mecanismos de acción de los ya conocidos, están permitiendo comprender nuevos aspectos de la carcinogénesis colorrectal que arrojan nueva luz sobre algunas de las observaciones de patrones de agregación familiar al cáncer de colon que permanecían inexplicadas

A proportion of colorectal cancers shows some type of genetic predisposition that can be recognised in clinical practice. From the classical dominant inheritance pattern of familial adenomatous polyposis or hereditary non-polyposis colorectal cancer, through the recessive transmission of the MYH associated polyposis, to the new syndromes of the “serrated pathway” or low-penetrance alleles, the discovery of new genes and a deeper understanding of the mechanisms of action of already-known ones are enabling us to understand new aspects of the colorectal carcinogenesis. This is throwing a new light on some of the observed familial aggregation patterns which had remained unexplained

Enfermedad de Still del adulto en una gestante: tratamiento y evolución / Still´s disease in a pregnant woman: treatment and outcome

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Effect of sausage ingredients and additives on the production of enterocin A and B by Enterococcus faecium CTC492. Optimization of in vitro production and anti-listerial effect in dry fermented sausages.

Enterocin A and B in Enterococcus faecium CTC492 were co-induced by the different factors assayed in this study (r = 0.93) and followed primary metabolic kinetics. Enterocin production was significantly inhibited by sausage ingredients and additives, with the exception of nitrate. The addition of sodium chloride and pepper decreased production 16-fold. The temperature and pH influenced enterocin production, with optima between 25 and 35 degrees C, and from 6.0 to 7.5 of initial pH. The maximum activity was achieved, under favourable growth conditions, with MRS supplemented with sucrose (2%) plus glucose (0.25%) and Tween-80 (1%). MRS concentration, NaCl plus pepper addition, absence of Tween-80 in the growth medium, incubation at 45 degrees C and an initial pH under 5.5 were detrimental to bacteriocin production. Stress conditions did not favour enterocin production. Desadsorption was Tween-dependent. Enterocin A activity in the crude extracts stored at -80 degrees C was better preserved than enterocin B (when tested against their specific indicator strain), but anti-listerial activity remained intact. Applied as anti-listerial additives in dry fermented sausages, enterocins significantly diminished Listeria counts by 1. 13 log (P < 0.001), while Enterococcus faecium CTC492 added as starter culture did not significantly reduce Listeria counts (P > 0. 1) compared with the standard starter culture (Bac-). Enterocins A and B could be considered as extra biopreservative hurdles for listeria prevention in dry fermented sausages.

[Descriptive study of hemodialysis in the critical patient. Report of 198 cases]. / Estudio descriptivo de la hemodiálisis en el paciente crítico. A propósito de 198 casos.

In the last five year, 198 critic patients developed acute renal failure, requiring hemodialysis in the hospital. We realized a descriptive study and analyzed the factors that were statistically associated with higher mortality: a surgical etiology, clinic criteria for the inicial of hemodialysis, respiratory failure, hemodynamic inestability, hepatic insufficciency, disseminated intravascular coagulacion and oliguric or anuria. The sepsis and the cardiorrespiratory complications were the cause of mortality most important. The 14% of the surviving requiring continue in the programs of hemodyalisis.