The Influence of Body Mass Index on Outcomes in Patients Undergoing Cardiac Surgery: Does the Obesity Paradox Really Exist?

Purpose

Obesity influences risk stratification in cardiac surgery in everyday practice. However, some studies have reported better outcomes in patients with a high body mass index (BMI): this is known as the obesity paradox. The aim of this study was to quantify the effect of diverse degrees of high BMI on clinical outcomes after cardiac surgery, and to assess the existence of an obesity paradox in our patients.

Methods

A total of 2,499 consecutive patients requiring all types of cardiac surgery with cardiopulmonary bypass between January 2004 and February 2009 were prospectively studied at our institution. Patients were divided into four groups based on BMI: normal weight (18.5–24.9 kg∙m⁻²; n = 523; 21.4%), overweight (25–29.9kg∙m⁻²; n = 1150; 47%), obese (≥30–≤34.9kg∙m⁻²; n = 624; 25.5%) and morbidly obese (≥35kg∙m⁻²; n = 152; 6.2%). Follow-up was performed in 2,379 patients during the first year.

Results

After adjusting for confounding factors, patients with higher BMI presented worse oxygenation and better nutritional status, reflected by lower PaO₂/FiO₂ at 24h and higher albumin levels 48h after admission respectively. Obese patients showed a higher risk for Perioperative Myocardial Infarction (OR: 1.768; 95% CI: 1.035–3.022; p = 0.037) and septicaemia (OR: 1.489; 95% CI: 1.282–1.997; p = 0.005). In-hospital mortality was 4.8% (n = 118) and 1-year mortality was 10.1% (n = 252). No differences were found regarding in-hospital mortality between BMI groups. The overweight group showed better 1-year survival than normal weight patients (91.2% vs. 87.6%; Log Rank: p = 0.029. HR: 1.496; 95% CI: 1.062–2.108; p = 0.021).

Conclusions

In our population, obesity increases Perioperative Myocardial Infarction and septicaemia after cardiac surgery, but does not influence in-hospital mortality. Although we found better 1-year survival in overweight patients, our results do not support any protective effect of obesity in patients undergoing cardiac surgery.     

NK cell immunophenotypic and genotypic analysis of infants with severe respiratory syncytial virus infection

Respiratory syncytial virus (RSV) is the leading cause of severe lower respiratory tract infection in infants. Reduced numbers of NK cells have been reported in infants with severe RSV infection; however, the precise role of NK cells during acute RSV infection is unclear. In this study the NK and T cell phenotypes, LILRB1 gene polymorphisms and KIR genotypes of infants hospitalized with RSV infection were analyzed. Compared to controls, infants with acute RSV infection showed a higher proportion of LILRB1+ T cells; in addition, a subgroup of infants with RSV infection showed an increase in LILRB1+ NK cells. No differences in NKG2C, NKG2A, or CD161 expression between RSV infected infants and controls were observed. LILRB1 genotype distribution of the rs3760860 A>G, and rs3760861 A>G single nucleotide polymorphisms differed between infants with RSV infection and healthy donors, whereas no differences in any of the KIR genes were observed. Our results suggest that LILRB1 participates in the pathogenesis of RSV infection. Further studies are needed to define the role of LILRB1+ NK in response to RSV and to confirm an association between LILRB1 polymorphisms and the risk of severe RSV infection.     

Electrophysiological Responses to Affective Stimuli in Neglectful Mothers

Results illustrating an atypical neural processing in the early and late differentiation of infant faces have been obtained with neglectful mothers. The present study explores whether a different pattern of response is observed when using non-infant affective pictures. We examined the event-related evoked potentials and induced delta, theta and alpha activity in 14 neglectful mothers and 14 control mothers elicited while categorizing positive, negative and neutral pictures from the International Affective Picture System. Self-reports of anhedonia and empathy were also recorded. Early posterior negativity, P200 and late positive potential components were modulated by the emotional content of pictures in both groups. However, the LPP waveform had a more delayed and more attenuated maximum in neglectful mothers than in control mothers. Oscillatory responses indicated lower power increases for neglectful mothers than for control mothers in delta (1–4 Hz), theta (4–8 Hz) and lower alpha (8–10 Hz) bands at frontal sites, and a more consistent increase for neglectful mothers in theta and lower alpha bands at occipital sites, especially for negative pictures. These findings help us to better understand the limits of emotional insensitivity in neglectful mothers.     

Integration of invasive <Emphasis Type="Italic">Opuntia</Emphasis> spp. by native and alien seed dispersers in the Mediterranean area and the Canary Islands

The success of many alien plant species depends on mutualistic relationships with other species. We describe the assemblage of seed dispersers on three species of alien Opuntia invading Mediterranean and Macaronesian habitats, and examine the quality of such plant-animal interactions. We identified vertebrates consuming O. maxima, O. dillenii and O. stricta fruits by direct observation and collecting droppings and pellets. Phenology of the alien species, as well as that of coexisting native species, was monitored for an entire year. Germination tests of ingested and non-ingested seeds were performed both in the greenhouse and in the field. Seed coat thickness and viability were also measured for all treatments. A great variety of taxa, including reptiles, birds and mammals actively participate in the seed dispersal of Opuntia. Phenology of Opuntia fruits in Menorca and Tenerife overlaps with only a few native fleshy-fruited plants present in the study areas, which suggests an advantage for the invader. Most seeds germinated during the second year of the experiment, independently of the effect produced by the dispersers’ guts. We found great variation in the germination percentage of Opuntia after gut passage and in the effects of ingestion on seed coat thickness. Seed viability was somewhat reduced after gut passage compared to manually depulped seeds. Our results show how different Opuntia species are integrated into native communities by means of mutualistic interactions, with both native and alien dispersers. Although with heterogeneous effects, either type of disperser potentially contributes to the spread of these alien cacti in the recipient areas.     

Epigenetic changes in B lymphocytes associated with house dust mite allergic asthma

Although there is no doubt about the influence of the genetic background in the onset of the allergic diseases, Epigenome-Wide Association Studies are needed to elucidate the possible relationship between allergic diseases and epigenomic dysregulation. In this study we aimed to analyze the epigenetic patterns, in terms of DNA methylation, of three well-characterized populations of house dust mite allergic subjects, aspirin-intolerant asthmatics and controls. As a first, genome-wide phase, we used the HELP assay to study the methylation patterns in CD19 (+) B lymphocytes in these populations, and found that there are reproducible epigenetic differences at limited numbers of loci distinguishing the groups, corroborated by bisulphite MassArray in a second validation phase of an expanded 40 subject group. These validated epigenetic changes occur at loci characterized as important for the immune response. One such locus is a new candidate gene, CYP26A1, which shows differential methylation patterns and expression levels between groups. Our results suggest that epigenomic dysregulation may contribute to the susceptibility to allergic diseases, showing for the first time differences in DNA methylation between allergic and non-allergic healthy subjects, both globally and at specific loci. These observations indicate that the epigenome may offer new pathophysiological insights and therapeutic targets in atopic diseases.     

Proteomic signature of Apolipoprotein J in the early phase of new-onset myocardial infarction

Acute myocardial infarction (AMI) is one of the major causes of mortality and morbidity worldwide. Despite all the efforts, there is a lack of early markers for prevention, diagnosis, and treatment of ischemic syndromes. By applying a proteomic expression profiling approach to identify biomarkers of early stages of AMI, we have detected significant changes in Apolipoprotein J/clusterin (ApoJ) in patients with an acute new-onset myocardial infarction. ApoJ characterization by bidimensional electrophoresis (2-DE), followed by mass spectrometry (MALDI-TOF) depicted a cluster of 13 spots (pI, 4.5-5.0; M(w), 37.1-47.3 kDa) with a significantly different distribution between AMI-patients and controls. Specifically, spots 2, 3, 7, 10, and 13 showed a 2-fold increase in their intensity in AMI-patients (P = 0.001). Western-blot analysis (WB) for total serum ApoJ depicted two bands of 40-45 and 65-70 kDa. When only glycosylated forms were analyzed, the band of 65-70 kDa was the most predominant one. A 25% decrease (P = 0.05) of ApoJ glycosylated forms in AMI-patients was detected by 2-DE. Serum ApoJ levels, determined by a commercial ELISA, were significantly lower (P < 0.001) in AMI-patients (n = 39) immediately after the event than in controls (n = 60). In 60% of patients, the lowest ApoJ level was detected within 6 h after the onset of AMI. Between 72 and 96 h after admission, ApoJ values in AMI-patients had reached control levels. Our results demonstrate alterations in ApoJ proteomic profile, due to a differential glycosylation pattern, in AMI-patients within the first 6 h after the onset of the event. Therefore, the analysis of this isoform glycosylation shift in patients with AMI may be of better use to understand ApoJ function than the total serum levels of ApoJ and this isoform shift may become an early marker of AMI.     

On the Atomic Velocities in Molecular and Langevin Dynamics Simulations of Soft-Sphere Systems

Abstract

Time dependent probability distributions of the changes of direction of atomic velocities are considered in order to examine in detail the shape of the trajectories obtained through molecular simulations. We have analysed the atomic motions obtained from molecular dynamics simulations of soft-sphere systems at three very different states, i.e. a dilute fluid, a liquid at high density, and a solid. The methodology has also been used to check the reliability of the velocity evolution obtained when it is assumed that a single particle obeys the generalized Langevin equation and the effect of the other particles is represented by friction and random forces.     

Modulation in Wistar Rats of Blood Corticosterone Compartmentation by Sex and a Cafeteria Diet

In the metabolic syndrome, glucocorticoid activity is increased, but circulating levels show little change. Most of blood glucocorticoids are bound to corticosteroid-binding globulin (CBG), which liver expression and circulating levels are higher in females than in males. Since blood hormones are also bound to blood cells, and the size of this compartment is considerable for androgens and estrogens, we analyzed whether sex or eating a cafeteria diet altered the compartmentation of corticosterone in rat blood. The main corticosterone compartment in rat blood is that specifically bound to plasma proteins, with smaller compartments bound to blood cells or free. Cafeteria diet increased the expression of liver CBG gene, binding plasma capacity and the proportion of blood cell-bound corticosterone. There were marked sex differences in blood corticosterone compartmentation in rats, which were unrelated to testosterone. The use of a monoclonal antibody ELISA and a polyclonal Western blot for plasma CBG compared with both specific plasma binding of corticosterone and CBG gene expression suggested the existence of different forms of CBG, with varying affinities for corticosterone in males and females, since ELISA data showed higher plasma CBG for males, but binding and Western blot analyses (plus liver gene expression) and higher physiological effectiveness for females. Good cross- reactivity to the antigen for polyclonal CBG antibody suggests that in all cases we were measuring CBG.The different immunoreactivity and binding affinity may help explain the marked sex-related differences in plasma hormone binding as sex-linked different proportions of CBG forms.     

PTEN Increases Autophagy and Inhibits the Ubiquitin-Proteasome Pathway in Glioma Cells Independently of its Lipid Phosphatase Activity

Two major mechanisms of intracellular protein degradation, autophagy and the ubiquitin-proteasome pathway, operate in mammalian cells. PTEN, which is frequently mutated in glioblastomas, is a tumor suppressor gene that encodes a dual specificity phosphatase that antagonizes the phosphatidylinositol 3-kinase class I/AKT/mTOR pathway, which is a key regulator of autophagy. Here, we investigated in U87MG human glioma cells the role of PTEN in the regulation of autophagy and the ubiquitin-proteasome pathway, because both are functionally linked and are relevant in cancer progression. Since U87MG glioma cells lack a functional PTEN, we used stable clones that express, under the control of a tetracycline-inducible system (Tet-on), wild-type PTEN and two of its mutants, G129E-PTEN and C124S-PTEN, which, respectively, lack the lipid phosphatase activity only and both the lipid and the protein phosphatase activities of this protein. Expression of PTEN in U87MG glioma cells decreased proteasome activity and also reduced protein ubiquitination. On the contrary, expression of PTEN increased the autophagic flux and the lysosomal mass. Interestingly, and although PTEN negatively regulates the phosphatidylinositol 3-kinase class I/AKT/mTOR signaling pathway by its lipid phosphatase activity, both effects in U87MG cells were independent of this activity. These results suggest a new mTOR-independent signaling pathway by which PTEN can regulate in opposite directions the main mechanisms of intracellular protein degradation.