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Previous trials have demonstrated that modifying dietary fat composition can influence the production of inflammation-related factors. Additionally, it has been suggested that not only the type of fat, but also the timing of fat intake can impact these factors. Therefore, the objective of the present study was to evaluate the effect of altering breakfast fat composition on inflammatory parameters. A 3-month crossover randomized trial was designed, involving 60 institutionalized women who alternately consumed a breakfast rich in polyunsaturated fatty acids (PUFA) (margarine), monounsaturated fatty acids (MUFA) (virgin olive oil), or saturated fatty acids (SFA) (butter), based on randomization. The following inflammatory markers were evaluated: epidermal growth factor (EGF), interferon (IFN)-α, interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor (TNF)-α, C-reactive protein (CRP), and vascular/endothelial growth factor (VEGF). The results showed that the most significant effects were observed with the high-MUFA breakfast, as there was a statistically significant decrease in plasma IL-6 ( p = 0.016) and VEGF values ( p = 0.035). Other factors, such as IL-1α and CRP, also decreased substantially, but did not reach the statistically significant level. On the other hand, the high-PUFA breakfast induced a significant decrease in EGF levels ( p < 0.001), whereas the high-SFA breakfast had no apparent effect on these factors. In conclusion, modifying breakfast fat, particularly by increasing MUFA or PUFA intake, appears to be sufficient for promoting a lower inflammatory marker synthesis profile and may be beneficial in improving cardiovascular complications.

Recent studies point out that not only the daily intake of energy and nutrients but the time of day when they are ingested notably regulates lipid metabolism and cardiovascular risk (CVR). Therefore, the aim of the study was to assess if the type of fat ingested at breakfast can modify lipid metabolism in women with CVR. A randomized, crossover clinical trial was performed. Sixty volunteers were randomly assigned to a (A) polyunsaturated fatty acid (PUFA)-rich breakfast, (B) saturated fatty acid (SFA)-rich breakfast, or (C) monounsaturated fatty acid (MUFA)-rich breakfast. Plasma lipoprotein and apolipoprotein subfractions were determined. Our data showed that the PUFA-rich breakfast decreased lipoprotein (a) (Lp(a)), very low-density lipoproteins (VLDL), and intermediate-density lipoproteins (IDL), and increased high-density lipoproteins (HDL). A similar trend was observed for the MUFA-rich breakfast, whereas the SFA-rich breakfast, although it decreased VLDL, also increased IDL and reduced HDL. The PUFA-rich breakfast also decreased β-lipoproteins and apolipoprotein-B. In summary, varying the type of fat eaten at breakfast is enough to significantly modify the lipid metabolism of women with CVR, which can be of great relevance to establish new therapeutic strategies for the treatment of these subjects.

How do protons and neutrons bind to form nuclei? This is the central question of ab initio nuclear structure theory. While the answer may seem as simple as the fact that nuclear forces are attractive, the full story is more complex and interesting. In this work we present numerical evidence from ab initio lattice simulations showing that nature is near a quantum phase transition, a zero-temperature transition driven by quantum fluctuations. Using lattice effective field theory, we perform Monte Carlo simulations for systems with up to twenty nucleons. For even and equal numbers of protons and neutrons, we discover a first-order transition at zero temperature from a Bose-condensed gas of alpha particles (^{4}He nuclei) to a nuclear liquid. Whether one has an alpha-particle gas or nuclear liquid is determined by the strength of the alpha-alpha interactions, and we show that the alpha-alpha interactions depend on the strength and locality of the nucleon-nucleon interactions. This insight should be useful in improving calculations of nuclear structure and important astrophysical reactions involving alpha capture on nuclei. Our findings also provide a tool to probe the structure of alpha cluster states such as the Hoyle state responsible for the production of carbon in red giant stars and point to a connection between nuclear states and the universal physics of bosons at large scattering length.

Objectives: To assess the prevalence of tobacco consumption in patients with inflammatory arthritis treated in our department and to raise awareness against tobacco in order to reduce the maximum number of active smokers., Method: A tobacco consumption survey was conducted to patients with inflammatory arthritis treated at the department of Rheumatology. Variables assessed: demographics, diagnosis, treatment, and current smoking. In smokers and former smokers patients: onset age of smoking, number of cigarettes per day, time exposure to tobacco and if they were active smokers before the diagnosis of their disease. All patients were also asked if received information about tobacco as a risk factor for inflammatory disease; and current to the active smokers if they wanted to stop. Awareness activities against tobacco were conducted., Results: Patients were included 198. The most prevalent diagnosis was rheumatoid arthritis (58.1%). Most patients were treated with biological therapy. Fifty percent of patients were non-smokers, 31% former smokers and 19% active smokers. Ninety-two percent of smokers and 89% former smokers already smoked before diagnosis of the disease. Thirty-five percent of all patients had received information about the risks of tobacco. Eighty percent of current smokers wanted to stop smoking., Conclusions: Active smoking was reported in 19% of patients with inflammatory arthropathies visited in our Arthritis. Department patients were willing to receive tobacco education. These results indicate the need to provide advice against tobacco in a systematic and structured manner.

Introduction: The diffusion of multidrug-resistant (MDR) bacteria has created the need to identify risk factors for acquiring resistant pathogens in patients living in the community., Objective: To analyze clinical features of patients with community-onset pneumonia due to MDR pathogens, to evaluate performance of existing scoring tools and to develop a bedside risk score for an early identification of these patients in the Emergency Department., Patients and Methods: This was an open, observational, prospective study of consecutive patients with pneumonia, coming from the community, from January 2011 to January 2013. The new score was validated on an external cohort of 929 patients with pneumonia admitted in internal medicine departments participating at a multicenter prospective study in Spain., Results: A total of 900 patients were included in the study. The final logistic regression model consisted of four variables: 1) one risk factor for HCAP, 2) bilateral pulmonary infiltration, 3) the presence of pleural effusion, and 4) the severity of respiratory impairment calculated by use of PaO2/FiO2 ratio. A new risk score, the ARUC score, was developed; compared to Aliberti, Shorr, and Shindo scores, this point score system has a good discrimination performance (AUC 0.76, 95% CI 0.71-0.82) and calibration (Hosmer-Lemeshow, χ2 = 7.64; p = 0.469). The new score outperformed HCAP definition in predicting etiology due to MDR organism. The performance of this bedside score was confirmed in the validation cohort (AUC 0.68, 95% CI 0.60-0.77)., Conclusion: Physicians working in ED should adopt simple risk scores, like ARUC score, to select the most appropriate antibiotic regimens. This individualized approach may help clinicians to identify those patients who need an empirical broad-spectrum antibiotic therapy.

Background: Pneumonia frequently affects solid organ transplant (SOT) recipients, with high morbidity and mortality. However, the few studies on pneumonia in this population are mainly retrospective, single-center, and long-term studies, or include patients with only one type of SOT or a specific etiology. We performed a point prevalence study to investigate epidemiology, diagnosis, therapy, and outcome of pneumonia in an unselected SOT population., Methods: Italian and Spanish transplant centers were invited to report on all SOT recipients with pneumonia treated during 2 separate weeks (1 each in February and June 2012)., Results: In total, 35 centers (18 in Italy, 17 in Spain) agreed to participate and collected 54 cases. The incidence of pneumonia was 10.1 episodes/1000 recipients/year. Pneumonia was classified as late (>6 months) in 70.4% of cases. Pneumonia was also classified as community-acquired (CAP), healthcare-associated (HCAP), and hospital-acquired (HAP) pneumonia in 40.7%, 38.9%, and 20.4% of cases, respectively. An attempt to microbiological diagnosis (≥1 sample) was made in 94.4% of patients, with a diagnostic yield of 60.7%. Causative agents included bacteria (87.1%), virus (29%), and fungi (6.4%). A multidrug-resistant bacterium was isolated in 18.2%, 40%, and 100% of patients with CAP, HCAP, and HAP (P = 0.007), respectively. Overall, 11.1% of patients were admitted to the intensive care unit, 3.7% developed graft rejection, and graft function deteriorated in 18.5%. In-hospital mortality was 1.9%., Conclusion: Pneumonia remains a frequent problem in SOT recipients, although it occurs later in patients who are in better physical health. Therefore, harmful pathogens and worse outcome are less common than previously thought., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Recent epidemiological surveillance studies have reported an increase in fungaemia caused by non-Candida albicans species, as well as a decrease in fluconazole susceptibility., Objectives: To evaluate changes in the epidemiology of fungaemia in Spain comparing data from a new surveillance epidemiological study conducted in 2009 with a previous study carried out from 1997 to 1999 (Pemán J, et al. Eur J Clin Microbiol Infect Dis. 2005)., Methods: From January 2009 to February 2010, 44 Spanish hospitals participated in a prospective multicentre fungaemia surveillance study to ascertain whether there have been changes in the epidemiology and fluconazole susceptibility. Susceptibility was determined by the colorimetric method Sensititre Yeast One. Demographic and clinical data and the first isolate of each episode were gathered., Results: A total of 1,377 isolates from 1,357 fungaemia episodes were collected, 46.7% from patients older than 64years and 8.6% from children less than 1 year old. C. albicans (44.7%), Candida parapsilosis (29.1%), Candida glabrata (11.5%), Candida tropicalis (8.2%), and Candida krusei (1.9%) were the most frequent species isolated. Distribution varied with the geographical area. C. albicans incidence has increased significantly in the last 10years in Cataluña (39.1 vs. 54.7%, P=0.03) and decreased in the Valencian Community (49.1 vs. 34.6%, P=0.002) and Extremadura (58.3 vs. 20%, P=0.01). Susceptibility to fluconazole was similar for all geographical areas, although resistance in C. albicans was ten times greater for patients aged more than 64years. The overall rate of fluconazole resistance (MIC > 32 mg/L) has decreased with respect to that obtained 10years ago (3.7 vs. 2.5%) mainly in C. albicans (3 vs. 1.6%)., Conclusions: In the last ten years, species distribution and fluconazole susceptibility have not significantly changed, although a lower rate of fluconazole resistance has been observed. Species distribution varies with hospital, hospitalization Unit and geographical area., (Copyright © 2010 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.)

Background: We sought to investigate the thickness of plantar fascia, measured by means of ultrasonographic evaluation in healthy, asymptomatic subjects, and its relationship to body mass index, ankle joint dorsiflexion range of motion, and foot pronation in static stance., Methods: One hundred two feet of 51 healthy volunteers were examined. Sonographic evaluation with a 10-MHz linear array transducer was performed 1 and 2 cm distal to its insertion. Physical examination was also performed to assess body mass index, ankle joint dorsiflexion, and degree of foot pronation in static stance. Both examinations were performed in a blinded manner., Results: Body mass index showed moderate correlation with plantar fascia thickness at the 1- and 2-cm locations. Ankle dorsiflexion range of motion showed no correlation at either location. Foot pronation showed an inverse correlation with plantar fascia thickness at the 2-cm location and no correlation at the 1-cm location., Conclusion: Body mass index and foot supination at the subtalar joint are related to increased thickness at the plantar fascia in healthy, asymptomatic subjects. Although the changes in thickness were small compared with those in patients with symptomatic plantar fasciitis, they could play a role in the mechanical properties of plantar fascia and in the development of plantar fasciitis.

Whereas significant insight exists as to how LTP-related changes can contribute to the formation of long-term memory, little is known about the role of hippocampal LTD-like changes in learning and memory storage. We describe a mouse lacking the transcription factor SRF in the adult forebrain. This mouse could not acquire a hippocampus-based immediate memory for a novel context even across a few minute timespan, which led to a profound but selective deficit in explicit spatial memory. These animals were also impaired in the induction of LTD, including LTD triggered by a cholinergic agonist. Moreover, genes regulating two processes essential for LTD-calcium release from intracellular stores and phosphatase activation-were abnormally expressed in knockouts. These findings suggest that for the hippocampus to form associative spatial memories through LTP-like processes, it must first undergo learning of the context per se through exploration and the learning of familiarity, which requires LTD-like processes.

Incorporation of Alzheimer's disease amyloid beta-proteins (AbetaPs) across natural and artificial bilayer membranes leads to the formation of cation-selective channels. To study the peptide-membrane interactions involved in channel formation, we used cation reporter dyes to measure AbetaP-induced influx of Na+, Ca2+, and K+ into liposomes formed from phosphatidylserine (PS), phosphatidylinositol (PI) and phosphatidylcholine (PC). We found that Abeta40, but not Abeta40-1 or Abeta28, caused a dose-dependent increase in the concentration of each cation in the lumen of liposomes formed from the acidic phospholipids PS and PI. The Abeta40-induced changes in cation concentration, which we attribute to ion entry through Abeta40 channels, were not observed when using liposomes formed from the neutral phospholipid PC. Using mixtures of phospholipids, the magnitude of the AbetaP40-induced ion entry increased with the acidic phospholipid content of the liposomes, with entry being observed with as little as 5% PS or PI. Thus, while negatively charged phospholipids are required for formation of cation-permeable channels by Abeta40, a small amount is sufficient to support the process. These results have implications for the mechanisms of AbetaP cytotoxicity, suggesting that even a small amount of externalized negative charge could render cells susceptible to the deleterious effects of unregulated ion influx through AbetaP channels.

We studied a mouse model of the haploinsufficiency form of Rubinstein-Taybi syndrome (RTS), an inheritable disorder caused by mutations in the gene encoding the CREB binding protein (CBP) and characterized by mental retardation and skeletal abnormalities. In these mice, chromatin acetylation, some forms of long-term memory, and the late phase of hippocampal long-term potentiation (L-LTP) were impaired. We ameliorated the L-LTP deficit in two ways: (1) by enhancing the expression of CREB-dependent genes, and (2) by inhibiting histone deacetyltransferase activity (HDAC), the molecular counterpart of the histone acetylation function of CBP. Inhibition of HDAC also reversed the memory defect observed in fear conditioning. These findings suggest that some of the cognitive and physiological deficits observed on RTS are not simply due to the reduction of CBP during development but may also result from the continued requirement throughout life for both the CREB co-activation and the histone acetylation function of CBP., (Copyright 2004 Cell Press)

The role of endogenous amyloid beta-peptides as causal factors of neurodegenerative diseases is largely unknown. We have previously reported that interactions between Alzheimer's disease A beta P[1-40] peptide in solution and planar bilayer membranes made from anionic phospholipids lead to the formation of cation-selective channels. We now find and report here that the spontaneous insertion of free A beta P[1-40] across the bilayer can be detected as an increase in bilayer capacity. To this end we recorded the displacement currents across planar bilayers (50 mM KCl on both sides) in response to sudden displacements of the membrane potential, from -300 to 300 mV in 20-mV increments. To monitor the A beta P[1-40]-specific displacement currents, we added A beta P[1-40] (1-5 microM) to the solution on either side of the membrane and noted that the direction of the displacement current depended on the side with A beta P[1-40]. The size of the A beta P[1-40]-specific charge displaced during a pulse was always equal to the charge returning to the original configuration after the pulse, suggesting that the dipole molecules are confined to the membrane. As a rule, the steady-state distribution of the A beta P[1-40]-specific charges within the bilayer could be fit by a Boltzmann distribution. The potential at which the charges were found to be equally distributed (V(o)) were approximately -135 mV (peptide added to the solution in the compartment electrically connected to earth) and 135 mV (peptide added to the solution connected to the input of the amplifier). The A beta P[1-40]-specific transfer of charge reached a maximum value (Q(max)) when the electrical potential of the side containing the amyloid beta-protein was taken to either -300 or 300 mV. For a circular membrane of 25-microm radius ( approximately 2000 microm(2)), the total A beta P[1-40]-specific charge Q(max) was estimated as 55 fC, corresponding to some 170 e.c./microm(2). Regardless of the side selected for the addition of A beta P[1-40], at V(o) the charge displaced underwent an e-fold change for a approximately 27-mV change in potential. The effective valence (a) of the A beta P[1-40] dipole (i.e., the actual valence Z multiplied by the fraction of the electric field chi acting on the dipole) varied from 1 to 2 electronic charges. We also tested, with negative results, the amyloid peptide with the reverse sequence (A beta P[40-1]). These data demonstrate that A beta P[1-40] molecules can span the low dielectric domain of the bilayer, exposing charged residues (D(1), E(3), R(5), H(6), D(7), E(11), H(13), and H(14)) to the electric field. Thus the A beta P[1-40] molecules in solution must spontaneously acquire suitable conformations (beta-pleated sheet) allowing specific interactions with charged phospholipids. Interestingly, the domain from residues 676 to 704 in the APP(751) is homologous with the consensus sequence for lipid binding found in other membrane proteins regulated by anionic phospholipids.

The present study describes the action of H2O2 on active transporting epithelium, and the partial blockade of this action by antioxidants. The addition of increasing concentrations of H2O2 (0.80; 8.0 and 24.0 mmol/l) to the mucosal surface of isolated toad skin causes an irreversible and dose-dependent inhibition of the short circuit current (SCC) and potential difference (PD). Quantitative determination of the parameters of the electrical equivalent circuit of the skin, by means of Isaacson's amiloride test, shows that the most affected parameters were the SCC, PD and shunt conductance. When the skins were preincubated with mannitol and vitamin E, the inhibition elicited by H2O2 was partially blocked; on the other hand, when the skins were preincubated with superoxide dismutase or allopurinol, this inhibition remains unchanged. The thiobarbituric acid method was used as an indirect quantification of lipid peroxidation. The inhibitory action of H2O2 in terms of the equivalent electrical circuit and the parallel production of lipid peroxidation points to free-radical formation. Furthermore, the significant blockade of this action by some enzymatic antioxidants is in agreement with this hypothesis.

We have examined the effects of GABA and several GABAA receptor modulators on isolated rat (1-160 days) superior cervical ganglion (SCG) neurons with whole-cell recordings. The neurons were sensitive to GABA within 12 h after birth, and the relationship between the current amplitude and GABA concentration (GABA50 = 19 microM) in these newborn neurons was fitted with a Hill coefficient close to 1.0. Adult neurons, on the other hand, had a GABA50 value of 30 microM, and the slope was steeper and fitted with a Hill coefficient of 1.6. Unlike the results of previous studies in cultured SCG neurons, we found that the concentration of Zn++ that reduced the response by 50% was 37 +/- 12 microM in newborns and 43 +/- 6 microM in adults. Bicuculline (10 microM) inhibited the current by 41 +/- 6% and 36 +/- 11% in newborn and adult neurons, respectively. With 5 microM GABA, diazepam and pentobarbital potentiated the response in newborn and adult neurons. No changes were found in the sensitivity of the receptor for these ligands, but their efficacy was enhanced 2-fold during development. Diazepam shifted the relationship between GABA and the response to the left in all the neurons studied. Ethanol (40 mM) reduced the amplitude of the GABA current to 64 +/- 12% of control in newborn neurons and to 85 +/- 4% in adult neurons. The inhibitory effect of 100 mM ethanol on the GABA current was noncompetitive. Addition of a very large concentration of ethanol (850 mM) to newborn neurons potentiated the response to 164 +/- 13% of control.(ABSTRACT TRUNCATED AT 250 WORDS)