Influence of docosahexaenoic acid on the interfacial behavior of cholesterol-containing lipid membranes: Interactions with small amphiphiles and hydration properties.

Cholesterol is known to significantly modify both the structural and the dynamical properties of lipid membranes. On one side, the presence of free cholesterol molecules has been determined to stiffen the membrane bilayer by stretching the hydrophobic tails. Additionally, recent experimental and computational findings have made evident the fact that cholesterol also alters the dynamics and the hydration properties of the polar head groups of DPPC model lipid membranes. In turn, we have recently shown that the Omega-3 fatty acid docosahexaenoic acid, DHA, counteracts the effect of cholesterol on DPPC membrane's mechanical properties by fluidizing the bilayer. However, such behavior represents in fact a global outcome dominated by the larger lipid hydrophobic tails that neither discriminates between the different parts of the membrane nor elucidates the effect on membrane hydration and binding properties. Thus, we now perform molecular dynamics simulations to scrutinize the influence of DHA on the interfacial behavior of cholesterol-containing lipid membranes by characterizing their hydration properties and their binding to amphiphiles. We find that while cholesterol destabilizes interactions with amphiphiles and slightly weakens the lipid's hydration layer, the incorporation of DHA practically restores the interfacial behavior of pure DPPC.

A certain proportion of docosahexaenoic acid tends to revert structural and dynamical effects of cholesterol on lipid membranes.

This work investigates how docosahexaenoic acid (DHA) modifies the effect of Cholesterol (Chol) on the structural and dynamical properties of dipalmitoylphosphatidylcholine (DPPC) membrane. We employ low-cost and non-invasive methods: zeta potential (ZP), conductivity, density, and ultrasound velocity, complemented by molecular dynamics simulations. Our studies reveal that 30% of DHA added to the DPPC-Chol system tends to revert Chol action on a model lipid bilayer. Results obtained in this work shed light on the effect of polyunsaturated fatty acids - particularly DHA - on lipid membranes, with potential preventive applications in many diseases, e.g. neuronal as, Alzheimer's disease, and viral, as Covid-19.

Effect of cholesterol on the hydration properties of ester and ether lipid membrane interphases.

Fluorescence spectroscopy and Molecular Dynamics results show that cholesterol reduces water along the chains in ether lipids by changing the water distribution pattern between tightly and loosely bound water molecules. Water distribution was followed by emission spectra and generalized polarization of 6-dodecanoyl-2-dimethyl aminonaphthalene (Laurdan) inserted in 1,2-dimiristoyl-sn-glycero-3-phosphocholine (DMPC) and 1,2-di-O-tetradecyl-sn-glycero-3-phosphocholine (14: 0 Diether PC) membranes. Molecular Dynamics simulations indicate that the action of cholesterol could be different in ether PC in comparison to ester PC. In addition, Cholesterol seems to act "per se" as an additional hydration center in ether lipids. Regardless of the phase state, cholesterol both in DMPC and 14:0 Diether PC vesicles, changed the distribution of water molecules decreasing the dipole relaxation of the lipid interphase generating an increase in the non-relaxable population. Above 10% Cholesterol/14:0 Diether PC ratio vesicles' interphase present an environment around Laurdan molecules similar to that corresponding to ester PC.

Interaction of hydroxy-xanthones with phosphatidylcholines: The effector decreases compressibility and increases the fluidity of membranes.

This work reports the effect of hydroxy-xanthones (XAs) on 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC) bilayers as determined by ultrasound velocimetry, densimetry and molecular dynamics simulations. XAs with different number of hydroxyl group were studied. Experimental results, in good agreement with molecular dynamics simulations, revealed that the presence of XAs in the systems studied increases fluidity while simultaneously decreses the compressibility of both membranes. This ´apparent contradiction´ ceases to exist when the particular geometrical structure of the xanthones is taken into account: the planar shape of their fused aromatic rings might allow them to pack efficiently among the hydrocarbon tails of the lipids, thus decreasing compressibility, while their presence weakens or disrupts methylene-methylene interchain interactions, thus increasing membrane fluidity and decreasing their melting temperature.

Experimental and computational studies of the effects of free DHA on a model phosphatidylcholine membrane.

Docosahexaenoic acid (DHA, 22:6) is a natural active compound that has raised considerable interest due to its several biological effects. In this work, effects of free DHA on the physicochemical properties of dipalmitoylphosphatidylcholine (DPPC) liposomes are investigated in terms of lipid membrane structure, by means of temperature-dependent zeta potential measurements, density studies and molecular dynamics simulations. Experimental results predict, in good agreement with simulations that DHA readily incorporates into DPPC liposomes, localizing at the lipid headgroup region. These data show that DHA induces changes in the lipid bilayer structure as well as in membrane fluidity.

A new method for characterization of small capacity wind turbines with permanent magnet synchronous generator: An experimental study.

This work presents a new and useful method to dimension wind turbines and control systems and to optimize their mechanical design. This method allows determining the principal curves for characterizing a small capacity wind turbine designed with a Permanent Magnet Synchronous Generator (PMSG). For the wind turbine characterization it was considered the losses in the process of energy transformation in the wind rotor, electric generator and in the bridge rectifier. The equivalent electric model of the synchronous generator was used to determine the electric parameter performance. The work of the wind rotor was considered in its maximum power curve and the PMSG performance in the linear region of its magnetization curve. This leads to develop a new methodology for the complete wind turbine characterization from the nominal parameters of the wind rotor and the electric generator. This method also allows obtaining the power curves and the parameters of voltage, current and efficiency around the wind speed domain and angular speed in the wind rotor. The method was tested for small-capacity wind turbine (1 kW and 10 kW) performances and the numerical and experimental results are described.

LISA: Surfactant administration in spontaneous breathing. Which evidence from the literature?

Recent human and animal studies demonstrated that surfactant can be delivered intratracheally without traditional intubation and bagging, but using a fine catheter inserted into the trachea of spontaneously breathing preterm infants on CPAP. This strategy, known as LISA (less invasive surfactant administration) or MIST (minimal invasive surfactant therapy), seems to reduce failure of non-invasive respiratory approach. Avoiding mechanical ventilation and manual inflation it is possible to reduce lung injury due to baro-volutrauma. Moreover leaving the infants supported by N-CPAP during the maneuver, it is possible to reduce the risk of lung derecruitment. Further studies are needed to confirm the promising effects due to this strategy to deliver surfactant.

Association between individual and combined SNPs in genes related to innate immunity and incidence of CMV infection in seropositive kidney transplant recipients.

In this study, we assessed the association between single-nucleotide polymorphisms (SNPs) in seven candidate genes involved in orchestrating the immune response against cytomegalovirus (CMV) and the 12-month incidence of CMV infection in 315 CMV-seropositive kidney transplant (KT) recipients. Patients were managed either by antiviral prophylaxis or preemptive therapy. CMV infection occurred in 140 patients (44.4%), including 13 episodes of disease. After adjusting for various clinical covariates, patients harboring T-allele genotypes of interleukin-28B (IL28B) (rs12979860) SNP had lower incidence of CMV infection (adjusted hazard ratio [aHR]: 0.66; 95% confidence interval [CI]: 0.46-0.96; p-value = 0.029). In the analysis restricted to patients not receiving prophylaxis, carriers of the TT genotype of toll-like receptor 9 (TLR9) (rs5743836) SNP had lower incidence of infection (aHR: 0.61; 95% CI: 0.38-0.96; p-value = 0.035), whereas the GG genotype of dendritic cell-specific ICAM 3-grabbing nonintegrin (DC-SIGN) (rs735240) SNP exerted the opposite effect (aHR: 1.86; 95% CI: 1.18-2.94; p-value = 0.008). An independent association was found between the number of unfavorable SNP genotypes carried by the patient and the incidence of CMV infection. In conclusion, specific SNPs in IL28B, TLR9 and DC-SIGN genes may play a role in modulating the susceptibility to CMV infection in CMV-seropositive KT recipients.

A decision support system for the treatment of patients with ventricular assist device support.

BACKGROUND: Heart failure (HF) is affecting millions of people every year and it is characterized by impaired ventricular performance, exercise intolerance and shortened life expectancy. Despite significant advancements in drug therapy, mortality of the disease remains excessively high, as heart transplant remains the gold standard treatment for end-stage HF when no contraindications subsist. Traditionally, implanted Ventricular Assist Devices (VADs) have been employed in order to provide circulatory support to patients who cannot survive the waiting time to transplantation, reducing the workload imposed on the heart. In many cases that process could recover its contractility performance. OBJECTIVES: The SensorART platform focuses on the management and remote treatment of patients suffering from HF. It provides an interoperable, extendable and VAD-independent solution, which incorporates various hardware and software components in a holistic approach, in order to improve the quality of the patients' treatment and the workflow of the specialists. This paper focuses on the description and analysis of Specialist's Decision Support System (SDSS), an innovative component of the SensorART platform. METHODS: The SDSS is a Web-based tool that assists specialists on designing the therapy plan for their patients before and after VAD implantation, analyzing patients' data, extracting new knowledge, and making informative decisions. RESULTS: SDSS offers support to medical and VAD experts through the different phases of VAD therapy, incorporating several tools covering all related fields; Statistics, Association Rules, Monitoring, Treatment, Weaning, Speed and Suction Detection. CONCLUSIONS: SDSS and its modules have been tested in a number of patients and the results are encouraging.

C-type natriuretic peptide transcriptomic profiling increases in human leukocytes of patients with chronic heart failure as a function of clinical severity.

The aim of this study was to evaluate the transcriptomic profiling of C-type natriuretic peptide (CNP) and of its specific receptor, NPR-B in human leukocytes of heart failure (HF) patients as a function of clinical severity, assessing the possible changes with respect to healthy subjects (C). mRNA expression was evaluated by Real-Time PCR and total RNA was extracted from leukocytes of C (n=8) and of HF patients (NYHA I-II, n=7; NYHA III-IV, n=13) with PAXgene Blood RNA Kit. Significantly higher levels of CNP mRNA expression were found in HF patients as a function of clinical severity (C=0.23±0.058, NYHA I-II=0.47±0.18, NYHA III-IV=2.58±0.71, p=0.005 C vs NYHA III-IV, p=0.017 NYHA I-II vs NYHA III-IV) and NPR-B transcript levels resulted down-regulated in HF patients with higher NYHA class (C=2.2±0.61, NYHA I-II=2.76±0.46, NYHA III-IV=0.29±0.13, p=0.001 C vs NYHA III-IV, p<0.0001 NYHA I-II vs NYHA III-IV). A significant negative correlation between CNP and NPR-B mRNA expression (r=0.5, p=0.03) was also observed. These results suggest a co-regulation of NPR-B and CNP expression supporting the relevance of this receptor in human disease characterized by a marked inflammatory/immune component and suggesting the possibility of manipulating inflammation via pharmacological agents selective for this receptor.

Neopterin levels are independently associated with cardiac remodeling in patients with chronic heart failure.

OBJECTIVES: Neopterin, a marker of inflammation and monocyte activation, is found increased in patients with heart failure (HF). This study investigates whether neopterin levels correlate with left ventricular (LV) remodeling and brain natriuretic peptide (BNP), a marker of cardiac stress, in chronic HF (CHF) patients with different severity of disease. DESIGN AND METHODS: The relationship between neopterin and LV dimensions, NT-proBNP, and pro-inflammatory cytokines were studied in 98 CHF patients, while nineteen healthy subjects were enrolled as controls. Nineteen (19%) patients were in NYHA class I, 38 (39%) in NYHA class II, 27 (28%) in NYHA class III, and 14 (14%) in NYHA class IV. RESULTS: Neopterin levels were higher in CHF patients than in age- and gender-matched healthy controls, and related with indexed LV end-diastolic volume (LVEDVi). Prospectively CHF patients were separated into tertiles of low, medium and high neopterin levels. Among patients, male gender, LVEDVi, diuretic treatment, NYHA class I, NT-proBNP and IL-8 levels were significant determinants of urine neopterin levels by bivariate analysis. Neopterin levels were associated only to LV remodeling, as assessed by LVEDVi, and IL-8 levels, a crucial monocyte chemoattractant, by multivariate ordinal regression analysis. CONCLUSIONS: The relationship between elevated neopterin levels and LV enlargement in CHF patients suggests a crucial role of monocyte activation in the development of cardiac dysfunction in CHF patients. Assessment of neopterin levels is a potential biomarker to evaluate the progression of LV remodeling in CHF patients.

The role of mesoscopic modelling in understanding the response of dental enamel to mid-infrared radiation.

Human dental enamel has a porous mesostructure at the nanometre to micrometre scales that affects its thermal and mechanical properties relevant to laser treatment. We exploit finite-element models to investigate the response of this mesostructured enamel to mid-infrared lasers (CO(2) at 10.6 microm and Er:YAG at 2.94 microm). Our models might easily be adapted to investigate ablation of other brittle composite materials. The studies clarify the role of pore water in ablation, and lead to an understanding of the different responses of enamel to CO(2) and Er:YAG lasers, even though enamel has very similar average properties at the two wavelengths. We are able to suggest effective operating parameters for dental laser ablation, which should aid the introduction of minimally-invasive laser dentistry. In particular, our results indicate that, if pulses of approximately 10 micros are used, the CO(2) laser can ablate dental enamel without melting, and with minimal damage to the pulp of the tooth. Our results also suggest that pulses with 0.1-1 micros duration can induce high stress transients which may cause unwanted cracking.

The prevalence of acne in the north of Portugal.

BACKGROUND: Acne is a disease that affects almost all teenagers (60-90%), and it is the pathology exhibiting the highest morbidity in the 10-24 year-olds age group. There are no consistent data at national level by which we can evaluate the preponderance of this pathology in the Portuguese population. OBJECTIVE: To estimate the prevalence of acne in teenage school students (10-12 year-olds). STUDY DESIGN: A study was carried out involving all 8 regions in the north of Portugal. One school per region was selected at random. RESULTS: As expected, the figure we obtained for the prevalence of this pathology was high (82.4%) with males being the most affected. Nevertheless, only 44% of the affected treated their acne, although the face is the part of the body most affected. In the females high androgenization (which is manifested by the presence of hair on the upper lip and on the side of the face) doubles the median of the degree of acne registered. Regional asymmetry was found in relation to information about the disorder. The degrees of acne are higher in schools in the interior. In the more rural areas, the pharmacist still plays an important role in prescribing treatment. CONCLUSION: As a rule, individuals are correctly informed about acne, confirming that the search for treatment and awareness of its value are generally helping to gradually eliminate some of the stigmas from the past.

The ethnobotanical study of local Mediterranean food plants as medicinal resources in Southern Spain.

We studied medicinal and food plant species, recording an extraordinary number of species and uses in Castilla-La Mancha, Murcia and Valencia in Spain. Focusing on two demographically distinct regions - Castilla-La Mancha and Lower Segura Valley. A high proportion of the flora (20 to 30 %) is known for its medicinal properties, and, interestingly, a high number of medicinal-food plants (5 to 7 %) is recorded. The concept of "Local Food" involves the whole repertory of species that characterises the local diet (incl. local cultivars and non-cultivated gathered food plants). The number of food plant species varies between 15 and 25 % of the vascular flora, and for the gathered food plants (GFP) this decreases to a 3 to 8 %. Those GFP that are also used for medicinal purposes are only 2 to 4 % of the total vascular flora. The relevant plant families are very similar in relative numbers along the different areas: Compositae, Rosaceae and Umbelliferae, followed of Boraginaceae, Liliaceae, Cruciferae, and Caryophyllaceae. Chenopodiaceae, Polygonaceae and Gramineae are less uniformly represented or in lesser numbers. The high species diversity does not imply a general dietary relevance of this particular plant family. For instance Caryophyllaceae with a relatively low number of species comprises the "collejas" (Silene vulgaris) that have shown to be the more widely consumed species. Information regarding 145 species has been recorded. Among the Gathered Food Plant Species 81 are used in medicine, in double proportion than the cultivated food plants. 61 are orally administered, in the same form as food.

Enhancement of nitric oxide synthesis by L-arginine supplementation in renal disease: is it good or bad?

L-Arginine is a important component of our diet characterized by multiple physiological and pharmacological actions. In the last decade, this amino acid has attracted major interest since it has been identified as the natural substrate of nitric oxide, and is now recognized to play a major role in the regulation of vascular tone. This review, while summarizing the knowledge of the renal actions of the L-arginine/nitric oxide pathway in health and renal disease, focuses on the potential therapeutic implications of the increase in nitric oxide synthesis attained by L-arginine supplementation.

Power spectral analysis of heart rate in elderly hypertensive subjects with or without silent coronary disease.

Much evidence indicates an involvement of the sympathetic nervous system in the genesis of silent myocardial ischemia. The authors assessed autonomic system activity by power spectrum analysis of heart rate variability in 21 elderly hypertensive men with and without angiographically confirmed coronary artery disease and compared the results with those from an age-matched control group. In the analysis an autoregressive algorithm was used to determine the power spectrum from an electrocardiographic recording of 512 consecutive RR intervals. The autonomic nervous system induces two distinct sinusoids: a low-frequency signal attributable to sympathetic activity and a high-frequency vagal response. In the hypertensive patients with coronary disease the authors also evaluated sympathetic activation after double-blind, placebo-controlled administration of metoprolol (100 mg/day), followed by amlodipine (10 mg/day), quinapril (20 mg/day), and amlodipine (5 mg/day) plus quinapril (10 mg/day).

Assessment of the potential malignancy of Epstein-Barr virus (EBV)-infected B cells in AIDS-related disorders.

Spontaneous lymphoblastoid cell lines (LCLs) were established from the peripheral blood of ten human immunodeficiency virus (HIV)-seropositive patients in order to investigate whether or not a progression of the cells toward a malignant state could be traced. The LCLs studied displayed no differences in their surface phenotype, karyotype, or tumorigenicity in nude mice when compared with a wide panel of control LCLs. However, four of the ten LCLs derived from HIV-seropositive patients formed colonies in agar with a cloning efficiency (0.1 to 0.9%) that was much lower than that of a control neoplastic B cell line (50%). Some sublines that were derived form the agar colonies expressed new activation markers (CD10 and Bac-1) but did not produce tumors in nude mice or display chromosomal abnormalities. These sublines might comprise cells that have progressed toward a more transformed state.