Renin-angiotensin-aldosterone system blockers effect in chronic kidney disease progression in hypertensive elderly patients without proteinuria: PROERCAN trial.

INTRODUCTION: Evidence about nefroprotective effect with RAAS blockers in elderly patients with chronic kidney disease (CKD) without proteinuria is lacking. The primary outcome of our study is to evaluate the impact of RAAS blockers in CKD progression in elderly patients without proteinuria. MATERIALS AND METHODS: Multicenter open-label, randomized controlled clinical trial including patients over 65 year-old with hypertension and CKD stages 3-4 without proteinuria. Patients were randomized in a 1:1 ratio to either receive RAAS blockers or other antihypertensive drugs and were followed up for three years. Primary outcome is estimated glomerular filtration rate (eGFR) decline at 3 years. Secondary outcome measures include BP control, renal and cardiovascular events and mortality. RESULTS: 88 patients were included with a mean age of 77.9±6.1 years and a follow up period of 3 years: 40 were randomized to RAAS group and 48 to standard treatment. Ethiology of CKD was: 53 vascular, 16 interstitial and 19 of unknown ethiology. In the RAAS group eGFR slope during follow up was -4.3±1.1ml/min, whereas in the standard treatment group an increase on eGFR was observed after 3 years (+4.6±0.4ml/min), p=0.024. We found no differences in blood pressure control, number of antihypertensive drugs, albuminuria, potassium serum levels, incidence of cardiovascular events nor mortality during the follow up period. CONCLUSIONS: In elderly patients without diabetes nor cardiopathy and with non proteinuric CKD the use of RAAS blockers does not show a reduction in CKD progression. The PROERCAN (PROgresión de Enfermedad Renal Crónica en ANcianos) trial (trial registration: NCT03195023).

Obesity related risk for chronic kidney disease progression and cardiovascular disease after propensity score matching.

INTRODUCTION: Obesity is a major health problem worldwide. It carries a markedly increased risk for multiple diseases such as type 2 diabetes mellitus, hypertension, cardiovascular disease (CVD) and chronic kidney disease (CKD). To complicate an already difficult topic a new subtype of obesity has been defined lately, the metabolically healthy obese. Our study aimed to clarify the association between obesity, metabolic syndrome and kidney disease progression. METHODS: Observational retrospective single centre study including 212 patients with stage 3-4 CKD with no previous history of rapid kidney disease progression. Patients were divided according to BMI status and presence of metabolic syndrome. Anthropometric, clinical and laboratory data were collected to follow-up. Propensity score matching was performed for age, albuminuria and baseline renal function. During follow-up renal and cardiovascular events were recorded. RESULTS: After a mean follow-up of 88.44±36.07 months a total of 18 patients reached the renal outcome in the non-obese group and 21 in the obese group. Differences were not statistically significant (log rank=0.21: p=0.64). Multiple Cox regression analysis showed that obesity was not predictor for worse renal outcomes [HR 1.01, 95% CI 0.45-2.24; p=0.97]. When stratifying the sample according to baseline metabolic syndrome and obesity presence there was no difference in renal survival (log rank=0.852; p=0.35) A total of 48 cardiovascular events were registered: seventeen in the non-obese group and thirty-one in the obese group. Differences in event-free time between both groups were statistically significant (log rank=4.44;p=0.035), especially after four years of follow-up. After stratifying for MS and obesity presence at baseline the event-free time differences where again statistically significant (log rank=16.86;p=0.001), specially for the obese patients with metabolic syndrome. CONCLUSIONS: Obesity has little impact on chronic kidney disease progression despite the presence or absence of metabolic syndrome in a cohort matched for age, baseline renal function and albuminuria. Obesity conferred greater cardiovascular risk when combined with metabolic syndrome.

Magnetosomes could be protective shields against metal stress in magnetotactic bacteria.

Magnetotactic bacteria are aquatic microorganisms with the ability to biomineralise membrane-enclosed magnetic nanoparticles, called magnetosomes. These magnetosomes are arranged into a chain that behaves as a magnetic compass, allowing the bacteria to align in and navigate along the Earth's magnetic field lines. According to the magneto-aerotactic hypothesis, the purpose of producing magnetosomes is to provide the bacteria with a more efficient movement within the stratified water column, in search of the optimal positions that satisfy their nutritional requirements. However, magnetosomes could have other physiological roles, as proposed in this work. Here we analyse the role of magnetosomes in the tolerance of Magnetospirillum gryphiswaldense MSR-1 to transition metals (Co, Mn, Ni, Zn, Cu). By exposing bacterial populations with and without magnetosomes to increasing concentrations of metals in the growth medium, we observe that the tolerance is significantly higher when bacteria have magnetosomes. The resistance mechanisms triggered in magnetosome-bearing bacteria under metal stress have been investigated by means of x-ray absorption near edge spectroscopy (XANES). XANES experiments were performed both on magnetosomes isolated from the bacteria and on the whole bacteria, aimed to assess whether bacteria use magnetosomes as metal storages, or whether they incorporate the excess metal in other cell compartments. Our findings reveal that the tolerance mechanisms are metal-specific: Mn, Zn and Cu are incorporated in both the magnetosomes and other cell compartments; Co is only incorporated in the magnetosomes, and Ni is incorporated in other cell compartments. In the case of Co, Zn and Mn, the metal is integrated in the magnetosome magnetite mineral core.

Investigating the Size and Microstrain Influence in the Magnetic Order/Disorder State of GdCu2 Nanoparticles.

A series of GdCu 2 nanoparticles with controlled sizes ranging from 7 nm to 40 nm has been produced via high-energy inert-gas ball milling. Rietveld refinements on the X-ray diffraction measurements ensure that the bulk crystalline I m m a structure is retained within the nanoparticles, thanks to the employed low milling times ranging from t = 0.5 to t = 5 h. The analysis of the magnetic measurements shows a crossover from Superantiferromagnetism (SAF) to a Super Spin Glass state as the size decreases at NP size of 〈 D 〉 ≈ 18 nm. The microstrain contribution, which is always kept below 1%, together with the increasing surface-to-core ratio of the magnetic moments, trigger the magnetic disorder. Additionally, an extra contribution to the magnetic disorder is revealed within the SAF state, as the oscillating RKKY indirect exchange achieves to couple with the aforementioned contribution that emerges from the size reduction. The combination of both sources of disorder leads to a maximised frustration for 〈 D 〉 ≈ 25 nm sized NPs.

The effect of renin-angiotensin-aldosterone system blockers on the progression of chronic kidney disease in hypertensive elderly patients without proteinuria: PROERCAN study. Rationale and design.

INTRODUCTION: Blood pressure (BP) control is fundamental to the care of patients with chronic kidney disease (CKD), and is relevant at all stages of CKD. Renin-angiotensin-aldosterone system (RAAS) blockers have shown to be effective, not only in BP control but also in reducing proteinuria and slowing CKD progression. However, there is a lack of evidence for recommending RAAS blockers in elderly patients with CKD without proteinuria. The primary outcome of the present study is to evaluate the impact of RAAS blockers on CKD progression in elderly patients without proteinuria. MATERIALS AND METHODS: The PROERCAN trial (trial registration, NCT03195023) is a multicentre open-label, randomized controlled clinical trial with 110 participants over 65 years-old with hypertension and CKD stages 3-4 without proteinuria. Patients will be randomized in a 1:1 ratio to either receive RAAS blockers or other antihypertensive drugs, and will be followed up for three years. Primary outcome is the estimated glomerular filtration rate (eGFR) decline at 3 years. Secondary outcomes include BP control, renal and cardiovascular events, and mortality. RESULTS AND CONCLUSIONS: The design of this trial is presented here. The results will show if antihypertensive treatment with RAAS blockers has an impact on CKD progression in elderly patients without proteinuria. Any differences in BP control, cardiovascular events, and mortality with each antihypertensive treatment will be also clarified.

Configuration of the magnetosome chain: a natural magnetic nanoarchitecture.

Magnetospirillum gryphiswaldense is a microorganism with the ability to biomineralize magnetite nanoparticles, called magnetosomes, and arrange them into a chain that behaves like a magnetic compass. Rather than straight lines, magnetosome chains are slightly bent, as evidenced by electron cryotomography. Our experimental and theoretical results suggest that due to the competition between the magnetocrystalline and shape anisotropies, the effective magnetic moment of individual magnetosomes is tilted out of the [111] crystallographic easy axis of magnetite. This tilt does not affect the direction of the chain net magnetic moment, which remains along the [111] axis, but explains the arrangement of magnetosomes in helical-like shaped chains. Indeed, we demonstrate that the chain shape can be reproduced by considering an interplay between the magnetic dipolar interactions between magnetosomes, ruled by the orientation of the magnetosome magnetic moment, and a lipid/protein-based mechanism, modeled as an elastic recovery force exerted on the magnetosomes.

Influence of the bacterial growth phase on the magnetic properties of magnetosomes synthesized by Magnetospirillum gryphiswaldense.

BACKGROUND: The magnetosome biosynthesis is a genetically controlled process but the physical properties of the magnetosomes can be slightly tuned by modifying the bacterial growth conditions. METHODS: We designed two time-resolved experiments in which iron-starved bacteria at the mid-logarithmic phase are transferred to Fe-supplemented medium to induce the magnetosomes biogenesis along the exponential growth or at the stationary phase. We used flow cytometry to determine the cell concentration, transmission electron microscopy to image the magnetosomes, DC and AC magnetometry methods for the magnetic characterization, and X-ray absorption spectroscopy to analyze the magnetosome structure. RESULTS: When the magnetosomes synthesis occurs during the exponential growth phase, they reach larger sizes and higher monodispersity, displaying a stoichiometric magnetite structure, as fingerprinted by the well defined Verwey temperature. On the contrary, the magnetosomes synthesized at the stationary phase reach smaller sizes and display a smeared Verwey transition, that suggests that these magnetosomes may deviate slightly from the perfect stoichiometry. CONCLUSIONS: Magnetosomes magnetically closer to stoichiometric magnetite are obtained when bacteria start synthesizing them at the exponential growth phase rather than at the stationary phase. GENERAL SIGNIFICANCE: The growth conditions influence the final properties of the biosynthesized magnetosomes. This article is part of a Special Issue entitled "Recent Advances in Bionanomaterials" Guest Editors: Dr. Marie-Louise Saboungi and Dr. Samuel D. Bader.

On the mineral core of ferritin-like proteins: structural and magnetic characterization.

It is generally accepted that the mineral core synthesized by ferritin-like proteins consists of a ferric oxy-hydroxide mineral similar to ferrihydrite in the case of horse spleen ferritin (HoSF) and an oxy-hydroxide-phosphate phase in plant and prokaryotic ferritins. The structure reflects a dynamic process of deposition and dissolution, influenced by different biological, chemical and physical variables. In this work we shed light on this matter by combining a structural (High Resolution Transmission Electron Microscopy (HRTEM) and Fe K-edge X-ray Absorption Spectroscopy (XAS)) and a magnetic study of the mineral core biomineralized by horse spleen ferritin (HoSF) and three prokaryotic ferritin-like proteins: bacterial ferritin (FtnA) and bacterioferritin (Bfr) from Escherichia coli and archaeal ferritin (PfFtn) from Pyrococcus furiosus. The prokaryotic ferritin-like proteins have been studied under native conditions and inside the cells for the sake of preserving their natural attributes. They share with HoSF a nanocrystalline structure rather than an amorphous one as has been frequently reported. However, the presence of phosphorus changes drastically the short-range order and magnetic response of the prokaryotic cores with respect to HoSF. The superparamagnetism observed in HoSF is absent in the prokaryotic proteins, which show a pure atomic-like paramagnetic behaviour attributed to phosphorus breaking the Fe-Fe exchange interaction.

Breakdown of magnetism in sub-nanometric Ni clusters embedded in Ag.

Downsizing to the nanoscale has opened up a spectrum of new magnetic phenomena yet to be discovered. In this context, we investigate the magnetic properties of Ni clusters embedded in a metallic Ag matrix. Unlike in Ni free-standing clusters, where the magnetic moment increases towards the atomic value when decreasing the cluster size, we show, by tuning the Ni cluster size down to the sub-nanoscale, that there is a size limit below which the clusters become non-magnetic when embedded in Ag. To this end, we have fabricated by DC-sputtering a system composed of sub-nanometer sized and non interacting Ni clusters embedded into a Ag matrix. A thorough experimental characterization by means of structural techniques (x-ray diffraction, x-ray absorption spectroscopy) and DC-magnetization confirms that the cluster size is in the sub-nanometric range and shows that the magnetization of the system is dramatically reduced, reaching only 38% of the bulk value. The experimental system has been reproduced by density functional theory calculations on Ni m clusters (m = 1-6, 10 and 13) embedded in Ag. The combination of the experimental and theoretical analysis points out that there is a breakdown of magnetism occurring below a cluster size of six atoms. According to our results, the loss of magnetic moment is not due to Ag-Ni hybridization but to charge transfer between the Ni sp and d orbitals, and the reduced magnetization observed experimentally is explained on the basis of the presence of a narrow cluster size-distribution where magnetic and non-magnetic clusters coexist.

Ni doped Fe3O4 magnetic nanoparticles.

In this work, the effect of nickel doping on the structural and magnetic properties of Fe3O4 nanoparticles is analysed. Ni(x)Fe(3-x)O4 nanoparticles (x = 0, 0.04, 0.06 and 0.11) were obtained by chemical co-precipitation method, starting from a mixture of FeCl2 x 4H2O and Ni(AcO)2 x 4H2O salts. The analysis of the structure and composition of the synthesized nanoparticles confirms their nanometer size (main sizes around 10 nm) and the inclusion of the Ni atoms in the characteristic spinel structure of the magnetite Fe3O4 phase. In order to characterize in detail the structure of the samples, X-ray absorption (XANES) measurements were performed on the Ni and Fe K-edges. The results indicate the oxidation of the Ni atoms to the 2+ state and the location of the Ni2+ cations in the Fe2+ octahedral sites. With respect to the magnetic properties, the samples display the characteristic superparamagnetic behaviour, with anhysteretic magnetic response at room temperature. The estimated magnetic moment confirms the partial substitution of the Fe2+ cations by Ni2+ atoms in the octahedral sites of the spinel structure.

Interfacial magnetic coupling between Fe nanoparticles in Fe­Ag granular alloys.

The role of the interface in mediating interparticle magnetic interactions has been analysed in Fe50Ag50 and Fe55Ag45 granular thin films deposited by the pulsed laser deposition technique (PLD). These samples are composed of crystalline bcc Fe (2­4 nm) nanoparticles and fcc Ag (10­12 nm) nanoparticles, separated by an amorphous Fe50Ag50 interface, occupying around 20% of the sample volume, as determined by x-ray diffraction (XRD), x-ray absorption spectroscopy (XAS), and high resolution transmission electron microscopy (HRTEM). Interfacial magnetic coupling between Fe nanoparticles is studied by dc magnetization and x-ray magnetic circular dichroism (XMCD) measurements at the Fe K and Ag L2,3 edges. This paper reveals that these thin films present two magnetic transitions, at low and high temperatures, which are strongly related to the magnetic state of the amorphous interface, which acts as a barrier for interparticle magnetic coupling.

Observation of the segregation and the dissolution of the Co and the Cu in CoCu metastable alloys.

Metastable Co(x)Cu100-x(x=5, 10, 15, 20) alloys have been annealed at increasing temperatures in order to study the evolution of the Co cluster and its relation with the magnetotransport properties. The structure was investigated by X-ray Absorption Spectroscopy on the Co K-edge as a function of composition and annealing temperature. An anomalous trend in the structural evolution has been evidenced and related to the preculiar features observed in the magnetotransport properties.

[Epidemiologic aspects of suicide in Asturias in relation to the climate, the seasons and other factors]. / Aspectos epidemiológicos del suicidio en Asturias en relación con la climatología, lo estacional y otros factores.

Based on epidemiologic methodology different factors related to suicide committed in Asturias (Spain) during 1983-1987 were analysed. The following factors were studied: age, sex, procedure of suicide, climate variables (atmospheric pressure, frequency of south-winds), seasons of the year and Moon phases in which suicides were committed. The incidence was 11.13/100,000. In respect to several factors significant differences were found (X2 test): age, sex and suicide procedure depending on sex. In relation to other factors, although some differences were observed in relation to sex, no significant differences were present.

[Thematic Apperception Test: psychodiagnosis in heroin-dependent patients]. / T.A.T.: psicodiagnóstico en pacientes heroinómanos.

The aim of our work is the search of some differential psychopathologic features or categories in the personality of the heroin addict, through the application of Murray TAT. Which, we try to contrast with another contributions carried out until the present time. On the other hand, other parameters of sociolaboral and demographic character have been valued. We do not detect a structure of uniform personality, through we observe clear differences with respect to people who are not dependent on drugs. According to the results we have found, there are a larger number of psychopathologic elements in the whole of the heroin addict personality, as a greater low self-esteem, a suicidal inclination, a problematic with authority models, an evasión of aggressiveness, feelings of anxiety and quiltiness, without being a universal pattern.

[Psychopathologic traits of patients addicted to heroin]. / Rasgos psicopatológicos en pacientes heroinómanos.

The aim of our work is the search for some differential psychopathologic features in the heroin addict personality, through the 16 PF of Cattell (A form), which we try to contrast with other contributions from studies carried out up to the present. Moreover, other parameters of demographic and socioeconomic interest have been evaluated. Through the results we have gotten, it seems that there is a larger number of psychopathologic elements in the personality of the heroin addict, such as greater introversion, frustration, culpability, radicalism, self-sufficiency, anxiety, over-excitement, actions influenced by their feelings, and a minor acceptance of the rules of the group, though these features do not constitute a standard structure of personality.