Influence of Obesity and Metabolic Disease on Carotid Atherosclerosis in Patients with Coronary Artery Disease (CordioPrev Study)

BackgroundRecent data suggest that the presence of associated metabolic abnormalities may be important modifiers of the association of obesity with a poorer prognosis in coronary heart disease. We determined the influence of isolated overweight and obesity on carotid intima media thickness (IMT-CC), and also assessed whether this influence was determined by the presence of metabolic abnormalities.Methods1002 participants from the CordioPrev study were studied at entry. We determined their metabolic phenotypes and performed carotid ultrasound assessment. We evaluated the influence of obesity, overweight and metabolic phenotypes on the IMT-CC.ResultsMetabolically sick participants (defined by the presence of two or more metabolic abnormalities) showed a greater IMT-CC than metabolically healthy individuals (p = 4 * 10⁻⁶). Overweight and normal weight patients who were metabolically healthy showed a lower IMT-CC than the metabolically abnormal groups (all p<0.05). When we evaluated only body weight (without considering metabolic phenotypes), overweight or obese patients did not differ significantly from normal-weight patients in their IMT-CC (p = 0.077). However, obesity was a determinant of IMT-CC when compared to the composite group of normal weight and overweight patients (all not obese).ConclusionsIn coronary patients, a metabolically abnormal phenotype is associated with a greater IMT-CC, and may be linked to a higher risk of suffering new cardiovascular events. The protection conferred in the IMT-CC by the absence of metabolic abnormality may be blunted by the presence of obesity.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00924937","term_id":"NCT00924937"}}NCT00924937     

Is it really you,Orthotrichum acuminatum? Ascertaining a new case of intercontinental disjunction in mosses

Intercontinental disjunct distributions are a main issue in current biogeography. Bryophytes usually have broad distribution ranges and therefore constitute an interesting subject of study in this context. During recent fieldwork in western North America and eastern Africa, we found new populations of a moss morphologically similar to Orthotrichum acuminatum. So far this species has been considered to be one of the most typical epiphytic mosses of the Mediterranean Basin. The new findings raise some puzzling questions. Do these new populations belong to cryptic species or do they belong to O. acuminatum, a species which then has a multiple‐continent disjunct range? In the latter case, how could such an intercontinental disjunction be explained? To answer these questions, an integrative study involving morphological and molecular approaches was conducted. Morphological results reveal that Californian and Ethiopian samples fall within the variability of those from the Mediterranean Basin. Similarly, phylogenetic analyses confirm the monophyly of these populations, showing that O. acuminatum is one of the few moss species with a distribution comprising the western Nearctic, the western Palaearctic and Palaeotropical eastern Africa. Pending a further genetic and phylogeographical study to support or reject the hypothesis, a process of long‐distance dispersal (LDD) is hypothesized to explain this distribution and the origin of the species is suggested to be the Mediterranean Basin, from where diaspores of the species may have migrated to California and Ethiopia. The spore release process in O. acuminatum is revisited to support the LDD hypothesis, © 2015 The Linnean Society of London, Botanical Journal of the Linnean Society, 2016, 180 , 30–49.     

Dysfunctional mitochondrial fission impairs cell reprogramming

We have recently shown that mitochondrial fission is induced early in reprogramming in a Drp1-dependent manner; however, the identity of the factors controlling Drp1 recruitment to mitochondria was unexplored. To investigate this, we used a panel of RNAi targeting factors involved in the regulation of mitochondrial dynamics and we observed that MiD51, Gdap1 and, to a lesser extent, Mff were found to play key roles in this process. Cells derived from Gdap1-null mice were used to further explore the role of this factor in cell reprogramming. Microarray data revealed a prominent down-regulation of cell cycle pathways in Gdap1-null cells early in reprogramming and cell cycle profiling uncovered a G2/M growth arrest in Gdap1-null cells undergoing reprogramming. High-Content analysis showed that this growth arrest was DNA damage-independent. We propose that lack of efficient mitochondrial fission impairs cell reprogramming by interfering with cell cycle progression in a DNA damage-independent manner.     

Cleaning behaviour of the cichlid Mesonauta festivus in the Pantanal wetlands: evidence of a potential freshwater cleaning station

Cleaning interactions are known among several groups of fishes, with a higher number of records for marine fish species. These temporary associations occur between one species that acts as the cleaner and the other species as the client. The interaction usually takes place within the boundaries defined by the cleaner. This site, known as the cleaning station, allows the client fish to strike a typical pose allowing the cleaner to approach, such as wide-open fins and inclined, motionless body. Few studies have reported on the cleaning behaviour of freshwater fish species, and none has reported on behaviour that could be interpreted as establishing a cleaning station. Herein we present a new record of the cleaning interaction in the Neotropics, between the cichlid Mesonauta festivus as the cleaner and three species of anostomid (Leporinus macrocephalus, Leporinus friderici and Schizodon borellii) as clients on Pantanal wetlands, as well as the establishment of a defined cleaning station.     

Multiparametric magnetic resonance imaging-guided salvage radiotherapy in prostate cancer

AimTo analyse the efficacy and toxicity of postprostatectomy SRT in patients with a BCR evaluated with mpMRI.BackgroundMultiparametric magnetic resonance imaging (mpMRI) has the ability to detect the site of pelvic recurrence in patients with biochemical recurrence (BCR) after radical prostatectomy (RP). However, we do not know the oncological outcomes of mpMRI-guided savage radiotherapy (SRT).ResultsLocal, lymph node, and pelvic bone recurrence was observed in 13, 4 and 2 patients, respectively. PSA levels were significantly lower in patients with negative mpMRI (0.4 ng/mL [0.4]) vs. positive mpMRI (2.2 ng/mL [4.1], p = 0.003). Median planning target volume doses in patients with visible vs. non-visible recurrences were 76 Gy vs. 70 Gy. Overall, mean follow-up was 41 months (6–81). Biochemical relapse-free survival (bRFS) at 3 years was 82.3% and 82.5%, respectively, for the negative and positive mpMRI groups (p = 0.800). Three-year rates of late grade ≥2 urinary and rectal toxicity were 14.8% and 1.9%, respectively; all but one patient recovered without sequelae.ConclusionSRT to the macroscopic recurrence identified by mpMRI is a feasible and well-tolerated option. In this study, there were no differences in bRFS between MRI-positive and MRI-negative patients, indicating effective targeting of MRI-positive lesions.     

Active‐Site Imprinting: Preparation of Fe–N–C Catalysts from Zinc Ion–Templated Ionothermal Nitrogen‐Doped Carbons

Atomically dispersed Fe–N–C catalysts are considered the most promising precious‐metal‐free alternative to state‐of‐the‐art Pt‐based oxygen reduction electrocatalysts for proton‐exchange membrane fuel cells. The exceptional progress in the field of research in the last ≈30 years is currently limited by the moderate active site density that can be obtained. Behind this stands the dilemma of metastability of the desired FeN₄ sites at the high temperatures that are believed to be a requirement for their formation. It is herein shown that Zn²⁺ ions can be utilized in the novel concept of active‐site imprinting based on a pyrolytic template ion reaction throughout the formation of nitrogen‐doped carbons. As obtained atomically dispersed Zn–N–Cs comprising ZnN₄ sites as well as metal‐free N₄ sites can be utilized for the coordination of Fe²⁺ and Fe³⁺ ions to form atomically dispersed Fe–N–C with Fe loadings as high as 3.12 wt%. The Fe–N–Cs are active electocatalysts for the oxygen reduction reaction in acidic media with an onset potential of E₀ = 0.85 V versus RHE in 0.1 m HClO₄. Identical location atomic resolution transmission electron microscopy imaging, as well as in situ electrochemical flow cell coupled to inductively coupled plasma mass spectrometry measurements, is employed to directly prove the concept of the active‐site imprinting approach.     

Nature-inspired pyrrolo[2,3-d]pyrimidines targeting the histamine H3 receptor

Inspired by marine compounds the derivatization of the natural pyrrolo[2,3-d]pyrimidine lead scaffold led to a series of novel compounds targeting the histamine H₃ receptor. The focus was set on improved binding towards the receptor and to establish an initial structure-activity relationship for this compound class based on the lead structure (compound V, K_i value of 126 nM). As highest binding affinities were found with 1,4-bipiperidines as basic part of the ligands, further optimization was focused on 4-([1,4′-bipiperidin]-1′-yl)-pyrrolo[2,3-d]pyrimidines. Related pyrrolo[2,3-d]pyrimidines that were isolated from marine sponges like 4-amino-5-bromopyrrolo[2,3-d]pyrimidine (compound III), showed variations in halogenation pattern, though in a next step the impact of halogenation at 2-position was evaluated. The chloro variations did not improve the affinity compared to the dehalogenated compounds. However, the simultaneous introduction of lipophilic cores with electron-withdrawing substitution patterns in 7-position and dehalogenation at 2-position (11b, 12b) resulted in compounds with significantly higher binding affinities (K_i values of 7 nM and 6 nM, respectively) than the initial lead structure compound V. The presented structures allow for a reasonable structure-activity relationship of pyrrolo[2,3-d]pyrimidines as histamine H₃ receptor ligands and yielded novel lead structures within the natural compound library against this target.