Chagas Cardiomiopathy: The Potential of Diastolic Dysfunction and Brain Natriuretic Peptide in the Early Identification of Cardiac Damage

Introduction

Chagas disease remains a major cause of mortality in several countries of Latin America and has become a potential public health problem in non-endemic countries as a result of migration flows. Cardiac involvement represents the main cause of mortality, but its diagnosis is still based on nonspecific criteria with poor sensitivity. Early identification of patients with cardiac involvement is desirable, since early treatment may improve prognosis. This study aimed to assess the role of diastolic dysfunction, abnormal myocardial strain and elevated brain natriuretic peptide (BNP) in the early identification of cardiac involvement in Chagas disease.

Methodology/Principal Findings

Fifty-four patients divided into 3 groups—group 1 (undetermined form: positive serology without ECG or 2D-echocardiographic abnormalities; N = 32), group 2 (typical ECG abnormalities of Chagas disease but normal 2D-echocardiography; N = 14), and group 3 (regional wall motion abnormalities, left ventricular [LV] end-diastolic diameter >55 mm or LV ejection fraction <50% on echocardiography; N = 8)—and 44 control subjects were studied. Patients with significant non-cardiac diseases, other heart diseases and previous treatment with benznidazol were excluded. The median age was 37 (20–58) years; 40% were men. BNP levels, longitudinal and radial myocardial strain and LV diastolic dysfunction increased progressively from group 1 to 3 (p for trend <0.01). Abnormal BNP levels (>37 pg/ml) were noted in 0%, 13%, 29% and 63% in controls and groups 1 to 3, respectively. Half of patients in the undetermined form had impaired relaxation patterns, whereas half of patients with ECG abnormalities suggestive of Chagas cardiomyopathy had normal diastolic function. In group 1, BNP levels were statistically higher in patients with diastolic dysfunction as compared to those with normal diastolic function (27±26 vs. 11±8 pg/ml, p = 0.03).

Conclusion/Significance

In conclusion, the combination of diastolic function and BNP measurement adds important information that could help to better stratify patients with Chagas disease.     

Biological properties of solid free form designed ceramic scaffolds with BMP-2: in vitro and in vivo evaluation

Porous ceramic scaffolds are widely studied in the tissue engineering field due to their potential in medical applications as bone substitutes or as bone-filling materials. Solid free form (SFF) fabrication methods allow fabrication of ceramic scaffolds with fully controlled pore architecture, which opens new perspectives in bone tissue regeneration materials. However, little experimentation has been performed about real biological properties and possible applications of SFF designed 3D ceramic scaffolds. Thus, here the biological properties of a specific SFF scaffold are evaluated first, both in vitro and in vivo, and later scaffolds are also implanted in pig maxillary defect, which is a model for a possible application in maxillofacial surgery. In vitro results show good biocompatibility of the scaffolds, promoting cell ingrowth. In vivo results indicate that material on its own conducts surrounding tissue and allow cell ingrowth, thanks to the designed pore size. Additional osteoinductive properties were obtained with BMP-2, which was loaded on scaffolds, and optimal bone formation was observed in pig implantation model. Collectively, data show that SFF scaffolds have real application possibilities for bone tissue engineering purposes, with the main advantage of being fully customizable 3D structures.     

Relating variation in the understorey of beech forests to ecological factors

A data set of beech (Fagus sylvatica) forests in the Basque Country (Northern Spain), including biotic (floristic relevés) and environmental data (pH, organic matter, slope, altitude, rock cover), is analyzed in order to describe the relationships between understorey composition and environmental parameters. An ordination technique (DCA) is used to display the floristic gradients, and the interpretation of the floristic space in environmental terms is carried out by a spatial analysis technique (kriging). The composition of the beech forest understorey responds to a complex environmental gradient in the study area. Forests growing on acid substrata differ markedly from those growing on soils with higher pH, as the sharp transition between the pH 5 and 6 isolines reflects. When pH values exceed 6, organic matter content becomes the most important factor explaining the vegetation pattern and the rate of change is greater as organic matter content tends to change at a smaller scale than sample size and, as a consequence many transitional forms are found.     

Degradation of the herbicide bentazon as related to enzyme production by Phanerochaete chrysosporium in two solid substrate fermentation systems

Enzyme production and degradation of the herbicide bentazon by Phanerochaete chrysosporium growing on straw (solid substrate fermentation, SSF) and the effect of nitrogen and the hydraulic retention time (HRT) were studied using a small bioreactor and batch cultures. The best degradation of bentazon was obtained in the low nitrogen treatments, indicating participation of the ligninolytic system of the fungus. The treatments that degraded bentazon also had manganese peroxidase (MnP) activity, which seemed to be necessary for degradation. Pure MnP (with Mn(II) and H₂O₂) did not oxidize bentazon. However, in the presence of MnP, Mn(II) and Tween 80, bentazon was slowly oxidized in a H₂O₂-independent reaction. Bentazon was a substrate of pure lignin peroxidase (LiP) and was oxidized significantly faster (22,000–29,000 times) as compared to the MnP-Tween 80 system. Although LiP was a better enzyme for bentazon oxidation in vitro, its role in the SSF systems remains unclear since it was detected only in treatments with high nitrogen and high HRT where no degradation of bentazon occurred. Inhibition of LiP activity may be due to phenols and extractives present in the straw.     

Residual Upper Arm Motor Function Primes Innervation of Paretic Forearm Muscles in Chronic Stroke after Brain-Machine Interface (BMI) Training

Background

Abnormal upper arm-forearm muscle synergies after stroke are poorly understood. We investigated whether upper arm function primes paralyzed forearm muscles in chronic stroke patients after Brain-Machine Interface (BMI)-based rehabilitation. Shaping upper arm-forearm muscle synergies may support individualized motor rehabilitation strategies.

Methods

Thirty-two chronic stroke patients with no active finger extensions were randomly assigned to experimental or sham groups and underwent daily BMI training followed by physiotherapy during four weeks. BMI sessions included desynchronization of ipsilesional brain activity and a robotic orthosis to move the paretic limb (experimental group, n = 16). In the sham group (n = 16) orthosis movements were random. Motor function was evaluated with electromyography (EMG) of forearm extensors, and upper arm and hand Fugl-Meyer assessment (FMA) scores. Patients performed distinct upper arm (e.g., shoulder flexion) and hand movements (finger extensions). Forearm EMG activity significantly higher during upper arm movements as compared to finger extensions was considered facilitation of forearm EMG activity. Intraclass correlation coefficient (ICC) was used to test inter-session reliability of facilitation of forearm EMG activity.

Results

Facilitation of forearm EMG activity ICC ranges from 0.52 to 0.83, indicating fair to high reliability before intervention in both limbs. Facilitation of forearm muscles is higher in the paretic as compared to the healthy limb (p<0.001). Upper arm FMA scores predict facilitation of forearm muscles after intervention in both groups (significant correlations ranged from R = 0.752, p = 0.002 to R = 0.779, p = 0.001), but only in the experimental group upper arm FMA scores predict changes in facilitation of forearm muscles after intervention (R = 0.709, p = 0.002; R = 0.827, p<0.001).

Conclusions

Residual upper arm motor function primes recruitment of paralyzed forearm muscles in chronic stroke patients and predicts changes in their recruitment after BMI training. This study suggests that changes in upper arm-forearm synergies contribute to stroke motor recovery, and provides candidacy guidelines for similar BMI-based clinical practice.     

The importance of phenol oxidase activity in lignin degradation by the white-rot fungus Sporotrichum pulverulentum

The lignin degradation abilities of wildtype, a phenol oxidase-less mutant and a phenol oxidase-positive revertant of Sporotrichum pulverulentum were compared to determine if phenol oxidase activity is necessary for lignin degradation by white-rot fungi. The phenol oxidase-less mutant was unable to degrade kraft lignin or wood. The phenol oxidase-positive revertant, however, regained the ability of the wildtype to degrade kraft lignin and all of the major components of wood. It was found that kraft lignin and lignin-related phenols decreased cellulase and xylanase production by the phenol oxidase-less mutant. Addition of highly purified laccase increased the production of endo-1,4--glucanase in the phenol oxidase-less mutant in the presence of vanillic acid and kraft lignin. After addition of laccase to kraft lignin agar plates, the phenol oxidase-less mutant could degrade kraft lignin.It is proposed that phenol oxidase function in regulating the production of both lignin-and polysaccharide-degrading enzymes by oxidation of lignin and lignin-related phenols when S. pulverulentum is growing on wood.Abbreviation WT wildtype Sporotrichum pulverulentum Research supported by a grant from Stiftelsen Nils and Dorthi Troëdssons forskningsfond     

Proprotein convertases blockage up-regulates specifically metallothioneins coding genes in human colon cancer stem cells

Despite continuous exertion made, colon cancer still represents a major health problem and its incidence continues being high worldwide. There is growing evidence in support of the cancer stem cells (CSCs) being central in the initiation of this cancer, and CSCs have been the focus of various studies for the identification of new ways of treatment. Lately, the proprotein convertases (PCs) were reported to regulate the maturation and expression of various molecules involved in the malignant phenotype of colon cancer cells, however, the identity of the molecules regulated by these serine proteases in CSCs is unknown. In this study, we used the general PCs inhibitor, the Decanoyl-RVKR-chloromethylketone (Decanoyl-RVKR-CMK) that inhibits all the PCs found in the secretory pathway, and analyzed its effect on CSCs using RNA-seq analysis. Remarkably, from the only 9 up-regulated genes in the human SW620-derived sphere-forming cells, we identified 7 of the 11 human metallothioneins, all of them localized on chromosome 16, and zinc related proteins as downstream effectors of the PCs. The importance of these molecules in the regulation of cell proliferation, differentiation and chemoresistance, and their reported potential tumor suppressor role and loss in colon cancer patients associated with worse prognosis, suggests that targeting PCs in the control of the malignant phenotype of CSCs is a new potential therapeutic strategy in colon cancer.     

Zooplankton adrift: investigating transportation by cyclonic eddy

Eddies are important not just because they have momentum and can transfer water properties, but also because they play an important role in increasing the trophic energy available to organisms, thereby enhancing primary productivity. This study was conducted to test the ‘suitcase hypothesis’ – the inclusion of organic matter (OM), plankton and larvae within the single water mass of an eddy, which are then highly conserved and transported to another location. Here we hypothesize that particulate OM (POM) and zooplankton from the continental shelf of Madagascar become trapped as the eddy forms and are transported westwards. We analysed stable isotope signatures of POM and zooplankton from samples collected from the continental shelf (CS) as well as within an eddy that had recently formed off the south-west coast of Madagascar. There was no statistical difference in the POM isotopic signature or C/N ratios between the continental shelf or any of the eddy regions. However, some C/N ratio values could suggest that some OM from close to the coastal region could have been transported by the eddy. This was not the case for zooplankton, however, with isotopic signatures on the CS greatly differing from those in the eddy. Several factors could account for these differences including feeding behaviour or tissue turnover rate. We conclude that our study did not gather enough evidence to support (or reject) the ‘suitcase’ hypothesis, and further studies are needed in order to fully understand the transport of material, including zooplankton and larvae, by eddies.     

Recent advances in the glycosylation of sphingosines and ceramides

Glycosphingolipids (GSLs) are ubiquitous components of eukaryotic cell membranes. They are highly bioactive and are involved in many aspects of cell signalling like cell-cell interaction, cell-substratum interaction and cell-pathogen interaction. GSLs also are involved in the modulation of signal transduction, resulting in regulation of cell proliferation and differentiation. The biological importance and complexity of these compounds afford many opportunities to prepare synthetic analogues for studies of their metabolism in intra- and intercellular processes. This review focuses on recent contributions in the synthesis of GSLs, highlighting improvements in glycosylation reactions leading to alpha and beta glycosyl sphingosines and ceramides and related compounds. Literature from 2000 to the present is covered. The glycosylation reactions leading to the synthesis of GSLs are classified in function of the configuration of the created glycosidic bond (alpha or beta) and of the acceptor used, either azido-sphingosine or ceramide.