Biomarkers in acute coronary syndromes and their role in diabetic patients

Diabetic patients with acute coronary syndromes are at high risk for cardiovascular complications but risk stratification in these patients remains challenging. Regularly, diabetic patients have a less typical clinical presentation, which could lead to delayed diagnosis and subsequent delayed initiation of treatment. Since diabetic patients derive particular benefit from aggressive anti-platelet therapy, early diagnostic and therapeutic risk stratification of these patients is of critical importance to improve their adverse outcome. Although the electrocardiogram remains a pivotal diagnostic tool in the evaluation of patients suspected of having an acute coronary syndrome, only significant STsegment changes provide reasonable prognostic information. Therefore, repeated assessment of circulating protein biomarkers represents a valuable diagnostic tool for improving efficacy and safety of decision-making in these patients. The combined use of biomarkers reflecting distinct pathophysiological aspects, such as myocardial necrosis, vascular inflammation, oxidative stress and neurohumoral activation, may significantly improve triage of patients with chest pain. These tools may identify those patients that are at particularly high risk for short-term and/or long-term cardiovascular events. Eventually, tailored medical and interventional treatment of diabetic patients should help to prevent these cardiac events in a cost-effective manner

Anti-proliferation Potential and Content of Fucoidan Extracted From Sporophyll of New Zealand Undaria Pinnatifida

Undaria pinnatifida is a species of brown seaweed known to contain rich amounts of fucoidan, a sulfated polysaccharide known to possess various biological activities. We isolated crude fucoidan (F0) from the sporophylls of U. pinnatifida grown in the Marlborough Sounds, New Zealand. Sulfate content, uronic acid content, and molecular weight of F0 were 15.02, 1.24, and >150 kDa, respectively. F0 was fractionated to yield three further fractions: F1, F2, and F3. Cytotoxicity of two major fractions was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The algal fucoidans specifically suppressed the proliferation of three cancer cell lines with less cytotoxicity against the normal cells. Selective cytotoxicity could relate to the distinctive structures of each fucoidan fraction. Results from this study provide evidence that fucoidan, especially from U. pinnatifida grown in New Zealand, possesses great potential to be used as a functional food to reduce cancer risk or supplement cancer treatment

Carriage niches and molecular epidemiology of Staphylococcus lugdunensis and methicillin-resistant S. lugdunensis among patients undergoing long-term renal replacement therapy

We collected nasal, axilla, and groin swabs from 252 adult patients from 2 nephrology centers in Hong Kong. Staphylococcus lugdunensis carriage was detected in 51.6% patients (groin, 39.3%; axilla, 19.8%; nose, 17.9%). The carriage rates of methicillin-sensitive S. lugdunensis and methicillin-resistant S. lugdunensis (MRSL) were 46.0% and 8.3%, respectively. Independent risk factors for S. lugdunensis carriage included male sex (odds ratio [OR], 4.4), hemodialysis (OR, 2.2), and aged 18–50 years (OR, 2.4). The isolates belonged to 10 pulsotype clusters (n = 129) and 8 singletons (n = 8). All MRSL and most gentamicin- and tetracycline-resistant strains were found in a predominating sequence type 3 clone, designated HKU1, which accounted for 51.8% of all colonizing S. lugdunensis strains. The 21 MRSL isolates had SCCmec type V (n = 18), type IV (n = 2), and type I (n = 1). The finding highlights the potential for dissemination of multidrug resistance through successful S. lugdunensis clones.postprin

The Nucleosome Assembly Protein TSPYL2 Regulates the Expression of NMDA Receptor Subunits GluN2A and GluN2B

published_or_final_versio

Characterization of kinetic and kinematic parameters for wearable robotics

The design process of a wearable robotic device for human assistance requires the characterization of both kinetic and kinematic parameters (KKP) of the human joints. The first step in this process is to extract the KKP from different gait analyses studies. This work is based on the human lower limb considering the following activities of daily living (ADL): walking over ground, stairs ascending/descending, ramp ascending/descending and chair standing up. The usage of different gait analyses in the characterization process, causes the data to have great variations from one study to another. Therefore, the data is graphically represented using Matlab® and Excel® to facilitate its assessment. Finally, the characterization of the KKP performed was proved to be useful in assessing the data reliability by directly comparing all the studies between each other; providing guidelines for the selection of actuator capacities depending on the end application; and highlighting optimization opportunities such as the implementation of agonist-antagonist actuators for particular human joints

α-Synuclein Suppression by Targeted Small Interfering RNA in the Primate Substantia Nigra

The protein α-synuclein is involved in the pathogenesis of Parkinson's disease and other neurodegenerative disorders. Its toxic potential appears to be enhanced by increased protein expression, providing a compelling rationale for therapeutic strategies aimed at reducing neuronal α-synuclein burden. Here, feasibility and safety of α-synuclein suppression were evaluated by treating monkeys with small interfering RNA (siRNA) directed against α-synuclein. The siRNA molecule was chemically modified to prevent degradation by exo- and endonucleases and directly infused into the left substantia nigra. Results compared levels of α-synuclein mRNA and protein in the infused (left) vs. untreated (right) hemisphere and revealed a significant 40–50% suppression of α-synuclein expression. These findings could not be attributable to non-specific effects of siRNA infusion since treatment of a separate set of animals with luciferase-targeting siRNA produced no changes in α-synuclein. Infusion with α-synuclein siRNA, while lowering α-synuclein expression, had no overt adverse consequences. In particular, it did not cause tissue inflammation and did not change (i) the number and phenotype of nigral dopaminergic neurons, and (ii) the concentrations of striatal dopamine and its metabolites. The data represent the first evidence of successful anti-α-synuclein intervention in the primate substantia nigra and support further development of RNA interference-based therapeutics

Embryonic Lethality in Mice Lacking the Nuclear Factor of Activated T Cells 5 Protein Due to Impaired Cardiac Development and Function

Nuclear factor of activated T cells 5 protein (NFAT5) is thought to be important for cellular adaptation to osmotic stress by regulating the transcription of genes responsible for the synthesis or transport of organic osmolytes. It is also thought to play a role in immune function, myogenesis and cancer invasion. To better understand the function of NFAT5, we developed NFAT5 gene knockout mice. Homozygous NFAT5 null (NFAT5−/−) mouse embryos failed to develop normally and died after 14.5 days of embryonic development (E14.5). The embryos showed peripheral edema, and abnormal heart development as indicated by thinner ventricular wall and reduced cell density at the compact and trabecular areas of myocardium. This is associated with reduced level of proliferating cell nuclear antigen and increased caspase-3 in these tissues. Cardiomyocytes from E14.5 NFAT5−/− embryos showed a significant reduction of beating rate and abnormal Ca2+ signaling profile as a consequence of reduced sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) and ryanodine receptor (RyR) expressions. Expression of NFAT5 target genes, such as HSP 70 and SMIT were reduced in NFAT5−/− cardiomyocytes. Our findings demonstrated an essential role of NFAT5 in cardiac development and Ca2+ signaling. Cardiac failure is most likely responsible for the peripheral edema and death of NFAT5−/− embryos at E14.5 days