Early invasive strategy (< 24 hours) in patients with acute coronary syndromes: Weighing the evidence

n

Virus-like Particle (VLP) Vaccines for Cancer Immunotherapy

Cancer vaccines are increasingly being studied as a possible strategy to prevent and treat cancers. While several prophylactic vaccines for virus-caused cancers are approved and efficiently used worldwide, the development of therapeutic cancer vaccines needs to be further implemented. Virus-like particles (VLPs) are self-assembled protein structures that mimic native viruses or bacteriophages but lack the replicative material. VLP platforms are designed to display single or multiple antigens with a high-density pattern, which can trigger both cellular and humoral responses. The aim of this review is to provide a comprehensive overview of preventive VLP-based vaccines currently approved worldwide against HBV and HPV infections or under evaluation to prevent virus-caused cancers. Furthermore, preclinical and early clinical data on prophylactic and therapeutic VLP-based cancer vaccines were summarized with a focus on HER-2-positive breast cancer

Cryptic loxP sites in mammalian genomes: genome-wide distribution and relevance for the efficiency of BAC/PAC recombineering techniques

Cre is widely used for DNA tailoring and, in combination with recombineering techniques, to modify BAC/PAC sequences for generating transgenic animals. However, mammalian genomes contain recombinase recognition sites (cryptic loxP sites) that can promote illegitimate DNA recombination and damage when cells express the Cre recombinase gene. We have created a new bioinformatic tool, FuzznucComparator, which searches for cryptic loxP sites and we have applied it to the analysis of the whole mouse genome. We found that cryptic loxP sites occur frequently and are homogeneously distributed in the genome. Given the mammalian nature of BAC/PAC genomic inserts, we hypothesised that the presence of cryptic loxP sites may affect the ability to grow and modify BAC and PAC clones in E. coli expressing Cre recombinase. We have observed a defect in bacterial growth when some BACs and PACs were transformed into EL350, a DH10B-derived bacterial strain that expresses Cre recombinase under the control of an arabinose-inducible promoter. In this study, we have demonstrated that Cre recombinase expression is leaky in un-induced EL350 cells and that some BAC/PAC sequences contain cryptic loxP sites, which are active and mediate the introduction of single-strand nicks in BAC/PAC genomic inserts

A Novel Method for Vibrotactile Proprioceptive Feedback Using Spatial Encoding and Gaussian Interpolation

Objective: The bidirectional communication between the user and the prosthesis is an important requirement when developing prosthetic hands. Proprioceptive feedback is fundamental to perceiving prosthesis movement without the need for constant visual attention. We propose a novel solution to encode wrist rotation using a vibromotor array and Gaussian interpolation of vibration intensity. The approach generates tactile sensation that smoothly rotates around the forearm congruently with prosthetic wrist rotation. The performance of this scheme was systematically assessed for a range of parameter values (number of motors and Gaussian standard deviation). Methods: Fifteen able-bodied subjects and one individual with congenital limb deficiency used vibrational feedback to control the virtual hand in the target-achievement test. Performance was assessed by end-point error and efficiency as well as subjective impressions. Results: The results showed a preference for smooth feedback and a higher number of motors (8 and 6 versus 4). With 8 and 6 motors, the standard deviation, determining the sensation spread and continuity, could be modulated through a broad range of values (0.1 - 2) without a significant performance loss (error: ∼ 10%; efficiency: ∼ 30%). For low values of standard deviation (0.1-0.5), the number of motors could be reduced to 4 without a significant performance decrease. Conclusion: The study demonstrated that the developed strategy provided meaningful rotation feedback. Moreover, the Gaussian standard deviation can be used as an independent parameter to encode an additional feedback variable. Significance: The proposed method is a flexible and effective approach to providing proprioceptive feedback while adjusting the trade-off between sensation quality and the number of vibromotors

Hannes Prosthesis Control Based on Regression Machine Learning Algorithms

The quality of life for upper limb amputees can be greatly improved by the adoption of poly-articulated myoelectric prostheses. Typically, in these applications, a pattern recognition algorithm is used to control the system by converting the recorded electromyographic activity (EMG) into complex multi-degrees of freedom (DoFs) movements. However, there is currently a trade-off between the intuitiveness of the control and the number of active DoFs. We here address this challenge by performing simultaneous multi-joint control of the Hannes system and testing several state-of-the-art classifiers to decode hand and wrist movements. The algorithms discriminated multi-DoF movements from forearm EMG signals of 10 healthy subjects reproducing hand opening-closing, wrist flexion-extension and wrist pronation-supination. We first explored the effect of the number of employed EMG electrodes on device performance through the classifiers optimization in terms of F1Score. We further improved classifiers by tuning their respective hyperparameters in terms of the Embedding Optimization Factor. Finally, three mono-lateral amputees tested the optimized algorithms to intuitively and simultaneously control the Hannes system. We found that the algorithms performances were similar to that of healthy subjects, particularly identifying the Non-Linear Regression classifier as the ideal candidate for prosthetic applications

Prognostic value of high-sensitivity cardiac troponin I early after coronary artery bypass graft surgery

Background: The diagnosis of periprocedural myocardial infarction (PMI) after coronary artery bypass graft (CABG) is based on biochemical markers along with clinical and instrumental findings. However, there is not a clear cutoff value of high-sensitivity cardiac troponin (hs-cTn) to identify PMI. We hypothesized that isolated hs-cTn concentrations in the first 24&nbsp;h following CABG could predict cardiac adverse events (in-hospital death and PMI) and/or left ventricular ejection fraction (LVEF) decrease. Methods: We retrospectively enrolled all consecutive adult patients undergoing CABG, alone or in association with other cardiac surgery procedures, over 1&nbsp;year. Hs-cTn I concentrations (Access, Beckman Coulter) were serially measured in the post-operative period and analyzed according to post-operative outcomes. Results: 300 patients were enrolled; 71.3% underwent CABG alone, 33.7% for acute coronary syndrome. Most patients showed hs-cTn I values superior to the limit required by the latest guidelines for the diagnosis of PMI. Five patients (1.7%) died, 8% developed a PMI, 10.6% showed a LVEF decrease ≥ 10%. Hs-cTn I concentrations did not significantly differ with respect to death and/or PMI whereas they were associated with LVEF decrease ≥ 10% (p value &lt; 0.005 at any time interval), in particular hs-cTn I values at 9–12&nbsp;h post-operatively. A hs-cTn I cutoff of 5556&nbsp;ng/L, a value 281 (for males) and 479 (for females) times higher than the URL, at 9–12&nbsp;h post-operatively was identified, representing the best balance between sensitivity (55%) and specificity (79%) in predicting LVEF decrease ≥ 10%. Conclusions: Hs-cTn I at 9–12&nbsp;h post-CABG may be useful to early identify patients at risk for LVEF decrease and to guide early investigation and management of possible post-operative complications

Measurements of the reaction pˉp→ϕη\bar{p}p \to \phi \eta of antiproton annihilation at rest at three hydrogen target densities

The proton-antiproton annihilation at rest into the $\phi\eta$ final state was measured for three different target densities: liquid hydrogen, gaseous hydrogen at NTP and at a low pressure of 5 mbar. The yield of this reaction in the liquid hydrogen target is smaller than in the low-pressure gas target. The branching ratios of the $\phi\eta$ channel were calculated on the basis of simultaneous analysis of the three data samples. The branching ratio for annihilation into $\phi\eta$ from the $^3S_1$ protonium state turns out to be about ten times smaller as compared to the one from the $^1P_1$ state.Comment: 10 pages, 3 Postscript figures. Accepted by Physics Letters

Late fetal and newborn granulopoiesis but not active renin is increased by maternal captopril treatment during perinatal kidney development

Renin expression follows vascular development through the mouse kidney, regressing to glomerular poles by about P10, where renin is stored in dense core granules in juxtaglomerular cells. Homeostatic challenge to blood pressure causes release of active renin from the granules and recruitment of the renin lineage cells. We investigated the response to homeostatic challenge during late fetal development and following birth in a transgenic line expressing GFP under the renin promotor. Pregnant females were treated with water or captopril (30mg/kg/day), which inhibits angiotensin converting enzyme, from E15.5. We found an increase in renin transcription and expression by P1 following captopril treatment, with granulation increased at the glomerular poles and major arteries from E18.5. At P1, the granules showed a wide variation in electron density. Notably, rough endoplasmic reticulum was expanded in vascular smooth muscle cells (VSMCs) of captopril-treated pups at both time-points suggesting increased transcriptional activity. Paracrystalline material was observed in granules of captopril treated fetuses at E18.5 and in both treated and untreated pups at P1. Renin expression and some granules were confirmed in the kidney VSMCs by immuno-gold staining against GFP at E18.5. Importantly, we found no difference in active renin content between kidneys from treated and untreated pups at either age group. We therefore demonstrate a disconnect between granulation and active renin production in newborns when exposed to homeostatic challenge in utero

Biofeedback Signals for Robotic Rehabilitation: Assessment of Wrist Muscle Activation Patterns in Healthy Humans

Electrophysiological recordings from human muscles can serve as control signals for robotic rehabilitation devices. Given that many diseases affecting the human sensorimotor system are associated with abnormal patterns of muscle activation, such biofeedback can optimize human-robot interaction and ultimately enhance motor recovery. To understand how mechanical constraints and forces imposed by a robot affect muscle synergies, we mapped the muscle activity of seven major arm muscles in healthy individuals performing goal-directed discrete wrist movements constrained by a wrist robot. We tested six movement directions and four force conditions typically experienced during robotic rehabilitation. We analyzed electromyographic (EMG) signals using a space-by-time decomposition and we identified a set of spatial and temporal modules that compactly described the EMG activity and were robust across subjects. For each trial, coefficients expressing the strength of each combination of modules and representing the underlying muscle recruitment, allowed for a highly reliable decoding of all experimental conditions. The decomposition provides compact representations of the observable muscle activation constrained by a robotic device. Results indicate that a low-dimensional control scheme incorporating EMG biofeedback could be an effective add-on for robotic rehabilitative protocols seeking to improve impaired motor function in humans

Analysis of charmonium production at fixed-target experiments in the NRQCD approach

We present an analysis of the existing data on charmonium hadro-production based on non-relativistic QCD (NRQCD) calculations at the next-to-leading order (NLO). All the data on J/psi and psi' production in fixed-target experiments and on pp collisions at low energy are included. We find that the amount of color octet contribution needed to describe the data is about 1/10 of that found at the Tevatron