Anti-ischaemic effect of ivabradine.

Ivabradine, the first representative of a new class of exclusive heart rate-reducing agents, selectively inhibits the I(f) current in the sinoatrial node. The direct electrophysiological consequence of this inhibition is a reduction in the slope of the diastolic depolarisation curve and a decrease in heart rate. Pharmacological inhibition of the I(f) current with ivabradine has been shown to preserve coronary vasodilatation upon exercise, i.e., myocardial perfusion, with no negative inotropic effects and maintenance of cardiac contractility. Ivabradine protects the myocardium during ischaemia, improves left ventricular function in congestive heart failure, and reduces remodelling subsequent to myocardial infarction. Pure heart rate reduction by specific and selective I(f) inhibition decreases oxygen demand, improves myocardial energetics and improves perfusion of the ischaemic myocardium. We can expect distinct clinical benefits from long-term heart rate reduction in patients with chronic ischaemic disease.     

Distant muscular (gluteus maximus muscle) metastasis from laryngeal squamous cell carcinoma

Clinical evidence of non-lymphatic distant metastasis has been reported in approximately 10% of cases of head and neck squamous cell carcinoma (HNSCC). The lungs are the commonest site of distant metastasis of HNSCC, followed by the bones, liver and skin. A 65-year-old male underwent supraglottic laryngectomy and left modified neck dissection for a carcinoma of the laryngeal surface of the epiglottis extending to both false cords. Eight months later the patient underwent right radical modified neck dissection for hypodermal metastatic disease involving the underlying (sternocleidomastoid) muscle. Thirty-two months later, surgical excision of a lesion in the right gluteus maximus muscle was performed. Histological study diagnosed a muscular metastasis with the same morphological aspect as the laryngeal carcinoma. The patient showed no evidence of cervical or distant recurrence at follow-up after 13 months. Although skeletal muscles represent approximately 50% of total body mass and receive a large proportion of total cardiac output, haematogenous metastases to skeletal muscle are extremely uncommon. Most skeletal muscle metastases are of pulmonary origin. Distant skeletal muscle metastasis from HNSCC is an extremely rare occurrence. Treatment options, depending upon the clinical setting, include observation, radiotherapy, chemotherapy and excision; these approaches rarely alter the patient outcome. The prognosis associated with skeletal muscle metastasis is thought to be poor, consistent with the fact that it generally occurs as a feature of systemic spread.     

Color Conversion Light-Emitting Diodes Based on Carbon Dots: A Review

This paper reviews the state-of-the-art technologies, characterizations, materials (precursors and encapsulants), and challenges concerning multicolor and white light-emitting diodes (LEDs) based on carbon dots (CDs) as color converters. Herein, CDs are exploited to achieve emission in LEDs at wavelengths longer than the pump wavelength. White LEDs are typically obtained by pumping broad band visible-emitting CDs by an UV LED, or yellow–green-emitting CDs by a blue LED. The most important methods used to produce CDs, top-down and bottom-up, are described in detail, together with the process that allows one to embed the synthetized CDs on the surface of the pumping LEDs. Experimental results show that CDs are very promising ecofriendly candidates with the potential to replace phosphors in traditional color conversion LEDs. The future for these devices is bright, but several goals must still be achieved to reach full maturity.     

Thermostructural Numerical Analysis of the Thrust Chamber of a Liquid Propellant Rocket Engine

The numerical simulation of rocket engine thrust chambers is very challenging as several damaging phenomena, such as plasticity, low-cycle-fatigue (LCF) and creep occur during its service life. The possibility of simulating the thermostructural behavior of the engine, by means of non-linear finite element analyses, allows the engineers to guarantee the structural safety of the structure. This document reports the numerical simulations developed with the aim of predicting the thermostructural behaviour and the service life of the thrust chamber of a liquid-propellant rocket engine. The work represents a step ahead of previous researches by the authors, with particular reference to the addition of the Smith-Watson-Topper (SWT) fatigue criterion, and to the implementation of a sub-modelling technique, for a more accurate assessment of the most critical section of the component. It was found that the equivalent plastic strains in the most critical nodes obtained through the sub-modelling technique were about 20% lower than those calculated without sub-modelling. Consistently with experimental tests from literature conducted on similar geometries, the most critical areas resulted to be on the internal surface of the chamber. The analyses demonstrated that the LCF damaging contribution was significant, with a life prediction for the thrust chamber of about 3400 cycles.     

Probiotics Administration in Cystic Fibrosis: What Is the Evidence?

In the last 20 years, gut microbiota in patients with cystic fibrosis (CF) has become an object of interest. It was shown that these patients had gut dysbiosis and this could explain not only the intestinal manifestations of the disease but also part of those involving the respiratory tract. The acquisition of previously unknown information about the importance of some bacteria, i.e., those partially or totally disappeared in the gut of CF patients, in the regulation of the activity and function of the gut and the lung was the base to suggest the use of probiotics in CF patients. The main aim of this paper is to discuss the biological basis for probiotic administration to CF patients and which results could be expected. Literature analysis showed that CF intestinal dysbiosis depends on the same genetic mutations that condition the clinical picture of the diseases and is aggravated by a series of therapeutic interventions, such as dietary modifications, the use of antibiotics, and the administration of antacids. All this translates into a significant worsening of the structure and function of organs, including the lung and intestine, already deeply penalized by the genetic alterations of CF. Probiotics can intervene on dysbiosis, reducing the negative effects derived from it. However, the available data cannot be considered sufficient to indicate that these bacteria are essential elements of CF therapy. Further studies that take into account the still unsolved aspects on how to use probiotics are absolutely necessary.     

Headache-related circuits and high frequencies evaluated by EEG,MRI, PET as potential biomarkers to differentiate chronic and episodic migraine: Evidence from a systematic review

BackgroundThe diagnosis of migraine is mainly clinical and self-reported, which makes additional examinations unnecessary in most cases. Migraine can be subtyped into chronic (CM) and episodic (EM). Despite the very high prevalence of migraine, there are no evidence-based guidelines for differentiating between these subtypes other than the number of days of migraine headache per month. Thus, we consider it timely to perform a systematic review to search for physiological evidence from functional activity (as opposed to anatomical structure) for the differentiation between CM and EM, as well as potential functional biomarkers. For this purpose, Web of Science (WoS), Scopus, and PubMed databases were screened.FindingsAmong the 24 studies included in this review, most of them (22) reported statistically significant differences between the groups of CM and EM. This finding is consistent regardless of brain activity acquisition modality, ictal stage, and recording condition for a wide variety of analyses. That speaks for a supramodal and domain-general differences between CM and EM that goes beyond a differentiation based on the days of migraine per month. Together, the reviewed studies demonstrates that electro- and magneto-physiological brain activity (M/EEG), as well as neurovascular and metabolic recordings from functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), show characteristic patterns that allow to differentiate between CM and EM groups.ConclusionsAlthough a clear brain activity-based biomarker has not yet been identified to distinguish these subtypes of migraine, research is approaching headache specialists to a migraine diagnosis based not only on symptoms and signs reported by patients. Future studies based on M/EEG should pay special attention to the brain activity in medium and fast frequency bands, mainly the beta band. On the other hand, fMRI and PET studies should focus on neural circuits and regions related to pain and emotional processing.     

Cellular pharmacology of P-ethoxy antisense oligonucleotides targeted to Bcl-2 in a follicular lymphoma cell line

A P-ethoxy oligonucleotide (oligo), 20 bases long and specific for the translation initiation site of human Bcl-2 mRNA, was incorporated into liposomes to increase its intracellular delivery. This oligo selectively inhibited Bcl-2 protein expression and induced growth inhibition in t(14;18)-positive transformed follicular lymphoma (FL) cell lines. We studied the inhibitory effects of shorter liposomal P-ethoxy oligos (7, 9, 11 or 15 mer) in order to determine the activity of different oligo chain lengths targeted to the same Bcl-2 mRNA. At 12 μM, all the oligos inhibited the growth of a FL cell line. We compared the 7-mer oligo with the 20-mer oligo. The two oligos inhibited Bcl-2 protein expression similarly: 66% and 60% for the 7- and 20-mer, respectively. The uptake and retention of both oligos were also very similar. Our results indicate that the Bcl-2 inhibitory activity is maintained with P-ethoxy antisense oligos ranging from 7 to 20 bases.