The frog skin-derived antimicrobial peptide esculentin-1a(1-21)nh2 promotes the migration of human hacat keratinocytes in an egf receptor-dependent manner: a novel promoter of human skin wound healing?

One of the many functions of skin is to protect the organism against a wide range of pathogens. Antimicrobial peptides (AMPs) produced by the skin epithelium provide an effective chemical shield against microbial pathogens. However, whereas antibacterial/antifungal activities of AMPs have been extensively characterized, much less is known regarding their wound healing-modulatory properties. By using an in vitro re-epithelialisation assay employing special cell-culture inserts, we detected that a derivative of the frog-skin AMP esculentin-1a, named esculentin-1a(1-21)NH2, significantly stimulates migration of immortalized human keratinocytes (HaCaT cells) over a wide range of peptide concentrations (0.025-4 μM), and this notably more efficiently than human cathelicidin (LL-37). This activity is preserved in primary human epidermal keratinocytes. By using appropriate inhibitors and an enzyme-linked immunosorbent assay we found that the peptide-induced cell migration involves activation of the epidermal growth factor receptor and STAT3 protein. These results suggest that esculentin-1a(1-21)NH2 now deserves to be tested in standard wound healing assays as a novel candidate promoter of skin re-epithelialisation. The established ability of esculentin-1a(1-21)NH2 to kill microbes without harming mammalian cells, namely its high anti-Pseudomonal activity, makes this AMP a particularly attractive candidate wound healing promoter, especially in the management of chronic, often Pseudomonas-infected, skin ulcers

Prompt and accurate diagnosis of ventricular arrhythmias with a novel index based on phase space reconstruction of ECG

Aim: to develop a statistical index based on the phase space reconstruction (PSR) of the electrocardiogram (ECG) for the accurate and timely diagnosis of ventricular tachycardia (VT) and ventricular fibrillation (VF).Methods: thirty-two ECGs with sinus rhythm (SR) and 32 ECGs with VT/VF were analyzed using the PSR technique. Firstly, the method of time delay embedding were employed with the insertion of delay “?” in the original time-series X(t), which produces the Y(t) = X(t ? ?). Afterwards, a PSR diagram was reconstructed by plotting Y(t) against X(t). The method of box counting was applied to analyze the behavior of the PSR trajectories. Measures as mean (?), standard deviation (?) and coefficient of variation (CV = ?/?), kurtosis (?) for the box counting of PSR diagrams were reported.Results: during SR, CV was always < 0.05, while with the onset of arrhythmia CV increased > 0.05. A similar pattern was observed with ? , where < 6 was considered as the cut-off point between SR and VT/VF. Therefore, the upper threshold for SR was considered CV th = 0.05 and ?th < 6. For optimisation of the accuracy, a new index (J ) was proposed: View the MathML sourceJ=wCVCVth+1?w??th.During SR the upper limit of J was the value of 1. Furthermore CV, ? and J crossed the cut-off point timely before the onset of arrhythmia (average time: 4 min 31 s; SD: 2 min 30 s); allowing sufficient time for preventive therapy.Conclusion: the J index improved ECG utility for arrhythmia monitoring and detection utility, allowing the prompt and accurate diagnosis of ventricular arrhythmias

Severe asthma features in children: A case–control online survey

Background: Very few studies have explored the distinguishing features of severe asthma in childhood in Europe, and only one study was conducted in Southern Europe. The aim of this study was to provide a detailed characterization of children with severe asthma treated in specialized pediatric asthma centers across Italy. Methods: We conducted a web-based data collection of family, environmental, clinical and laboratory characteristics of 41 patients aged 6–17 years with severe asthma, defined according to the recent guidelines of the European Respiratory Society and the American Thoracic Society, and 78 age-matched peers with non-severe persistent asthma. The patients have been enrolled from 16 hospital-based pediatric pulmonology and allergy centers in Northern, Central, and Southern Italy. Logistic regression analysis assessed the relationship between patients’ characteristics and severe asthma or non-severe persistent asthma. Results: Features independently and significantly associated with severe asthma included lifetime sensitization to food allergens [Odds ratio (OR), 4.73; 95% Confidence Interval (CI), 1.21–18.53; p = 0.03], lifetime hospitalization for asthma (OR, 3.71; 95% CI, 1.11–12.33; p = 0.03), emergency-department visits for asthma during the past year (OR = 11.98; 95% CI, 2.70–53.11; p = 0.001), and symptoms triggered by physical activity (OR = 12.78; 95% CI, 2.66–61.40; p = 0.001). Quality-of-life score was worse in patients with severe asthma than in subjects with non-severe persistent asthma (5.9 versus 6.6, p = 0.005). Self-perception of wellbeing was compromised in more than 40% of patients in both groups. Children with severe asthma had lower spirometric z scores than non-severe asthmatic peers (all p < 0.001), although 56% of them had a normal forced expiratory volume in 1 s. No differences were found between the two groups for parental education, home environment, patients’ comorbidities, adherence to therapy, exhaled nitric oxide values, and serum eosinophils and IgE. Conclusions: As expected, children with severe asthma had more severe clinical course and worse lung function than peers with non-severe persistent asthma. Unlike previous reports, we found greater sensitization to food allergens and similar environmental and personal characteristics in patients with severe asthma compared to those with non-severe persistent asthma. Psychological aspects are compromised in a large number of cases and deserve further investigation

Dectin-1 diversifies Aspergillus fumigatus–specific T cell responses by inhibiting T helper type 1 CD4 T cell differentiation

By modifying dendritic cell cytokine production, Dectin-1 suppresses Th1 differentiation in mice infected with the fungal pathogen Aspergillus fumigatus

Towards improved treatment planning for head and neck microwave hyperthermia

Hyperthermia is an emerging cancer treatment modality which involves applying heat to the malignant tumor. The heating can be delivered using electromagnetic energy, mostly in the radiofrequency or microwave range. Accurate patient-specific hyperthermia treatment planning is essential for effective and safe treatment, in particular for deep and loco-regional hyperthermia. An important aspect of hyperthermia treatment planning is the ability to focus microwave energy and heating into the tumour while reducing the occurrence of hotspots in surrounding healthy tissue. Typically, a multi-element antenna phase array hyperthermia system is used to focus the electromagnetic waves at the target region. This thesis presents methods for optimising the specific absorption rate distribution and resulting temperature distribution for head and neck cancer hyperthermia treatment. Several optimisation algorithms and objective functions have been evaluated to optimise the antenna amplitudes and phases of the hyperthermia systems. Evolutionary optimisation algorithms have been considered in this thesis and compared with a particle swarm optimisation method already in clinical use for the treatment of head and neck cancers. A differential evolution algorithm is proposed to improve target coverage. The differential evolution algorithm is shown to offer improved performance compared to the particle swarm optimisation algorithm. Most optimisation techniques reported in literature use static antenna settings throughout the treatment; however, in this thesis a dynamic approach is investigated. A time-multiplexed hyperthermia strategy is developed in order to better focus heating on the tumour while preserving predetermined areas in the healthy tissue. First, a multi-objective genetic algorithm is introduced, which generates multiple antenna settings which are applied sequentially. Thermal simulations are used to evaluate the performance of time-multiplexed steering. The results demonstrate the ability to enhance target heating while reducing hotspot temperatures. Finally, the time-multiplexing steering is evaluated against thermal tissue properties variation and is shown to be robust to temperature dependent thermal tissue properties

A Phase Space Box-counting based Method for Arrhythmia Prediction from Electrocardiogram Time Series

Arrhythmia is one kind of cardiovascular diseases that give rise to the number of deaths and potentially yields immedicable danger. Arrhythmia is a life threatening condition originating from disorganized propagation of electrical signals in heart resulting in desynchronization among different chambers of the heart. Fundamentally, the synchronization process means that the phase relationship of electrical activities between the chambers remains coherent, maintaining a constant phase difference over time. If desynchronization occurs due to arrhythmia, the coherent phase relationship breaks down resulting in chaotic rhythm affecting the regular pumping mechanism of heart. This phenomenon was explored by using the phase space reconstruction technique which is a standard analysis technique of time series data generated from nonlinear dynamical system. In this project a novel index is presented for predicting the onset of ventricular arrhythmias. Analysis of continuously captured long-term ECG data recordings was conducted up to the onset of arrhythmia by the phase space reconstruction method, obtaining 2-dimensional images, analysed by the box counting method. The method was tested using the ECG data set of three different kinds including normal (NR), Ventricular Tachycardia (VT), Ventricular Fibrillation (VF), extracted from the Physionet ECG database. Statistical measures like mean (μ), standard deviation (σ) and coefficient of variation (σ/μ) for the box-counting in phase space diagrams are derived for a sliding window of 10 beats of ECG signal. From the results of these statistical analyses, a threshold was derived as an upper bound of Coefficient of Variation (CV) for box-counting of ECG phase portraits which is capable of reliably predicting the impeding arrhythmia long before its actual occurrence. As future work of research, it was planned to validate this prediction tool over a wider population of patients affected by different kind of arrhythmia, like atrial fibrillation, bundle and brunch block, and set different thresholds for them, in order to confirm its clinical applicability

Towards improved treatment planning for head and neck microwave hyperthermia

Hyperthermia is an emerging cancer treatment modality which involves applying heat to the malignant tumor. The heating can be delivered using electromagnetic energy, mostly in the radiofrequency or microwave range. Accurate patient-specific hyperthermia treatment planning is essential for effective and safe treatment, in particular for deep and loco-regional hyperthermia. An important aspect of hyperthermia treatment planning is the ability to focus microwave energy and heating into the tumour while reducing the occurrence of hotspots in surrounding healthy tissue. Typically, a multi-element antenna phase array hyperthermia system is used to focus the electromagnetic waves at the target region. This thesis presents methods for optimising the specific absorption rate distribution and resulting temperature distribution for head and neck cancer hyperthermia treatment. Several optimisation algorithms and objective functions have been evaluated to optimise the antenna amplitudes and phases of the hyperthermia systems. Evolutionary optimisation algorithms have been considered in this thesis and compared with a particle swarm optimisation method already in clinical use for the treatment of head and neck cancers. A differential evolution algorithm is proposed to improve target coverage. The differential evolution algorithm is shown to offer improved performance compared to the particle swarm optimisation algorithm. Most optimisation techniques reported in literature use static antenna settings throughout the treatment; however, in this thesis a dynamic approach is investigated. A time-multiplexed hyperthermia strategy is developed in order to better focus heating on the tumour while preserving predetermined areas in the healthy tissue. First, a multi-objective genetic algorithm is introduced, which generates multiple antenna settings which are applied sequentially. Thermal simulations are used to evaluate the performance of time-multiplexed steering. The results demonstrate the ability to enhance target heating while reducing hotspot temperatures. Finally, the time-multiplexing steering is evaluated against thermal tissue properties variation and is shown to be robust to temperature dependent thermal tissue properties

Naturally occurring peptides from Rana temporaria: antimicrobial properties and more

The extensive search for alternative therapeutics against microbial pathogens has led to the discovery of cationic peptides as new anti-infectives with a novel mode of action. Particular interest has been devoted to small linear peptides that can be efficiently made by chemical synthesis at competitive costs. The most promising originate from a large family of short, naturally occurring peptides found in the skin of amphibia of Rana genus, i.e. the temporins. This review is mainly focused on the recent structure-function studies of the earliest known temporin isoforms (TA, TB and TL) and their potential clinical role as novel antimicrobial agents. The development of novel antibiotics is an urgent public health concern due to the increased resistance of microorganisms to conventional antibiotics, particularly in the hospital setting