How I prevent erysipelas and its consequences and recurrences.

peer reviewedErysipelas is a serious infection of the skin. In case of delay in initiating adequate antibiotic treatment, complications, sometimes dismal, can supervene. In addition, erysipelas shows a tendancy to recurrences. The prevention of an episode of erysipelas calls for correct personal hygiene and adequate use of topical antiseptics in case of skin effraction, even when minimal. When erysipelas is established, a rapidly initiated antibiotic treatment for a prolonged period prevents streptococcal gangrene complications. Elastic contention of any leg edema from venous or lymphatic origin and prophylactic antisepsis of discrete wounds help in preventing erysipelas recurrences

Mutant and chimeric recobinant plasminogen activatorsproduction in eukaryotic cellsand preliminary characterization

Mutant urokinase-type plasminogen activator (u-PA) genes and hybrid genes between tissue-type plasminogen activator (t-PA) and u-PA have been designed to direct the synthesis of new plasminogen activators and to investigate the structure-function relationship in these molecules. The following classes of constructs were made starting from cDNA encoding human t-PA or u-PA: 1) u-PA mutants in which the Arg156 and Lys158 were substituted with threonine, thus preventing cleavage by thrombin and plasmin; 2) hybrid molecules in which the NH2-terminal regions of t-PA (amino acid residues 1-67, 1-262, or 1-313) were fused with the COOH-terminal region of u-PA (amino acids 136-411, 139-411, or 195-411, respectively); and 3) a hybrid molecule in which the second kringle of t-PA (amino acids 173-262) was inserted between amino acids 130 and 139 of u-PA. In all cases but one, the recombinant proteins, produced by transfected eukaryotic cells, were efficiently secreted in the culture medium. The translation products have been tested for their ability to activate plasminogen after in situ binding to an insolubilized monoclonal antibody directed against urokinase. All recombinant enzymes were shown to be active, except those in which Lys158 of u-PA was substituted with threonine. Recombination of structural regions derived from t-PA, such as the finger, the kringle 2, or most of the A-chain sequences, with the protease part or the complete u-PA molecule did not impair the catalytic activity of the hybrid polypeptides. This observation supports the hypothesis that structural domains in t-PA and u-PA fold independently from one to another

Cervical artery dissection: An atypical presentation with Ehlers-Danlos-like collagen pathology?

The authors took skin biopsies of the macroscopically normal skin of seven consecutive patients with spontaneous cervical artery dissection (SCAD). Histologically, alterations of the collagen and elastic fiber networks were found in six patients. In five, the histologic, immunohistochemical, and ultrastructural changes were similar to those usually found in Ehlers-Danlos syndrome (EDS). This suggests that SCAD is frequently associated with the dermal alterations seen in EDS

Nutrition and the circadian system

The human circadian system anticipates and adapts to daily environmental changes to optimise behaviour according to time of day and temporally partitions incompatible physiological processes. At the helm of this system is a master clock in the suprachiasmatic nuclei (SCN) of the anterior hypothalamus. The SCN are primarily synchronised to the 24-h day by the light/dark cycle; however, feeding/fasting cycles are the primary time cues for clocks in peripheral tissues. Aligning feeding/fasting cycles with clock-regulated metabolic changes optimises metabolism, and studies of other animals suggest that feeding at inappropriate times disrupts circadian system organisation, and thereby contributes to adverse metabolic consequences and chronic disease development. ‘High-fat diets’ (HFD) produce particularly deleterious effects on circadian system organisation in rodents by blunting feeding/fasting cycles. Time-of-day-restricted feeding, where food availability is restricted to a period of several hours, offsets many adverse consequences of HFD in these animals; however, further evidence is required to assess whether the same is true in humans. Several nutritional compounds have robust effects on the circadian system. Caffeine, for example, can speed synchronisation to new time zones after jetlag. An appreciation of the circadian system has many implications for nutritional science and may ultimately help reduce the burden of chronic diseases

Phase Field Modelling of Failure in Thermoset Composites Under Cure-Induced Residual Stress

This study examines the residual stress induced by manufacturing and its effect on failure in thermosetting unidirectional composites under quasi-static loading, using Finite Element-based computational models. During the curing process, the composite material develops residual stress fields due to various phenomena. These stress fields are predicted using a constitutive viscoelastic model and subsequently initialized within a damage-driven Phase Field model. Structural tensors are used to modify the stress-based failure criteria to account for inherent transverse isotropy. This influence is incorporated into the crack phase field evolution equation, enabling a modular framework that retains all residual stress information through a heat-transfer analogy. The proposed coupled computational model is validated through a representative numerical case study involving L-shaped composite parts. The findings reveal that cure-induced residual stresses, in conjunction with discontinuities, play a critical role in matrix cracking and significantly affect the structural load-carrying capacity. The proposed coupled numerical approach provides an initial estimation of the influence of manufacturing defects and streamlines the optimization of cure profiles to enhance manufacturing quality. Among the investigated curing strategies, the three-dwell cure cycle emerged as the most effective solution

Particle filter-based prognostics for composite curing process

Process-induced deformation (PID) arises in thermoset parts due to internal residual stress developed from their anisotropic properties, resulting in distortions. While passive numerical manufacturing control exists, active manufacturing control is crucial for enhancing the manufacturing process. The work focuses on diagnosing the polymerization reaction, known as the curing process, to consider the influence of uncertainties in thermal loading conditions on the behavior of cure kinetics. This is achieved using a Particle Filter approach, wherein a posterior distribution of cure evolution is recursively approximated based on observed measurements from characterization tests. The algorithm is designed to simultaneously perform the diagnosis and prognosis of the Degree of Cure and PID. This approach adopts the augmented cure formulation to address various scenarios with uncertainties in thermal loading conditions. It offers the advantage of providing comparable PID predictions with minimal computational costs. C-shaped thermoset parts made of epoxy/carbon fibers with varying thicknesses are cured using the Manufacturing Recommended Curing Cycle, and the predictions with the developed algorithm are validated against experimental measures. Upon validation, the converged prognosis capability of the Particle Filter model is employed to assess the impact of thermal loading uncertainty on cure profiles, which, in turn, affects the final PIDs outcome. Highlights: A Bayesian sampling approach enables the estimation of cure kinetics parameters. The estimated stochastic parameters forecast the process-induced deformations. The augmented Degree of Cure accounts for uncertainties linked to thermal loadings. Analysis on AS4/8552 C-shaped parts shows the cure kinetics impact. The framework reduces the computational costs required for active control

Prediction of shape distortions in thermosetting composite parts using neural network interfaced visco-elastic constitutive model

The work aims to enhance the capabilities of a Finite Element tool, specifically related to a rheological thermo-chemo-viscoelastic constitutive model. This enhancement is intended to improve the tool’s ability to predict the distortions in composite parts caused by the polymerization of the thermoset composite matrix. These distortions occur due to internal residual stress generated by the inherent anisotropic properties of the thermoset composite material, including coefficients of thermal expansion and chemical shrinkage. The research work’s improvement is tied to the precise modelling of curing behaviour, which literature acknowledges as having a significant impact on manufacturing defects. In order to accommodate the influence of curing behaviour on various process variables—specifically, different thermal loading rates—a neural network model is implemented as an alternative to a standard diffusion cure-kinetics model. The neural network model is trained using Differential Scanning Calorimetry data and is integrated with the classical visco-elastic constitutive model to more accurately predict the progression of distinct thermoset resin states. This transition between cure states is assessed using two cure state variables: the degree of cure and the glass transition temperature. The enhanced predictions of state transitions lead to accurate assessments of internal residual stresses, especially when dealing with thick components subjected to thermal fluctuations. The anisotropic properties of thermoset composites, crucial for numerical analysis, are captured at various stages of cure. Ultimately, this methodology is employed to compare process-induced defects in the case study of the Z-shaped carbon/epoxy woven part, and the defects closely align with experimental measurements

Guidelines for pre-operative cardiac risk assessment and perioperative cardiac management in non-cardiac surgery : the Task Force for Preoperative Cardiac Risk Assessment and Perioperative Cardiac Management in Non-cardiac Surgery of the European Society of Cardiology (ESC) and endorsed by the European Society of Anaesthesiology (ESA)

Non-cardiac surgery; Pre-operative cardiac risk assessment; Pre-operative cardiac testing; Pre-operative coronary artery revascularization; Perioperative cardiac management; Renal disease; Pulmonary disease; Neurological disease; Anaesthesiology; Post-operative cardiac surveillanc

Aortic stiffness as a marker of cardiac function and myocardial strain in patients undergoing aortic valve replacement

Background: Cardiac function and myocardial strain are affected by cardiac afterload, which is in part due to the stiffness of the aortic wall. In this study, we hypothesize that aortic pulse wave velocity (PWV) as a marker of aortic stiffness correlates with conventional clinical and biochemical markers of cardiac function and perioperative myocardial strain in aortic valve replacement (AVR). Methods: Patients undergoing AVR for aortic stenosis between June 2010 and August 2012 were recruited for inclusion in this study. PWV, NYHA class and left ventricular (LV) function were assessed pre-operatively. PWV was analysed both as a continuous and dichotomous variable according to age-standardized reference values. B-type natriuretic peptide (BNP) was measured pre-operatively, and at 3 h and 18-24 h after cardiopulmonary bypass (CPB). NYHA class, leg edema, and LV function were recorded at follow-up (409 ± 159 days). Results: Fifty-six patients (16 females) with a mean age of 71 ± 8.4 years were included, with 50 (89%) patients completing follow-up. The NYHA class of PWV-norm patients was significantly lower than PWV-high patients both pre- and post-operatively. Multiple logistic regression also highlighted PWV-cut off as an independent predictor of NYHA class pre- and post-operatively (OR 8.3, 95%CI [2.27,33.33] and OR 14.44, 95%CI [1.49,139.31] respectively). No significant relationship was observed between PWV and either LV function or plasma BNP. Conclusion: In patients undergoing AVR for aortic stenosis, PWV is independently related to pre- and post-operative NYHA class but not to LV function or BNP. These findings provisionally support the use of perioperative PWV as a non-invasive marker of clinical functional status, which when used in conjunction with biomarkers of myocardial strain such as BNP, may provide a holistic functional assessment of patients undergoing aortic valve surgery. However, in order for PWV assessment to be translated into clinical practice and utilised as more than simply a research tool, further validation is required in the form of larger prospective studies specifically designed to assess the relationship between PWV and these functional clinical outcomes

Etest® versus broth microdilution for ceftaroline MIC determination with Staphylococcus aureus: results from PREMIUM, a European multicentre study

Objectives: To compare the concordance of ceftaroline MIC values 24 by reference broth microdilution (BMD) and Etest (BioMérieux, France) for MSSA and MRSA isolates, respectively, in isolates from PREMIUM (D372SL00001), a European multi-centre study.  Methods: Ceftaroline MICs were determined by reference BMD and by Etest for 1,242 MSSA and MRSA from adult patients with community-acquired pneumonia or complicated skin and soft tissue infections collected between February and May 2012; tests were performed across six European laboratories. Selected isolates with ceftaroline resistance in broth (MIC >1 mg/L) were retested in three central laboratories to confirm their behaviour.  Results: Overall concordance between BMD and Etest was good, with >97% essential agreement and >95% categorical agreement. Nevertheless, 12 of the 26 MRSA isolates found resistant by BMD scored as susceptible by Etest, with MICs ≤1 mg/L, thus counting as very major errors, whereas only five of 380 MRSA found ceftaroline susceptible in BMD were mis-categorised as resistant by Etest. Twenty-one of the 26 isolates with MICs of 2 mg/L by BMD were then re-tested twice by each of three central laboratories: BMD MICs of 2 mg/L were consistently found for 19 of the 21 isolates. Among 147 Etest results for these 21 isolates (original plus six repeats per isolate) 112 were >1 mg/L.  Conclusions: BMD and Etest have good overall agreement for ceftaroline against Staphylococcus aureus; nevertheless, reliable Etest-based discrimination of the minority of ceftaroline-resistant (MIC 2 mg/L) MRSA is extremely challenging, requiring careful reading of strips, ideally with duplicate testing