The potential use of asparaginases has gained tremendous significance in the treatment of acute lymphoblastic leukemia (ALL). Earlier studies suggest L-asparaginases (L-ASP) extracted from Escherichia coli and Erwinia aroideae regulates L-asparagine (L-Asn) from the circulating blood. Prolonged exposure to these enzymes may lead to hypersensitivity reactions. So, it is important to find novel asparaginases with anti-cancer properties. The three-dimensional structure of L-ASP I from Vibrio campbellii was determined by homology modeling using EasyModeller v.4.0. The structure was validated with quality indexing tools and was deposited in Protein Model DataBase. Molecular docking was performed between L-ASP I and ligand substrate L-Asn to study enzyme-substrate interactions. Qualitative and quantitative analysis of L-ASP I enzyme was found to be reliable and stable with a significant protein quality factor (LG score: 7.129). The enzyme is a dimer, belongs to α/β class of proteins. The active sites comprises of N-glycosylation site and a catalytic triad (T14-S117-D92). The binding energy of the docked complex was calculated to be -7.45 kcal/mol. The amino acid T14 identified as a primary nucleophile essential for catalytic reaction. The enzyme L-ASP I of V. campbellii provides a detailed view of structure and functional aspects with ligand substrate L-Asn. This in silico investigation has explicitly demonstrated for the first time that cytosolic L-ASP Type I of V. campbellii to have a catalytic triad which was attributed only to periplasmic L-ASP Type II. Thus, L-ASP I can serve as anti-leukemic agent in the treatment, management and control of ALL.
C-terminal amidation is a common feature of wild type membrane disrupting antimicrobial peptides (AMPs). Empirical evidence suggests that this modification increases antimicrobial efficacy. However, the actual role of C-terminal amidation in the molecular mechanism of action of AMPs is not fully understood. Amidation alters two key properties simultaneously: the net charge and helicity of the peptide, both of which are implicated in the mechanism of action. However, the differences between the physicochemical properties of the carboxyl and amide moieties have been disregarded in former studies. In this study we assessed whether the difference in activity is only caused by changes in the helicity and overall charge of a peptide, i.e. whether the chemistry of the terminus is otherwise irrelevant. To do so, the membrane disrupting activity of a modified aurein 1.2 peptide was studied in which a secondary amide was formed with a terminal methyl group, instead of the primary amide as in the wild type peptide. Results of quartz crystal microbalance, dye leakage and circular dichroism experiments show that the activity of the modified peptide is substantially reduced compared to the wild type peptide, in particular that the modified peptide exhibited a much-reduced ability to bind to the membrane. Thus, the primary amide at the C-terminus is required to bind to the membrane, and a secondary amide cannot serve the same purpose. We hypothesize that this difference is related to the hydration state of the terminus. The lack of membrane binding ability of the modified peptide identifies the primary amide moiety at the C terminus as a specific membrane binding motif.
Impedance cardiography (ICG) is a non-invasive method of hemodynamic measurement, mostly known for estimation of stroke volume and cardiac output based on characteristic features of the signal. Compared with electrocardiography, the knowledge on the morphology of the ICG signal is scarce, especially with respect to age-dependent changes in ICG waveforms. Based on recordings from ten younger (20–29 years) and ten older (60–79) healthy human subjects after three different levels of physical activity, the typical interbeat ICG waveforms were derived based on ensemble averages. Comparison of these waveforms between the age groups indicates the following differences: a later initial upward deflection for the younger group, an additional hump in the waveform from many older subjects not presented in the younger group, and a more pronounced second wave in the younger group. The explanation for these differences is not clear, but may be related to arterial stiffness. Further studies are suggested to determine whether these morphological differences have clinical value.
Overall survival of oncologic patients is strongly influenced by the incidence of malnutrition, with subsequent loss of muscle mass until sarcopenia. In this respect, the assessment of body composition has a pivotal role in order to manage the clinical consequences of muscle loss.
This study focuses on the body composition assessment in oncologic patients, following a diet plan in order to detect and contrast neoplastic cachexia.
Materials and Method:
35 oncologic patients were enrolled and divided into two groups: 24 responders (R) and 11 non-responders (NR). Anthropometric data were collected and body composition was assessed through bioimpedentiometry. All patients received an individualized normocaloric diet. Energetic content was assigned on the basis of individual basal metabolic rate estimated by BIA. All patients were revaluated by anthropometry and bioimpedentiometry 3 and 6 months thereafter.
Comparing the two male groups R and NR after 6 months, the former maintained almost the same confidence interval, unlike the latter whose interval increased, indicating a light worsening both of body composition and of clinical conditions. Furthermore, in the same male responder group, an improvement of the phase angle (PhA), a positive prognostic factor, was found, with an average weight loss between 2,6 – 3 kg of fat mass (FM). Besides, data show how the R female group maintained the confidence interval unlike the NR female group, whose confidence interval remarkably increased, therefore indicating an important alteration of body composition and subsequently a clinical conditions worsening. Finally, comparing the NR male group with the NR female group after 6 months, a remarkable worsening of body composition (marker of tissue decay and damage) could be noticed in the latter group.
After 6 months, NR patients show worse results (both in the body composition and in the clinical conditions) compared to the responders, with particularly worse results in females, probably because of a genetically determined sex-related smaller muscle cells and inferior muscular strength. A multidimensional assessment of oncologic patient is necessary, with a special attention to nutritional evaluation and body composition monitoring, in order to avoid malnutrition and subsequent further clinical worsening.
Sixteen volunteers each drank 700 ml sugar-containing soft drink during two successive periods and the blood sugar was measured at 10 min intervals together with electrical impedance spectroscopy and near infrared spectroscopy (NIR). A maximum correlation of 0.46 was found for the electrical measurements but no clear separation between low and high blood glucose levels were found in the NIR measurements. The latter was attributed to the experimental design where the NIR probe was removed from the skin between each measurement.
A circuit is presented that enables measurement of skin electrical conductance, susceptance, and potential simultaneously beneath the same monopolar electrode. Example measurements are shown to confirm the function of the circuit. The measurements are also in accordance with earlier findings that changes in skin conductance and potential do not always correspond and hence contain unique information.
The objective of this study was to determine the potential value of electrical impedance myography (EIM) for assessing lumbosacral paraspinal muscle (LPM) condition in lower back pain (LBP) patients. Standard methods for assessing the condition of LPMs, such as magnetic resonance imaging, are inconvenient and expensive. One tool that could be useful for this purpose is electrical impedance myography (EIM) a technique that can be performed rapidly at the bedside. After undergoing a screening history and examination, subjects were studied with the mView EIM device (Myolex, Inc, Boston). Bilateral LPMs were measured three times each and the two closest sets of measurements averaged on each side. Data analysis included non-parametric two-group comparisons between healthy subjects and back pain patients, receiver-operating curve analyses, and correlation analyses to age and body mass index. A total of 86 healthy individuals (median age (interquartile range) (IQR), 45.5 years (30.3–56.0 years), 42 men, 44 women) and 47 LBP (median age 51.0 year (39.5–57.5) years, 21 men, 26 women) were enrolled. Median EIM 100kHz phase was lower in the LBP patients (9.3°(IQR 8.4°–10.6°) versus 11.4°(IQR 9.4°–13.0°), p = 0.0007). Significantly increased normalized side-to-side differences were present for all three EIM variables (e.g., median 100 kHz phase 0.15 (IQR 0.07–0.31 in LBP patients versus 0.09 (IQR 0.04–0.17) in healthy individuals). A significant correlation between 100 kHz EIM phase and reactance was found with age (Rspearman=−0.46, P=0.0002 and Rspearman=−0.440, P=0.0003) but not for resistance. This study provides early evidence supporting that EIM has the potential to serve as a useful tool for evaluating the condition of LPMs.
Electrical impedance spectroscopy (EIS) measurements on cells is a proven method to assess stem cell proliferation and differentiation. Cell regenerative medicine (CRM) is an emerging field where the need to develop and deploy stem cell assessment techniques is paramount as experimental treatments reach pre-clinical and clinical stages. However, EIS measurements on cells is a method requiring extensive post-processing and analysis. As a contribution to address this concern, we developed three machine learning models for three different stem cell lines able to classify the measured data as proliferation or differentiation laying the stone for future studies on using machine learning to profile EIS measurements on stem cells spectra.
Electrical impedance tomography (EIT) has a large potential as a two dimensional imaging technique and is gaining attention among researchers across various fields of engineering. Beamforming techniques stem from the array signal processing field and is used for spatial filtering of array data to evaluate the location of objects. In this work the circular electrodes are treated as an array of sensors and beamforming technique is used to localize the object(s) in an electrical field. The conductivity distributions within a test tank is obtained by an EIT system in terms of electrode voltages. These voltages are then interpolated using elliptic partial differential equations. Finally, a narrowband beamformer detects the peak in the output response signal to localize the test object(s). Test results show that the beamforming technique can be used as a secondary method that may provide complementary information about accurate position of the test object(s) using an eight electrode EIT system. This method could possibly open new avenues for spatial EIT data filtering techniques with an understanding that the inverse problem is more likely considered here as a source localization algorithm instead as an image reconstruction algorithm.
An electrical measurement is non-linear when it is affected by the applied stimulus, i.e. when the measured phenomenon changes with amplitude. If pinched hysteresis loops can be observed in the voltage current representation, the underlying tissue can be classified as a memristor. Several biological memristors have been published, like human skin and apples. However, changes in the polarization impedance of electrodes may also cause pinched hysteresis loops. The question whether the reported biological memristors are real or whether the results just reflect changes in the polarization impedance arises. If the impedance of the measured object is close to or smaller than the polarization impedance of the used electrodes, the latter may dominate the measurement.
In this study, we investigated the non-linear electrical properties of silver/silver chloride electrodes in a sodium chloride solution that has a similar concentration as human sweat and compared these to results from human skin. First of all, we found that silver/silver chloride electrodes in sodium chloride solution can be classified as memristors. However, the currents obtained from the sodium chloride solution are much higher than the currents recorded from human skin and there is a qualitative difference in the pinched hysteresis loops in both cases. We can conclude that the non-linear electrical measurements with silver/silver chloride on human skin are actually dominated by the skin and we can confirm that the human skin memristor really exists.