Post-radiation xerostomia therapy with allogeneic mesenchymal stromal stem cells in patients with head and neck cancer: study protocol for phase I clinical trial.

Background: Xerostomia is a common side effect of radiotherapy in patients with head and neck tumors that negatively affects quality of life. There is no known effective standard treatment for xerostomia. Here, we present the study protocol used to evaluate the safety and preliminary efficacy of allogeneic mesenchymal stromal stem cells (MSCs) derived from umbilical cord tissue.

Substrate-dependent inactivation of recombinant paraoxonase 1 during catalytic dihydrocoumarin turnover and the protective properties of surfactants.

Human paraoxonase-1 (PON1) is the most studied member of the paraoxonases (PONs) family and catalyzes the hydrolysis of various substrates (lactones, aryl esters, and paraoxon). Numerous studies link PON1 to oxidative stress-related diseases such as cardiovascular disease, diabetes, HIV infection, autism, Parkinson's, and Alzheimer's, where the kinetic behavior of an enzyme is characterized by initial rates or by modern methods that obtain enzyme kinetic parameters by fitting the computed curves over the entire time-courses of product formation (progress curves). In the analysis of progress curves, the behavior of PON1 during hydrolytically catalyzed turnover cycles is unknown.

Investigation of Paraoxonase-1 Genotype and Enzyme-Kinetic Parameters in the Context of Cognitive Impairment in Parkinson's Disease.

Cognitive impairment is a common non-motor symptom of Parkinson's disease (PD), which often progresses to PD dementia. PD patients with and without dementia may differ in certain biochemical parameters, which could thus be used as biomarkers for PD dementia. The enzyme paraoxonase 1 (PON1) has previously been investigated as a potential biomarker in the context of other types of dementia.

Automated step detection with 6-minute walk test smartphone sensors signals for fall risk classification in lower limb amputees.

Predictive models for fall risk classification are valuable for early identification and intervention. However, lower limb amputees are often neglected in fall risk research despite having increased fall risk compared to age-matched able-bodied individuals. A random forest model was previously shown to be effective for fall risk classification of lower limb amputees, however manual labelling of foot strikes was required.

iFIT: An automated web tool for determining enzyme-kinetic parameters based on the high-curvature region of progress curves.

The area where progress curve exhibits maximum curvature contains the most information about kinetic parameters. To determine these parameters more accurately from progress curves, we propose an iterative approach that calculates the area of maximum curvature based on an estimate of kinetic parameters and then recalculates the parameters based on time-concentration data points within this area. Based on this algorithm, we developed a computer script called iFIT as a free web application at http://www.

Amputee Fall Risk Classification Using Machine Learning and Smartphone Sensor Data from 2-Minute and 6-Minute Walk Tests.

The 6-min walk test (6MWT) is commonly used to assess a person’s physical mobility and aerobic capacity. However, richer knowledge can be extracted from movement assessments using artificial intelligence (AI) models, such as fall risk status. The 2-min walk test (2MWT) is an alternate assessment for people with reduced mobility who cannot complete the full 6MWT, including some people with lower limb amputations; therefore, this research investigated automated foot strike (FS) detection and fall risk classification using data from a 2MWT.

The Removal of Time-Concentration Data Points from Progress Curves Improves the Determination of : The Example of Paraoxonase 1.

Several approaches for determining an enzyme's kinetic parameter (Michaelis constant) from progress curves have been developed in recent decades. In the present article, we compare different approaches on a set of experimental measurements of lactonase activity of paraoxonase 1 (PON1): (1) a differential-equation-based Michaelis-Menten (MM) reaction model in the program Dynafit; (2) an integrated MM rate equation, based on an approximation of the Lambert W function, in the program GraphPad Prism; (3) various techniques based on initial rates; and (4) the novel program "iFIT", based on a method that removes data points outside the area of maximum curvature from the progress curve, before analysis with the integrated MM rate equation. We concluded that the integrated MM rate equation alone does not determine kinetic parameters precisely enough; however, when coupled with a method that removes data points (e.

Fall risk classification for people with lower extremity amputations using random forests and smartphone sensor features from a 6-minute walk test.

Fall-risk classification is a challenging but necessary task to enable the recommendation of preventative programs for individuals identified at risk for falling. Existing research has primarily focused on older adults, with no predictive fall-risk models for lower limb amputees, despite their greater likelihood of fall-risk than older adults. In this study, 89 amputees with varying degrees of lower limb amputation were asked if they had fallen in the past 6 months.

A new valid Walking Aid Scale better predicts distance walked by prosthesis users than Prosthetic Mobility Questionnaire 2.0 and Activities-Specific Balance Confidence Scale.

The availability of psychometrically-sound and parsimonious outcome measures is key for optimizing decision-making about prosthetic fitting and rehabilitation in lower limb prosthesis users. Despite the increasing clinical use of observational and self-reported scales for assessing mobility and balance, there is currently no scale that accounts for the use of assistive devices while walking under conditions of increasing difficulty. Therefore, the purpose of this study was to develop and validate a Walking Aid Scale (WAS) in a cross-sectional sample of 144 prosthesis users.

The Structure and Function of Paraoxonase-1 and Its Comparison to Paraoxonase-2 and -3.

Serum paraoxonase-1 (PON1) is the most studied member of the group of paraoxonases (PONs). This enzyme possesses three enzymatic activities: lactonase, arylesterase, and paraoxonase activity. PON1 and its isoforms play an important role in drug metabolism as well as in the prevention of cardiovascular and neurodegenerative diseases.

A Multi-Omics Analysis of PON1 Lactonase Activity in Relation to Human Health and Disease.

Paraoxonase 1 (PON1) enzyme has antioxidative properties and is present in mammalian blood and several other body fluids. In blood, PON1 is usually integrated into the high-density lipoprotein (HDL) cholesterol. PON1 is a highly versatile enzyme displaying diverse functions such as arylesterase, lactonase, and paraoxonase, among others.

Sociodemographic predictors of pain in old people : Serbian population-based study.

Background: With the growing increase in the older proportion of the world population, there is also an increase in specific age-related chronic diseases and conditions, including pain. We aimed to evaluate the association of sociodemographic factors with the presence and different degrees of pain intensity in people aged 65 years and older.

Methods: The population-based study, conducted in 2013, included 3540 individuals from Serbia.

Validation of the Activities-Specific Balance Confidence Scale With 5-Option Response Format in Slovene Lower-Limb Prosthetic Users.

Objective: To examine the psychometric properties of the Activities-specific Balance Confidence (ABC) scale administered in the Slovene version with a simplified 5-option response format (ABC-5/SLO) using Rasch analysis.

Design: Methodological research on data gathered in a cross-sectional study.

Setting: Outpatient university rehabilitation clinic.

Fall-Risk Classification in Amputees Using Smartphone Sensor Based Features in Turns.

Identifying people at risk of falling can prevent life altering injury. Existing research has demonstrated fall-risk classifier effectiveness in older adults from accelerometer-based data. The amputee population should similarly benefit from these classification techniques; however, validation is still required.

Interactions of Paraoxonase-1 with Pharmacologically Relevant Carbamates.

Mammalian paraoxonase-1 hydrolyses a very broad spectrum of esters such as certain drugs and xenobiotics. The aim of this study was to determine whether carbamates influence the activity of recombinant PON1 (rePON1). Carbamates were selected having a variety of applications: bambuterol and physostigmine are drugs, carbofuran is used as a pesticide, while Ro 02-0683 is diagnostic reagent.

Evaluation of the paraoxonase-1 kinetic parameters of the lactonase activity by nonlinear fit of progress curves.

Although paraoxonase-1 (PON1) activity has been demonstrated to be a reliable biomarker of various diseases, clinical studies have been based only on relative comparison of specific enzyme activities, which capture differences mainly due to (usually unknown) PON1 concentration. Hence, the aim of this report is to present for the first time the simple evaluation method for determining autonomous kinetic parameter of PON1 that could be also associated with polymorphic forms and diseases; i.e.

The Prosthetic Mobility Questionnaire, a tool for assessing mobility in people with lower-limb amputation: validation of PMQ 2.0 in Slovenia.

The aim of this study was to examine the metric properties of the Prosthetic Mobility Questionnaire, an outcome measure of mobility following lower-limb amputation, in Slovene outpatients undergoing rehabilitation. The 12-item Prosthetic Mobility Questionnaire was administered to 148 Slovene adults (74% men) with unilateral lower-limb amputation since >12 months and regularly wearing a prosthesis. The psychometric analysis included classical test theory methods and Rasch models.

Exploring the aryl esterase catalysis of paraoxonase-1 through solvent kinetic isotope effects and phosphonate-based isosteric analogues of the tetrahedral reaction intermediate.

Although a recent study of Debord et al. in Biochimie (2014; 97:72-77) described the thermodynamics of the catalysed hydrolysis of phenyl acetate by human paraoxonase-1, the mechanistic details along the reaction route of this enzyme remain unclear. Therefore, we briefly present the solvent kinetic isotope effects on the phenyl acetate esterase activity of paraoxonase-1 and its inhibition with the phenyl methylphosphonate anion, which is a stable isosteric analogue that mimics the high-energy tetrahedral intermediate on the hydroxide-promoted hydrolysis pathway.

(Poly)peptide-based therapy for diabetes mellitus: insulins versus incretins.

Insulin therapy remains the standard of care for achieving and maintaining adequate glycemic control, especially in hospitalized patients with critical and noncritical illnesses. Insulin therapy is more effective against elevated fasting glycaemia but less in the reduction of postprandial hyperglycaemia. It is associated with a high incidence of hypoglycemia and weight gain.

Mono-ADP-ribosyltransferase as a potential pharmacological drug target in the GLP-1 based therapy of obesity and diabetes mellitus type 2.

Glucagon-like peptide-1 (GLP-1) based therapy is well established for treating diabetes mellitus type 2. Moreover, GLP-1 receptor agonists influence weight loss, and have potential for treating obesity. GLP-1 receptor agonists should be administered in low doses, together with drugs that potentiate insulin release, to avoid some minor side effects.

Glucagon like-peptide-1 receptor is covalently modified by endogenous mono-ADP-ribosyltransferase.

Our previous study revealed a mono-ADP-ribosyltransferase mediated in vitro mono-ADP-ribosylation of IC(3) peptide, a peptide with sequence corresponded to third intracellular loop of glucagon like-peptide-1 (GLP-1) receptor. Furthermore, Arg(348) was shown to be modified amino acid residue although its mutation did not eliminate mono-ADP-ribosylation completely. In order to further study the signaling mechanisms of GLP-1 receptor, we took on lease a possibility that an alternative site of enzymatic modification exist so mono-ADP-ribosylation of Cys(341) was hypothesized.

Third intracellular loop of glucagon like-peptide-1 receptor is coupled with endogenous mono-ADP-ribosyltransferase - novel type of receptor regulation?

Our previous studies revealed the main role of the third intracellular loop (IC(3)) of glucagon-like peptide-1 receptor (GLP-1 receptor), in G-protein activation, where the presence or absence of agonist and the receptor phosphorylation seemed to be the only regulatory mechanisms. In order to further study the signaling mechanisms of GLP-1 receptor, we investigated the effect of the third intracellular loop-derived peptide on endogenous mono-ADP-ribosyltransferase mediated mono-ADP-ribosylation of G-proteins β subunit in CHO cells. Results showed an inhibitory effect of IC(3) peptide on mono-ADP-ribosylation of β subunit, obviously via the mechanism of competitive inhibition.

Structure, Function and Regulation of Group IV Phospholipase A2 Family.

The Group IV phospholipase A2 family is consisted of six intracellular enzymes. They catalyze hydrolysis of the sn-2 ester bond of glycerophospholipids, releasing fatty acid metabolites and lysophospholipids. Agonist-induced release of arachidonic acid for the production of eicosanoids by PLA2IValpha enzyme is important in regulating normal and pathological processes in a variety of target tissues.

Functional characterization of N-terminally GFP-tagged GLP-1 receptor.

The glucagon-like peptide-1 receptor (GLP-1 receptor) mediates important effects on peripheral tissues and the central nervous system. It seems one of the most promising therapeutic targets for treatment of diabetes mellitus type 2. Surprisingly, very little is known about the cellular mechanisms that regulate its function in vivo.