Impact Analysis of 20-Week Multimodal Progressive Functional-Proprioceptive Training among Sedentary Workers Affected by Non-Specific Low-Back Pain: An Interventional Cohort Study.

According to the latest data published by the WHO, 1.71 billion people suffer from musculoskeletal disorders and 568 million are affected by back pain, making these the most significant occupational health problems. The aim of this study was to analyze the effects of a newly developed Multimodal Workplace Training Program implemented among young sedentary employees in order to treat and prevent these problems. The 20-week Training Program was conducted at the National Instruments Corporations' Hungarian subsidiary in Debrecen between January and June, 2019. Pre- and post-intervention questionnaires were used to assess subjective parameters. Baseline and follow-up physical examinations were performed using the SpinalMouse, Y-Balance, Sit and Reach, Prone and Side Plank, Timed Abdominal Curl, and Biering-Sorensen tests. The results for 76 subjects were eligible for statistical analysis. Our Training Program was effective in several aspects, including a reduction in musculoskeletal symptoms and improvements in posture (p < 0.001), in dynamic (p < 0.01) and static-isometric (p < 0.001) core strength, in flexibility (p < 0.001), in spinal inclination in the sagittal (p < 0.001) and frontal (p < 0.01) plane, and in balance and coordination (p < 0.05). The Multimodal Progressive Functional-Proprioceptive Training was highly effective, and the application of such a complex training program can be recommended in workplace settings.

Functional Analysis of the Spine with the Idiag SpinalMouse System among Sedentary Workers Affected by Non-Specific Low Back Pain.

WHO describes "low back pain" (LBP) as the most common problem in overall occupational-related diseases. The aim of this study was to evaluate characteristics of spinal functionality among sedentary workers and determine usability of the SpinalMouse® skin-surface measurement device in workplace settings in a risk population for LBP. The spinal examination was implemented at National Instruments Corporations' Hungarian subsidiary, Debrecen in October, 2015, involving 95 white-collar employees as volunteers to assess spinal posture and functional movements. Data from the physical examination of 91 subjects (age: 34.22 ± 7.97 years) were analyzed. Results showed significant differences (p < 0.05) in posture and mobility of the spinal regions in sitting compared to standing position. Significant positive correlations were observed between values measured in standing and sitting positions in all observed regions and aspects of the spine (p < 0.05) except posture of lumbar extension (p = 0.07) and mobility of sacrum/hip in E-F (p = 0.818). Significant (p < 0.001) difference (5.70°) was found between the spinal inclination in sitting 6.47 ± 3.55° compared to standing 0.77 ± 2.53 position. Sitting position has a negative effect on the posture and mobility of the spine among white-collar employees. The SpinalMouse can be used effectively to determine spinal posture and mobility in cross-sectional studies and impact analysis of physical exercise interventions.

Mechanistic model and analysis of doxorubicin release from liposomal formulations.

Reliable and predictive models of drug release kinetics in vitro and in vivo are still lacking for liposomal formulations. Developing robust, predictive release models requires systematic, quantitative characterization of these complex drug delivery systems with respect to the physicochemical properties governing the driving force for release. These models must also incorporate changes in release due to the dissolution media and methods employed to monitor release. This paper demonstrates the successful development and application of a mathematical mechanistic model capable of predicting doxorubicin (DXR) release kinetics from liposomal formulations resembling the FDA-approved nanoformulation DOXIL® using dynamic dialysis. The model accounts for DXR equilibria (e.g. self-association, precipitation, ionization), the change in intravesicular pH due to ammonia release, and dialysis membrane transport of DXR. The model was tested using a Box-Behnken experimental design in which release conditions including extravesicular pH, ammonia concentration in the release medium, and the dilution of the formulation (i.e. suspension concentration) were varied. Mechanistic model predictions agreed with observed DXR release up to 19h. The predictions were similar to a computer fit of the release data using an empirical model often employed for analyzing data generated from this type of experimental design. Unlike the empirical model, the mechanistic model was also able to provide reasonable predictions of release outside the tested design space. These results illustrate the usefulness of mechanistic modeling to predict drug release from liposomal formulations in vitro and its potential for future development of in vitro - in vivo correlations for complex nanoformulations.

Determination of key parameters for a mechanism-based model to predict Doxorubicin release from actively loaded liposomes.

Despite extensive study of liposomal drug formulations, reliable predictive models of release kinetics in vitro and in vivo are still lacking. Progress in the development of robust, predictive release models has been hindered by a lack of systematic, quantitative characterization of these complex drug delivery systems with respect to the myriad of factors that may influence drug release kinetics and the wide range of dissolution media/methods employed to monitor release. In this paper, the key processes and parameters needed to develop a complete mechanism-based model for doxorubicin release from actively loaded liposomal formulations resembling Doxil(®) are determined. Quantitative models must account for the driving force(s) [i.e., activity gradient(s) of the permeable species between the intraliposomal and external media] and the permeability-area product(s) for lipid bilayer transport. These factors are intertwined as membrane permeability-area products require knowledge of the drug species and concentrations that account for the release. The necessary information includes values for the drug pKa, identity of the permeable species and species permeability coefficients, a model to describe drug self-association and the relevant equilibrium constant(s), the bilayer/water partition coefficient of the predominant drug species under relevant pH conditions, and the solubility product (Ksp ) for intraliposomal precipitates that exist in such formulations.

Design, selection, and characterization of a split chorismate mutase.

Split proteins are versatile tools for detecting protein-protein interactions and studying protein folding. Here, we report a new, particularly small split enzyme, engineered from a thermostable chorismate mutase (CM). Upon dissecting the helical-bundle CM from Methanococcus jannaschii into a short N-terminal helix and a 3-helix segment and attaching an antiparallel leucine zipper dimerization domain to the individual fragments, we obtained a weakly active heterodimeric mutase. Using combinatorial mutagenesis and in vivo selection, we optimized the short linker sequences connecting the leucine zipper to the enzyme domain. One of the selected CMs was characterized in detail. It spontaneously assembles from the separately inactive fragments and exhibits wild-type like CM activity. Owing to the availability of a well characterized selection system, the simple 4-helix bundle topology, and the small size of the N-terminal helix, the heterodimeric CM could be a valuable scaffold for enzyme engineering efforts and as a split sensor for specifically oriented protein-protein interactions.

The use of proteolysis to study the structure of nardilysin.

Treatment of a 128 kDa mouse nardilysin with trypsin initially produced an active 105 kDa N-terminally cleaved form. Continued trypsin digestion occurred at the C-terminus, producing inactive core species of approximately 92, 76.5, and 62 kDa. Protease V8 digestion generated a stable approximately 105 kDa form, nardilysin(V8), that was cleaved near the N-terminal trypsin site. The approximately 105 kDa nardilysin(V8) exhibited the same K(m) as did the uncleaved enzyme for substrates of the type Abz-GGFX(1)X(2)X(3)VGQ-EDDnp, where X residues were varied. However, k(cat) for nardilysin(V8) was 5-6 times greater. Both uncleaved nardilysin and nardilysin(V8) are inhibited by NaCl; however, nardilysin(V8) exhibits an IC(50) of approximately 2 mM compared to an IC(50) of approximately 50 mM for uncleaved nardilysin. Nardilysin(V8) is more sensitive to inhibition by phosphate buffer. Treatment of nardilysin(V8) with trypsin generated primarily the 92 kDa form which was inactive. Attempts to express nardilysin as a 105 kDa truncated N-terminal form or as a C-terminally truncated form led to inactive proteins.