Clinical Experience of Neurological Mitochondrial Diseases in Children and Adults: A Single-Center Study.

The goal of the study was to retrospectively evaluate a cohort of children and adults with mitochondrial diseases (MDs) in a single-center experience. Neurological clinical examination, brain magnetic resonance imaging (MRI) and spectroscopy, muscle biopsy, metabolic and molecular-genetic analysis were evaluated in 26 children and 36 adult patients with MD in Slovenia from 2004 to 2018. Nijmegen MD criteria (MDC) were applied to all patients and the need for a muscle biopsy was estimated. Exome-sequencing was used in half of the patients. Twenty children (77.0%) and 12 adults (35.0%) scored a total of ≥8 on MDC, a result that is compatible with the diagnosis of definite MD. Yield of exome-sequencing was 7/22 (31.0%), but the method was not applied systematically in all patients from the beginning of diagnostics. Brain MRI morphological changes, which can be an imaging clue for the diagnosis of MD, were found in 17/24 children (71.0%). In 7/26 (29.0%) children, and in 20/30 (67.0%) adults, abnormal mitochondria were found on electron microscopy (EM) and ragged-red fibers were found in 16/30 (53.0%) adults. Respiratory chain enzymes (RCEs) and/or pyruvate dehydrogenase complex (PDHc) activities were abnormal in all the children and six adult cases. First, our data revealed that MDC was useful in the clinical diagnosis of MD, and second, until the use of NGS methods, extensive, laborious and invasive diagnostic procedures were performed to reach a final diagnosis. In patients with suspected MD, there is a need to prioritize molecular diagnosis with the more modern next-generation sequencing (NGS) method.

Physicochemical and electrochemical characterisation of imidazolium based IL + GBL mixtures as electrolytes for lithium-ion batteries.

Ionic liquid/organic solvent mixtures are investigated as potential optimal electrolytes for lithium-ion batteries (LIBs) that can combine low flammability, good thermal stability and high electrical conductivity. In this work the standard ionic association constants of different 1-alkyl-3-methylimidazolium ([Cnmim]+, n is the number of C in the alkyl side chain - 2, 4, 6 or 8) TFSI- based ionic liquids (ILs) in γ-butyrolactone (GBL) are determined using the low concentration Chemical Model (lcCM). Based on the values of for ILs in GBL and earlier physicochemical systematic investigations in that solvent, the system with the lowest was selected for the preparation of the LiTFSI/C2mimTFSI/GBL electrolyte for testing TiO2 nanotube arrays as anode material for LIBs. In an attempt to realize LIBs with enhanced safety, we report herein a comparative study of the electrochemical properties of LiTFSI/C2mimTFSI/GBL and an electrolyte containing an IL without acidic C(2)H on the imidazolium cation, namely, LiTFSI/C2mmimTFSI/GBL. The presence of GBL can improve the reduction stability of imidazolium-based ILs and GBL in LiTFSI/IL/GBL-based electrolytes. It was shown that TiO2 nanotube structures display stable galvanostatic cycling in the LiTFSI/C2mimTFSI/GBL electrolyte after 350 full (dis-)charge cycles and after cell exposure to T = 328.15 K.

Study of interactions between hyaluronan and cationic surfactants by means of calorimetry, turbidimetry, potentiometry and conductometry.

The thermodynamics of the micelle formation of the cationic surfactants tetradecyltrimethylammonium bromide (TTAB) and cetyltrimethylammonium bromide (CTAB) with and without the addition of hyaluronan of two molecular weights was studied in aqueous solution by titration calorimetry. Macroscopic phase separation, which was detected by calorimetry and also by conductometry, occurs when charges on the surfactant and hyaluronan are balanced. In contrast, turbidimetry and potentiometry showed hyaluronan-surfactant interactions at very low surfactant concentrations. The observed differences between systems prepared with CTAB and TTAB indicate that besides the electrostatic interactions, which probably predominate, hydrophobic effects also play a significant role in hyaluronan interactions with cationic surfactants.

Interpretation of conductivity results from 5 to 45 degrees C on three micellar systems below and above the CMC.

Electrical conductivity has been used at different temperatures to study three micellar systems: tetradecyltrimethylammonium chloride (TTACl), dodecyltrimethylammonium chloride (DTACl), and decyltrimethylammonium chloride (DeTACl). A phenomenon of premicellization is observed for DeTACl and DTACl below the critical micellar concentration (CMC). Association constants are introduced in the MSA-transport theory to correctly reproduce experimental conductivity and also calculate the effective charge of the micelles and their degree of dissociation. Various mechanisms are considered to explain premicellization. The formation of a neutral pair followed by an association involving two monomers and a counterion appears to be the most probable first step in the premicellization process.

The effect of internal structure of selected water-Tween 40-Imwitor 308-IPM microemulsions on ketoprofene release.

Microemulsions are a promising vehicle for administrating drugs. In order to lay the basis for predicting drug release under in vivo conditions, where the microemulsion composition is continuously varying, we have studied the release of ketoprofene as a model drug, from microemulsions on a dilution line containing, initially, 20 wt.% of isopropyl miristate (IPM) and 80 wt.% of the surfactant (Tween 40/co-surfactant (Imwitor 308, 1:1 wt.% mixture. Mixture compositions corresponding to the different types and structure of microemulsion were identified by measuring density, surface tension, electric conductivity, pH and differential scanning calorimetry. Ketoprofene release was then measured for each type and structure. The main factor influencing ketoprofene release was shown to be the strength of the interactions between microemulsion components. Strong interactions prevented rapid ketoprofene release in the water-in oil region, although the release was not dependent on the degree of percolation. Release kinetics in all cases follow zero order kinetics, indicating that the release rate is dependent on the diffusion of ketoprofene inside the microemulsion carrier. Combining different methods to obtain the physical and structural properties of microemulsions can be thus used to predict the release of ketoprofen from a microemulsion.

Structural characterisation of water-Tween 40/Imwitor 308-isopropyl myristate microemulsions using different experimental methods.

Pharmaceutically usable microemulsion systems were prepared from water and isopropyl myristate with a constant amount of Tween 40 and Imwitor 308 at a mass ratio of 1. Their type and structure were examined by measuring density and surface tension, and by viscometry, electric conductivity, differential scanning calorimetry (DSC) and small-angle X-ray scattering (SAXS), and the degree of agreement between the techniques was assessed. A model based on monodisperse hard spheres adequately fits the SAXS data in W/O microemulsions predicting, depending on composition, elongated or spherical droplets. It also suggests the involvement of strong attractive interactions in O/W systems. Results of conductivity, viscosity, density and surface tension measurements confirm the prediction of a percolation transition to a bicontinuous structure. DSC detects the degree of water interaction with surfactants thus identifying the type of microemulsion. The conclusions from all the techniques agree well and indicate that such studies could also be carried out on more complex systems. In future, the ability to determine type and structure of such microemulsion systems could enable partitioning and release rates of drugs from microemulsions to be predicted.

Using data warehousing and OLAP in public health care.

The paper describes the possibilities of using data warehousing and OLAP technologies in public health care in general and then our own experience with these technologies gained during the implementation of a data warehouse of outpatient data at the national level. Such a data warehouse serves as a basis for advanced decision support systems based on statistical, OLAP or data mining methods. We used OLAP to enable interactive exploration and analysis of the data. We found out that data warehousing and OLAP are suitable for the domain of public health and that they enable new analytical possibilities in addition to the traditional statistical approaches.

Uniforming of outpatient health care statistics.

In the process of developing the health care information system, the Public Health Institute of the Republic of Slovenia harmonized the outpatient health care statistics at the national level. This paper presents the goals, contents, methodology and a brief analysis of the new data structure. The main functions of the ZUBSTAT computer program, user training methods, and planned further activities in this field are described.