A Szerencsejáték Súlyossága Kérdőív magyar változatának (PGSI-HU) bemutatása

Háttér és célkitûzés: A szerencsejáték széleskörû elterjedése a kapcsolódó problémák fokozott megjelenésével jár együtt, így szükségessé válnak azok a mérôeszközök, melyek segítségével a problémás/patológiás szerencsejáték gyorsan és megbízhatóan azonosítható. Vizsgálatunk célja a Szerencsejáték Probléma Súlyossága Kérdôív hazai változatának (Problem Gambling Severity Index, PGSI) pszichometriai jellemzése, valamint a mérôeszközzel nyert elsô eredmények bemutatása. Módszer: A mérôeszköz budapesti, felnôtt mintán került felvételre. A 777 fôs minta (466 férfi, 311 nô) tagjait lottózókban és játéktermekben toboroztuk. A kérdôív strukturális validálását konfirmátoros faktorelemzéssel végeztük el, míg konkurrens validitását a South Oaks Szerencsejáték Kérdôívvel (SOGS-HU) vizsgáltuk. Eredmények: A mérôeszköz pszichometriai mutatói megfelelôek. A minta 61,6%-a nem jelzett problémát, míg 20,2% alacsony problémájú, 11,8% közepesen problémás, 6,3% pedig patológiás szerencsejátékosnak bizonyult. A PGSI és a SOGS továbbá magas, szignifikáns korrelációs kapcsolatban állnak (r=0,802; p<0,001). Következtetések: A PGSI-HU érvényes és megbízható eszköz a problémás/patológiás szerencsejáték azonosítására. Klinikai és kutatási célú használatát indokolja rövidsége és könnyû kiértékelhetôsége

Analysis of the shear stresses in a filling line of parenteral products

Drug manufacturing consists of a series of operations, generally referred to as formulation, filling, and finishing. Filling represents the most critical step, in which the drug product undergoes different processes, including mixing, pumping, filtration, and final filling into vials. As filling lines operate under faster and faster conditions, there is concern over stability of protein-based products, which may be sensitive to temperature changes, oxidation, light, ionic strength and shear stress. Among these, shear stress has gained interest over the past decades because of its frequent occurrence in filling lines. Exposure of protein-based parenteral drugs to such stresses is believed to promote unfolding and subsequent aggregation, which might alter the biological activity of the drug and raise the potential for side effects. Several studies conducted in recent years have tried to shed light on the actual impact of shear stress on drug products, but the presence of additional stresses (such as interfacial stress) has complicated the interpretation of the results. In this controversial landscape, it is therefore necessary to quantify shear stress in the operating units of the filling process as a first step for broader experimental investigations. Therefore, starting from some typical operating units, we developed a model for calculating the shear stress distribution using a shear history-based approach. In detail, we considered a representative number of particles within the domain and followed their trajectories, which allowed us to determine the average shear stress. Several operating units were analyzed and the resulting shear stress exposures were determined. The field of scale-down approaches, used to scale the commercial process down to the laboratory level, was also explored. They allow to perform product characterization experiments using smaller volumes of the drug products. A new approach for scaling down the commercial process was proposed, which was compared with traditional approaches and shown to provide greater representativeness between the two scales

Viability of a Five-Strain Mixture of Listeria monocytogenes in Vacuum-Sealed Packages of Frankfurters, Commercially Prepared with and without 2.0 or 3.0% Added Potassium Lactate, during Extended Storage at 4 and 10° C†‡

The viability of Listeria monocytogenes was monitored on frankfurters containing added potassium lactate that were obtained directly from a commercial manufacturer. Eight links (ca. 56 g each) were transferred aseptically from the original vacuum-sealed bulk packages into nylon-polyethylene bags. Each bag then received a 4-ml portion of a five-strain mixture of the pathogen. Frankfurters containing 2.0 or 3.0% potassium lactate were evaluated using 20 CFU per package, and frankfurters containing 3.0% potassium lactate were evaluated using 500 CFU per package. The packages were vacuum-sealed and stored at 4 or 10°C for up to 90 or 60 days, respectively. During storage at 4°C, pathogen numbers remained at about 1.6 log10 CFU per package over 90 days in packages containing frankfurters with 2.0% potassium lactate that were inoculated with about 20 CFU. In packages containing frankfurters with 3.0% potassium lactate that were inoculated with about 20 CFU and stored at 4°C, pathogen numbers remained at about 1..

Cellular localization of Y-box binding protein 1 in brain tissue of rats, macaques, and humans

Background: The Y-box binding protein 1 (YB-1) is considered to be one of the key regulators of transcription and translation. However, so far only limited knowledge exists regarding its cellular distribution in the adult brain. Results: Analysis of YB-1 immunolabelling as well as double-labelling with the neuronal marker NeuN in rat brain tissue revealed a predominant neuronal expression in the dentate gyrus, the cornu ammonis pyramidal cell layer, layer III of the piriform cortex as well as throughout all layers of the parahippocampal cortex. In the hilus of the hippocampus single neurons expressed YB-1. The neuronal expression pattern was comparable in the hippocampus and parahippocampal cortex of adult macaques and humans. Double-labelling of YB-1 with the endothelial cell marker Glut-1, the multidrug transporter P-glycoprotein, and the astrocytic marker GFAP did not indicate a co-localization. Following status epilepticus in rats, no induction of YB-1 occurred in brain capillary endothelial cells and neurons. Conclusion: In conclusion, our study demonstrates that YB-1 is predominantly expressed in neurons in the adult brain of rats, macaques and humans. Lack of a co-localization with Glut-1 and P-glycoprotein argues against a direct role of YB-1 in the regulation of blood-brain barrier P-glycoprotein

Revisiting promyelocytic leukemia protein targeting by human cytomegalovirus immediate-early protein 1

This work was supported by a grant (MR/P022146/1) from the Medical Research Council (https://mrc.ukri.org) to MMN, a grant (T16/28) from Tenovus Scotland (https://tenovus-scotland.org.uk) to CP, a European Union Erasmus+ grant (https://www.erasmusplus.org.uk) to BW and the Wellcome Trust Institutional Strategic Support Fund (https://wellcome.ac.uk) to CP and MMN.Promyelocytic leukemia (PML) bodies are nuclear organelles implicated in intrinsic and innate antiviral defense. The eponymous PML proteins, central to the self-organization of PML bodies, and other restriction factors found in these organelles are common targets of viral antagonism. The 72-kDa immediate-early protein 1 (IE1) is the principal antagonist of PML bodies encoded by the human cytomegalovirus (hCMV). IE1 is believed to disrupt PML bodies by inhibiting PML SUMOylation, while PML was proposed to act as an E3 ligase for IE1 SUMOylation. PML targeting by IE1 is considered to be crucial for hCMV replication at low multiplicities of infection, in part via counteracting antiviral gene induction linked to the cellular interferon (IFN) response. However, current concepts of IE1-PML interaction are largely derived from mutant IE1 proteins known or predicted to be metabolically unstable and globally misfolded. We performed systematic clustered charge-to-alanine scanning mutagenesis and identified a stable IE1 mutant protein (IE1cc172-176) with wild-type characteristics except for neither interacting with PML proteins nor inhibiting PML SUMOylation. Consequently, IE1cc172-176 does not associate with PML bodies and is selectively impaired for disrupting these organelles. Surprisingly, functional analysis of IE1cc172-176 revealed that the protein is hypermodified by mixed SUMO chains and that IE1 SUMOylation depends on nucleosome rather than PML binding. Furthermore, a mutant hCMV expressing IE1cc172-176 was only slightly attenuated compared to an IE1-null virus even at low multiplicities of infection. Finally, hCMV-induced expression of cytokine and IFN-stimulated genes turned out to be reduced rather than increased in the presence of IE1cc172-176 relative to wild-type IE1. Our findings challenge present views on the relationship of IE1 with PML and the role of PML in hCMV replication. This study also provides initial evidence for the idea that disruption of PML bodies upon viral infection is linked to activation rather than inhibition of innate immunity.Publisher PDFPeer reviewe