Fused deposition modelling (FDM) is a process of additive manufacturing allowing creating of highly precise complex three-dimensional objects for a large range of applications. The principle of FDM is an extrusion of the molten filament and gradual deposition of layers and their solidification. Potential applications in pharmaceutical and medical fields require the development of biodegradable and biocompatible thermoplastics for the processing of filaments. In this work, the potential of production of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P(3HB-co-4HB)) filaments for FDM was investigated in respect to its thermal stability. Copolymer P(3HB-co-4HB) was biosynthesised by Cupriavidus malaysiensis. Rheological and mechanical properties of the copolymer were modified by the addition of plasticizers or blending with poly(lactic acid). Thermal stability of mixtures was studied employing thermogravimetric analysis and rheological analyses by monitoring the time-dependent changes in the complex viscosity of melt samples. The plasticization of P(3HB-co-4HB) slightly hindered its thermal degradation but the best stabilization effect was found in case of the copolymer blended with poly(lactic acid). Overall, rheological, thermal and mechanical properties demonstrated that the plasticized P(3HB-co-4HB) is a potential candidate of biodegradable polymer for FDM processes.

• Klíčová slova
• 3D printing, Cupriavidus malaysiensis, Fused deposition modelling, Poly(3-hydroxybutyrate-co-4-hydroxybutyrate), Poly(lactic acid), Rheological properties,
• MeSH
• Cupriavidus metabolismus   MeSH
• hydroxybutyráty chemie   MeSH
• molekulární struktura MeSH
• molekulová hmotnost MeSH
• polyestery chemie   MeSH
• reologie MeSH
• teplota MeSH
• změkčovadla chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• hydroxybutyráty MeSH
• poly(3-hydroxybutyrate-co-4-hydroxybutyrate) MeSH Prohlížeč
• poly(lactide) MeSH Prohlížeč
• polyestery MeSH
• změkčovadla MeSH

OBJECTIVE: To evaluate the host- and biomechanical response to a fully absorbable poly-4-hydroxybutyrate (P4HB) scaffold in comparison with the response to polypropylene (PP) mesh. DESIGN: In vivo animal experiment. SETTING: KU Leuven Center for Surgical Technologies. POPULATION: Fourteen parous female Mule sheep. METHODS: P4HB scaffolds were surgically implanted in the posterior vaginal wall of sheep. The comparative PP mesh data were obtained from an identical study protocol performed previously. MAIN OUTCOME MEASURES: Gross necropsy, host response and biomechanical evaluation of explants, and the in vivo P4HB scaffold degradation were evaluated at 60- and 180-days post-implantation. Data are reported as mean ± standard deviation (SD) or standard error of the mean (SEM). RESULTS: Gross necropsy revealed no implant-related adverse events using P4HB scaffolds. The tensile stiffness of the P4HB explants increased at 180-days (12.498 ± 2.66 N/mm SEM [p =0.019]) as compared to 60-days (4.585 ± 1.57 N/mm) post-implantation, while P4HB degraded gradually. P4HB scaffolds exhibited excellent tissue integration with dense connective tissue and a moderate initial host response. P4HB scaffolds induced a significantly higher M2/M1 ratio (1.70 ± 0.67 SD, score 0-4), as compared to PP mesh(0.99 ± 0.78 SD, score 0-4) at 180-days. CONCLUSIONS: P4HB scaffold facilitated a gradual load transfer to vaginal tissue over time. The fully absorbable P4HB scaffold, in comparison to PP mesh, has a favorable host response with comparable load-bearing capacity. If these results are also observed at longer follow-up in-vivo, a clinical study using P4HB for vaginal POP surgery may be warranted to demonstrate efficacy. TWEETABLE ABSTRACT: Degradable vaginal P4HB implant might be a solution for treatment of POP.

• Klíčová slova
• biomechanics, degradable scaffold, host response, pelvic organ prolapse, poly-4-hydroxybutyrate, vaginal surgery,
• MeSH
• biomechanika MeSH
• chirurgické síťky * škodlivé účinky   MeSH
• hydroxybutyráty MeSH
• lidé MeSH
• ovce MeSH
• polypropyleny * MeSH
• vagina chirurgie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• hydroxybutyráty MeSH
• polypropyleny * MeSH

The terpolymer of 3-hydroxybutyrate (3HB), 3-hydroxyvalerate (3HV), and 4-hydroxybutyrate (4HB) was produced employing Cupriavidus sp. DSM 19379. Growth in the presence of γ-butyrolactone, ε-caprolactone, 1,4-butanediol, and 1,6-hexanediol resulted in the synthesis of a polymer consisting of 3HB and 4HB monomers. Single and two-stage terpolymer production strategies were utilized to incorporate the 3HV subunit into the polymer structure. At the single-stage cultivation mode, γ-butyrolactone or 1,4-butanediol served as the primary substrate and propionic and valeric acid as the precursor of 3HV. In the two-stage production, glycerol was used in the growth phase, and precursors for the formation of the terpolymer in combination with the nitrogen limitation in the medium were used in the second phase. The aim of this work was to maximize the Polyhydroxyalkanoates (PHA) yields with a high proportion of 3HV and 4HB using different culture strategies. The obtained polymers contained 0-29 mol% of 3HV and 16-32 mol% of 4HB. Selected polymers were subjected to a material properties analysis such as differential scanning calorimetry (DSC), thermogravimetry, and size exclusion chromatography coupled with multi angle light scattering (SEC-MALS) for determination of the molecular weight. The number of polymers in the biomass, as well as the monomer composition of the polymer were determined by gas chromatography.

• Klíčová slova
• Cupriavidus malaysiensis, P(3HB-co-3HV-co-4HB), polyhydroxyalkanoates, terpolymer,
• Publikační typ
• časopisecké články MeSH

Aneurinibacillus thermoaerophilus CCM 8960 is a thermophilic bacterium isolated from compost in Brno. The bacterium accumulates polyhydroxyalkanoates (PHAs), a biodegradable and renewable alternative to petrochemical polymers. The bacterium reveals several features that make it a very interesting candidate for the industrial production of PHA. At first, due to its thermophilic character, the bacterium can be utilized in agreement with the concept of next-generation industrial biotechnology (NGIB), which relies on extremophiles. Second, the bacterium is capable of producing PHA copolymers containing a very high portion of 4-hydroxybutyrate (4HB). Such materials possess unique properties and can be advantageously used in multiple applications, including but not limited to medicine and healthcare. Therefore, this work focuses on the in-depth characterization of A. thermoaerophilus CCM 8960. In particular, we sequenced and assembled the genome of the bacterium and identified its most important genetic features, such as the presence of plasmids, prophages, CRISPR arrays, antibiotic-resistant genes, and restriction-modification (R-M) systems, which might be crucial for the development of genome editing tools. Furthermore, we focused on genes directly involved in PHA metabolism. We also experimentally studied the kinetics of glycerol and 1,4-butanediol (1,4BD) utilization as well as biomass growth and PHA production during cultivation. Based on these data, we constructed a metabolic model to reveal metabolic fluxes and nodes of glycerol and 1,4BD concerning their incorporation into the poly(3-hydroxybutyrate-co-4-hydroxybutyrate (P(3HB-co-4HB)) structure. KEY POINTS: • Aneurinibacillus sp. H1 was identified as Aneurinibacillus thermoaerophilus. • PHA metabolism pathway with associated genes was presented. • Unique monomer composition of produced PHAs was reported.

• Klíčová slova
• 4-hydroxybutyrate, Aneurinibacillus species H1, De novo assembly, Next-generation industrial biotechnology, PHA, Plasmid pAT1,
• MeSH
• Bacillales MeSH
• butylenglykoly MeSH
• glycerol MeSH
• kyselina 3-hydroxymáselná MeSH
• polyestery metabolismus   MeSH
• polyhydroxyalkanoáty * MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• butylenglykoly MeSH
• glycerol MeSH
• kyselina 3-hydroxymáselná MeSH
• polyestery MeSH
• polyhydroxyalkanoáty * MeSH

1. The influence of a diminished hydrogen supply on the regulation of oxidative phosphorylation of isolated rat liver mitochondria in dependence on the extramitochondrial (ATP)/(ADP) ratio was investigated. 2. The hydrogen supply was diminished by using various (beta-hydroxybutyrate)/(acetoacetate) ratios as a redox buffer and the results were compared with those of experiments using perifusion of immobilized mitochondria with non-saturating substrate concentrations. 3. In both experimental approaches the influence of a diminished hydrogen pressure on the maximum (ATP)/(ADP) ratio at minimum flux was low. An extreme decrease in the (beta-hydroxybutyrate)/(acetoacetate) ratio by more than two orders of magnetitude causes the (APT)/(ADP) ratio to decrease by about 50%. 4. The load capacity of oxidative phosphorylation (maximum flux) is considerably decreased by diminished hydrogen pressure. 5. The borderline cases of purely kinetic and thermodynamic limitations of hydrogen supply were calculated by computer simulation with respect to the regulating behaviour of oxidative phosphorylation and changes in the control strength of adenine nucleotide translocator and hydrogen supply in the overall reaction. 6. A prevalent thermodynamic influence of hydrogen supply on oxidative energy transformation in the cell is discussed in the light of experimental data.

• MeSH
• acetoacetáty * MeSH
• adeninnukleotidy metabolismus   MeSH
• adenosindifosfát metabolismus   MeSH
• adenosintrifosfát metabolismus   MeSH
• hydroxybutyráty farmakologie   MeSH
• jaterní mitochondrie účinky léků   metabolismus   MeSH
• ketokyseliny farmakologie   MeSH
• krysa rodu Rattus MeSH
• kyselina 3-hydroxymáselná MeSH
• oxidace-redukce MeSH
• oxidativní fosforylace MeSH
• termodynamika MeSH
• vodík metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• acetoacetáty * MeSH
• acetoacetic acid MeSH Prohlížeč
• adeninnukleotidy MeSH
• adenosindifosfát MeSH
• adenosintrifosfát MeSH
• hydroxybutyráty MeSH
• ketokyseliny MeSH
• kyselina 3-hydroxymáselná MeSH
• vodík MeSH

• MeSH
• anthraceny farmakologie   MeSH
• asociační učení účinky léků   MeSH
• dospělí MeSH
• hydroxybutyráty farmakologie   MeSH
• lidé MeSH
• norbornany farmakologie   MeSH
• oxybát sodný farmakologie   MeSH
• učení účinky léků   MeSH
• verbální chování účinky léků   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• anthraceny MeSH
• hydroxybutyráty MeSH
• norbornany MeSH
• oxybát sodný MeSH

• Klíčová slova
• ANESTHESIA, INTRAVENOUS *, ANESTHETICS *, CHEMISTRY, PHARMACEUTICAL *, HYDROXYBUTYRATES *,
• MeSH
• anestetika intravenózní * MeSH
• anestetika * MeSH
• anestezie * MeSH
• farmaceutická chemie * MeSH
• hydroxybutyráty * MeSH
• intravenózní anestezie * MeSH
• lidé MeSH
• oxybát sodný * MeSH
• sodík * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 4-hydroxybutyric acid MeSH Prohlížeč
• anestetika intravenózní * MeSH
• anestetika * MeSH
• hydroxybutyráty * MeSH
• oxybát sodný * MeSH
• sodík * MeSH

Gamma-hydroxybutyrate (GHB) Misuse or Abuse and Interpretation of Toxicological Findings The paper presented is a review of important information on gamma-hydroxybutyrate abuse or misuse, its toxicological findings under various circumstances, endogenous concentrations and potentional neoformation, with stressing the difficulties of interpretation which shall be done very carefully.

• MeSH
• lidé MeSH
• odhalování abúzu drog * metody   MeSH
• oxybát sodný * analýza   farmakokinetika   otrava   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• oxybát sodný * MeSH

BACKGROUND AND PURPOSE: Narcolepsy is an uncommon hypothalamic disorder of presumed autoimmune origin that usually requires lifelong treatment. This paper aims to provide evidence-based guidelines for the management of narcolepsy in both adults and children. METHODS: The European Academy of Neurology (EAN), European Sleep Research Society (ESRS), and European Narcolepsy Network (EU-NN) nominated a task force of 18 narcolepsy specialists. According to the EAN recommendations, 10 relevant clinical questions were formulated in PICO format. Following a systematic review of the literature (performed in Fall 2018 and updated in July 2020) recommendations were developed according to the GRADE approach. RESULTS: A total of 10,247 references were evaluated, 308 studies were assessed and 155 finally included. The main recommendations can be summarized as follows: (i) excessive daytime sleepiness (EDS) in adults-scheduled naps, modafinil, pitolisant, sodium oxybate (SXB), solriamfetol (all strong); methylphenidate, amphetamine derivatives (both weak); (ii) cataplexy in adults-SXB, venlafaxine, clomipramine (all strong) and pitolisant (weak); (iii) EDS in children-scheduled naps, SXB (both strong), modafinil, methylphenidate, pitolisant, amphetamine derivatives (all weak); (iv) cataplexy in children-SXB (strong), antidepressants (weak). Treatment choices should be tailored to each patient's symptoms, comorbidities, tolerance and risk of potential drug interactions. CONCLUSION: The management of narcolepsy involves non-pharmacological and pharmacological approaches with an increasing number of symptomatic treatment options for adults and children that have been studied in some detail.

• Klíčová slova
• European, cataplexy, guideline, management, narcolepsy,
• MeSH
• dítě MeSH
• dospělí MeSH
• kataplexie * MeSH
• lidé MeSH
• modafinil terapeutické užití   MeSH
• narkolepsie * diagnóza   farmakoterapie   MeSH
• oxybát sodný * terapeutické užití   MeSH
• spánek MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• systematický přehled MeSH
• Názvy látek
• modafinil MeSH
• oxybát sodný * MeSH

BACKGROUND AND AIM: Narcolepsy is an uncommon hypothalamic disorder of presumed autoimmune origin that usually requires lifelong treatment. This paper aims to provide evidence-based guidelines for the management of narcolepsy in both adults and children. METHODS: The European Academy of Neurology (EAN), European Sleep Research Society (ESRS) and European Narcolepsy Network (EU-NN) nominated a task force of 18 narcolepsy specialists. According to the EAN recommendations, 10 relevant clinical questions were formulated in PICO format. Following a systematic review of the literature (performed in Fall 2018 and updated in July 2020) recommendations were developed according to the GRADE approach. RESULTS: A total of 10,247 references were evaluated, 308 studies were assessed and 155 finally included. The main recommendations can be summarized as follows: (i) excessive daytime sleepiness in adults-scheduled naps, modafinil, pitolisant, sodium oxybate (SXB), solriamfetol (all strong), methylphenidate, amphetamine derivates (both weak); (ii) cataplexy in adults-SXB, venlafaxine, clomipramine (all strong) and pitolisant (weak); (iii) excessive daytime sleepiness in children-scheduled naps, SXB (both strong), modafinil, methylphenidate, pitolisant, amphetamine derivates (all weak); (iv) cataplexy in children-SXB (strong), antidepressants (weak). Treatment choices should be tailored to each patient's symptoms, comorbidities, tolerance and risk of potential drug interactions. CONCLUSION: The management of narcolepsy involves non-pharmacological and pharmacological approaches with an increasing number of symptomatic treatment options for adults and children that have been studied in some detail.

• Klíčová slova
• European, cataplexy, guideline, management, narcolepsy,
• MeSH
• dítě MeSH
• dospělí MeSH
• kataplexie * MeSH
• lidé MeSH
• modafinil terapeutické užití   MeSH
• narkolepsie * diagnóza   farmakoterapie   MeSH
• oxybát sodný * terapeutické užití   MeSH
• spánek MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• systematický přehled MeSH
• Názvy látek
• modafinil MeSH
• oxybát sodný * MeSH