Gambling encompasses a wide variety of activities, and the structural characteristics of each form contribute to its potential risk. However, the literature does not fully agree on the risk levels of certain gambling forms. In this study, we classify less risky gambling forms (soft forms) based on public perceptions of their riskiness. We examine the link between gambling experience and problem gambling prevalence. A survey was conducted in a model region of the Czech Republic, a post-socialist country with high gambling availability, with N = 2,498 respondents. A typology of gambling forms (lotteries, betting, and casino games) was created based on perceived risk similarities. Lotteries are the most frequently played gambling form, with 86.3% reporting lifetime participation. Among those who exclusively engage in lottery-type forms, 15 percentage points more women than men participated in the last year, and the gap widens to 31 points over a lifetime. Forms of gambling perceived as more risky show a lower proportion of non-problem gamblers, both for recent and lifetime participation. Furthermore, individuals who gambled within the past month or year are at higher risk of developing gambling problems compared to those whose gambling experiences were less recent.

• MeSH
• dospělí MeSH
• hráčství * psychologie   klasifikace   epidemiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• návykové chování * psychologie   epidemiologie   klasifikace   MeSH
• prevalence MeSH
• průzkumy a dotazníky MeSH
• riskování * MeSH
• rizikové faktory MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

BACKGROUND: Current guidelines discourage prophylactic plasma use in non-bleeding patients. This study assesses global plasma transfusion practices in the intensive care unit (ICU) and their alignment with current guidelines. STUDY DESIGN AND METHODS: This was a sub-study of an international, prospective, observational cohort. Primary outcomes were in-ICU occurrence rate of plasma transfusion, proportion of plasma events of total blood products events, and number of plasma units per event. Secondary outcomes included transfusion indications, INR/PT, and proportion of events for non-bleeding indications. RESULTS: Of 3643 patients included, 356 patients (10%) experienced 547 plasma transfusion events, accounting for 18% of total transfusion events. A median of 2 (IQR 1, 2) units was given per event excluding massive transfusion protocol (MTP) and 3 (IQR 2, 6) when MTP was activated. MTP accounted for 39 (7%) of events. Indications of non-MTP events included active bleeding (54%), prophylactic (25%), and pre-procedure (12%). Target INR/PT was stated for 43% of transfusion events; pre-transfusion INR/PT or visco-elastic hemostatic assays (VHA) were reported for 73%. Thirty-seven percent of events were administered for non-bleeding indications, 54% with a pre-transfusion INR < 3.0 and 30% with an INR < 1.5. DISCUSSION: Plasma transfusions occurred in 10% of ICU patients. Over a third were given for non-bleeding indications and might have been avoidable. Target INR/PT was not stated in more than half of transfusions, and pre-transfusion INR/PT or VHA was not reported for 27%. Further research and education is needed to optimize guideline implementation and to identify appropriate indications for plasma transfusion.

• MeSH
• jednotky intenzivní péče * MeSH
• krevní plazma * MeSH
• krvácení terapie   etiologie   prevence a kontrola   MeSH
• lidé středního věku MeSH
• lidé MeSH
• převod jednotlivých krevních složek * MeSH
• prospektivní studie MeSH
• senioři MeSH
• směrnice pro lékařskou praxi jako téma MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro) autocatalytically releases itself out of the viral polyprotein to form a fully active mature dimer in a manner that is not fully understood. Here, we introduce several tools to help elucidate differences between cis (intramolecular) and trans (intermolecular) proteolytic processing and to evaluate inhibition of precursor Mpro. We found that many mutations at the P1 position of the N-terminal autoprocessing site do not block cis autoprocessing but do inhibit trans processing. Notably, substituting the WT glutamine at the P1 position with isoleucine retains Mpro in an unprocessed precursor form that can be purified and further studied. We also developed a cell-based reporter assay suitable for compound library screening and evaluation in HEK293T cells. This assay can detect both overall Mpro inhibition and the fraction of uncleaved precursor form of Mpro through separable fluorescent signals. We observed that inhibitory compounds preferentially block mature Mpro. Bofutrelvir and a novel compound designed in-house showed the lowest selectivity between precursor and mature Mpro, indicating that inhibition of both forms may be possible. Additionally, we observed positive modulation of precursor activity at low concentrations of inhibitors. Our findings help expand understanding of the SARS-CoV-2 viral life cycle and may facilitate development of strategies to target precursor form of Mpro for inhibition or premature activation of Mpro.

• MeSH
• antivirové látky * farmakologie   chemie   MeSH
• farmakoterapie COVID-19 MeSH
• HEK293 buňky MeSH
• inhibitory proteas farmakologie   chemie   MeSH
• koronavirové proteasy 3C * metabolismus   antagonisté a inhibitory   chemie   genetika   MeSH
• lidé MeSH
• mutace MeSH
• objevování léků * metody   MeSH
• proteolýza MeSH
• SARS-CoV-2 * enzymologie   účinky léků   metabolismus   genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Advancing the retrograde microcatheter (MC) into the antegrade guide catheter during retrograde chronic total occlusion (CTO) percutaneous coronary intervention (PCI) can be challenging or impossible, preventing guidewire externalization. OBJECTIVES: To detail and evaluate all the techniques focused on wiring to achieve intubation of the distal tip of a microcatheter, balloon, or stent with an antegrade or retrograde guidewire, aiming to reduce complications by minimizing tension on fragile collaterals during externalization and enabling rapid antegrade conversion in various clinical scenarios. METHODS: We describe the two main techniques, tip-in and rendezvous, and their derivatives such a facilitated tip-in, manual MC-tip modification, tip-in the balloon, tip-in the stent, deep dive rendezvous, catch-it and antegrade microcatheter probing. We provide case studies that demonstrate the effectiveness of these techniques in complex scenarios involving extreme vessel angulation, severe calcification, fragile collaterals, and challenging retrograde MC crossing without externalization. CONCLUSION: The development of advanced variants along with traditional techniques to establish retrograde guidewire connection and antegrade conversion has led to the establishment of a cohesive group of methods known as portal techniques. These approaches serve as strategic advantages in retrograde CTO-PCI, providing a valuable and feasible alternative to conventional retrograde connection techniques, particularly when those techniques fail. Their ability to avoid the externalization process reduces potential damage to collateral channels and the ostium of the donor artery, potentially leading to a reduction in complication rates.

• MeSH
• balónková koronární angioplastika přístrojové vybavení   škodlivé účinky   MeSH
• chronická nemoc MeSH
• design vybavení MeSH
• koronární angioplastika přístrojové vybavení   škodlivé účinky   MeSH
• koronární okluze * diagnostické zobrazování   terapie   patofyziologie   MeSH
• lidé MeSH
• miniaturizace MeSH
• srdeční katétry * MeSH
• stenty * MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND CONTEXT: Spondylodiscitis management presents significant clinical challenges, particularly in critically ill patients, where the risks and benefits of surgical intervention must be carefully balanced. The optimal timing of surgery in this context remains a subject of debate. PURPOSE: This study aims to evaluate the effectiveness of early surgery versus delayed surgery or conservative management in critically ill patients with de novo pyogenic spondylodiscitis. STUDY DESIGN/SETTING: This is an international, multicenter retrospective cohort study involving 24 centers, primarily in Europe. PATIENT SAMPLE: The study included 192 critically ill patients (65.63% male) with a median age of 69 years, all severely affected by pyogenic spondylodiscitis characterized by an initial CRP level >200 mg/l or the presence of two out of four Systemic Inflammatory Response Syndrome criteria upon admission. OUTCOME MEASURES: The primary outcome was 30-day mortality. Secondary outcomes included length of ICU stay, length of hospital stay, and relapse rates of spondylodiscitis. METHODS: Patients were divided into three groups: early surgery (within three days of admission), delayed surgery (after three days of admission), and conservative therapy. Propensity score matching and multivariate regression analyses were performed to adjust for baseline differences and assess the impact of treatment modalities on mortality and other clinical outcomes. RESULTS: Delayed surgery was associated with significantly lower 30-day mortality (4.05%) compared to early surgery (27.85%) and conservative therapy (27.78%) (p<.001). Delayed surgery also resulted in shorter hospital stays (42.76 days) compared to conservative therapy (55.53 days) and early surgery (26.33 days) (p<.001), and shorter ICU stays (4.52 days) compared to conservative therapy (16.48 days) and early surgery (7.92 days) (p<.001). The optimal window for surgery, minimizing mortality, was identified as ten to fourteen days postadmission (p=.02). Risk factors for increased mortality included age (p<.05), multiple organ failure (p<.05), and vertebral body destruction (p<.05), whereas delayed surgery (p<.05) and the presence of an epidural abscess were associated with reduced mortality (p<.05). CONCLUSIONS: Delayed surgery, optimally between 10 to 14 days postadmission, was associated with lower mortality in critically ill spondylodiscitis patients. These findings highlight the potential benefits of considering surgical timing to improve patient outcomes.

• MeSH
• antibakteriální látky terapeutické užití   MeSH
• délka pobytu MeSH
• discitida * terapie   mortalita   chirurgie   mikrobiologie   MeSH
• konzervativní terapie MeSH
• kritický stav MeSH
• lidé středního věku MeSH
• lidé MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

INTRODUCTION AND OBJECTIVES: With increases in obesity and metabolic syndrome because of lifestyle-related factors, the prevalence of non-alcoholic fatty liver disease (NAFLD) also is increasing worldwide. In a subset of patients with NAFLD, an inflammatory process arises in the steatotic liver, known as non-alcoholic steatohepatitis, that leads to liver fibrosis and liver cirrhosis. In selected patients with obesity, bariatric surgery, and bariatric endoscopy are important therapeutic options. MATERIALS AND METHODS: This prospective interventional pilot study was conducted to investigate two types of intragastric balloons (IGB). The IGBs were the Orbera and the Spatz3. Liver fibrosis changes were monitored non-invasively using point and 2D shear wave ultrasound elastography (SWE) and transient elastography that allowed for quantification of liver steatosis using the controlled attenuation parameter (CAP). Patients were followed for 12 months. RESULTS: Of 34 patients implanted with an IGB, 30 completed follow-up at month 12; results for one patient were excluded because of initiation of obesity pharmacotherapy. Fifteen patients received the Orbera IGB, and nineteen patients received the Spatz3 type. In month 12, total and excess weight loss was 7.88 % and 30.13 %. Elastography values decreased from baseline (3.88 kPa) to 3.61 kPa at month 12 (p 0.024). 2D SWE values decreased from baseline (5.42 kPa) to a value of 4.91 kPa at month twelve (p 0.135). Transient elastography values decreased from baseline (5.62 kPa) to a value of 4.17 kPa at month twelve (p 0.009). CONCLUSIONS: Bariatric endoscopy in the form of IGB implantation leads to weight reduction and improvement of liver fibrosis and steatosis. GOV REGISTRATION: NCT04895943.

• MeSH
• bariatrická chirurgie * MeSH
• časové faktory MeSH
• design vybavení MeSH
• dospělí MeSH
• elastografie MeSH
• hmotnostní úbytek MeSH
• jaterní cirhóza * etiologie   diagnostické zobrazování   diagnóza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nealkoholová steatóza jater * diagnostické zobrazování   diagnóza   etiologie   MeSH
• obezita * komplikace   chirurgie   diagnóza   MeSH
• pilotní projekty MeSH
• prospektivní studie MeSH
• výsledek terapie MeSH
• žaludeční balónek * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH

OBJECTIVE: Transgenic mice with fluorescent protein (FP) reporters take full advantage of new in vivo imaging technologies. Therefore, we generated a TRPC5- and a TRPA1-reporter mouse based on FP C-terminal fusion, providing us with better alternatives for studying the physiology, interaction and coeffectors of these two TRP channels at the cellular and tissue level. METHODS: We generated transgenic constructs of the murine TRPC5- and TRPA1-gene with a 3*GGGGS linker and C-terminal fusion to mCherry and mTagBFP, respectively. We microinjected zygotes to generate reporter mice. Reporter mice were examined for visible fluorescence in trigeminal ganglia with two-photon microscopy, immunohistochemistry and calcium imaging. RESULTS: Both TRPC5-mCherry and TRPA1-mTagBFP knock-in mouse models were successful at the DNA and RNA level. However, at the protein level, TRPC5 resulted in no mCherry fluorescence. In contrast, sensory neurons derived from the TRPA1-reporter mice exhibited visible mTag-BFP fluorescence, although TRPA1 had apparently lost its ion channel function. CONCLUSIONS: Creating transgenic mice with a TRP channel tagged at the C-terminus with a FP requires detailed investigation of the structural and functional consequences in a given cellular context and fine-tuning the design of specific constructs for a given TRP channel subtype. Different degrees of functional impairment of TRPA1 and TRPC5 constructs suggest a specific importance of the distal C-terminus for the regulation of these two channels in trigeminal neurons.

• MeSH
• červený fluorescenční protein MeSH
• ganglion trigeminale metabolismus   MeSH
• genový knockin * MeSH
• kationtové kanály TRPC * genetika   metabolismus   MeSH
• kationtový kanál TRPA1 * genetika   metabolismus   MeSH
• luminescentní proteiny * genetika   metabolismus   MeSH
• myši transgenní * MeSH
• myši MeSH
• rekombinantní fúzní proteiny metabolismus   genetika   MeSH
• vápník metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The extracellular matrix (ECM)-and its mechanobiology-regulates key cellular functions that drive tumor growth and development. Accordingly, mechanotherapy is emerging as an effective approach to treat fibrotic diseases such as cancer. Through restoring the ECM to healthy-like conditions, this treatment aims to improve tissue perfusion, facilitating the delivery of chemotherapies. In particular, the manipulation of ECM is gaining interest as a valuable strategy for developing innovative treatments based on nanoparticles (NPs). However, further progress is required; for instance, it is known that the presence of a dense ECM, which hampers the penetration of NPs, primarily impacts the efficacy of nanomedicines. Furthermore, most 2D in vitro studies fail to recapitulate the physiological deposition of matrix components. To address these issues, a comprehensive understanding of the interactions between the ECM and NPs is needed. This review focuses on the main features of the ECM and its complex interplay with NPs. Recent advances in mechanotherapy are discussed and insights are offered into how its combination with nanomedicine can help improve nanomaterials design and advance their clinical translation.

• MeSH
• extracelulární matrix * metabolismus   MeSH
• lidé MeSH
• nádory * terapie   MeSH
• nanočástice * chemie   MeSH
• nanomedicína * metody   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The endorsement of conspiracy theories may be increased by subjectively perceived stress. Yet, it is not known whether this correlation is caused by the effects of the acute stress reaction on the brain or other psychological, social, or methodological factors. The effect of an experimentally induced acute stress reaction on conspiracy thinking was tested on a sample (n = 115) of students of medicine. Although the stress procedure caused a substantial increase in salivary cortisol, there was no significant effect on endorsing conspiracy theories or adopting conspiracy interpretations of novel information. The results confirmed no effect of the acute stress reaction on conspiracy thinking, suggesting it may be absent or weaker than expected. The study demonstrated the viability of psychophysiological experimental design in conspiracy research and may inspire further examination of the physiological mechanisms underlying susceptibility to conspiracy theories.

• MeSH
• dospělí MeSH
• hydrokortison analýza   metabolismus   MeSH
• lidé MeSH
• mladý dospělý MeSH
• psychický stres * psychologie   MeSH
• sliny chemie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Glucocorticoids are potent anti-inflammatory drugs, although their use is associated with severe side effects. Loading glucocorticoids into suitable nanocarriers can significantly reduce these undesirable effects. Macrophages play a crucial role in inflammation, making them strategic targets for glucocorticoid-loaded nanocarriers. The main objective of this study is to develop a glucocorticoid-loaded PLGA nanocarrier specifically targeting liver macrophages, thereby enabling the localized release of glucocorticoids at the site of inflammation. Dexamethasone acetate (DA)-loaded PLGA nanospheres designed for passive macrophage targeting are synthesized using the nanoprecipitation method. Two types of PLGA NSs in the size range of 100-300 nm are prepared, achieving a DA-loading efficiency of 19 %. Sustained DA release from nanospheres over 3 days is demonstrated. Flow cytometry analysis using murine bone marrow-derived macrophages demonstrates the efficient internalization of fluorescent dye-labeled PLGA nanospheres, particularly into pro-inflammatory macrophages. Significant down-regulation in pro-inflammatory cytokine genes mRNA is observed without apparent cytotoxicity after treatment with DA-loaded PLGA nanospheres. Subsequent experiments in mice confirm liver macrophage-specific nanospheres accumulation following intravenous administration using in vivo imaging, flow cytometry, and fluorescence microscopy. Taken together, the data show that the DA-loaded PLGA nanospheres are a promising drug-delivery system for the treatment of inflammatory liver diseases.

• MeSH
• antiflogistika farmakologie   chemie   MeSH
• dexamethason * farmakologie   chemie   analogy a deriváty   MeSH
• játra * účinky léků   metabolismus   MeSH
• kopolymer kyseliny glykolové a mléčné * chemie   MeSH
• makrofágy * účinky léků   metabolismus   MeSH
• myši MeSH
• nanokuličky * chemie   MeSH
• nosiče léků chemie   farmakologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH