In the presented study, the cells of the glacial alga Ancylonema alaskanum collected in the Austrian Alps were analyzed. Algae were imaged both in their natural environment and in laboratory conditions using transmitted light and fluorescence microscopy. Using appropriate fluorochromes, the cell wall and cell organelles were studied. Oval nuclei located in the middle of the cell next to the chloroplasts and active mitochondria as well as lipid thylakoids of chloroplasts were imaged. Scanning electron microscopy showed that the surface of the algal cell wall was not significantly differentiated, and atomic force microscope imaging recorded little roughness. The SEM EDS analysis revealed that carbon, nitrogen, oxygen, and magnesium were the main components of the cells. It is worth emphasizing that the analyzed living algal cells were obtained directly from the glacier surface and demonstrated normal respiratory processes i.e. undisturbed physiological functions. Additionally, the mineral material accompanying the cells in their natural environment - fragments of the rock were imaged by Differential Interference Contrast microscopy and analyzed by Fourier Transform Infrared Spectroscopy. The study provides new data on the morphology and physicochemical characteristics of A. alaskanum, contributing to a more comprehensive characterization of their place in this harsh ecosystem.

• MeSH
• ledový příkrov * MeSH
• mikroskopie elektronová rastrovací MeSH
• spektroskopie infračervená s Fourierovou transformací MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Rakousko MeSH

PURPOSE: The authors evaluated a cohort of 12 patients with histologically verified pigmented villonodular synovitis of the TMJ between 2018 and 2023. METHODS: The authors evaluated 12 patients (12 women). Only unilateral involvement was present in all patients. The mean age of the patients was 49.5 years. The authors focused on the evaluation of clinical symptoms, imaging findings, and arthroscopic findings. They also evaluated the effect of therapy, including the incidence of recurrence. The evaluation of therapy was performed at a minimum of 12 months after therapy and a maximum of 4.5 years after therapy. RESULTS: Pain was the predominant clinical symptom (12 patients, 100%). Therapy consisted of arthroscopy and open surgery. Radiographs were taken in all patients. In 5 patients (42%) the joint structures were without obvious pathological changes, in 7 patients (58%) there was a finding of irregularities on the joint head. Magnetic resonance imaging was performed in all patients, and in 10 cases (83%) there was a finding of joint space enlargement, effusion. Therapy consisted of TMJ arthroscopy with removal of pathological tissue. If the joint was completely filled with pathological tissue, after histological verification, open surgery with complete removal of joint structures and subsequent reconstruction of the TMJ was indicated. Recurrence of PVNS was not reported in the cohort. CONCLUSION: PVNS is an uncommon benign lesion affecting the TMJ. In the authors' study, pain was the predominant symptom and effusion was the predominant finding on magnetic resonance imaging. Long-term follow-up is appropriate in patients with proven PVNS. This is due to the risk of recurrence, which is also associated with the difficulty of complete repair of the lesion in the anatomically limited space of the TMJ. The authors recommend 1,3,6 months after surgery, and annually for the first 5 years after surgery. One, two, and five years after surgery, they recommend a follow-up MRI. The results of the study support the view that MRI should always be indicated in patients with pain of arthrogenic origin lasting more than 3 months, and if effusion is found, arthroscopy should always be the next step. This procedure will ensure early detection of PVNS.

• MeSH
• artroskopie MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• nemoci temporomandibulárního kloubu * chirurgie   diagnostické zobrazování   patologie   MeSH
• recidiva MeSH
• retrospektivní studie MeSH
• synovitida pigmentová vilonodulární * chirurgie   diagnostické zobrazování   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: The optimal first-line therapy for metastatic renal cell carcinoma (mRCC) remains uncertain, despite recent advancements in immune-based combinations. This retrospective study compares the effectiveness of pembrolizumab plus axitinib (PA) and nivolumab plus cabozantinib (NC) as first-line treatments for mRCC in a real-world setting. METHODS: Patient data were collected from 55 centers across 16 countries, encompassing individuals diagnosed with mRCC receiving first-line treatment with PA or NC between January 2016 and October 2023. Clinical and tumor features and treatment responses were recorded. The primary endpoints were overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and time to second progression. Statistical analyses included Kaplan-Meier survival estimates, Cox proportional hazard models, and chi-square tests. RESULTS: A total of 760 patients with a median age of 64 years (range, 29-88) were included. Of them, 607 received PA, and only 153 NC. In the overall study population, ORR was 59% for and 49% for PA. Median OS was 55.7 months and not reached (NR) for PA and NC, respectively (P = .51), while median PFS was longer with NC (27.6 months) than for PA (16.2 months, P = .003). Subgroup analysis suggested a PFS benefits for NC in male, younger patients, intermediate risk group, clear cell histology, and lung involvement, as well as ORR favored NC in good risk patients. Multivariate analysis identified first-line therapy as a significant factor associated with PFS. CONCLUSIONS: In this certainly biased retrospective comparison, NC demonstrated superior ORR and longer PFS compared to PA in mRCC. These findings underscore the importance of considering individual patient characteristics and risk profiles when selecting first-line therapy for mRCC.

• MeSH
• anilidy * terapeutické užití   farmakologie   aplikace a dávkování   MeSH
• axitinib * terapeutické užití   farmakologie   aplikace a dávkování   MeSH
• dospělí MeSH
• humanizované monoklonální protilátky * terapeutické užití   farmakologie   aplikace a dávkování   MeSH
• karcinom z renálních buněk * farmakoterapie   mortalita   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory ledvin * farmakoterapie   patologie   mortalita   MeSH
• nivolumab * terapeutické užití   farmakologie   aplikace a dávkování   MeSH
• protokoly protinádorové kombinované chemoterapie * terapeutické užití   MeSH
• pyridiny terapeutické užití   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• 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
• srovnávací studie MeSH

Hepatectomies play a crucial role in the multidisciplinary management of primary and secondary liver malignancies but are associated with significant risks, including 30-day mortality, morbidity, prolonged hospitalization, and increased resource utilization. Optimizing perioperative care remains a challenge; however, enhanced recovery programs have shown improved patient outcomes. The EUPEMEN (EUropean PErioperative MEdical Networking) protocol focuses on improving the perioperative management of liver resections through the establishment of interdisciplinary principles based on practical experience and theoretical frameworks from five European countries. This paper outlines the core elements of the EUPEMEN protocol, emphasizing strategies to minimize surgical stress, optimize perioperative care, and enhance postoperative recovery. The protocol is systematically designed to reduce postoperative mortality and morbidity, shorten hospital stays, and improve patient outcomes. The EUPEMEN guidelines address inconsistencies in surgical practice across Europe and are structured for implementation in various healthcare environments. "The protocol's approach is designed to support improvements in perioperative care standards in liver resections and may serve as a practical and efficient tool for healthcare professionals, pending further clinical validation. The EUPEMEN protocol offers a standardized, evidence-based framework to enhance perioperative management in hepatectomies. By integrating multidisciplinary principles, the main target is to eliminate complications, improve surgical outcomes, and promote faster recovery. Its implementation across diverse clinical settings may contribute to advancing perioperative care standards for liver resections in Europe.

• MeSH
• hepatektomie * metody   normy   MeSH
• klinické protokoly MeSH
• lidé MeSH
• nádory jater chirurgie   MeSH
• perioperační péče * metody   normy   MeSH
• pooperační komplikace prevence a kontrola   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Geografické názvy
• Evropa MeSH

BACKGROUND: The development of child's lifestyle occurs within regular 24-hour movement patterns under the guidance of parents. Accelerometer-based monitoring allows for the capture of these 24-hour movement patterns of behaviour. Therefore, the aim of this study was to reveal whether active participation in organised physical activity (OPA) contributed to the achievement of the World Health Organization's (WHO) 24-hour movement behaviour guidelines (24-hMBGS) among 3-10-year-old children, considering the influence of parents' movement behaviour and families' material background. METHODS: The 24-hour movement behaviour (24-hMB) of 348 child-parent pairs (with at least one parent) was continuously monitored for 7 days via ActiGraph accelerometers placed on the non-dominant wrist. Children's adherence to the WHO's 24-hMBGS was analysed using logistic regression analysis. The socioeconomic status (SES) of families was measured using the Family Affluence Scale. Body mass level was determined according to body mass index gender- and age-specific WHO reference data. Univariate analysis of variance/Pearson's chi-square test was used to test differences in sedentary behaviour duration/excess body weight between active participants and non-participants in OPA. RESULTS: Active 3-10-year-old participants in OPA, compared to non-participants, were significantly more likely to meet at least two of the 24-hMBGS (77.7% vs. 66.4%, p = 0.008), had significantly shorter daily sedentary time (by 30 min per day, p = 0.001), and a significantly lower prevalence of excessive body weight (10.26% vs. 24.87% p < 0.001). Engaging in OPA significantly (p < 0.01) helped 3-10-year-old children achieve at least two of the 24-hMBGS, regardless of their gender, age, excess body weight, or family SES. In addition, a mother's non-excessive body weight and achievement of at least two of the WHO's 24-hMBGS significantly (p < 0.05) contributed to children attaining at least two of the WHO's 24-hMBGS. CONCLUSIONS: Even in young children, active participation in OPA tend to contribute to a healthier lifestyle profile, characterised by shorter sedentary behaviour and lower excess body weight, with a significant influence from the mother's movement behaviour.

• MeSH
• akcelerometrie MeSH
• cvičení * MeSH
• dítě MeSH
• lidé MeSH
• předškolní dítě MeSH
• rodiče MeSH
• sedavý životní styl * MeSH
• směrnice jako téma * MeSH
• spánek MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Nedd4-2 E3 ligase regulates Na+ homeostasis by ubiquitinating various channels and membrane transporters, including the epithelial sodium channel ENaC. In turn, Nedd4-2 dysregulation leads to various conditions, including electrolytic imbalance, respiratory distress, hypertension, and kidney diseases. However, Nedd4-2 regulation remains mostly unclear. The present study aims at elucidating Nedd4-2 regulation by structurally characterizing Nedd4-2 and its complexes using several biophysical techniques. Our cryo-EM reconstruction shows that the C2 domain blocks the E2-binding surface of the HECT domain. This blockage, ubiquitin-binding exosite masking by the WW1 domain, catalytic C922 blockage and HECT domain stabilization provide the structural basis for Nedd4-2 autoinhibition. Furthermore, Ca2+-dependent C2 membrane binding disrupts C2/HECT interactions, but not Ca2+ alone, whereas 14-3-3 protein binds to a flexible region of Nedd4-2 containing the WW2 and WW3 domains, thereby inhibiting its catalytic activity and membrane binding. Overall, our data provide key mechanistic insights into Nedd4-2 regulation toward fostering the development of strategies targeting Nedd4-2 function.

• MeSH
• elektronová kryomikroskopie MeSH
• HEK293 buňky MeSH
• lidé MeSH
• molekulární modely MeSH
• proteinové domény MeSH
• proteiny 14-3-3 * metabolismus   chemie   MeSH
• ubikvitinace MeSH
• ubikvitinligasy Nedd4 * metabolismus   chemie   genetika   ultrastruktura   MeSH
• vápník * metabolismus   MeSH
• vazba proteinů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Genomic alterations and enormous monoclonal immunoglobulin production cause multiple myeloma to heavily depend on proteostasis mechanisms, including protein folding and degradation. These findings support the use of proteasome inhibitors for treating multiple myeloma and mantle cell lymphoma. Myeloma treatment has evolved, especially with the availability of new drugs, such as proteasome inhibitors, into therapeutic strategies for both frontline and relapsed/refractory disease settings. However, proteasome inhibitors are generally not effective enough to cure most patients. Natural resistance and eventual acquired resistance led to relapsed/refractory disease and poor prognosis. Advances in the understanding of cellular proteostasis and the development of innovative drugs that also target other proteostasis network components offer opportunities to exploit the intrinsic vulnerability of myeloma cells. This review outlines recent findings on the molecular mechanisms regulating cellular proteostasis pathways, as well as resistance, sensitivity, and escape strategies developed against proteasome inhibitors and provides a rationale and examples for novel combinations of proteasome inhibitors with FDA-approved drugs and investigational drugs targeting the NRF1 (NFE2L1)-mediated proteasome bounce-back response, redox homeostasis, heat shock response, unfolding protein response, autophagy, and VCP/p97 to increase proteotoxic stress, which can improve the efficacy of antimyeloma therapy based on proteasome inhibitors.

• MeSH
• chemorezistence MeSH
• homeostáze proteinů * účinky léků   MeSH
• inhibitory proteasomu * terapeutické užití   farmakologie   MeSH
• lidé MeSH
• mnohočetný myelom * farmakoterapie   metabolismus   MeSH
• protinádorové látky * terapeutické užití   farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The objective of this study was to characterize the virulence characteristics of a collection of Klebsiella pneumoniae isolates collected from different clinical sources. A collection of 60 non-repetitive K. pneumoniae isolates, was studied. In vitro, virulence was analyzed by testing the survival of bacteria in pooled human serum. Isolates were typed by MLST. The genomes of 23 K. pneumoniae isolates, representatives of different STs and virulence profiles, were completely sequenced using the Illumina platform. Of note, 26/60 of K. pneumoniae isolates were resistant to killing by complement. Serum-resistant isolates belonged to distinct STs. Analysis of WGS data with VFDB showed the presence of several virulence genes related various virulence functions. Specifically, serum-resistant isolates carried a higher number of ORFs, which were associated with serum resistance, compared to serum-sensitive isolates. Additionally, analysis of WGS data showed the presence of multiple plasmid replicons that could be involved with the spread and acquisition of resistance and virulence genes. In conclusion, analysis of virulence characteristics showed that an important percentage (31.6%) of K. pneumoniae isolates were in vitro virulent by exhibiting resistance to serum. Thus, the presence of several virulence factors, in combination with the presence of multidrug resistance, could challenge antimicrobial therapy of infections caused by such bacteria.

• MeSH
• faktory virulence * genetika   MeSH
• genom bakteriální MeSH
• infekce bakteriemi rodu Klebsiella * mikrobiologie   genetika   MeSH
• Klebsiella pneumoniae * genetika   patogenita   izolace a purifikace   MeSH
• lidé MeSH
• multilokusová sekvenční typizace MeSH
• nemocnice MeSH
• plazmidy genetika   MeSH
• sekvenování celého genomu MeSH
• virulence genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Řecko MeSH

• MeSH
• agonisté receptoru pro glukagonu podobný peptid 1 farmakologie   terapeutické užití   MeSH
• diabetes mellitus * MeSH
• glifloziny farmakologie   terapeutické užití   MeSH
• kardiovaskulární nemoci mortalita   MeSH
• klinické zkoušky jako téma MeSH
• kombinovaná farmakoterapie MeSH
• lidé MeSH
• metaanalýza jako téma MeSH
• nemoci ledvin farmakoterapie   prevence a kontrola   MeSH
• renální insuficience mortalita   MeSH
• rizikové faktory MeSH
• Check Tag
• lidé MeSH

BACKGROUND: Advances in technology have led to the introduction of the suction ureteral access sheaths (SUASs) in ureteroscopy (URS) and retrograde intrarenal surgery (RIRS), with their clinical benefits becoming widely acknowledged. We aimed to evaluate the efficacy and safety of using SUASs during URS and RIRS. METHODS: A systematic search was conducted in April 2024 across the MEDLINE, Scopus, and Web of Science databases. Our focus was on studies investigating the use of SUASs during URS/RIRS for urinary stones. To compare the stone-free rate (SFR) and perioperative outcomes between URS/RIRS procedures with and without SUASs, standard pairwise meta-analyses were conducted. Risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were employed utilizing a random-effects model (PROSPERO: CRD42024538956). RESULTS: Seven studies (n=1,746) were identified. The use of SUASs significantly improved immediate SFR compared to non-SUAS group (RR: 1.23; 95% CI: 1.02 to 1.47; P=0.03), while no significant difference was observed in SFR at one month follow-up. The use of SUASs significantly reduced operation time (MD: -7.98 minutes; 95% CI: -13.46 to -2.50; P=0.004) and overall complication rate (RR: 0.49; 95% CI: 0.34 to 0.71; P<0.001). CONCLUSIONS: Our meta-analyses indicate that the use of SUASs during URS/RIRS significantly improves immediate SFR and offers better perioperative outcomes compared to no use of SUASs. To establish SUASs as standard of care, well-designed randomized controlled trials are needed.

• Publikační typ
• časopisecké články MeSH