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Nadežda Jankelová, Zuzana Joniaková, Jana Blštáková, Zuzana Skorková, Katarína ProcházkováDepartment of Management, Faculty of Business Management, University of Economics in Bratislava, Bratislava, SlovakiaCorrespondence: Nadežda JankelováDepartment of Management, Faculty of Business Management, University of Economics in Bratislava, Dolnozemská Cesta 1, Bratislava, 852 35, SlovakiaTel +421 911 232 927Email nadezda.jankelova@euba.skPurpose: The fast and shocking onset of the crisis caused by the COVID-19 virus created the need for a complete crisis management of healthcare facilities to manage the current stage of the crisis. The purpose of our research is to examine the relations between the competences of crisis management in healthcare facilities and the performance of employees, measured during the acute stage of the crisis by their feeling of satisfaction, safety and creation of conditions for work, whereby we assume that these variables are mutually interlinked by the sharing of information, teamwork and cognitive diversity of the work teams.Materials and Methods: A questionnaire survey was created and used based on a sample of 216 mid-level managers of health care facilities in Slovakia, which took place during the first month after the outbreak of the crisis (during the month of March/April 2020). The Baron and Kenny mediator model has been used for research purposes and the Freedman–Schatzkin test has been used to test the mediator effect. Regression analysis has been used to verify the hypotheses. The control variables were the size of the healthcare facility based on the number of employees, gender and age of the manager, his position in the management hierarchy and the duration of practice in a management position. The ANOVA analysis of variance was used to analyze multiple dependencies. The level of significance was 5%. The research sample consisted of 216 managers at different types of healthcare facilities.Results: The hypothesis for the dependency between the crisis competences of management and performance of teams during the acute stage of the crisis, facilitated by sharing information, teamwork and cognitive diversity of crisis management was confirmed. It is a multilateral incomplete mediation, where almost two thirds of the total effect are facilitated by mediators, of which the sharing of information has the greatest effect (35%).Conclusion: Based on our mediation model, healthcare facilities, which strive to implement crisis management during the acute stage of the crisis, should place emphasis especially on reliable background information and the fast sharing of information, supporting the performance of healthcare teams. The strategies for achieving these goals should also include education focused on the development of managerial competences.Keywords: crisis management, sharing information, teamwork, team performance, cognitive diversity

Copyright of Česká a Slovenská Neurologie a Neurochirurgie is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: Tracheostomy is one of the most frequent surgical procedures in critical care patients. Tracheostomy in burn injury patients is, however, very specific topic. The purpose of our research is the evaluation of such topic. Methods: We conducted a retrospective study of patients hospitalized at ICU of Department of Burn Injuries at University Hospital Královské Vinohrady and Third Faculty of Medicine, Charles University in Prague between 1. 1. 2012 - 31. 12. 2017, who underwent tracheostomy performed by an otorhinolaryngologist. 47 patients were enrolled to the study. We evaluated the complications of tracheostomy and its correlation to the factors of the site of the burn injury, timing of tracheostomy and experience of the surgeon. Results: There was no significant difference between the group with burn injury in the neck region versus burn injury outside the neck in terms of surgical complications, stoma infections, postoperative pneumonia, colonization of the respiratory tract mucosa by multi-resistant bacteria nor mortality. Regarding the timing of tracheostomy, we found higher occurrence of multi resistant nosocomial bacteria in lower respiratory tract in the late tracheostomy group (p=0.07). Although the overall complications rate was higher in tracheostomies performer by resident otorhinolaryngologists, the difference was not statistically significant. Conclusion: Tracheostomy in burn injury is a specific topic given the patient's primary illness. The management usually follows the international societies' guidelines. The most controversial long-term airway management is in the presence of burn trauma directly in the neck region. According to our study results, there was no higher incidence of complications in such patients though. Timing of tracheostomy may play role in multi-resistant bacteria colonization of the lower respiratory tract. The choice of a level of experience of a surgeon to be performing tracheostomy in burn injury should be carefully considered. [ABSTRACT FROM AUTHOR]

Copyright of Česká a Slovenská Neurologie a Neurochirurgie is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Research paper is summarizing results of project focus on business models and strategies of startups. The research was focused on identification of business models and strategies of startups. Research sample was creating from more than 70 startups at the beginning of the research and we finished research 3 years later with 53 startups. This research paper is partial output that analyze startups in global business environment in terms of doing business abroad and making strategic steps. The aim of paper is identify basic strategic steps and decision making of startups through selected indicators such as market presence and entry modes focusing on the last stage of research. Startups business model were also analyze and part of the output is mapping the shifts in business model Canvas of startups.

We conducted a trial to compare the effects of two frequently prescribed drugs against tinnitus - gingko biloba extract EGb 761® and pentoxifylline. The treatment effects were assessed according to their ability to lower the tinnitus perception and also to reduce psycho-social disturbances such as anxiety, depression and overall disability symptoms of the subjects. Two hundred patients with sub-chronic or chronic tinnitus were enrolled in this double-blind trial and randomized to receive 120 mg EGb 761® or 600 mg pentoxifylline, each twice a day and in double-dummy fashion over a 12-week period. Treatment effects were assessed as changes in 11-Point Box Scales for tinnitus loudness and annoyance, the abridged Tinnitus Questionnaire (Mini- TQ), the Hospital Anxiety and Depression Scale (HADS), and the Sheehan Disability Scale (SDS). For both treatment groups, significant improvements were observed in the Mini-TQ, the 11-Point Box Scales for tinnitus loudness and annoyance, the HADS anxiety score and the SDS. There was no relevant difference regarding tinnitus- related outcomes between the two treatment groups. Twenty adverse events were documented for 19 subjects treated with EGb 761® and 36 adverse events were reported for 27 patients receiving pentoxifylline. Patients suffering from chronic or sub-chronic tinnitus are very challenging to treat. Both investigational products were based on perfusion enhancement and prove their efficacy in decreasing the loudness and annoyance of tinnitus. EGb 76T demonstrated stronger effects in patients with depression and anxiety symptoms which we attribute to its nootropic activity. EGb 761® and pentoxifylline were similarly effective in reducing the loudness and annoyance of tinnitus as well as overall suffering of the patients. The EGb 761® treatment group however showed better improvement in patients with elevated depression scores and provided higher incidence of improved patients in anxiety score categories. The incidence of adverse events was lower in the EGb 761" group, therefore the tolerability of EGb 761® was distinctly better. [ABSTRACT FROM AUTHOR]

Background/objective: Hormone receptor (HR) status is one of the key factors in determining the treatment of breast cancer. Previous studies suggested that HR status may change in metastatic tissue. However, available studies focused mainly on primary biopsies and there are only few trials comparing HR status in the primary tumour and the metastasis using material from complete resection. The aim of the study was to determine the frequency of HR alterations in metastatic breast cancer., Materials and Methods: The study retrospectively examines a total of 50 patients who underwent brain, lung, or liver metastasectomy for metastatic breast cancer between January 2000 and January 2019., Results: HR conversion was observed in a total of 30 cases (60.0%), while HER-2/neu (human epidermal growth factor receptor 2) discrepancy surprisingly occurred only in one case (2.0%). A change in immunophenotype occurred in 28% of cases. Triple-negativity was more frequent in brain metastases (p = 0.039)., Conclusions: We have confirmed that HR conversion between the primary tumour and its metastases occurs in a significant number of cases, which has important implications for further treatment decisions., Competing Interests: Conflict of interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Greater Poland Cancer Centre.)

Introduction: The medical and social interest in the SARS-CoV-2 infection is currently high. This infection can, in severe cases, be accompanied by a series of complications, such as thromboembolic disease or pulmonary parenchymal haemorrhage., Case Reports: The paper presents two rare cases of massive intrathoracic haemorrhage caused by pulmonary parenchymal haemorrhage and exacerbated by full anticoagulant treatment of thromboembolic disease., Results: In both cases, the haemorrhage originated in the left lower lobe and was life threatening, requiring urgent anatomical lung resection - left lower lobectomy., Conclusions: The combinaion of anticoagulant therapy and thromboembolic events related to COVID-19 can cause, in rare cases, massive pulmonary haemorrhage. This rare complication proved lethal in one out of two of the cases described in this paper. An imminent and adequate reaction is necessary when the first signs of haemorrhage appear.

Introduction: Diaphragmatic rupture is a rare but life-threatening condition that occurs in 0.85% of surgically managed thoracoabdominal injuries. In most cases, the condition is accompanied by associated traumas responsible for poor prognosis. Signs of diaphragmatic rupture are often masked by more serious manifestations of the associated trauma. The rupture is usually revealed by an X-ray of the chest or CT scan. However, a minor defect may be missed, especially if the patient is not indicated for urgent surgery., Methods: The authors present 2 case reports of patients treated for chronic diaphragmatic rupture at the Department of Surgery of the Faculty of Medicine, Charles University and University Hospital in Pilsen between 01 January 2009 and 31 December 2021. The aim was to analyze the clinical data and to compare this data with literature., Results: Both patients with the chronic diaphragmatic rupture were men in their productive age. The mechanism of their primary trauma was a traffic accident. In the first case, the rupture was diagnosed 6 years after the trauma. The second case was diagnosed 14 years after the primary trauma. The diaphragmatic rupture was present on the left side in the first case and on the right in the other. Both patients underwent suture of the diaphragmatic defect via thoracotomy., Conclusion: Unrecognized diaphragmatic rupture is a severe condition that can result in a life-threatening complication, namely incarceration of abdominal organs dislocated to the chest. It is necessary to keep this diagnosis in mind in patients with gastrointestinal or respiratory problems after a previous high-energy, blunt-force abdominal and thoracic injury, even many years after the trauma.

Telomerase, an essential enzyme that maintains chromosome ends, is important for genome integrity and organism development. Various hypotheses have been proposed in human, ciliate and yeast systems to explain the coordination of telomerase holoenzyme assembly and the timing of telomerase performance at telomeres during DNA replication or repair. However, a general model is still unclear, especially pathways connecting telomerase with proposed non-telomeric functions. To strengthen our understanding of telomerase function during its intracellular life, we report on interactions of several groups of proteins with the Arabidopsis telomerase protein subunit (AtTERT) and/or a component of telomerase holoenzyme, POT1a protein. Among these are the nucleosome assembly proteins (NAP) and the minichromosome maintenance (MCM) system, which reveal new insights into the telomerase interaction network with links to telomere chromatin assembly and replication. A targeted investigation of 176 candidate proteins demonstrated numerous interactions with nucleolar, transport and ribosomal proteins, as well as molecular chaperones, shedding light on interactions during telomerase biogenesis. We further identified protein domains responsible for binding and analyzed the subcellular localization of these interactions. Moreover, additional interaction networks of NAP proteins and the DOMINO1 protein were identified. Our data support an image of functional telomerase contacts with multiprotein complexes including chromatin remodeling and cell differentiation pathways.

Acylation modifications, such as the succinylation of lysine, are post-translational modifications and a powerful means of regulating protein activity. Some acylations occur nonenzymatically, driven by an increase in the concentration of acyl group donors. Lysine succinylation has a profound effect on the corresponding site within the protein, as it dramatically changes the charge of the residue. In eukaryotes, it predominantly affects mitochondrial proteins because the donor of succinate, succinyl-CoA, is primarily generated in the tricarboxylic acid cycle. Although numerous succinylated mitochondrial proteins have been identified in Saccharomyces cerevisiae, a more detailed characterization of the yeast mitochondrial succinylome is still lacking. Here, we performed a proteomic MS analysis of purified yeast mitochondria and detected 314 succinylated mitochondrial proteins with 1763 novel succinylation sites. The mitochondrial nucleoid, a complex of mitochondrial DNA and mitochondrial proteins, is one of the structures whose protein components are affected by succinylation. We found that Abf2p, the principal component of mitochondrial nucleoids responsible for compacting mitochondrial DNA in S. cerevisiae, can be succinylated in vivo on at least thirteen lysine residues. Abf2p succinylation in vitro inhibits its DNA-binding activity and reduces its sensitivity to digestion by the ATP-dependent ScLon protease. We conclude that changes in the metabolic state of a cell resulting in an increase in the concentration of tricarboxylic acid intermediates may affect mitochondrial functions., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background/aim: The aim of this study was to determine the importance of surgical treatment, utility of hormone receptor status and selected biomarkers in the prognosis of patients with liver metastases from breast cancer (BCLM)., Patients and Methods: Thirty female underwent surgery for BCLM between 1/2000 and 1/2019., Results: The type of surgery (resection/radiofrequency ablation) had no impact on overall survival (OS) - (p=0.894). Having more than one BCLM (p=0.003), expression of human epidermal receptor 2 in metastases (p=0.034), as well as an elevated presurgical level of carbohydrate antigen 19-9 (p=0.017) and postsurgical thymidine kinase (p=0.034) were negative prognostics factor for recurrence-free survival. The factors affecting OS included the number of liver procedures (p=0.021), the degree of proliferative activity (p=0.008) and elevated postsurgical carcinoembryonic antigen level (p=0.038)., Conclusion: The type of surgery had no impact on OS. Markers and hormonal status of liver metastases are important factors affecting prognosis., (Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The lungs are the second most common site of cancer dissemination. The aim of this study was to analyze a cohort of patients operated for pulmonary metastases from colorectal carcinoma over a period of 18 years., Patients and Methods: In a group of 104 patients, relations were sought between overall survival or disease-free survival and preoperative levels of selected biomarkers, number of metastases and the condition of the intrathoracic lymphatic nodes. Median observation period was 63 months., Results: The 5-year survival rate was 54.3%. Risk of disease progression and risk of death increases in case of occurrence of 2 or more metastases, affection of intrathoracic lymph nodes and levels of CA 19-9, TPS or CEA above cut-off value., Conclusion: Prognostic factors that determine overall survival as well as disease-free survival are the number of metastases, the condition of intrathoracic lymphatic nodes and the preoperative levels of biomarkers., (Copyright © 2020 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Mitochondrial DNA (mtDNA) molecules are packaged into compact nucleo-protein structures called mitochondrial nucleoids (mt-nucleoids). Their compaction is mediated in part by high-mobility group (HMG)-box containing proteins (mtHMG proteins), whose additional roles include the protection of mtDNA against damage, the regulation of gene expression and the segregation of mtDNA into daughter organelles. The molecular mechanisms underlying these functions have been identified through extensive biochemical, genetic, and structural studies, particularly on yeast (Abf2) and mammalian mitochondrial transcription factor A (TFAM) mtHMG proteins. The aim of this paper is to provide a comprehensive overview of the biochemical properties of mtHMG proteins, the structural basis of their interaction with DNA, their roles in various mtDNA transactions, and the evolutionary trajectories leading to their rapid diversification. We also describe how defects in the maintenance of mtDNA in cells with dysfunctional mtHMG proteins lead to different pathologies at the cellular and organismal level.

Repetitive DNA sequences and some genes are epigenetically repressed by transcriptional gene silencing (TGS). When genetic mutants are not available or problematic to use, TGS can be suppressed by chemical inhibitors. However, informed use of epigenetic inhibitors is partially hampered by the absence of any systematic comparison. In addition, there is emerging evidence that epigenetic inhibitors cause genomic instability, but the nature of this damage and its repair remain unclear. To bridge these gaps, we compared the effects of 5-azacytidine (AC), 2'-deoxy-5-azacytidine (DAC), zebularine and 3-deazaneplanocin A (DZNep) on TGS and DNA damage repair. The most effective inhibitor of TGS was DAC, followed by DZNep, zebularine and AC. We confirmed that all inhibitors induce DNA damage and suggest that this damage is repaired by multiple pathways with a critical role of homologous recombination and of the SMC5/6 complex. A strong positive link between the degree of cytidine analog-induced DNA demethylation and the amount of DNA damage suggests that DNA damage is an integral part of cytidine analog-induced DNA demethylation. This helps us to understand the function of DNA methylation in plants and opens the possibility of using epigenetic inhibitors in biotechnology., (© 2019 The Authors. The Plant Journal © 2019 John Wiley & Sons Ltd.)

Objectives: Rete testis invasion by germ cell tumors is frequently concomitant with lymphovascular or spermatic cord invasion (LVI/SCI); independent implications for staging are uncertain., Methods: In total, 171 seminomas and 178 nonseminomatous germ cell tumors (NSGCTs; 46 had 1%-60% seminoma component) came from five institutions. Metastatic status at presentation, as a proxy for severity, was available for all; relapse data were unavailable for 152. Rete direct invasion (ReteD) and rete pagetoid spread (ReteP) were assessed., Results: ReteP and ReteD were more frequent in seminoma than NSGCT. In seminoma, tumor size bifurcated at 3 cm or more or less than 3 cm predicted metastatic status. Tumors with ReteP or ReteD did not differ in size from those without invasions but were less than with LVI/SCI; metastatic status or relapse did not show differences. In NSGCT, ReteP/ReteD did not correlate with size, metastatic status, or relapse., Conclusions: Findings support retaining American Joint Committee for Cancer pathologic T1 stage designation for rete testis invasion and pT1a/pT1b substaging of seminoma., (© American Society for Clinical Pathology, 2018. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Clear cell renal cell carcinoma (ccRCC) is the most common kidney tumor. If feasible, metastasectomy is preferably indicated in metastatic disease., Objective: The aim of this study was to determine the outcome of patients after pulmonary metastasectomy (PM)., Methods: PM for ccRCC was performed in 35 patients in the period of January 2001-2019. Clinical characteristics, type of surgery, histopathology results, and follow-up data were recorded. Progression-free survival (PFS) after PM and overall survival (OS) were defined as outcome endpoints., Results: A total of 77 PMs were performed in 35 patients after nephrectomy for ccRCC. The mean size of pulmonary metastasis was 19.0 mm (4-90). With a median follow-up after PM of 79.2 months, the 3- and 5-year OS rates were 63.5 and 44.9%, respectively. The only statistically significant prognostic factor affecting both PFS (p = 0.019) and OS (p = 0.015) was the dimension of pulmonary metastases., Conclusions: The prognosis of metastatic ccRCC is generally poor, particularly in cases of larger size of metastasis. PM might improve the individual prognosis of patients with lung metastasis even in cases with higher number of metastases, bilaterality, synchronous metastasis, or a short progression-free interval after nephrectomy., (© 2019 S. Karger AG, Basel.)

Background Ginkgo biloba extract EGb 761 ® and pentoxifylline are frequently prescribed for the treatment of tinnitus. Objective To compare the treatment effects of Ginkgo biloba extract EGb 761R and pentoxifylline. Setting The study was performed at Department of Otorhinolaryngology of University Hospital Královské Vinohrady and 3rd Medical Faculty, Charles University in Prague. Method Patients with sub-chronic or chronic tinnitus were enrolled in double-blind trial and randomized to receive 120 mg EGb 761 ® or 600 mg pentoxifylline, each twice a day and in double-dummy fashion over a 12-week period. Main outcome measure changes in 11-Point Box Scales for tinnitus loudness and annoyance, the abridged Tinnitus Questionnaire (Mini-TQ), the Hospital Anxiety and Depression Scale (HADS), and the Sheehan Disability Scale (SDS). Results Full analysis set for efficacy analysis comprised 197 patients (EGb 761 ® , 99; pentoxifylline 98). For both treatment groups, significant improvements were observed in the Mini-TQ, the 11-Point Box Scales for tinnitus loudness and annoyance, the HADS anxiety score and the SDS. There was no relevant difference with regard to tinnitus-related outcomes between the two treatment groups. 20 adverse events were documented in EGb 761 ® group and 36 adverse events were reported for pentoxifylline group. No serious adverse event was reported during the study. Conclusion EGb 761 ® and pentoxifylline were similarly effective in reducing the loudness and annoyance of tinnitus as well as overall suffering of the patients. The incidence of adverse events was lower in the EGb 761 ® group.

The article Ginkgo biloba extract EGb 761 ® versus pentoxifylline in chronic tinnitus: a randomized, double-blind clinical trial, written by Klára Procházková, Ivan Šejna, Jan Skutil and Aleš Hahn, was originally published electronically on the publisher's internet portal (currently SpringerLink).

Aim: The aim of this study was to determine the proportion of cystic tumors according to preoperative CT (Bosniak III, IV) among surgically treated patients with histologically confirmed papillary renal cell carcinoma (pRCC) and to assess progression rates among patients with and without cystic appearance on imaging., Methods: A total of 138 patients with pRCC histology surgically treated in the period of January 2007-March 2017 were included. Clinical and radiological characteristics, type of surgery, histopathology results, and follow-up data were recorded and statistically evaluated., Results: Forty-one cases (29.7%) of cystic lesions (10× BIIF, 14× BIII, 17× BIV) were detected by CT. Patients with pRCC1 significantly more frequently presented with cystic appearance on CT (33/78; 42.3%) in comparison to other papillary types (8/60; 13.3%; p = 0.0002). During a median follow-up time of 49.4 months, only 2 patients with cystic lesions progressed after surgery., Conclusions: Cystic appearance on imaging methods is mainly a characteristic of pRCC1 (42.3%). Cystic morphology on imaging might predict a relatively indolent behavior of all pRCC types. Preoperative scoring systems including tumor growth patterns (cystic vs. solid) are needed for further classification., (© 2018 S. Karger AG, Basel.)

The activity of transdermal permeation enhancers is usually evaluated in vitro on human or animal skin, but skin samples can be hard to source and highly variable. To provide a more consistent basis for evaluating the activity of permeation enhancers, we prepared relatively simple and inexpensive artificial membranes that imitate the stratum corneum (SC) lipid matrix. Our membranes were composed of stearic acid, cholesterol, cholesterol sulfate and a ceramide (CER) component consisting of N-2-hydroxystearoyl phytosphingosine (CER[AP]) and/or N-stearoyl phytosphingosine (CER[NP]). First, the permeation of theophylline (TH) and indomethacin (IND) through these membranes was compared with their permeation through porcine skin. Because the mixed CER[AP]/[NP] membrane gave the closest results to skin, this membrane was then used to test the effects of two permeation enhancers: N-dodecyl azepan-2-one (Azone) and (S)-N-acetylproline dodecyl ester (L-Pro2). Both enhancers significantly increased the flux of TH and IND through the skin and, even more markedly, through the lipid membrane, L-Pro2 having a stronger effect than Azone. Thus, our simplified model of the SC lipid membrane based on phytosphingosine CERs appears to be suitable for mimicking skin permeation., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Combined infusions of propofol and sufentanil preparations are frequently used in clinical practice to induce anesthesia and analgesia. However, the stability of propofol emulsions can be affected by dilution with another preparation, sometimes leading to particle coalescence and enlargement. Such unwanted effects can lead to fat embolism syndrome after intravenous application. This study describes the physical stability of 5 commercially available propofol preparations mixed with sufentanil citrate solutions., Methods: Two common markers of emulsion stability were used in this study; namely, the zeta potential and size distribution of the emulsion droplets. Both were measured using dynamic light scattering. The data for the pure propofol preparations and their mixtures with sufentanil citrate solution were compared., Results: The absolute value of zeta potential decreased in 4 of the 5 propofol preparations after they had been mixed with sufentanil citrate. This effect indicates a lowering of repulsive interactions between the emulsion droplets. Although this phenomenon tends to cause agglomeration, none of the studied mixtures displayed a substantial increase in droplet size within 24 hours of blending. However, our long-term stability study revealed the instability of some of the propofol-sufentanil samples. Two of the 5 studied mixtures displayed a continual increase in particle size. The same 2 preparations showed the greatest reductions in the absolute value of zeta potential, thereby confirming the correlation of both measurement methods. The increase in particle size was more distinct in the samples stored at higher temperatures and with higher sufentanil concentrations., Conclusions: To ensure the microbial stability of an emulsion infusion preparation, clinical regulations require that such preparations should be applied to patients within 12 hours of opening. In this respect, we can confirm that during this period, none of the studied propofol-sufentanil mixtures displayed any physical instability that could lead to particle enlargement; thus, fat embolism should not be a risk after their intravenous application. However, our long-term stability study revealed differences between commercially available preparations containing the same active ingredient; some of the mixtures showed an increase in particle size and polydispersity over a longer period. Although our results should not be generalized beyond the particular propofol-sufentanil preparations and concentrations studied here, they do suggest that, as a general principle, a compatibility study should be performed for any preparation before the first intravenous application to exclude the risk of droplet aggregation.

Aim: Papillary renal cell carcinoma type 1 (pRCC1) represents the second most common type of malignant renal epithelial tumour. The origin of its characteristic appearance, its growth mechanism, and the long-term efficiency of its surgical treatment remain uncertain. Our aim was to determine typical characteristics of surgically treated pRCC1., Methods: pRCC1 was verified in 83 of 1,629 (5.1%) kidney tumours surgically treated in the period of January 2007-January 2016. The clinical and radiological characteristics, type of surgery, histopathology results and follow up data were recorded. Spearman correlation, Kruskal-Wallis analysis of variance, Fisher's exact, and chi-square test were used to analyse appropriate variables. The overall survival rate was evaluated using the Gehan-Wilcoxon test and the Cox proportional hazards model., Results: The mean tumour size was 52.0 mm (15-180); 98.8% of the tumours showed a spherical shape and in 82.1%, exophytic growth was observed. Partial nephrectomy was performed in 80.7%. A majority (81.9%) were classified as pT1. Tumours, 89.2% of them, belonged to Fuhrman grade 1 or 2. The mean follow-up was 46.8 months. The overall survival was associated with pT category (p ≤ 0.0001)., Conclusions: Typical signs of pRCC1 are a spherical shape, exophytic growth and low Fuhrman's grade. More than three-fourths of pRCC1 could be treated by the nephron-sparing surgery., (© 2016 S. Karger AG, Basel.)

Introduction: The aim of this article is to generally describe the roles of main surgical modalities in treatment of renal tumors, especially in the CT1a category in clinical practice. Surgical modalities include the following: laparoscopic or open resection (LR, OR) and laparoscopic or open nephrectomy (LN, ON). Representation of these methods has been changing over years due to improved operative skills and equipment and due to a shift of tumors to the lower T categories., Material and Methods: The sources of data were surgeries performed for renal tumors at the institution of the main author during the period 2002 to III/2016, reaching a total of 2204 cases (546 ONs, 647 LNs, 668 ORs and 343 LRs). Patients indicated for percutaneous ablative therapy or active surveillance were not included., Results: During the whole period, the proportions of methods were: ONs 24.8%, LNs 29.4%, ORs 30.3%, LRs 15.6%. But during the years 2014 - III/2016, these changed to 12.6%:26.3%:31.6%:29.4% (in cT1a 1.7%:8.3%:37.8%:52.2%). Category cT1a constitutes in the years 2007 - III/2016 41.3%, in 2014 - III/2016 50.9%., Conclusions: Resections and minimally invasive approaches are being performed more frequently and are the preferred methods in surgical treatment of kidney tumors. Resection is now indicated in about 60% of cases (open vs. laparoscopic resection are used nearly equally with a slight tendency for laparascopic predomination). In the cT1a category (amounting to approximately 50% of all surgically treated tumors), resection is possible in about 85-90% of cases., Competing Interests: The authors declare no conflicts of interest.

Lens epithelium-derived growth factor (LEDGF/p75) is an epigenetic reader and attractive therapeutic target involved in HIV integration and the development of mixed lineage leukaemia (MLL1) fusion-driven leukaemia. Besides HIV integrase and the MLL1-menin complex, LEDGF/p75 interacts with various cellular proteins via its integrase binding domain (IBD). Here we present structural characterization of IBD interactions with transcriptional repressor JPO2 and domesticated transposase PogZ, and show that the PogZ interaction is nearly identical to the interaction of LEDGF/p75 with MLL1. The interaction with the IBD is maintained by an intrinsically disordered IBD-binding motif (IBM) common to all known cellular partners of LEDGF/p75. In addition, based on IBM conservation, we identify and validate IWS1 as a novel LEDGF/p75 interaction partner. Our results also reveal how HIV integrase efficiently displaces cellular binding partners from LEDGF/p75. Finally, the similar binding modes of LEDGF/p75 interaction partners represent a new challenge for the development of selective interaction inhibitors.

In Bacillus subtilis, the arabinose repressor AraR negatively controls the expression of genes in the metabolic pathway of arabinose-containing polysaccharides. The protein is composed of two domains of different phylogenetic origin and function: an N-terminal DNA-binding domain belonging to the GntR family and a C-terminal effector-binding domain that shows similarity to members of the GalR/LacI family. The crystal structure of the C-terminal effector-binding domain of AraR in complex with the effector L-arabinose has been determined at 2.2 Å resolution. The L-arabinose binding affinity was characterized by isothermal titration calorimetry and differential scanning fluorimetry; the K(d) value was 8.4 ± 0.4 µM. The effect of L-arabinose on the protein oligomeric state was investigated in solution and detailed analysis of the crystal identified a dimer organization which is distinctive from that of other members of the GalR/LacI family.

Repeats-in-toxin (RTX) exoproteins of Gram-negative bacteria form a steadily growing family of proteins with diverse biological functions. Their common feature is the unique mode of export across the bacterial envelope via the type I secretion system and the characteristic, typically nonapeptide, glycine- and aspartate-rich repeats binding Ca(2+) ions. In this review, we summarize the current state of knowledge on the organization of rtx loci and on the biological and biochemical activities of therein encoded proteins. Applying several types of bioinformatic screens on the steadily growing set of sequenced bacterial genomes, over 1000 RTX family members were detected, with the biological functions of most of them remaining to be characterized. Activities of the so far characterized RTX family members are then discussed and classified according to functional categories, ranging from the historically first characterized pore-forming RTX leukotoxins, through the large multifunctional enzymatic toxins, bacteriocins, nodulation proteins, surface layer proteins, up to secreted hydrolytic enzymes exhibiting metalloprotease or lipase activities of industrial interest.

Clinical isolates of Neisseria meningitidis produce a repeat in toxin (RTX) protein, FrpC, of unknown biological activity. Here we show that physiological concentrations of calcium ions induce a novel type of autocatalytic cleavage of the peptide bond between residues Asp(414) and Pro(415) of FrpC that is insensitive to inhibitors of serine, cysteine, aspartate, and metalloproteases. Moreover, as a result of processing, the newly generated amino-terminal fragment of FrpC can be covalently linked to another protein molecule by a novel type of Asp-Lys isopeptide bond that forms between the carboxyl group of its carboxyl-terminal Asp(414) residue and the epsilon-amino group of an internal lysine of another FrpC molecule. Point substitutions of negatively charged residues possibly involved in calcium binding (D499K, D510A, D521K, and E532A) dramatically reduced the self-processing activity of FrpC. The segment necessary and sufficient for FrpC processing was localized by deletion mutagenesis within residues 400-657, and sequences homologous to this segment were identified in several other RTX proteins. The same type of calcium-dependent processing and cross-linking activity was observed also for the purified ApxIVA protein of Actinobacillus pleuropneumoniae. These results define a protein cleavage and cross-linking module of a new class of RTX proteins of Gram-negative pathogens of man, animals, and plants. In the calcium-rich environments colonized by these bacteria this novel activity is likely to be of biological importance.