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Purpose: To compare the two most used digital alignment systems regarding precision, repeatability and loss of track., Methods: 15 eyes of 15 patients older than 21 years with cataracts were included in this prospective study. The two systems were intraoperatively superimposed and recorded, and the alignment of the two displayed alignment axes was analysed regarding precision, repeatability and loss of track., Results: There was a significant difference in precision and repeatability between the two digital alignment systems regarding the projected alignment axis. The deviation from the actual target axis was significantly different, with a mean of 0.34°±0.75° for the Zeiss system and 1.60°±1.08° for the Alcon system (p=0.03, n=14). The within-subject SD was significantly lower with 0.21° for the Zeiss system and 0.34° for the Alcon system (p=0.03, n=14)., Conclusions: The Zeiss Callisto system showed a significantly lower deviation from the target axis, higher stability with eye movements and less need for microscope illumination than the Alcon system. Both systems showed high precision when compared with manual marking methods., Trial Registration Number: NCT05220683., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Although cognitive control and flexibility have been examined in the past, this study examines their relationship in a stressful working environment, focusing on intrinsic job satisfaction using cognitive behavioral theory as a framework. This study examined cognitive factors (cognitive control and cognitive flexibility) and emotional state (intrinsic job satisfaction) while assessing the mediating role of social isolation, an external work environment variable. The study focused on intrinsic job satisfaction with extrinsic job satisfaction as a covariate. A cross-sectional questionnaire method was used. Two hundred and ten nurses from twelve intensive care units participated. Model one examined cognitive control while model two examined cognitive flexibility, accounting for 32% and 38% of the variance in intrinsic job satisfaction, respectively. Model one accounted for 13% of the variance in social isolation through cognitive control and extrinsic job satisfaction while model two accounted for approximately 14.91% of the variance in social isolation through cognitive flexibility and extrinsic job satisfaction. Combining the two models accounted for 17% of the variance in social isolation and 37.4% of the variation in intrinsic job satisfaction. The results emphasize the importance of training nurses in cognitive control and flexibility to increase intrinsic job satisfaction.

Background: With the rapid improvement in healthcare technologies, the security and privacy of the most sensitive data are at risk. Patient privacy has many components, even when data are in electronic format. Although patient privacy has extensively been discussed in the literature, there is no study that has presented all components of patient privacy., Methods: This study presents a complete assessment framework, develops an inventory as an assessment tool, and examines the reliability and validity of the inventory. The study was carried out in three phases: conceptual framework development, inventory development, and an evaluation case study. Fuzzy conjoint analysis was used in the evaluation to deal with subjectivity and ambiguity. As a result of the evaluation, the case study institution was given a patient privacy maturity level between 1 and 5, where 1 is the worst and 5 is the best., Results: The case study evaluated the largest hospital in Turkey, which employs 800 nurses. Half of the nurses, 400, participated in the study. According to the literature, healthcare institutions do not invest enough in protecting patients' privacy, and the results of the study support this finding. The institution's maturity level was 2, which is poor., Conclusions: This study measured privacy maturity with many assessment components. The result of the assessment explains to patients and the public whether their data are secure or not. With the implementation of this maturity level, patients have an idea about which institution to choose, and the public can infer the reliability of institutions in terms of patient privacy.

Modular Cloning (MoClo) is based on libraries of standardized genetic parts that can be directionally assembled via Golden Gate cloning in one-pot reactions into transcription units and multigene constructs. Here, a team of bachelor students established a MoClo toolkit for the protist Leishmania tarentolae in the frame of the international Genetically Engineered Machine (iGEM) competition. Our modular toolkit is based on a domesticated version of a commercial LEXSY expression vector and comprises 34 genetic parts encoding various affinity tags, targeting signals as well as fluorescent and luminescent proteins. We demonstrated the utility of our kit by the successful production of 16 different tagged versions of the receptor binding domain (RBD) of the SARS-CoV-2 spike protein in L. tarentolae liquid cultures. While highest yields of secreted recombinant RBD were obtained for GST-tagged fusion proteins 48 h post induction, C-terminal peptide tags were often degraded and resulted in lower yields of secreted RBD. Fusing secreted RBD to a synthetic O -glycosylation SP20 module resulted in an apparent molecular mass shift around 10 kDa. No disadvantage regarding the production of RBD was detected when the three antibiotics of the LEXSY system were omitted during the 48-h induction phase. Furthermore, the successful purification of secreted RBD from the supernatant of L. tarentolae liquid cultures was demonstrated in pilot experiments. In summary, we established a MoClo toolkit and exemplified its application for the production of recombinant proteins in L. tarentolae ., Competing Interests: Conflict of Interest: The authors declare that there are no conflicts of interest., (Copyright: © 2024 Hieronimus et al.)

Introduction: Cataract surgery is a relatively safe procedure with satisfactory postoperative results in most patients. However, in rare cases severe complications can occur shortly after the intervention. Therefore, patients are advised to undergo an ophthalmological examination postoperatively, which should be performed as soon as possible in case of emergencies. However, exactly when these follow-up visits should take place is still discussed. A time- and cost-saving alternative to this could be short-term postoperative telemedical approaches. The aim of this study was to analyze patient complaints as well as satisfaction with and the best timepoint to perform telephone calls after cataract surgery., Methods: Patients scheduled for cataract surgery received a telephone call on the surgery day or the day after (study group) during which they were asked about complaints or additional examination visits. Patients without telephone calls served as control group. All patients had a follow-up visit one week after the intervention during which a questionnaire was filled out and the study group was asked about their satisfaction with the telephone calls., Results: 181 patients were recruited in this study. Ocular surface problems were the most common postoperative symptom. More than 80% of the patients were very satisfied with the telephone calls, with patients being contacted on the day of surgery being more calmed than those called on the next day. No difference in additional and planned follow-up visits was found between the study and the control group (P > .40). Postoperative patient complaints (Phi 0.372, P < .001) and additional prescribed therapy (Phi 0.480, P < .001) were moderately associated with additional visits., Conclusion: Satisfaction with telephone reviews shortly after cataract surgery was very high and contacting patients on the evening of the day of the procedure could be a time- and cost-saving alternative to short-term in-house follow-up visits., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ruiss et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: To analyse the outcome of coronary artery bypass grafting (CABG) in octogenarians with coronary multivessel disease and the impact of different graft strategies and other factors., Methods: Out of 1654 patients with multivessel disease who underwent CABG at our institution between January 2014 and March 2020, we investigated 225 consecutive patients with a median age of 82.1 years for survival prediction and need for coronary reintervention; a detailed outcome analysis was performed., Results: At mean follow-up of 3.3 years, the overall survival was 76.4%. An indication for emergency operation (p = 0.002), age (p <0.001), chronic pulmonary disease (p = 0.024), and reduced renal or ventricular function (p <0.001) had the highest impact on limited survival. The combination outcome of survival and coronary reintervention was 1.7-fold improved (p = 0.024) after use of the bilateral internal thoracic artery (BITA) (66.2%). Off-pump CABG (12%) revealed no impact on survival. Smokers showed a poorer outcome (p = 0.004). The logistic European System for Cardiac Operative Risk Evaluation was highly effective for evaluating long-term outcomes (p <0.001)., Conclusions: BITA grafting normalizes survival and reveals a better outcome in octogenarians with multivessel disease. However, patients at risk of poorer survival were operated under emergency conditions and those with pulmonary disease and reduced ventricular or renal function.

Introduction: Treatment-refractory, acute graft- versus -host disease (GvHD) of the lower gastrointestinal tract (GI) after allogeneic hematopoietic stem cell transplantation is life threatening and lacks effective treatment options. While fecal microbiota transplantation (FMT) was shown to ameliorate GI-GvHD, its mechanisms of action and the factors influencing the treatment response in humans remain unclear.The objective of this study is to assess response to FMT treatment, factors influencing response, and to study the mucosal immune cell composition in treatment-refractory GI-GvHD., Methods: Consecutive patients with treatment-refractory GI-GvHD were treated with up to six endoscopically applied FMTs., Results: We observed the response to FMT in four out of nine patients with severe, treatment refractory GI-GvHD, associated with a significant survival benefit ( p  = 0.017). The concomitant use of broad-spectrum antibiotics was the main factor associated with FMT failure ( p  = 0.048). In addition, antibiotic administration hindered the establishment of donor microbiota after FMT. Unlike in non-responders, the microbiota characteristics (e.g. α- and β-diversity, abundance of anaerobe butyrate-producers) in responders were more significantly similar to those of FMT donors. During active refractory GI-GvHD, an increased infiltrate of T cells, mainly Th17 and CD8 + T cells, was observed in the ileocolonic mucosa of patients, while the number of immunomodulatory cells such as regulatory T-cells and type 3 innate lymphoid cells decreased. After FMT, a change in immune cell patterns was induced, depending on the clinical response., Conclusion: This study increases the knowledge about the crucial effects of antibiotics in patients given FMT for treatment refractory GI-GvHD and defines the characteristic alterations of ileocolonic mucosal immune cells in this setting., Competing Interests: Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: W.S. received speakers’ fees from Oesterreichische Gesellschaft fuer Gastroenterologie und Hepatologie, Aerztekammer fuer Steiermark, and AbbVie and received travel support from Boston Scientific. B.H.-K. received support for participation in meetings from Teva Ratiopharm, Novartis, Neovii, Celgene, Takeda, and Gilead. E.S. received Congress support from Amgen, Incyte, Jazz, Janssen, Novartis, Roche, and Takeda; participated in advisory boards of Amgen and Celgene; and received honoraria from Amgen and Novartis. B.U. was supported by a Research Grant of the Austrian Society of Hematology & Medical Oncology and received support for participation in conferences from Neovii, Novartis, Sanofi, Sobi, and Takeda. P.N. participated in advisory boards or had consultancy with and received honoraria from AbbVie, Takeda, BMS/Celgene, and Janssen. P.K. received research funding from Bristol Meyer Squibb and Ipsen and participated in advisory boards and received honoraria from Janssen, Ipsen, Novartis, AbbVie, Takeda, Gebro, Merck Sharp & Dohme (MSD), and Pfizer. H.G. received honoraria for presentations in scientific meetings and consultations from Novartis, Celgene/ Bristol-Myers Squibb (BMS), Janssen, Sanofi, and Therakos. CH received a research grant from Seres Therapeutics. B.H., N.B., V.B., L.K., A.D., L.G., S.H., G.G., and G.S. declare that they have no conflict of interest. The authors declare that none of the mentioned relationships were related to the development and the content of this article., (© The Author(s), 2021.)

Graft-versus-host disease (GVHD) is the leading cause of mortality after hematopoietic stem cell transplantation and primarily affects barrier organs such as the skin. One-third of cases are refractory to steroid treatment resulting in poor outcomes and the need for novel therapies. Longitudinal analysis of T-cell transcriptomes in patients before the appearance of GVHD symptoms revealed the upregulation of anti-apoptotic regulator B-cell lymphoma 2 (BCL2) at GVHD initiation. To determine the potential of BCL2 inhibition in active GVHD, we analyzed tissues of 88 patients with acute or chronic GVHD. BCL2 RNA was elevated in multiple organs affected by GVHD and expression correlated with transplant-related mortality and steroid-refractory GVHD. BCL2-expressing lymphocytes were present in skin lesions and peripheral blood of patients with acute and chronic GVHD. Inhibition of BCL2 increased the CD4 to CD8 ratio in allogeneic T cells in vitro and induced apoptosis of T cells from patients with steroid-pretreated chronic GVHD ex vivo. In addition, the higher ratio of regulatory to nonregulatory T cells upon blockage of BCL2 could add to the anti-inflammatory effect of BCL2 blockage. Collectively, our results highlight BCL2 as an important factor for GVHD development and introduce BCL2 inhibition as previously unreported and urgently needed targeted therapy in the treatment of steroid-refractory GVHD., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Bilateral internal mammary artery (BIMA) in coronary artery bypass grafting (CABG) has traditionally been limited. This review looks at the recent outcome data on BIMA in CABG focusing on the management of risk factors for mediastinitis, one of the potential barriers for more extensive BIMA utilization. A combination of pre-, intra- and postoperative strategies are essential to reduce mediastinitis. Limited data indicate that the incidence of mediastinitis can be reduced using closed incision negative-pressure wound therapy as a part of these strategies with the possibility of offering patients best treatment options by extending BIMA to those with a higher risk of mediastinitis. Recent economic data imply that the technology may challenge the current low uptake of BIMA by reducing the short-term cost differentials between single internal mammary artery and BIMA. Given that most published randomized controlled trials and meta-analyses of observational long-term outcome data favor BIMA, if short-term complications of BIMA including mediastinitis can be controlled adequately, there may be opportunities for more extensive use of BIMA leading to improved long-term outcomes. An ongoing study looking at BIMA in high-risk patients may provide evidence to support the hypothesis that mediastinitis should not be a factor in limiting the use of BIMA in CABG.

Background: The study was performed to analyze the results of open-heart surgery and bleeding complications after administration of novel oral anticoagulants (NOAC)., Methods: We investigated 81 consecutive patients (median age 74 years, interquartile range [IQR]: 68 to 78) who underwent open-heart operations at our institution between July 2014 and June 2016. All patients presented for surgery while on NOAC therapy: 37 received rivaroxaban (45.7%), 35 apixaban (43.2%), and 9 dabigatran (11.1%). The calculated risk using the European System for Cardiac Operative Risk Evaluation II was 3.5% (IQR: 2.0% to 8.1%)., Results: Surgery was performed at a median 4 days (IQR: 3 to 6) after NOAC withdrawal. Reduced renal function was predictive for length of intensive care unit stay and administration of red blood cells (p < 0.0001 and p = 0.0291, respectively). The NOAC withdrawal interval significantly influenced postoperative drainage volume (p = 0.0056). Five patients needed rethoracotomy because of relevant bleeding (6.2%), 4 after apixaban (11.4%) and 1 after rivaroxaban therapy (2.7%). Apixaban showed a borderline influence on prolonged intensive care unit stay (p = 0.0736). Prolonged cardiopulmonary bypass time was predictive for thrombocyte administration (p = 0.0249). Intensive care unit stay was 2 days after NOAC withdrawal of 10 days, compared with 4.2 days without termination. Thirty-day mortality was 3.7%., Conclusions: A lengthy NOAC withdrawal period, particularly for patients with reduced renal function, is essential for safe open-heart surgery. We conclude that despite official recommendations, patients should whenever possible not be considered for elective cardiac surgery within 10 days of terminating NOAC treatment., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to determine the behaviours of students studying dialysis and health personnel working at dialysis centers and the influencing factors., Methods: Students studying dialysis department at Turgut Özal University (n=70) and healthcare personnel working at eight Dialysis Centers located in the center of Ankara (n=83) were recruited. Data was collected from personal information forms and Healthy Life Style Behaviours (HLSB)-II scale. Data were analysed Student's t test, Man Whitney U test, Kruskal Wallis Test and Pearson correlation analysis; p.

Posttranslational modification of the neural cell adhesion molecule (NCAM) by polysialic acid (polySia) is well studied in the nervous system and described as a dynamic modulator of plastic processes like precursor cell migration, axon fasciculation, and synaptic plasticity. Here, we describe a novel function of polysialylated NCAM (polySia-NCAM) in innate immunity of the lung. In mature lung tissue of healthy donors, polySia was exclusively attached to the transmembrane isoform NCAM-140 and located to intracellular compartments of epithelial cells. In patients with chronic obstructive pulmonary disease, however, increased polySia levels and processing of the NCAM carrier were observed. Processing of polysialylated NCAM was reproduced in a mouse model by bleomycin administration leading to an activation of the inflammasome and secretion of interleukin (IL)-1β. As shown in a cell culture model, polySia-NCAM-140 was kept in the late trans-Golgi apparatus of lung epithelial cells and stimulation by IL-1β or lipopolysaccharide induced metalloprotease-mediated ectodomain shedding, resulting in the secretion of soluble polySia-NCAM. Interestingly, polySia chains of secreted NCAM neutralized the cytotoxic activity of extracellular histones as well as DNA/histone-network-containing "neutrophil extracellular traps", which are formed during invasion of microorganisms. Thus, shedding of polySia-NCAM by lung epithelial cells may provide a host-protective mechanism to reduce tissue damage during inflammatory processes.

Background and Purpose: Weekend admissions are associated with higher in-hospital mortality. However, limited information is available concerning the "weekend effect" on stroke mortality. Our aim was to evaluate the impact of weekend admissions on stroke mortality in different settings., Methods: We analyzed all hospital admissions for ischemic stroke from April 2003 to March 2004 through the Hospital Morbidity Database. The Hospital Morbidity Database is a national database that contains patient-level sociodemographic, diagnostic, procedural, and administrative information including all acute care facilities across Canada. The major inclusion criterion was admission to an acute care facility with a principal diagnosis of ischemic stroke. Clinical variables and facility characteristics were included in the analysis., Results: Overall, 26,676 patients were admitted to 606 hospitals for ischemic stroke. Weekend admissions comprised 6629 (24.8%) of all admissions. Seven-day stroke mortality was 7.6%. Weekend admissions were associated with a higher stroke mortality than weekday admissions (8.5% vs 7.4%; odds ratio, 1.17; 95% CI, 1.06 to 1.29). Mortality was similarly affected among patients admitted to rural versus urban hospitals or when the most responsible physician was a general practitioner versus specialist. In the multivariable analysis, weekend admissions were associated with higher early mortality (odds ratio, 1.14; 95% CI, 1.02 to 1.26) after adjusting for age, sex, comorbidities, and medical complications., Conclusions: Stroke patients admitted on weekends had a higher risk-adjusted mortality than did patients admitted on weekdays. Disparities in resources, expertise, and healthcare providers working during weekends may explain the observed differences in weekend mortality.

The effect of virus uncoating on endosome integrity during the early steps in viral infection was investigated. Using fluid-phase uptake of 10- and 70-kDa dextrans labeled with a pH-dependent fluorophore (fluorescein isothiocyanate [FITC]) and a pH-independent fluorophore (cyanine 5 [Cy5]), we determined the pHs of labeled compartments in intact HeLa cells by fluorescence-activated cell sorting analysis. Subsequently, the number and pH of fluorescent endosomes in cell homogenates were determined by single-organelle flow analysis. Cointernalization of adenovirus and 70-kDa FITC- and Cy5-labeled dextran (FITC/Cy5-dextran) led to virus-induced endosomal rupture, resulting in the release of the marker from the low-pH environment into the neutral cytosol. Consequently, in the presence of adenovirus, the number of fluorescent endosomes was reduced by 40% compared to that in the control. When human rhinovirus serotype 2 (HRV2) was cointernalized with 10-and 70-kDa FITC/Cy5-dextrans, the 10-kDa dextran was released, whereas the 70-kDa dextran remained within the endosomes, which also maintained their low pH. These data demonstrate that pores are generated in the membrane during HRV2 uncoating and RNA penetration into the cytosol without gross damage of the endosomes; 10-kDa dextran can access the cytosol through these pores. Whereas rhinovirus-mediated pore formation was prevented by the vacuolar ATPase inhibitor bafilomycin A1, adenovirus-mediated endosomal rupture also occurred in the presence of the inhibitor. This finding is in keeping with the low-pH requirement of HRV2 infection; for adenovirus, no pH dependence for endosomal escape was found with this drug.

Many viruses gain access to the cell via the endosomal route and require low endosomal pH for infectivity. The GTPase dynamin is essential for clathrin-dependent endocytosis, and in HeLa cells overexpressing the nonfunctional dynaminK44A mutant the formation of clathrin-coated vesicles is halted. HRV2, a human minor group rhinovirus, is internalized by members of the low-density lipoprotein receptor family in a clathrin-independent manner. The low endosomal pH then leads to conversion of the capsid to C-antigen, which is required for release (uncoating) and transfer of the viral RNA into the cytosol and de novo synthesis of infectious virus. We here demonstrate that overexpression of dynaminK44A reduces this antigenic conversion and results in diminished viral synthesis. In contrast, lysosomal degradation is unaffected. The kinetics of the formation of C-antigen in vitro and in vivo suggest that the pH in endosomes is elevated by about 0.4 units upon overexpression of dynaminK44A. As a consequence, HRV2 uncoating is diminished early after internalization but attains control levels upon prolonged internalization. Thus, overexpression of dynaminK44A, in addition to trafficking defects, results in an elevated endosomal pH and thereby affects virus infection and most likely endosomal sorting and processing.

Minor group human rhinoviruses (exemplified by human rhinovirus serotype 2 (HRV2)) use members of the low density lipoprotein receptor family for cell entry; all these receptors possess clathrin-coated pit localization signals. Viral infection should thus be inhibited under conditions of impaired clathrin-mediated endocytosis. However, Madshus et al. reported an increase in the cytopathic effect of HRV2 infection in HEp-2 cells upon suppression of clathrin-dependent endocytosis by hypotonic shock and potassium depletion (Madshus, I. H., Sandvig, K., Olsnes, S., and van Deurs, B. (1987) J. Cell. Physiol. 131, 14-22.) To resolve this apparent contradiction, we investigated the binding, internalization, conformational changes, and productive uncoating of HRV2 in HeLa cells subjected to hypotonic shock and potassium depletion. This treatment led to an increase in HRV2 binding, with internalization being barely affected. The generation of C-antigenic particles requiring pH

Bafilomycin A1 (baf), a specific inhibitor of vacuolar proton ATPases, is commonly employed to demonstrate the requirement of low endosomal pH for viral uncoating. However, in certain cell types baf also affects the transport of endocytosed material from early to late endocytic compartments. To characterize the endocytic route in HeLa cells that are frequently used to study early events in viral infection, we used 35S-labeled human rhinovirus serotype 2 (HRV2) together with various fluid-phase markers. These virions are taken up via receptor-mediated endocytosis and undergo a conformational change to C-antigenic particles at a pH of <5.6, resulting in release of the genomic RNA and ultimately in infection (E. Prchla, E. Kuechler, D. Blaas, and R. Fuchs, J. Virol. 68:3713-3723, 1994). As revealed by fluorescence microscopy and subcellular fractionation of microsomes by free-flow electrophoresis (FFE), baf arrests the transport of all markers in early endosomes. In contrast, the microtubule-disrupting agent nocodazole was found to inhibit transport by accumulating marker in endosomal carrier vesicles (ECV), a compartment intermediate between early and late endosomes. Accordingly, lysosomal degradation of HRV2 was suppressed, whereas its conformational change and infectivity remained unaffected by this drug. Analysis of the subcellular distribution of HRV2 and fluid-phase markers in the presence of nocodazole by FFE revealed no difference from the control incubation in the absence of nocodazole. ECV and late endosomes thus have identical electrophoretic mobilities, and intraluminal pHs of <5.6 and allow uncoating of HRV2. As bafilomycin not only dissipates the low endosomal pH but also blocks transport from early to late endosomes in HeLa cells, its inhibitory effect on viral infection could in part also be attributed to trapping of virus in early endosomes which might lack components essential for uncoating. Consequently, inhibition of viral uncoating by bafilomycin cannot be taken to indicate a low pH requirement only.