Development of clinical items to identify dysphagia in patients with dementia-An e-Delphi study.

AIM: To identify clinical observable items that can be used to identify dysphagia while observing a typical eating situation. DESIGN: A three-round e-Delphi survey. METHODS: An expert panel consisting of five nurses, eight speech language therapists and five physicians participated in this three-round e-Delphi survey from November 2022 to January 2023. Round 1 presented the results of a literature research conducted in September 2022 and an open question to the participants. The answers were analysed using the content analysis method. In the following rounds, the results were presented back to the participants with a request to rate them for usefulness. Means, standard deviations, ANOVA and Fisher's exact test were used to demonstrate the panel's opinion, level of agreement, demographic characteristics of the participants as well as differences between the professional groups in regard of the rating of the items. Methods and results are reported in accordance with the 'Guidance on Conducting and Reporting Delphi Studies' (CREDES). RESULTS: The content analysis initially generated 36 items suggested by the expert panel. Seven additional items were incorporated from the literature review. In rounds 2 and 3, a 4-point Likert scale was used to rate each item and to calculate the level of agreement. The predetermined level of agreement exceeded 70% for 23 items. CONCLUSION: Based on the expert opinions, it is possible for nurses to identify dysphagia in patients with dementia by using the determined 23 items while observing a typical eating situation. PATIENT OR PUBLIC CONTRIBUTIONS: The expert panel contributed to the creation of this study by participating in the Delphi rounds. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: The 23 items determined in this e-Delphi study enable nurses to make dietary adjustments or consult other members of the multidisciplinary team based on available evidence, enabling complications to be avoided. IMPACT: What problem did the study address? This study provides evidence regarding the identification of dysphagia in patients with dementia by nurses. What were the main findings? Twenty-three items were determined by an expert panel that can be used by nurses to identify dysphagia in patients with dementia while observing a typical eating situation. Where and on whom will the research have an impact? This research will have an impact on patients with dementia and the nurses caring for them. REPORTING METHOD: Methods and results are reported in accordance with the 'Guidance on Conducting and Reporting Delphi Studies' (CREDES) (Jünger et al., 2017), which promotes consistency and quality in conducting Delphi studies.

Nursing Professional Values Scale (NPVS-3) in an Austrian context: validation of a scale and reliability assessment.

BACKGROUND: The Nurses Professional Values Scale-3 (NPVS-3) is a psychometric instrument derived from a set of values initially established by the American Nurses Association (ANA) Code of Ethics. The present study evaluates the reliability of the NPVS-3 scale for nursing students and nurses in Austria. METHODS: A cross-sectional methodological study was conducted on 209 research participants, comprising 139 nursing students and 70 nurses, with the objective of determining the reliability of the Austrian version of the scale. A multilevel approach was employed in the study, encompassing cultural and linguistic validation, content validity, face validity, and construct validity. The scale translation was performed per the established translation stages of back-translation and was subsequently reviewed by an expert committee. The translated instrument was applied to the participants who completed an online survey between April and July 2023. Internal consistency was evaluated using Cronbach's alpha, while construct validity was assessed using confirmatory factor analysis (CFA). RESULTS: The Cronbach's alpha values obtained were deemed appropriate, with the following results: Caring (0.852), Activism (0.832), and Professionalism (0.676). Through factorial analysis, three factors were identified as original NPVS-3 and construct validity was verified. CONCLUSION: The Austrian version of the NPVS-3 demonstrated satisfactory validity, efficiently evaluating the professional values of nurses and nursing students in Austria.

Implementation and evaluation of an individualized physical exercise promotion program in people with manifested risk factors for multimorbidity (MultiPill-Exercise): a study protocol for a pragmatic randomized controlled trial.

BACKGROUND: Multimorbidity is a major problem in Europe, increasing the need for prevention and rehabilitation programs. In Germany no guidelines have been developed that focus on patients with multiple chronic non-communicable diseases (NCDs). Benefits of physical activity (PA) and exercise in NCDs have been proven, but most interventions focus on single conditions. The evaluation of the effectiveness, efficiency and safety of PA programs in patients suffering from multiple NCDs and the feasibility of the implementation within the health care service remain open research questions. METHODS: The multi-site randomized controlled pragmatic trial includes 320 sedentary subjects with at least two of the following NCDs, either manifested or in a pre-stage with evident risk factors: Cardio-vascular disease, Diabetes mellitus type 2, knee/ hip osteoarthritis and obesity. Participants will be recruited from general practitioners and medical specialists and randomized to standard care of a statutory health insurance or MultiPill-Exercise. Standard care includes a choice of one or a maximum of two 8- to 12-week health programs, including nutrition, exercise, relaxation or special disease management programs. MultiPill-Exercise is based on the bio-psycho-social health model, considering a person-oriented perspective in light of given individual characteristics and context factors. The 24-weeks intervention focuses on aerobic and strengthening exercises in line with the WHO PA recommendations. Psychological and pedagogical elements along with behavior change techniques are implemented to ease the initiation and maintenance of exercise participation and lifestyle change, including nutrition. Primary outcome will be short- and long-term PA measured with the European Health Interview Survey-Physical Activity Questionnaire (EHIS-PAQ). Secondly, the effectiveness of the program on generic, disease specific, economic, and exercise behavioral parameters, as well as program adherence and safety will be evaluated. DISCUSSION: Results of this trial evaluate the PA intervention program in people with multiple NCDs in a real-life scenario. It will serve as a proof of concept with the opportunity of translation into routine practice. This approach, as a multi-site RCT with its rigorous methods and standardized operating procedures for the conduction of the intervention, will allow valid conclusions for the implementation of PA interventions in people with multimorbidity. TRIAL REGISTRATION: The trial was registered at www.drks.de (ID: DRKS00025033 ) on 30th September 2021.

[Psychological Stress and its Consequences for the Cost of Illness: a Longitudinal Study in Germany]. / Psychische Belastung und ihre Folgen für die Krankheitskosten ­ eine Längsschnittstudie in Deutschland.

OBJECTIVE: The aim of this study was to examine the effects of mental illness on the level and composition of medical costs (outpatient costs, hospital costs, rehabilitation costs, drug costs) over time. METHOD: In a longitudinal design, we examined the psychological distress of 3,287 study participants from the adult general population using the Hospital Anxiety and Depression Scale (HADS) and its effect on the level and composition of medical costs resulting from mental illness in the year of survey t0 and the two subsequent years [t1] {t2}. RESULTS: Compared to the reference group with no mental distress, the cost of illness was significantly increased by a factor of 2.0 [2.2] {1.5} in the low mental distress group, by a factor of 3.7 [4.2] {3.1} in those with moderate mental distress, and by a factor of 7.5 [9.0] {5.2} in those with severe mental distress. Over time, significant effects on illness costs appeared only at the two outer edges of psychological distress levels (no and severe distress levels). As the level of mental distress increased, hospital costs dominated total costs due to mental distress and the proportion of outpatient medical costs in total costs decreased. CONCLUSIONS: The costs of illness rise steeply with the degree of mental stress. Preventing the progression of mental illness is therefore important not only from an individual but also from a health economic perspective.

Protein Phosphatases: A Neglected Target Family for Drug Discovery.

The gene family of protein phosphatases is a rich but under-exploited source of therapeutically validated drug targets modulating signal transduction pathways. Unlike the kinase family, research and development activities have not yet yielded any approved small-molecule drugs against a phosphatase. Approximately 20 years ago, the phosphatase family was classified as undruggable and intractable. This was primarily due to the spectacular failure of the cumulated industry-wide drug discovery efforts to develop PTP1B inhibitors. Recently, allosteric inhibitors against SHP2, a member of the phosphatase family, have entered clinical trails, which has reawakened industry's interest towards this neglected enzyme family. This contribution reviews the recent R&D trends around small-molecule efforts towards phosphatase modulators over the last years, rather than providing an exhaustive review of the field of allosteric phosphatase inhibitors.

The social and spiritual dimensions of parental experiences on end-of-life care of their child with cancer: A narrative review.

OBJECTIVE: Having a child with cancer is a burdensome experience for parents. Nurses need to better understand beliefs, hopes, and values of parents to holistically support them, which may have an impact on grief and depression. Thus, the aim of this paper was to highlight the social and spiritual dimensions of parental experiences on end-of-life care of their child with cancer. METHOD: A narrative literature review was conducted by systematically searching databases (CINAHL Complete, Academic Search Elite, MEDLINE) for relevant literature. The contents of included studies were critically appraised regarding their methodological quality. RESULTS: Eleven studies were included. In terms of the social dimension, three categories emerged that are important for parents: Being a Parent, Being in Relationship with the Child, and Being in Relationship with Health Professionals. Parents tried to maintain normality and joy for their child, but also kept control over the situation. They wanted to protect their child from suffering but also felt the need to talk to them about dying. Parents had ambivalent experiences with helpful but also burdensome staff. The spiritual dimension comprised two main categories, Hope and Faith and a Unique Bond. Hope was found to be an important source of strength, while Faith was only mentioned by some parents. For parents the emotional connection with their child constituted a source of meaning as well as a foundation, on which they based their decisions on. SIGNIFICANCE OF RESULTS: A therapeutic relationship and a supportive environment can be established by healthcare professionals by noticing, encouraging the unique bond between parents and their children, as well as by reflecting and addressing the parents' challenging situation.

Severely destructive unilateral wrist arthritis as a rare variant of rheumatoid arthritis: analysis of clinical and imaging features.

OBJECTIVES: Rheumatoid arthritis (RA) is a common autoimmune disease typically affecting joints symmetrically. A small number of patients develop unilateral and severely destructive wrist arthritis (DWA). The objective of our study was to characterise patients with this type of affection. METHODS: This was a retrospective cohort study of RA patients with positive RF/anti-CCP antibodies. Clinical characteristics, including, age, gender, disease duration, dexterity, occupational history, smoking status, and the number of prescribed DMARDs were recorded. Conventional radiographs were evaluated using the modified Sharp/van der Heijde scoring (mSS) method. RESULTS: We analysed our laboratory database of 1247 patients and identified 559 patients with a clinical diagnosis of RA. For 395 of the patients, radiographs of the hands were available for evaluation. 25 patients had extensive unilateral DWA, corresponding to a prevalence of 6.3% (25 of 395 patients). 11 patients were excluded due to incomplete data. Of the remaining 14 patients, 13 were female with a median age of 61 (33-83) years, and median disease duration of 18 (1-33) years. 8 of 11 (72.7%) patients were smokers; in three, smoking status was not known. 80% with known dexterity developed unilateral DWA in the dominant hand. Total mSS was significantly higher on the affected side (39, interquartile range 35.25-46.25) versus non-affected (13, IQR 3-23). MSS were not different if the carpal bones were excluded from scoring. Side of involvement (left vs. right), or dominant versus non-dominant hand, did not result in a different mSS. CONCLUSIONS: Unilateral DWA is a rare variant of RA which predominantly affects women who smoke.

Drivers of productivity: Being physically active increases yet sedentary bouts and lack of sleep decrease work ability.

Physical behavior (ie, physical activity, sedentary behavior, and sleep) is a crucial lifestyle factor for preventing and managing diseases across the lifespan. However, less is known about potential work-related psychological and cognitive outcomes such as productivity. The present study examined within-person associations between physical behavior and self-perceived work ability. To investigate the degree to which physical behavior parameters influence self-perceived work ability in everyday life, we conducted an Ambulatory Assessment study in 103 university students over 5 days. Physical behavior was assessed continuously via a multi-sensor system. Self-perceived work ability was assessed repeatedly up to six times per day on smartphones. We employed multilevel modeling to analyze the within-person effects of physical behavior on self-perceived work ability. Physical activity intensity (MET) (ß = 0.15 ± 0.06, t = 2.59, p = 0.012) and sit-to-stand transitions (ß = 0.07 ± 0.03, t = 2.44, p = 0.015) were positively associated with self-perceived work ability. Sedentary bouts (≥20 min) (ß = -0.21 ± 0.08, t = -2.74, p = 0.006) and deviation from a recommended sleep duration (ie, 8 h) (ß = -0.1 ± 0.04, t = -2.38, p = 0.018) were negatively associated with self-perceived work ability. Exploratory analyses supported the robustness of our findings by comparing various time frames. Total sedentary time and sleep quality were not associated with self-perceived work ability. Regular sleep durations, breaking up sedentary time through sit-to-stand transitions, and higher intensities of physical activity may be important for the regulation of self-perceived work ability in university students' daily lives.

Socio-economic consequences of mental distress: quantifying the impact of self-reported mental distress on the days of incapacity to work and medical costs in a two-year period: a longitudinal study in Germany.

BACKGROUND: Mental disorders are related to high individual suffering and significant socio-economic burdens. However, it remains unclear to what extent self-reported mental distress is related to individuals' days of incapacity to work and their medical costs. This study aims to investigate the impact of self-reported mental distress for specific and non-specific days of incapacity to work and specific and non-specific medical costs over a two-year span. METHOD: Within a longitudinal research design, 2287 study participants' mental distress was assessed using the Hospital Anxiety and Depression Scale (HADS). HADS scores were included as predictors in generalized linear models with a Tweedie distribution with log link function to predict participants' days of incapacity to work and medical costs retrieved from their health insurance routine data during the following two-year period. RESULTS: Current mental distress was found to be significantly related to the number of specific days absent from work and medical costs. Compared to participants classified as no cases by the HADS (2.6 days), severe case participants showed 27.3-times as many specific days of incapacity to work in the first year (72 days) and 10.3-times as many days in the second year (44 days), and resulted in 11.4-times more medical costs in the first year (2272 EUR) and 6.2-times more in the second year (1319 EUR). The relationship of mental distress to non-specific days of incapacity to work and non-specific medical costs was also significant, but mainly driven from specific absent days and specific medical costs. Our results also indicate that the prevalence of presenteeism is considerably high: 42% of individuals continued to go to work despite severe mental distress. CONCLUSIONS: Our results show that self-reported mental distress, assessed by the HADS, is highly related to the days of incapacity to work and medical costs in the two-year period. Reducing mental distress by improving preventive structures for at-risk populations and increasing access to evidence-based treatments for individuals with mental disorders might, therefore, pay for itself and could help to reduce public costs.

Calreticulin Deficiency Disturbs Ribosome Biogenesis and Results in Retardation in Embryonic Kidney Development.

Nephrogenesis is driven by complex signaling pathways that control cell growth and differentiation. The endoplasmic reticulum chaperone calreticulin (Calr) is well known for its function in calcium storage and in the folding of glycoproteins. Its role in kidney development is still not understood. We provide evidence for a pivotal role of Calr in nephrogenesis in this investigation. We show that Calr deficiency results in the disrupted formation of an intact nephrogenic zone and in retardation of nephrogenesis, as evidenced by the disturbance in the formation of comma-shaped and s-shaped bodies. Using proteomics and transcriptomics approaches, we demonstrated that in addition to an alteration in Wnt-signaling key proteins, embryonic kidneys from Calr-/- showed an overall impairment in expression of ribosomal proteins which reveals disturbances in protein synthesis and nephrogenesis. CRISPR/cas9 mediated knockout confirmed that Calr deficiency is associated with a deficiency of several ribosomal proteins and key proteins in ribosome biogenesis. Our data highlights a direct link between Calr expression and the ribosome biogenesis.

[Make nursing practice visible through nursing science in times of COVID-19]. / Pflegepraxis durch Pflegewissenschaft in Zeiten von COVID-19 sichtbar machen.

Due to coronavirus disease 2019 (COVID-19) nursing practice is facing enormous challenges. Nevertheless, nursing science was hardly actively represented as a mouthpiece for the practice in the public discussions on the COVID-19 pandemic. Therefore, the question arises which projects with a focus on nursing and COVID-19 have been carried out at Austrian universities. Overall, six projects were identified using the snowball method. Of the studies one showed that an increased wearing time of masks is associated with an increased stress level for nursing personnel. An additional study result showed that almost 50% of lay people used masks incorrectly. Individual experiences, interventions undertaken and solution approaches from the perspective of the nursing staff with respect to ethical challenges in nursing homes were collected in a further project. This and other projects show that nursing science, with its knowledge and as a voice for nursing practice, has taken the initiative and contributes to the COVID-19 discourse. Additionally, the findings of the projects can be used as a basis for making future political decisions.

NMR in target driven drug discovery: why not?

No matter the source of compounds, drug discovery campaigns focused directly on the target are entirely dependent on a consistent stream of reliable data that reports on how a putative ligand interacts with the protein of interest. The data will derive from many sources including enzyme assays and many types of biophysical binding assays such as TR-FRET, SPR, thermophoresis and many others. Each method has its strengths and weaknesses, but none is as information rich and broadly applicable as NMR. Here we provide a number of examples of the utility of NMR for enabling and providing ongoing support for the early pre-clinical phase of small molecule drug discovery efforts. The examples have been selected for their usefulness in a commercial setting, with full understanding of the need for speed, cost-effectiveness and ease of implementation.

Prevalence of affective disorders and dementia in inflammatory polyarthropathies.

Comorbid disorders are common in psychiatric diseases and understanding the risk of secondary diseases can aid successful clinical treatment. The objective of this study was to compare the frequency of comorbid dementia, affective disorders, and inflammatory polyarthropathies. Healthcare data obtained via the German Hospital Fees Act from two independent databases with more than 7.4 million cases were analyzed to compare the prevalence of comorbid disorders. Comorbid inflammatory polyarthropathy was observed in 2.27% of patients diagnosed with affective disorders and 1.35% of patients with dementia (p < 0.001). Among patients with a primary diagnosis of inflammatory polyarthropathy, 1.27% of patients were diagnosed with dementia, whereas 4.55% of age-matched patients without inflammatory polyarthropathies had comorbid dementia (p < 0.001). The opposite effect was demonstrated for affective disorders, as 5.77% of patients with a primary diagnosis of inflammatory polyarthropathy also had comorbid affective disorders, while 4.87% of age-matched patients without inflammatory polyarthropathy had an accompanying affective disease (p < 0.001). These findings show an association between the occurrence of inflammatory polyarthropathies, dementia, and affective disorders. This correlation might improve diagnosis and treatment for patients with comorbidities. Moreover, further exploration of the molecular pathophysiology underlying these relationships could be relevant for the development of novel treatment options.

Oral health-related quality of life in different rheumatic diseases.

OBJECTIVES: Aim of this cross-sectional study was to investigate oral health-related quality of life (OHRQoL) of patients with different rheumatic diseases. SUBJECTS AND METHODS: Patients with rheumatic disease, including rheumatoid arthritis (RA), systemic lupus erythematodes (SLE), systemic sclerosis (SSc), ankylosing spondylitis (AS), psoriatic arthritis (PsA) and vasculitis were included. OHRQoL was assessed with the German short form of oral health impact profile (OHIP G14). Age, disease duration, leukocytes, c-reactive protein (CRP) and haemoglobin counts were considered as disease related parameters. RESULTS: A total of 356 patients, assigned to the groups RA (n = 218), SLE (n = 36), AS (n = 36), PsA (n = 33), vasculitis (n = 19) and SSc (n = 14) were included. The OHIP G14 sub-scale psychosocial impact differed significantly between groups (p = .02). The OHIP G14 sum score was also significantly different between groups (p < .01). A medium-sized correlation was found for CRP with OHIP G14 sum score within SLE group (r = .344, p = .04). A large correlation was detected for leukocytes within PsA group (r = .525, p < .01). The reliability of the applied OHIP G14 was high. CONCLUSION: Patients with rheumatic disease show a reduced OHRQoL, with several differences between the entities. Psychosocial aspects appear to be of relevance and should be considered in multidisciplinary dental care of these patients.

Constitutive Atg5 overexpression in mouse bone marrow endothelial progenitor cells improves experimental acute kidney injury.

BACKGROUND: Endothelial Progenitor Cells have been shown as effective tool in experimental AKI. Several pharmacological strategies for improving EPC-mediated AKI protection were identified in recent years. Aim of the current study was to analyze consequences of constitutive Atg5 activation in murine EPCs, utilized for AKI therapy. METHODS: Ischemic AKI was induced in male C57/Bl6N mice. Cultured murine EPCs were systemically injected post-ischemia, either natively or after Atg5 transfection (Adenovirus-based approach). Mice were analyzed 48 h and 6 weeks later. RESULTS: Both, native and transfected EPCs (EPCsAtg5) improved persisting kidney dysfunction at week 6, such effects were more pronounced after injecting EPCsAtg5. While matrix deposition and mesenchymal transdifferentiation of endothelial cells remained unaffected by cell therapy, EPCs, particularly EPCsAtg5 completely prevented the post-ischemic loss of peritubular capillaries. The cells finally augmented the augophagocytic flux in endothelial cells. CONCLUSIONS: Constitutive Atg5 activation augments AKI-protective effects of murine EPCs. The exact clinical consequences need to be determined.

Disease activity, morning stiffness and missing teeth are associated with oral health-related quality of life in individuals with rheumatoid arthritis.

OBJECTIVES: The aim of this cross-sectional study was to assess oral health-related quality of life (OHRQoL) in patients with rheumatoid arthritis (RA) and its relation to specific RA characteristics. MATERIAL AND METHODS: Within the oral examination, the need for dental (carious teeth showing cavitation) and periodontal treatment (presence of a probing depth ≥ 3.5 mm) and the number of missing teeth (M-T) were recorded. OHRQoL was assessed with the German short version of the Oral Health Impact Profile (OHIP G14). The disease activity score (DAS28-ESR), disease duration, number of swollen/painful joints and duration of morning stiffness were retrieved from the patient records. RESULTS: A total of 176 patients with a mean age of 62.5 ± 10.2 years were included. The overall OHIP G14 sum score was 5.4 ± 7.1. The M-T showed a significant correlation with the dimensions of oral function (r = 0.25, p = 0.001) and psychosocial impact (r = 0.20, p = 0.009) and the sum score (r = 0.26, p = 0.001). The DAS28-ESR showed a significant correlation with psychosocial impact (r = 0.19, p = 0.012) and the sum score (r = 0.16, p = 0.041). The duration of morning stiffness was correlated with oral function (r = 0.19, p = 0.019), psychosocial impact (r = 0.18, p = 0.024) and the sum score (r = 0.22, p = 0.006). The effect size of these correlations was interpreted as small. CONCLUSION: Disease activity, morning stiffness and missing teeth are associated to OHRQoL of patients with RA. Accordingly, multidisciplinary dental care appears necessary for these patients. CLINICAL RELEVANCE: The prevention of tooth loss as well as the consideration of psychosocial and disease-specific parameters in the multidisciplinary dental care of RA patients is necessary.

Dickkopf-3 in aberrant endothelial secretome triggers renal fibroblast activation and endothelial-mesenchymal transition.

Background: Our laboratory has previously demonstrated that Sirt1endo-/- mice show endothelial dysfunction and exaggerated renal fibrosis, whereas mice with silenced endothelial transforming growth factor beta (TGF-ß) signaling are resistant to fibrogenic signals. Considering the fact that the only difference between these mutant mice is confined to the vascular endothelium, this indicates that secreted substances contribute to these contrasting responses. Methods: We performed an unbiased proteomic analysis of the secretome of renal microvascular endothelial cells (RMVECs) isolated from these two mutants. We cultured renal fibroblasts and RMVECs and used microfluidic devices for coculturing. Results: Dickkopf-3 (DKK3), a putative ligand of the Wnt/ß-catenin pathway, was present exclusively in the fibrogenic secretome. In cultured fibroblasts, DKK3 potently induced myofibroblast activation. In addition, DKK3 antagonized effects of DKK1, a known inhibitor of the Wnt pathway, in conversion of fibroblasts to myofibroblasts. In RMVECs, DKK3 induced endothelial-mesenchymal transition and impaired their angiogenic competence. The inhibition of endothelial outgrowth, enhanced myofibroblast formation and endothelial-mesenchymal transition were confirmed in coculture. In reporter DKK3-eGFP × Col3.6-GFPcyan mice, DKK3 was marginally expressed under basal conditions. Adriamycin-induced nephropathy resulted in upregulation of DKK3 expression in tubular and, to a lesser degree, endothelial compartments. Sulindac sulfide was found to exhibit superior Wnt pathway-suppressive action and decreased DKK3 signals and the extent of renal fibrosis. Conclusions: In conclusion, this unbiased proteomic screen of the profibrogenic endothelial secretome revealed DKK3 acting as an agonist of the Wnt pathway, enhancing formation of myofibroblasts and endothelial-mesenchymal transition and impairing angiogenesis. A potent inhibitor of the Wnt pathway, sulindac sulfide, suppressed nephropathy-induced DKK3 expression and renal fibrosis.

Novel SAR for quinazoline inhibitors of EHMT1 and EHMT2.

Detailed structure activity relationship of two series of quinazoline EHMT1/EHMT2 inhibitors (UNC0224 and UNC0638) have been elaborated. New and active alternatives are presented for the ubiquitous substitution patterns found in literature for the linker to the lysine mimicking region and the lysine mimic itself. These findings could allow for advancing EHMT1/EHMT2 inhibitors of that type beyond tool compounds by fine-tuning physicochemical properties making these inhibitors more drug-like. .

Cytokine profiling in anti neutrophil cytoplasmic antibody-associated vasculitis: a cross-sectional cohort study.

ANCA-associated vasculitides (AAV) are severe diseases, potentially affecting lungs, kidney, and other organs. Nevertheless, risk profiling remains difficult. Aim of the current study was to analyze serological characteristics in AAV. The principal goal was to identify diagnostic markers that potentially allow a more sophisticated risk profiling in AAV. AAV subjects were recruited and evaluated for disease activity, disease stage, medication, and laboratory findings. Serum concentrations of the following parameters were measured: IL-1ß, IL-6, IL-17 A, IL-17 F, IL-21, IL-22, IL-23, TNF-α, sCD40L, IL-4, IL-10, IL-25, IL-31, IL-33, and INF-γ. A total number of 62 AAV subjects was included in the study (39 females; 23 males). Forty-five subjects were PR3+, 17 subjects showed ANCA specificity for MPO. The majority of all cytokines fell under the lower detection limit of the assay. Serum IL-10 was higher in both, AAV and SSc as compared to controls; it was also higher in early systemic AAV. Serum IL-33 was elevated in AAV and SSc; in AAV, higher levels were found in non-necrotizing GN and RTX untreated subjects. Serum CD40L was raised in AAV as well; higher concentrations were also found in PR3+ and MPO+ patients and early systemic, generalized, and refractory AAV. IL-10 may potentially serve as a marker of early systemic AAV. IL-33 may help to identify subjects with a higher risk for necrotizing GN in AAV.

Risk factors for catheter-related infections in patients receiving permanent dialysis catheter.

BACKGROUND: Due to rising vascular comorbidities of patients undergoing dialysis, the prevalence of permanent hemodialysis catheters as hemodialysis access is increasing. However, infection is a major complication of these catheters. Therefore, identification of potential predicting risk factors leading to early infection related complications is valuable, in particular the significance the CRP (C-reactive protein)-value is of interest. METHODS: In this retrospective study 151 permanent hemodialysis catheters implanted in 130 patients were examined. The following data were collected at the time of catheter implantation: CRP-value, history of catheter-related infection, microbiological status, immunosuppression and diabetes mellitus. The primary outcomes were recorded over the 3 months following the implantation: catheter-related infection, days of hospital stay and death. Catheter removal or revision, rehospitalization and use of antibiotics were identified as secondary outcomes. RESULTS: We identified a total of 27 (17.9%) infections (systemic infection: 2.26 episodes/ 1000 catheter days, local infection: 0.6 episodes/ 1000 catheter days). The development of an infection was independent of the CRP-value (p = 0.66) as well as the presence of diabetes mellitus (p = 0.64) or immunosuppression (p = 0.71). Univariate analysis revealed that infection was more frequent in patients with MRSA-carriage (p < 0.001), in case of previous catheter-related infection (p < 0.05) and of bacteremia or bacteriuria in the period of 3 months before catheter implantation (p < 0.001). Catheter removal or revision (p = 0.002), rehospitalization (p = 0.001) and use of antibiotics (p = 0.02) were also more often observed in patients with MRSA-carriage. CONCLUSIONS: The CRP-value at the time of implantation of a permanent hemodialysis catheter is not associated with the development of early catheter related infections, but an individual history of catheter-related infection, MRSA-carriage and bacteremia or bacteriuria in the period of 3 months prior to catheter implantation are significant risk factors.