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Main goal of this paper was to draw more attention to the pervasiveness of technostress in the consulting environment. As TS tends to be perceived differently in terms of what it entails, authors have focused, instead, on its relationship with such demographical variables as gender, age, work level and family status in the research. Study was conducted using a quantitative questionnaire. Sample consisted of 702 consulting employees (417 men and 275 women) aged 18-65. Data analysis was based on ANOVA and stepwise regression models. Results reveal that female participants and employees older than 35, experience significantly more Techno-Complexity compared to other groups. No significant effect of family status on Techno-Complexity was found. Senior-rank employees experience more Techno-Overload and Techno-Invasion, compared to co-workers in more junior positions. The authors’ findings point out to the necessity of workplace-stress prevention solutions focusing specifically on gender, age and the seniority level of an employee. The Results imply that such focus can prove essential in the prevention of burnout and considerable decrease in individual stress levels, loss of workplace focus and overall workplace productivity

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Background: Autoimmune hepatitis (AIH) is a rare entity; in addition, single-nucleotide polymorphisms (SNPs) may impact its course and outcome. We investigated liver-related SNPs regarding its activity, as well as in relation to its stage and treatment response in a Central European AIH cohort., Methods: A total of 113 AIH patients (i.e., 30 male/83 female, median 57.9 years) were identified. In 81, genotyping of PNPLA3-rs738409, MBOAT7-rs626238, TM6SF2-rs58542926, and HSD17B13-rs72613567:TA, as well as both biochemical and clinical data at baseline and follow-up, were available., Results: The median time of follow-up was 2.8 years; five patients died and one underwent liver transplantation. The PNPLA3-G/G homozygosity was linked to a worse treatment response when compared to wildtype [wt] (ALT 1.7 vs. 0.6 × ULN, p < 0.001). The MBOAT7-C/C homozygosity was linked to non-response vs. wt and heterozygosity ( p = 0.022). Male gender was associated with non-response (OR 14.5, p = 0.012) and a higher prevalence of PNPLA3 (G/G vs. C/G vs. wt 41.9/40.0/15.0% males, p = 0.03). The MBOAT7 wt was linked to less histological fibrosis ( p = 0.008), while no effects for other SNPs were noted. A polygenic risk score was utilized comprising all the SNPs and correlated with the treatment response ( p = 0.04)., Conclusions: Our data suggest that genetic risk variants impact the treatment response of AIH in a gene-dosage-dependent manner. Furthermore, MBOAT7 and PNPLA3 mediated most of the observed effects, the latter explaining, in part, the predisposition of male subjects to worse treatment responses.

Tangential flow filtration (TFF) is a central step in manufacturing of biopharmaceutics. Membrane clogging leads to decreased permeate flux, longer process time and potentially complete failure of the process. The effect of peristaltic pumping with tubings made of three different materials on protein particle formation during TFF was monitored via micro flow imaging, turbidity and photo documentation. At low protein concentrations, pumping with a membrane pump resulted in a stable flux with low protein particle concentration. Using a peristaltic pump led to markedly higher protein particle formation dependent on tubing type. With increasing protein particle formation propensity of the tubing, the permeate flux rate became lower and the process took longer. The protein particles formed in the pump were captured in the cassette and accumulated on the membrane leading to blocking. Using tubing with a hydrophilic copolymer modification counteracted membrane clogging and flux decrease by reducing protein particle formation. In ultrafiltration mode the permeate flux decrease was governed by the viscosity increase rather than by the protein aggregation; but using modified tubing is still beneficial due to a lower particle burden of the product. In summary, using tubing material for peristaltic pumping in TFF processes which leads a less protein particle formation, especially tubing material with hydrophilic modification, is highly beneficial for membrane flux and particle burden of the product., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate potential clinical parameters having an impact on visual outcome after endoscopic optic nerve decompression in acute optic neuropathy patients., Methods: A retrospective chart review of patients with acute optic neuropathy, who underwent endoscopic optic nerve decompression between June 2001 and November 2018 at an academic center was performed. Patients were divided into groups according to visual improvement after surgical treatment (yes/no). Following clinical parameters were compared between groups: perioperative steroid use, evidence of optic nerve affection in preoperative neuroimaging, additional optic nerve sheath incision, surgery delay and preoperative C-reactive protein (CRP) levels. Further subgroups analyses were conducted based on etiology (trauma/tumor)., Results: Among 32 included cases, 16 patients (50%) reported visual improvement after endoscopic optic nerve decompression. There was no significant difference in visual improvement between etiology subgroups (trauma: n = 9/20 (45%) vs. tumor: n = 7/12 (58.3%), p = 0.465). Tumor subgroup patients with visual improvement had a significantly higher prevalence of optic nerve affection in preoperative neuroimaging than those without visual improvement (p = 0.018, φ = 0.683). Perioperative steroid administration was negatively associated with visual outcome (p = 0.034, φ = 0.375). Nerve sheath incision, surgery delay and preoperative CRP levels did not have a significant impact on visual outcome (p > 0.05)., Conclusion: Radiological findings can help as an indicator for surgical treatment since an affected optic nerve in preoperative neuroimaging resulted in better visual outcome after surgery. The use of steroids should be considered more carefully since it did not show any beneficial effect., (© 2021. The Author(s).)

Objectives: In the general population, increased afamin concentrations are associated with the prevalence and incidence of metabolic syndrome as well as type 2 diabetes. Although metabolic syndrome is commonly associated with nonalcoholic fatty liver disease (NAFLD), there exist no information on afamin and NAFLD., Methods: Afamin concentrations were cross-sectionally measured in 146 Austrian patients with NAFLD, in 45 patients without NAFLD, and in 292 age- and sex-matched healthy controls. Furthermore, the feasibility of afamin to predict incident NAFLD was evaluated in 1,434 adult participants in the population-based Cardiovascular Risk in Young Finns Study during a 10-year follow-up., Results: Median afamin concentrations were significantly higher in NAFLD patients (83.6 mg/L) than in patients without NAFLD (61.6 mg/L, p<0.0001) or in healthy controls (63.9 mg/L, p<0.0001). In age- and sex-adjusted logistic regression analyses a 10 mg/L increase of afamin was associated with a 1.5-fold increase of having NAFLD as compared with patients without NAFLD and the risk was even two-fold when compared with healthy controls. In the population-based cohort, afamin concentrations at baseline were significantly lower in participants without NAFLD (n=1,195) than in 239 participants who developed NAFLD (56.5 vs. 66.9 mg/L, p<0.0001) during the 10-year follow up, with highest afamin values observed in individuals developing severe forms of NAFLD. After adjustment for several potentially confounding parameters, afamin remained an independent predictor for the development of NAFLD (OR=1.37 [95% CI 1.23-1.54] per 10 mg/L increase, p<0.0001)., Conclusions: Afamin concentrations are increased in patients with NAFLD and independently predict the development of NAFLD in a population-based cohort., (© 2021 Niina Pitkänen et al., published by De Gruyter, Berlin/Boston.)

Context: Recently, the novel metabolic dysfunction-associated fatty liver disease (MAFLD) definition has been introduced., Objective: To assess the relevance of MAFLD for mortality., Methods: Single-center cohort-study using colorectal cancer screening program involving 4718 subjects aged 45 to 80 who were grouped according to their body mass index (BMI) and the presence or absence of MAFLD. Mortality was compared among these groups by performing a systematic read-out of the national health insurance system, fatty liver (FL) was diagnosed using ultrasound., Results: Overall prevalence of FL was 47.9%: 1200 (25.4%) patients were lean (BMI < 25 kg/m2) and did not have MAFLD, 73 (1.5%) patients were lean and had nonalcoholic fatty liver disease but did not fulfill criteria for MAFLD, and 221 (4.7%) patients were lean and fulfilled criteria for MAFLD. Additionally, 1043 (22.1%) and 925 (19.6%) subjects had MAFLD with overweight (BMI 25-30 kg/m2) and obesity (BMI ≥ 30 kg/m2), respectively, while 1041 (22.1%) and 215 (4.6%) had overweight and obesity, respectively, without FL. During a median follow-up of 7.5 (interquartile range: 4.0-9.6) years, 278 deaths (5.9%) occurred. Of these, 98 (2.1%) were cancer-related, 65 (1.4%) were cardiovascular, and 17 (0.4%) were liver-related. Overall survival was similar between patient strata (after 5 years: 93.9%-98.2%) with lean MAFLD having the numerically worst survival. Although lean and overweight patients with MAFLD had a numerically worse outcome compared to their non-MAFLD counterparts, this association was driven by age and metabolic comorbidities (predominantly diabetes) rather than the presence of MAFLD., Conclusion: Presence of MAFLD does not increase mortality in a cohort of individuals aged 45 to 80 years., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Belatacept is an attractive option for immunosuppression after renal transplantation. Renal allograft function is superior when compared to calcineurin inhibitor (CNI) based therapy in "de novo" treated patients and it has also been proposed that individuals at high cardiovascular (CV) risk may benefit most. In this retrospective cohort study, we assessed the efficacy and safety of treating patients at high cardiovascular risk with Belatacept ( n = 34, for 1194 observation months) when compared to a matched control group of 150 individuals under CNI immunosuppression (for 7309 months of observation). The estimated glomerular filtration rate (eGFR) increased for patients taking Belatacept but decreased during CNI-based therapy (+2.60 vs. -0.89 mL/min/1.73 m 2 /year, p = 0.006). In a multivariate Cox regression model, Belatacept remained the only significant factor associated with the improvement of eGFR (HR 4.35, 95%CI 2.39-7.93). Belatacept treatment was not a significant risk factor for renal allograft rejection or graft loss. In terms of safety, the only significant risk factor for de novo cardiovascular events was a pre-existing cerebrovascular disease, but Belatacept was not associated with a significant risk reduction. Belatacept treatment was not associated with an increased risk of severe infections, cytomegalo virus (CMV) or BK-virus reactivation, malignancy or death in the multivariate Cox regression analysis. Belatacept is an efficient and safe option for patients after renal transplantation at high cardiovascular risk.

In this study, we investigated the tissue expression levels, alpha subunit composition and distribution of Shaker-related voltage-dependent potassium Kv1 channels in human hippocampus by combining western blotting experiments, toxin autoradiography, in vivo radioligand binding studies, immunoprecipitation and immunohistochemistry. Tissue expression of Kv1.1 and Kv1.2 α-subunits in human post-mortem brain tissue was confirmed in immunoblot analysis using a panel of specific monoclonal and polyclonal antibodies. Immunoprecipitation experiments using toxin-prelabeled Kv1 channels revealed that all toxin-sensitive Kv1 channels in human hippocampus contained either a Kv1.1 or Kv1.2 α-subunit with the majority being composed of Kv1.1/Kv1.2 heterotetramers. Receptor autoradiography suggested Kv1.1/Kv1.2 channel expression in the molecular layer of dentate gyrus. In accordance, immunohistochemical experiments also observed Kv1.1 and Kv1.2 α-subunits in the molecular layer of the dentate gyrus, in addition to the CA3 stratum lucidum and the CA1 stratum oriens. These findings indicate expression in axons and terminals of hippocampal pathways, namely the perforant path, the mossy fiber pathway and the Schaffer collaterals. Herein we present the first direct demonstration that Kv1.1 and Kv1.2 channel proteins are targeted to distinct compartments of the human hippocampal formation and that this expression pattern largely reflects their distribution profile in murine brain.

Background: Blended interventions aim to capitalise on the strengths of both computer-based and face-to-face therapy. Studies on this innovative treatment format remain scare. This especially accounts for the group treatment of depression., Method: The present study applied eclectic psychotherapy methods to an adult sample exhibiting a variety of depressive symptoms (N = 46). Participants were recruited by a newspaper inlet and randomised either to a treatment or a waiting list condition. Computer supported components were multimedia group sessions, e-learning, online videos and worksheets, remote therapist-patient communication and online pre-post-assessment., Results: Large between-group effect sizes on primary outcome depressiveness (CES-D) ( F (1,44)  = 4.88, p  = 0.032; d  = 0.87) and secondary outcome personal resources (resource scales) ( F (1,44)  = 9.04, p  = 0.004; d  = 0.73 to F (1,44)  = 8.82 p  = 0.005, d  = 1.15) were found in the intention to treat analysis (ANOVA). Subjective evaluation of the intervention revealed high treatment adherence (91%) and high perceived relevance of supportive computer and multimedia components. Participants rated computer and multimedia components comparable to treatment elements such as group interaction or specific cognitive behavioural exercises, and 25% associated the utilisation of those components with treatment success. Depressiveness and age did not predict the utilisation and the appraisal of computer and multimedia components., Discussion: Results provide preliminary support for the acceptability and feasibility of the investigated blended treatment in a group with non-specific depressive symptoms. However, small sample size and lack of diagnostics restrict generalizability. Additional research in clinical settings is needed.

SK2 (KCa2.2) channels are voltage-independent Ca 2+ -activated K + channels that regulate neuronal excitability in brain regions important for memory formation. In this study, we investigated the distribution and expression of SK2 channels in human brain by Western blot analysis and immunohistochemistry. Immunoblot analysis of human brain indicated expression of four distinct SK2 channel isoforms: the standard, the long and two short isoforms. Immunohistochemistry in paraffin-embedded post-mortem brain sections was performed in the hippocampal formation, amygdala and neocortex. In hippocampus, SK2-like immunoreactivity could be detected in strata oriens and radiatum of area CA1-CA2 and in the molecular layer. In the amygdala, SK2-like immunoreactivity was highest in the basolateral nuclei, while in neocortex, staining was mainly found enriched in layer V. Activation of SK2 channels is thought to regulate neuronal excitability in brain by contributing to the medium afterhyperpolarization. However, SK2 channels are blocked by apamin with a sensitivity that suggests heteromeric channels. The herein first shown expression of SK2 human isoform b in brain could explain the variability of electrophysiological findings observed with SK2 channels.

Background: We aimed to compare head-to-head the diagnostic and prognostic capabilities of galectin-3, soluble ST2 (sST2) and B-type natriuretic peptide (BNP) for heart failure (HF) in an emergency setting., Methods: We studied 251 consecutive patients with dyspnoea as a chief compliant presenting to an emergency department. The diagnosis of HF was based on the Framingham score for HF plus echocardiographic evidence of systolic or diastolic dysfunction. All-cause mortality was assessed at one year. Plasma concentrations of galectin-3 and BNP were measured with two commercially available assays from Abbott Diagnostics, plasma concentrations of sST2 were quantified with the Presage ST2 assay. The diagnostic and prognostic accuracies of galectin-3, sST2 and BNP were assessed by receiver operating characteristic (ROC) curve analysis., Results: Of the 251 patients, 137 had dyspnoea attributable to acute HF and 114 had dyspnoea attributable to other reasons. BNP had a higher area under the curve (AUC) for the diagnosis of HF (0.92; 95% CI, 0.87-0.95) than galectin-3 (0.57; 95% CI, 0.51-0.64) and sST2 (0.63; 95% CI, 0.56-0.69). Of the 137 patients with acute HF, 41 died and 96 survived during follow up. The AUC of BNP for the prediction of one-year all-cause mortality in HF patients (0.72; 95% CI, 0.63-0.79) was not different from the AUCs of galectin-3 (0.70; 95% CI, 0.62-0.78) and sST2 (0.75; 95% CI, 0.67-0.82)., Conclusions: In this study, galectin-3, sST2 and BNP were equally useful for the prediction of one-year all-cause mortality in patients with acute HF. However, in contrast to BNP, galectin-3 and sST2 were not useful as an aid in the diagnosis of acute HF in short of breath patients presenting to an emergency department., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: The aim of this study was to compare the prognostic value of interleukin 6 (IL-6), galectin 3, growth differentiation factor 15 (GDF-15), and soluble ST2 (sST2) in an unselected cohort of critically ill patients., Methods: During a study period of 1 year, we recruited 530 consecutive patients admitted to a medical intensive care unit of a tertiary care hospital. We examined a combination of inflammatory, renal, and cardiac biomarkers for the prediction of 90-day all-cause mortality., Results: During follow-up, 118 patients died (22%). In univariate analyses, increased IL-6, galectin 3, GDF-15, and sST2 plasma concentrations at baseline were strong prognostic markers. However, in the multivariate models, only IL-6 and sST2 remained independent biomarkers adding additional prognostic information to the routinely used Simplified Acute Physiology Score (SAPS) II. Using a simple multimarker approach, patients with increased SAPS II, IL-6, and sST2 (ie, SAPS II >35, IL-6 >32.3pg/mL, and sST2 >103ng/mL) had the poorest outcome., Conclusions: In this heterogeneous group of critically ill patients, only SAPS II, IL-6, and sST2 remained independent and additive prognostic markers for 90-day all-cause mortality. A combination of the SAPS II with the 2 complementary biomarkers might provide a valuable tool for risk stratification of critically ill patients., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Here we describe the determination of upper reference limits (URL) for galectin-3, high-sensitivity cardiac troponin I (hs-cTnI) and high-sensitivity cardiac troponin T (hs-cTnT) in a single cohort of healthy blood donors using routine assays., Methods: For this reference value study, we used a cohort of 402 consecutive blood donors (64% were male and 36% were female). The median individuals' age was 35.0 years (range, 18.0-64.4). Individuals of this reference population were free of cardiovascular disease, diabetes mellitus, renal disease, cancer, current infection and chronic inflammatory disease. Plasma concentrations of galectin-3 were measured with the "routine Galectin-3" assay (Abbott Diagnostics), of hs-cTnI with the "STAT High Sensitive Troponin-I" assay (Abbott Diagnostics), and of hs-cTnT with the "Troponin T hs" assay (Roche Diagnostics). URLs were calculated by using a non-parametric percentile method., Results: The 97.5th percentile URL for galectin-3 was 16 ng/mL in males and 17 ng/mL in females; the 99 th percentile URL for hs-cTnI was 39 ng/L in males and 24 ng/L in females; and the 99 th percentile URL for hs-cTnT was 14 ng/L in males and 11 ng/L in females. Those individuals with hs-cTnI values ≥ 15 ng/L (n=8) were different from those individuals with hs-cTnT values ≥ 10 ng/L (n=7). Of the 402 individuals, none had galectin-3 values below the limit of detection (LOD, <1.0 ng/mL), 290 (72%) had hs-cTnI values below the LOD (i.e., 1.9 ng/L), and 359 (89%) had hs-cTnT values below the LOD (i.e., 5.0 ng/L)., Conclusion: Plasma concentrations of galectin-3, hs-cTnI and hs-cTnT and corresponding 99 th percentile URLs were rather low in our cohort of healthy blood donors compared with previously published data. In our reference population, analyte plasma concentrations above the LOD were detectable in 100% of the individuals with the Abbott galectin-3 assay, but only in less than 50% for both the Abbott hs-cTnI assay and the Roche hs-cTnT assay., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: Biomarkers are useful for establishing disease severity or prognosis in patients with chronic kidney disease. The aim of our study was to determine the plasma concentrations of novel cardiovascular biomarkers in patients on chronic hemodialysis in the context of published upper reference limits (URL) of these biomarkers; and to compare the plasma concentrations of those same analytes before and after hemodialysis session., Design and Methods: Plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP), mid-regional pro-A-type natriuretic peptide (MR-proANP), mid-regional pro-adrenomedullin (MR-proADM), C-terminal pro-endothelin-1 (CT-proET-1), C-terminal pro-arginine vasopressin (CT-proAVP, also known as Copeptin) and soluble ST2 (sST2) were measured in 28 patients before and after dialysis session. Of the 28 patients with conventional hemodialysis, 24 had low-flux hemofiltration and 4 had high-flux hemodiafiltration., Results: Median plasma concentrations of the biomarkers obtained before hemodialysis were as follows: NT-proBNP, 11,307ng/L (URL, 500ng/L); MR-proANP, 778pmol/L (URL, 250pmol/L); MR-proADM, 2.57nmol/L (URL, 0.52nmol/L); median CT-proET-1, 252pmol/L (URL, 75pmol/L); median CT-proAVP, 142pmol/L (URL, 19pmol/L); and median sST2, 27ng/mL (URL, 50ng/mL). Median relative analyte changes after low-flux vs. high-flux dialysis compared to predialysis values were +19% vs. -43% for NT-proBNP; +7% vs. -45% for MR-proANP; -2% vs. -63% for MR-proADM; -19% vs. -61% for CT-proET-1; +13% vs. -64% for CT-proAVP; and +2% vs. +3% for sST2., Conclusions: Plasma concentrations of the investigated biomarkers were markedly increased in chronic hemodialysis patients (with the exception of sST2). After hemodialysis session, analyte concentrations (with the exception of sST2) decreased significantly using a high-flux membrane but not if using a low-flux membrane., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The biomarkers soluble ST2 (sST2), galectin-3, and growth-differentiation factor-15 (GDF-15) provide prognostic information in patients with heart failure (HF). The aim of this study was to evaluate to which extent plasma concentrations of these biomarkers are increased in HF compared with diverse non-cardiac conditions such as infectious disease or chronic kidney disease., Methods: We recruited 15 patients in each of the following clinical categories: HF without co-morbidity, pneumonia without co-morbidity, chronic obstructive pulmonary disease (COPD) without co-morbidity, HF and a co-morbidity of pneumonia, renal disease without co-morbidity, and sepsis. We used 22 healthy individuals as control group. In each of the 112 study participants, we measured plasma concentrations of sST2 (Presage assay), galectin-3 (Abbott assay) and GDF-15 (Roche assay)., Results: Compared to controls, the median sST2 concentration was ~2.5-fold increased in HF, ~3.5-fold in pneumonia, ~5.0-fold in COPD, ~5.8-fold in HF+pneumonia, and ~70-fold in sepsis (p<0.001 for all). sST2 was not significantly increased in renal disease. Compared to controls, the median galectin-3 concentration was ~1.5-fold increased in HF, ~1.4-fold in pneumonia, ~2.4-fold in HF+pneumonia, ~2.5-fold in renal disease, and ~2.7-fold in sepsis (p<0.001 for all). Galectin-3 was not significantly increased in COPD. Compared to controls, the median GDF-15 concentration was ~4.4-fold increased in HF, ~5.4-fold in pneumonia, ~2.1-fold in COPD, ~8.3-fold in HF+pneumonia, ~5.1-fold in renal disease, and ~27-fold in sepsis (p<0.001). In the 112 study participants, correlation analyses revealed a relatively strong association between galectin-3 and GDF-15 (correlation coefficient, 0.739; p<0.001)., Conclusion: Because increased plasma concentrations of sST2, galectin-3, and GDF-15 are not specific for a distinct disease group, the three biomarkers are not useful for diagnostic purposes. The results of our study are novel with respect to sST2, galectin-3 and GDF-15 as markers of inflammatory diseases and should encourage further studies., (Copyright © 2015. Published by Elsevier B.V.)

PGC-1α (peroxisome proliferator-activated receptor γ co-activator 1α) is an important regulator of mitochondrial biogenesis and a master regulator of enzymes involved in oxidative phosphorylation. Recent evidence demonstrated that the Gly482Ser single nucleotide polymorphism (SNP) in the PGC-1α gene affects insulin sensitivity, blood lipid metabolism and binding to myocyte enhancer factor 2 (MEF2). Individuals carrying this SNP were shown to have a reduced cardiorespiratory fitness and a higher risk to develop type 2 diabetes. Here, we investigated the responses of untrained men with the Gly482Ser SNP to a 10 week programme of endurance training (cycling, 3 x 60 min/week, heart rate at 70-90% VO2peak). Quantitative data from analysis of biopsies from vastus lateralis muscle revealed that the SNP group, in contrast to the control group, lacked a training-induced increase in content of slow contracting oxidative fibres. Capillary supply, mitochondrial density, mitochondrial enzyme activities and intramyocellular lipid content increased similarly in both groups. These results indicate that the impaired binding of MEF2 to PGC-1α in humans with this SNP impedes exercise-induced fast-to-slow muscle fibre transformation.