Afamin predicts the prevalence and incidence of nonalcoholic fatty liver disease.

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.

Genetic Variants Determine Treatment Response in Autoimmune Hepatitis.

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.

Optic nerve injury in preoperative imaging is associated with visual improvement outcome in endoscopic optic nerve decompression.

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.

Self-Reported and Parental Assessments of Internet Gaming Disorder, and Their Accordance with DSM-5 Criteria in a Clinical Relevant Population.

Internet gaming disorder (IGD) is of growing importance as a research field and in clinical settings, as documented by the inclusion of the diagnosis in Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and the preliminary International Classification of Diseases. Studies using screening tools to assess IGD and comparison with expert evaluations in clinical relevant populations are rare. Furthermore, concerned parents are often the first source of information in clinical practice, and their assessment of addictive behavior often differs widely from their child's self-evaluation. In two studies (N = 95) we investigated the usefulness of the Internet Addiction Test (IAT) and the Compulsive Internet Use Scale (CIUS) with adolescents at risk of IGD, either in parental company (Study 1) or alone (Study 2). Self-reported assessments on the scales were compared with parental ratings (only Study 1) and an expert face-to-face evaluation according to DSM-5 (both studies). We found higher correlations between expert evaluations of IGD criteria and screening scores for self-reported compared with parental ratings. Quality of categorization into persons with and without IGD confirmed that parental assessments were not conclusive in this setting. In this context, different cutoff values, sensitivity, and specificity for the screening instruments are discussed. We conclude that IAT and CIUS provide tentative usefulness for self-evaluation of adolescents at risk of IGD, and suggestions for using different cutoff scores for varying purposes are provided. In our study, parental assessments on the screening tools lead to an overestimation of IGD and are, therefore, not recommended as a sole source of information in clinical settings.

Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD)-Rather a Bystander Than a Driver of Mortality.

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.

Risk of PTSD Due to the COVID-19 Pandemic Among Patients in Opioid Substitution Treatment.

Background: The impact of the COVID-19 pandemic on the mental health of patients suffering from addictive disorders is of major concern. This study aimed to explore the presence and potential increase in post-traumatic stress disorder (PTSD) symptoms, depression, and anxiety since the beginning of the pandemic for patients in opioid substitution therapy (OST). Methods: This cross-sectional survey study evaluated a clinical sample of patients in OST (N = 123). Symptoms of post-traumatic stress disorder (PTSD) due to the COVID-19 pandemic were assessed by an adapted version of the impact of event scale (IES-R), resulting in two subgroups of low and high risk for PTSD. The depression, anxiety, and stress scale (DASS-21) was applied to collect data on the respective symptoms, and changes since the onset of the pandemic were reported on separate scales. Sociodemographic and COVID-19 related factors, as well as data on craving, consumption patterns, concomitant use, and the drug market were further assessed. Results: A binary logistic regression analysis confirmed the impact of self-perceived higher burden by psychological and economic factors on the elevated risk for PTSD due to the pandemic. The high-risk PTSD group also showed higher levels of depression, anxiety and stress, as well as a more pronounced deterioration in these symptoms since the pandemic. While reported levels of craving did not differ between the two groups, the high-risk PTSD group indicated a significantly higher increase in craving since the crisis, when compared to the low-risk group. Discussion: Our findings demonstrate elevated levels of clinical symptoms among patients in OST, with more than a quarter of patients found at risk for PTSD due to the COVID-19 pandemic. Furthermore, about 30-50% of our patients reported concerning levels of depression, anxiety, or stress. Special attention should be drawn to these findings, and potential deterioration of the situation should be addressed by health care facilities. Particularly, psychological, and financial burden due to the crisis were identified as factors increasing the risk for PTSD. These factors can easily be evaluated during routine anamneses, and might be a valuable source of information, when special attention is needed.

Nalmefene in the Treatment of Internet Pornography Addiction - A Case Report and Review of Literature.

: The mu-opioid antagonist nalmefene (18 mg per day) was administered in the treatment of a heterosexual male with internet pornography addiction. The patient had no other co-addictions or psychiatric comorbidities, allowing a direct measurement for the effectiveness of nalmefene on internet pornography addiction. Over a period of 72 weeks and an assessment frequency between 1 and 18 weeks, self-monitoring assessments of craving and pornography consumption were collected on different craving and obsessive-compulsive scales. Results indicate that nalmefene impressively decreased addictive symptoms. Importantly, the patient-induced discontinuation of nalmefene led to an immediate increase of craving scores and addictive behavior, which dropped again after restarting the medication. The patient has been in complete remission of symptoms for over a year under our supervision, and for further 2 years after that according to his account. Therefore, nalmefene seems to be a useful adjunction for patients with internet pornography addiction.

Developments in Drug Addiction During COVID-19-An Austrian Perspective Based on a Clinical Sample.

Concerns about the negative consequences of the COVID-19 pandemic on people with substance use disorder (SUD) were raised by experts in the field around the world. Here we provide an Austrian perspective, discussing the impact of the pandemic on help-seeking patient with drug use disorder during the initial stage of the pandemic. Our perspectives are based on the situation as perceived at our clinical facility, and supported by original data collected from a small clinical sample of patients with drug use disorder (N = 32). The viewpoints and related descriptive data include the perceived individual impact of COVID-19, as well as various aspects of drug use behavior and the Austrian drug market before and after the onset of the pandemic. The consequences for a subgroup of patients in opioid substitution treatment (N = 24) are discussed. Surprisingly and in contrast to anticipated developments, we had the impression of a rather stable situation in Austria, at least at this early stage of the pandemic. The immediate impact of COVID-19 on these help-seeking patients with high levels of drug dependency seemed less severe than anticipated so far. Importantly, this observation might be a short-term effect for this already fragile group and careful monitoring of further developments as well as preparation of long-term strategies are advised. In general, problematic drug use is associated with many health risk factors and finding appropriate long-term health care strategies has to remain a top priority facing the pandemic. Our perspectives are restricted to observations from help-seeking patients at our clinic, and no conclusions for the general population can be directly drawn.

Impact of the COVID-19 Pandemic on Patients With Alcohol Use Disorder and Associated Risk Factors for Relapse.

Background: The impact of the ongoing COVID-19 pandemic on vulnerable groups like patients suffering from substance use disorders is expected to be tremendous, and corresponding concerns were raised early on by many experts around the world. Psychosocial distress, financial insecurities and physiological problems associated with the COVID-19 crisis could be especially challenging for this group of patients. Methods: In the current study data was collected from a clinical sample of patients with alcohol use disorder (AUD; N = 127) during the initial stage of the pandemic. The impact of various COVID-19 related factors (physiological, psychosocial, economic and others) on patients' personal life was evaluated. Alcohol consumption, craving, and potential posttraumatic stress disorder (PTSD) symptoms were assessed using different scales and their associations were analyzed. Furthermore, differences regarding these variables between comparably sized groups of patients who remained abstinent (N = 37), relapsed (N = 41), or reported unaltered drinking behavior (consuming subgroup, N = 49) were investigated. The impact of sociodemographic and COVID-19 factors on relapse (in comparison to abstinence) was evaluated using binary logistic regression analysis. Results: Our results confirmed the expected positive associations between alcohol consumption, craving, and PTSD symptoms, respectively, among patients with AUD. Furthermore, group differences indicate significantly lower levels on all three scales for abstinent patients. Although generally low PTSD scores were observed, 8% of our participants were found to be at risk of PTSD. Results of a binary logistic regression analysis indicated the presence of psychosocial COVID-19 factors (e.g., isolation, anxiety, and depression) as well as living alone as two major risk factors for relapse. Discussion: Our findings based on actual patient data support the anticipated negative consequences of the pandemic on persons with AUD. Crucially, our results regarding relapse emphasized psychosocial COVID-19 factors and isolation as especially challenging circumstances for persons with AUD, whereas economic and physiological health aspects seemed of minor impact on relapse. Our results reflect the initial stage of the pandemic, whereas long-term developments should be closely monitored.

Exploring blended group interventions for depression: Randomised controlled feasibility study of a blended computer- and multimedia-supported psychoeducational group intervention for adults with depressive symptoms.

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.

Diagnostic and prognostic accuracy of galectin-3 and soluble ST2 for acute heart failure.

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.

Reference values of galectin-3 and cardiac troponins derived from a single cohort of healthy blood donors.

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.

Interleukin 6, galectin 3, growth differentiation factor 15, and soluble ST2 for mortality prediction in critically ill patients.

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.

Association of the biomarkers soluble ST2, galectin-3 and growth-differentiation factor-15 with heart failure and other non-cardiac diseases.

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.

Plasma concentrations of novel cardiac biomarkers before and after hemodialysis session.

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.

The single nucleotide polymorphism Gly482Ser in the PGC-1α gene impairs exercise-induced slow-twitch muscle fibre transformation in humans.

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.