Albumin of People with Diabetes Mellitus Is More Reduced at Low HbA1c.

Oxidative stress is involved in the development, progression, and complications of diabetes mellitus (DM). Oxidative modification of human serum albumin's cysteine-34 is a marker for oxidative stress-related pathological conditions. We aimed to evaluate the redox state of albumin in patients with DM to investigate possible correlations with age, diabetes duration, and disease control status. Plasma aliquots were collected from 52 participants (26 type 1 and 26 type 2 DM). Patients were divided into two groups according to their glycated hemoglobin levels less than or equal to and greater than 58 mmol/L. Albumin redox state was assessed with high-performance liquid chromatography by fractionating it into human mercaptalbumin (HMA) and human nonmercaptalbumin 1 and 2 (HNA1 and HNA2). Albumin redox fractions were differently related to the age of study participants. In age-matched T1DM and T2DM groups, the albumin redox state was essentially the same. Irreversibly oxidized HNA2 was positively correlated with diabetes duration, especially in the T1DM group. HNA was increased in people with an increased HbA1c (>58 mmol/mol). Our results support the hypothesis that oxidative stress plays a crucial role in DM pathogenesis and emphasize the importance of diabetes control on systemic oxidative burden.

Metformin Impedes Oxidation of LDL In Vitro.

Metformin is the most commonly prescribed glucose-lowering drug for the treatment of type 2 diabetes. The aim of this study was to investigate whether metformin is capable of impeding the oxidation of LDL, a crucial step in the development of endothelial dysfunction and atherosclerosis. LDL was oxidized by addition of CuCl2 in the presence of increasing concentrations of metformin. The extent of LDL oxidation was assessed by measuring lipid hydroperoxide and malondialdehyde concentrations, relative electrophoretic mobilities, and oxidation-specific immune epitopes. Cytotoxicity of oxLDL in the vascular endothelial cell line EA.hy926 was assessed using the alamarBlue viability test. Quantum chemical calculations were performed to determine free energies of reactions between metformin and radicals typical for lipid oxidation. Metformin concentration-dependently impeded the formation of lipid hydroperoxides, malondialdehyde, and oxidation-specific immune epitopes when oxidation of LDL was initiated by addition of Cu2+. The cytotoxicity of oxLDL was reduced when it was obtained under increasing concentrations of metformin. The quantum chemical calculations revealed that only the reaction of metformin with hydroxyl radicals is exergonic, whereas the reactions with hydroperoxyl radicals or superoxide radical anions are endergonic. Metformin, beside its glucose-lowering effect, might be a suitable agent to impede the development of atherosclerosis and associated CVD. This is due to its capability to impede LDL oxidation, most likely by scavenging hydroxyl radicals.

Prediction of Enzyme Catalysis by Computing Reaction Energy Barriers via Steered QM/MM Molecular Dynamics Simulations and Machine Learning.

The prediction of enzyme activity is one of the main challenges in catalysis. With computer-aided methods, it is possible to simulate the reaction mechanism at the atomic level. However, these methods are usually expensive if they are to be used on a large scale, as they are needed for protein engineering campaigns. To alleviate this situation, machine learning methods can help in the generation of predictive-decision models. Herein, we test different regression algorithms for the prediction of the reaction energy barrier of the rate-limiting step of the hydrolysis of mono-(2-hydroxyethyl)terephthalic acid by the MHETase ofIdeonella sakaiensis. As a training data set, we use steered quantum mechanics/molecular mechanics (QM/MM) molecular dynamics (MD) simulation snapshots and their corresponding pulling work values. We have explored three algorithms together with three chemical representations. As an outcome, our trained models are able to predict pulling works along the steered QM/MM MD simulations with a mean absolute error below 3 kcal mol-1 and a score value above 0.90. More challenging is the prediction of the energy maximum with a single geometry. Whereas the use of the initial snapshot of the QM/MM MD trajectory as input geometry yields a very poor prediction of the reaction energy barrier, the use of an intermediate snapshot of the former trajectory brings the score value above 0.40 with a low mean absolute error (ca. 3 kcal mol-1). Altogether, we have faced in this work some initial challenges of the final goal of getting an efficient workflow for the semiautomatic prediction of enzyme-catalyzed energy barriers and catalytic efficiencies.

Determination of binding characteristics as a measure for effective albumin using different methods.

BACKGROUND & AIMS: Transport functions of albumin are of clinical and pharmacological interest and are determined by albumin's properties like posttranslational modifications or bound ligands. Both are affected in pathological conditions and in therapeutic grade albumin solutions. The term effective albumin concentration was introduced as a measure of functionally intact albumin. Our aim was to evaluate the impact of ligands and modifications with different approaches as a measure of effective albumin. APPROACH & RESULTS: We used a spin labelled fatty acid and dansylsarcosine to characterize binding properties of albumin i) prepared from plasma of patients and healthy control donors, ii) measured directly out of plasma, iii) research grade albumin, iv) in vitro modified albumin, and v) therapeutic infusion solutions before and after removal of stabilizers. Bilirubin is the main determinant for binding function in patients' albumin. In in vitro prepared albumin bound fatty acids correlated with impaired binding. Human nonmercaptalbumin1, not human nonmercaptalbumin2, showed reduced binding properties. Binding and transport function of therapeutic albumin was severely impaired and restored by filtration. Glycation of research grade albumin had no effect on the binding of dansylsarcosine and only a minor effect on fatty acid binding. CONCLUSIONS: Our results suggest that effective albumin -in terms of binding properties- is primarily determined by bound ligands and only to a minor extent by posttranslational modifications. Characterizing albumin directly from plasma better reflects the physiological situation whereas in the case of therapeutic grade albumin stabilizers should be removed to make its binding properties accessible.

Location matters: Overlooked ethnic-geographic effect in China and Austria on propofol/cisatracurium sex differences among a population pharmacokinetic/pharmacodynamic (PopPK/PD) covariate analysis in men, women, and one transgender subject.

A quick literature search using "sex/gender" vs. the commonly used hypnotic propofol or neuromuscular-blocking agent cisatracurium will reveal numerous contradictory sex difference publications depending on the ethnic-geographic location of where these studies were conducted. We induced anesthesia with cisatracurium besylate (GlaxoSmithKline) 100 µg kg-1 administered exactly 1 minute following propofol (AstraZeneca) 2 mg kg-1 . In 20 male and 20 female ethnic Han-Chinese test set patients (Xi'an China), and in similar ethnic white Austrian validation set patients (Graz Austria), we quantified propofol/cisatracurium pharmacodynamic parameters namely propofol onset time, lag time, plasma concentrations (Cp ) at loss-of-behavioral response (LOBR) using bispectral index (BIS); cisatracurium onset time, lag time, and Cp at T1 % (first twitch of train-of-four) complete twitch suppression using mechanomyography (MMG). Serial arterial blood samples were collected for population pharmacokinetic (PopPK) analysis of all demographic and biological covariates (region, sex, age, weight, and height) versus volumes of distribution and clearances pharmacokinetic parameters. In Chinese women (but not in white women), propofol Cp at LOBR was 33.60% lower than men and cisatracurium Cp at T1 % complete twitch suppression was 21.49% lower than men, a clear pharmacodynamic assertion. Region and weight were significant PopPK covariates. We demonstrated that sex differences are influenced by ethnic-geographic location as only in Chinese women (but not in white women) propofol Cp at LOBR and cisatracurium Cp at T1 % complete twitch suppression were lower than in men. When defining sex differences, ethnic-geographic location should be taken into consideration as a predictive factor for optimizing propofol/cisatracurium initial loading recommended dosages.

Only Subclinical Alterations in the Haemostatic System of People with Diabetes after COVID-19 Vaccination.

People with diabetes have an increased risk of experiencing adverse COVID-19 outcomes. COVID-19 vaccination is, therefore, highly recommended. However, people with diabetes have an inherently elevated risk of thrombotic events and the impact of the vaccination on the coagulation system in this patient population remains to be elucidated. The aim of this study was to investigate the impact of COVID-19 vaccination on the haemostatic system in people with type 1 or type 2 diabetes. We evaluated the effects of COVID-19 vaccination (BioNTech Pfizer, Moderna, AstraZeneca) on standard coagulation parameters, whole blood coagulation (Thrombelastometry), platelet function (impedance aggregation), and thrombin generation (calibrated automated thrombography) in people with type 1 diabetes mellitus (n = 41) and type 2 diabetes mellitus (n = 37). Blood sampling points were prior to vaccination and two weeks after the respective vaccination. Thrombelastometry measurements indicated moderately increased clot formation post-vaccination in people with type 1, as well as with type 2, diabetes: "Clot formation times" were significantly shorter, and both "maximum clot firmness" and "alpha angles" were significantly higher, as compared to the respective pre-vaccination values. Therefore, TEM parameters were not altered after vaccination in patients receiving ASA. Moreover, platelet aggregation was enhanced in people with type 1 diabetes, and plasma levels of D-Dimer were increased in people with type 2 diabetes, following COVID-19 vaccination. All other standard coagulation parameters, as well as thrombin generation, were not affected by the vaccination. The coagulation responses of people with diabetes to COVID-19 vaccination were only subclinical and comparable to those observed in healthy individuals. Our findings suggest that people with diabetes do not face an increased activation of the coagulation post-vaccination.

Propofol-Bispectral Index (BIS) Electroencephalography (EEG) Pharmacokinetic-Pharmacodynamic Model in Patients With Post-Cerebral Hemorrhage Hydrocephalus.

Background. Titrating hypnotic agents for patients who suffer from a cerebral insult is a challenging task. To date there is no real gold standard to precisely quantify electroencephalography (EEG) response in a fashion that could be utilized for patients with post-cerebral hemorrhage hydrocephaly. While we must administer "as per usual" analgesics for noxious stimuli, we have to administer the hypnotic agents more "sparingly" due to lack of objective monitoring. Methods. We compared 15 adult post-cerebral hemorrhage hydrocephalus patients undergoing ventriculo-peritoneal shunt placement with 15 controls matched for gender and approximate age. We set propofol target controlled infusion estimated plasma concentrations (Cp) to gradually reach 4 µg/mL over 4 minutes. To precisely quantify post-cerebral hemorrhage mental dysfunction, we used electronically retrieved bispectral index (BIS) and propofol Cp data points to create individual inhibitory monophasic mathematical model for each patient that incorporates an independent hysteresis "lag" function. Results. In post-cerebral hemorrhage patients Cp-BIS curve, C50 (propofol concentration associated with inhibitory 50% BIS response) cutoff point was significantly shifted to the left by 39%. Whereas before infusion and at stable propofol 4 µg/mL aneurismal surgical sides ipsilateral (75 ± 13, 25 ± 9) and contralateral (73 ± 15, 27 ± 9) mean ± SD BIS values were significantly lower than ipsilateral (95 ± 3, 46 ± 12) and contralateral (94 ± 3, 46 ± 12) matched controls. Conclusions. Using BIS as surrogate marker of propofol hypnotic effect, BIS monitoring in patients with post-cerebral hemorrhage hydrocephaly showed a pattern of change and trend that was similar albeit 39% significantly lower than subjects without.

Coagulation Changes during Central Hypovolemia across Seasons.

Lower body negative pressure (LBNP) application simulates hemorrhage. We investigated how seasons affect coagulation values at rest and during LBNP. Healthy participants were tested in cold (November-April) and warm (May-October) months. Following a 30-min supine period, LBNP was started at -10 mmHg and increased by -10 mmHg every five minutes until a maximum of -40 mmHg. Recovery was for 10 min. Blood was collected at baseline, end of LBNP, and end of recovery. Hemostatic profiling included standard coagulation tests, calibrated automated thrombogram, thrombelastometry, impedance aggregometry, and thrombin formation markers. Seven men (25.0 ± 3.6 years, 79.7 ± 7.8 kg weight, 182.4 ± 3.3 cm height, and 23.8 ± 2.3 kg/m2 BMI) and six women (25.0 ± 2.4 years, 61.0 ± 8.4 kg weight, 167 ± 4.7 cm height, and 21.8 ± 2.4 kg/m2 BMI) participated. Baseline levels of prothrombin (FII), tissue factor (TF) and markers for thrombin generation F1+2 and the thrombin/antithrombin complex (TAT) were higher during summer. Factor VIII, prothrombin fragment 1+2 (F1+2), TAT and the coagulation time showed significant increases during LBNP in both seasons. Some calibrated automated thrombography variables (Calibrated automated thrombography (CAT): lag, time to peak (ttPeak), peak) shifted in a procoagulant direction during LBNP in summer. Red blood cell counts (RBC), hemoglobin and white blood cell counts (WBC) decreased during LBNP. LBNP application reduced prothrombin time in winter and activated partial thromboplastin time in summer. Greater levels of FII, TF, F1+2, and TAT-a more pronounced LBNP-induced procoagulative effect, especially in CAT parameters (lag time (LT), Peak, ttPeak, Velindex)-were seen in summer. These results could have substantial medical implications.

Menstrual Phase Affects Coagulation and Hematological Parameters during Central Hypovolemia.

BACKGROUND: It has been reported that women have a higher number of heart attacks in the "follicular phase" of the menstrual cycle. We, therefore, tested the hypothesis that women in the follicular phase exhibit higher coagulability. As lower body negative pressure (LBNP) has been used previously to assess coagulation changes in whole blood (WB) samples in men and women, effects of menstrual phase on coagulation was assessed during LBNP. METHODS: Seven women, all healthy young participants, with no histories of thrombotic disorders and not on medications, were tested in two phases of the menstrual cycle (early follicular (EF) and mid-luteal (ML)). LBNP was commenced at -10 mmHg and increased by -10 mmHg every 5 min until a maximum of -40 mmHg. Recovery up to 10 min was also monitored. Blood samples were collected at baseline, at end of LBNP, and at end of recovery. Hemostatic profiling included comparing the effects of LBNP on coagulation values in both phases of the menstrual cycle using standard coagulation tests, calibrated automated thrombogram, thrombelastometry, impedance aggregometry, and markers of thrombin formation. RESULTS: LBNP led to coagulation activation determined in both plasma and WB samples. During both phases, coagulation was affected during LBNP, as reflected in their decreased partial thromboplastin time (PTT) and elevated coagulation factor VIII FVIII, F1 + 2, and thrombin-antithrombin (TAT) levels. Additionally, during the ML phase, greater PT [%] and shorter time to peak (ttPeak) values (implying faster maximum thrombin formation) suggest that women in the ML phase are relatively hypercoagulable compared to the early follicular phase. CONCLUSIONS: These results suggest that thrombosis occurs more during the midluteal phase, a finding with substantial medical implications.

Age progression from vicenarians (20-29 year) to nonagenarians (90-99 year) among a population pharmacokinetic/pharmacodynamic (PopPk-PD) covariate analysis of propofol-bispectral index (BIS) electroencephalography.

BACKGROUND: Pharmacokinetic/pharmacodynamic (PK/PD) modeling has made an enormous contribution to intravenous anesthesia. Because of their altered physiological, pharmacological and pathological aspects, titrating general anesthesia in the elderly is a challenging task. METHODS: Eighty patients were consecutively enrolled divided by decades from vicenarians (20-29 year) to nonagenarians (90-99 year) into eight groups. Using target controlled infusion (TCI) and electroencephalographic (EEG)-derived bispectral index (BIS) we set propofol plasma concentration (Cp) to gradually reach 3.5 µg mL-1 over 3.5-min. In each patient, we constructed a PK/PD model and conducted a population PK/PD (PopPK-PD) covariate analysis. RESULTS: Age was significant covariate for baseline BIS effect (E0), inhibitory propofol concentration at 50% BIS decline (IC50) and maximum BIS decline (Emax). First-order rate constant Ke0 of 0.47 min-1 in vicenarians (20-29 year) gradually increased with age-progression to 1.85 min-1 in nonagenarians (90-99 year). Simulation modelling showed that clinically recommended Cp of 3.5 µg mL-1 for 20-29 year BIS 50 should be reduced to 3.0 for 30-49 year, 2.5 for 50-69 year and 2.0 for 80-89 year. CONCLUSION: We quantified and graded EEG-BIS age-progression among different age groups divided by decades. We demonstrated deeper BIS values with decades' age progression. Our data has important implications for propofol dosing. The practical information for physicians in their daily clinical practice is using propofol Cp of 3.5 µg mL-1 might not yield BIS value of 50 in elderly patients. Our simulations showed that the recommended regimen of Cp 3.5 µg mL-1 for 20-29 year should be gradually decreased to 2.0 µg mL-1 for 80-89 year. CLINICAL TRIAL REGISTRY NUMBERS: European Community Clinical Trials Database EudraCT (http://eudract.emea.eu) initial trial registration number: 2011-002847-81, and subsequently registered at www.clinicaltrials.gov; trial registration number: NCT02585284. Xijing Hospital of Fourth Military Medical University ethics committee approval number 20110707-4.

Gender differences in albumin and ascorbic acid in the vitreous antioxidant system.

Ascorbic acid is present at high concentrations in the vitreous and plays a central role in vitreous redox chemistry. Albumin is the main protein in the vitreous with antioxidant properties and occurs in different oxidation states, which can be used as redox indicators, but have not been studied in the vitreous. This study, therefore, addressed the vitreous redox state of cysteine-34 of albumin in relation to the ascorbic acid content, which has been suggested to exert a main function in detoxifying reactive oxygen in the vitreous. A total of 58 vitreous samples obtained from patients undergoing vitrectomy were analyzed for (i) human mercaptalbumin (HMA), the reduced thiol form; (ii) human non-mercaptalbumin1 (HNA1), a reversible oxidative modification with a disulfide at cysteine-34; and (iii) human non-mercaptalbumin2 (HNA2), a non-reversibly (highly) oxidized form of albumin; as well as (iv) ascorbic acid concentrations, to study possible relations. In addition, blood samples were taken to compare albumin redox state between plasma and the vitreous. Vitreous albumin showed greater variability in the redox state of cysteine-34 and a shift to the oxidized fractions compared to plasma albumin (P < 0.001). A strong positive relation was observed between the vitreous ascorbic acid concentrations and the reversibly oxidized form, HNA1 (P < 0.001), and a negative relation with the reduced form, HMA. Positive relations between ascorbic acid and HNA1 in the vitreous were stronger in men than in women. In contrast to HMA and HNA1, there was a distinct gender difference noted for the irreversibly oxidized form, HNA2. While males showed a positive relation between the vitreous ascorbic acid concentrations and HNA2, there was no correlation found with HNA2 in females. Our results support the view that ascorbic acid, by decreasing either directly or indirectly the concentrations of molecular oxygen, generates hydrogen peroxide, and that thiols, including HMA, are acting as antioxidants. This study for the first time provides evidence that vitreous albumin can be used as a marker molecule for the appearance of reactive oxygen species in the vitreous of patients undergoing vitrectomy. Moreover, it can be shown that there are gender differences in vitreous ascorbic acid and albumin concentrations as well as in oxidation state of vitreous albumin.

Mortality in dialysis patients with cinacalcet use: A large observational registry study.

BACKGROUND: Secondary hyperparathyroidism (sHPT) is associated with higher mortality in dialysis patients. The calcimimetic cinacalcet reduces intact parathyroid hormone (iPTH) in dialysis patients. The randomized controlled EVOLVE trial failed to unequivocally prove survival advantage of cinacalcet in dialysis patients. However, recent post hoc analyses suggested a benefit in subgroups of dialysis patients. Large observational cohort studies may represent an option to better determine such subgroups. METHODS: Data from the nationwide Austrian registry of dialysis patients between January 2004 and December 2009 were analyzed with follow-up until December 2010. All-cause and cardiovascular mortality analyses were performed using the Kaplan-Meier and Cox proportional hazards regression. To reduce confounding effects a propensity score (PS) based method (matching by stratification) was used for group comparison. RESULTS: The cohort included 7983 dialysis patients, 1572 (19.7%) were prescribed cinacalcet. During a median follow-up of 2.7years, 3574 (44.8%) patients died, including 1342 (16.8%) deaths from cardiovascular causes. Survival analyses in the PS-matched study population (n=6109) showed lower all-cause mortality for cinacalcet-treated as compared to untreated patients only in subsets characterized by younger age, low prevalence of diabetes, iPTH levels between 300 and 599pg/mL, concomitant therapy with vitamin D and phosphate binders. CONCLUSIONS: Our data suggest that a subgroup of dialysis patients, namely those with moderate sHPT, younger age and without diabetes benefit from cinacalcet with reduced overall and cardiovascular mortality. These findings may help to identify populations for further controlled trials and may allow a more individualized sHPT treatment using cinacalcet in specific patient subgroups.

Orthostatic Challenge Shifts the Hemostatic System of Patients Recovered from Stroke toward Hypercoagulability.

Aims: The objective of our study was to assess the effects of orthostatic challenge on the coagulation system in patients with a history of thromboembolic events and to assess how they compared with age-matched healthy controls. Methods: Twenty-two patients with histories of ischemic stroke and 22 healthy age-matched controls performed a sit-to-stand test. Blood was collected prior to- and at the end of- standing in the upright position for 6 min. Hemostatic profiling was performed by determining thrombelastometry and calibrated automated thrombogram values, indices of thrombin generation, standard coagulation times, markers of endothelial activation, plasma levels of coagulation factors and copeptin, and hematocrit. Results: Orthostatic challenge caused a significant endothelial and coagulation activation in patients (Group 1) and healthy controls (Group 2): Plasma levels of prothrombin fragment F1+2 were increased by approximately 35% and thrombin/antithrombin-complex (TAT) increased 5-fold. Several coagulation variables were significantly altered in Group 1 but not in Group 2: Coagulation times (CTs) were significantly shortened and alpha angles, peak rate of thrombin generation (VELINDEX), tissue factor (TF) and copeptin plasma levels were significantly increased (comparison between standing and baseline). Moreover, the shortening of CTs and the rise of copeptin plasma levels were significantly higher in Group 1 vs. Group 2 (comparison between groups). Conclusion: The coagulation system of patients with a history of ischemic stroke can be more easily shifted toward a hypercoagulable state than that of healthy controls. Attentive and long-term anticoagulant treatment is essential to keep patients from recurrence of vascular events.

Medical University admission test: a confirmatory factor analysis of the results.

BACKGROUND: The Graz Admission Test has been applied since the academic year 2006/2007. The validity of the Test was demonstrated by a significant improvement of study success and a significant reduction of dropout rate. The purpose of this study was a detailed analysis of the internal correlation structure of the various components of the Graz Admission Test. In particular, the question investigated was whether or not the various test parts constitute a suitable construct which might be designated as "Basic Knowledge in Natural Science." METHODS: This study is an observational investigation, analyzing the results of the Graz Admission Test for the study of human medicine and dentistry. A total of 4741 applicants were included in the analysis. Principal component factor analysis (PCFA) as well as techniques from structural equation modeling, specifically confirmatory factor analysis (CFA), were employed to detect potential underlying latent variables governing the behavior of the measured variables. RESULTS: PCFA showed good clustering of the science test parts, including also text comprehension. A putative latent variable "Basic Knowledge in Natural Science," investigated by CFA, was indeed shown to govern the response behavior of the applicants in biology, chemistry, physics, and mathematics as well as text comprehension. The analysis of the correlation structure of the various test parts confirmed that the science test parts together with text comprehension constitute a satisfactory instrument for measuring a latent construct variable "Basic Knowledge in Natural Science." CONCLUSIONS: The present results suggest the fundamental importance of basic science knowledge for results obtained in the framework of the admission process for medical universities.

The chronic kidney disease epidemiology collaboration equation combining creatinine and cystatin C accurately assesses renal function in patients with cirrhosis.

BACKGROUND: Accurate measurement of renal function in cirrhotic patients is still challenging. To find the best test for the determination of the true glomerular filtration rate (GFR) in cirrhotic patients this study prospectively compared measured (m)GFR, the gold standard, with estimated (e)GFR using equations based on serum levels of creatinine and cystatin C. METHODS: GFR was measured by sinistrin clearance using the bolus method in 50 patients with cirrhosis (Child Turcotte Pugh score A, B and C) and 24 age-matched healthy subjects as controls. Measured (m)GFR was compared to eGFR using bias, accuracy 10 % and 30 %, as well as correlation coefficients. RESULTS: Creatinine-based equations generally overestimated GFR in patients with cirrhosis and showed a bias (average difference between mGFR and eGFR) of -40 (CG), -12 (MDRD) and -9 (CKD-EPI-Cr) ml/min/1.73 m(2). Cystatin C-based equations underestimated GFR, especially in patients with Child Turcotte Pugh score C (bias 17 ml/min/1.73 m(2)for CKD-EPI-CysC). Of these equations, the CKD-EPI equation that combines creatinine and cystatin C (CKD-EPI-Cr-CysC) showed a bias of 0.12 ml/min/1.73 m(2) as compared to measured GFR. CONCLUSIONS: The CKD-EPI equation that combines serum creatinine and cystatin C measurements shows the best performance for accurate estimation of GFR in cirrhosis, especially at advanced stages.

Effects of Exercise and Nutrition on the Coagulation System During Bedrest Immobilization.

Immobilization in hospitalized medical patients or during simulation of spaceflight induced deconditioning has been shown to be associated with loss of muscle mass and bone. Resistance vibrating exercise (RVE) and/or high protein diet are countermeasures, which are capable of mitigating the adverse effects of immobilization. We investigated the effect of these countermeasures on the coagulation system. Two groups of volunteers, each of whom performed such countermeasures, were enrolled in the study. Volunteers, who did nothing while bed rested, served as controls. The berest and the intervention protocols were carried out at Clinique d' Investigation, MEDES, Toulouse, France. Eleven healthy men volunteered for this randomized crossover study. The subjects underwent 21 day of 6° head down bed rest (HDBR) followed by a washout period of 4 months. The first group followed an exercise schedule using resistance-vibrating exercise (RVE group). The second group also used the RVE but complemented it with high-protein supplement diet (NeX group). The third group only did bed rest. The highly sensitive methods calibrated automated thrombography (CAT) and thrombelastometry (TEM) were applied to monitor hemostatic changes. In all 3 groups, the hemostatic system shifted toward hypocoagulability during bed rest. For example, peak and thrombin formation velocity (VELINDEX) reduced in this period. Interestingly, a tendency toward hypercoagulation was observed during re-ambulation. In all 3 groups, ttPeak and StartTail were reduced, and Peak and VELINDEX (except in the RVE group) were significantly higher in relation to baseline values. Influence of bed rest on the coagulation system in the 2 groups performing countermeasures (RVE and NeX group) was the same as in the control bed-rested group. Clotting does not seem to be worsened by prolonged immobilization, or by countermeasures such as RVE/exercise or high-protein supplementation during immobilization. Therefore, only hospitalized medical patients at an elevated risk for thrombosis should be treated with anticoagulants. However, clinicians have to be aware that the re-ambulation period following immobilization might be associated with an elevated risk of thrombotic events.

Situational judgment test as an additional tool in a medical admission test: an observational investigation.

BACKGROUND: In the framework of medical university admission procedures the assessment of non-cognitive abilities is increasingly demanded. As tool for assessing personal qualities or the ability to handle theoretical social constructs in complex situations, the Situational Judgment Test (SJT), among other measurement instruments, is discussed in the literature. This study focuses on the development and the results of the SJT as part of the admission test for the study of human medicine and dentistry at one medical university in Austria. METHODS: Observational investigation focusing on the results of the SJT. 4741 applicants were included in the study. To yield comparable results for the different test parts, "relative scores" for each test part were calculated. Performance differences between women and men in the various test parts are analyzed using effect sizes based on comparison of mean values (Cohen's d). The associations between the relative scores achieved in the various test parts were assessed by computing pairwise linear correlation coefficients between all test parts and visualized by bivariate scatterplots. RESULTS: Among successful candidates, men consistently outperform women. Men perform better in physics and mathematics. Women perform better in the SJT part. The least discriminatory test part was the SJT. A strong correlation between biology and chemistry and moderate correlations between the other test parts except SJT is obvious. The relative scores are not symmetrically distributed. CONCLUSIONS: The cognitive loading of the performed SJTs points to the low correlation between the SJTs and cognitive abilities. Adding the SJT part into the admission test, in order to cover more than only knowledge and understanding of natural sciences among the applicants has been quite successful.

The Effect of Mammalian Target of Rapamycin Versus Calcineurin Inhibitor-based Immunosuppression on Measured Versus Estimated Glomerular Filtration Rate After Orthotopic Liver Transplantation.

INTRODUCTION: Mammalian target of rapamycin (mTOR) inhibitors have been proposed to preserve renal function in patients after orthotopic liver transplantation (OLT) based on estimated glomerular filtration rate (eGFR). The presented study evaluated their effect on renal function in comparison to calcineurin inhibitors (CNIs) defined by measured GFR. METHODS: Renal function was measured in patients on mTOR-based (n=28) or on CNI-based (n=51) immunosuppression after OLT by performing inulin clearance (IC) as well as eGFR based on the Modification of Diet in Renal Disease (MDRD4) Study and the chronic kidney disease epidermiology (CKD-EPI) formula at baseline, 6, 12, 18, and 24 months. Statistical analysis was performed by using analysis of variance and serial measurement testing. RESULTS: The MDRD4 and the IC values differed significantly at study inclusion in both groups (mTOR and CNI group, P=0.001), whereas the CKD-EPI and the IC values did not. Estimated GFR by the MDRD4 results declined throughout the study period in patients on CNI and in patients on mTOR (CNI, 81 vs. 61 mL/min/1.73 m(2), P=0.01; 82 vs. 60 mL/min/1.73 m(2), P=0.01), whereas CKD EPI and measured GFR did not change throughout the study period in the CNI. CONCLUSION: The use of eGFR especially the MDRD-based formula, in OLT patients, leads to incorrect interpretation of their renal function.

Time: an underestimated variable in minimizing the gender gap in medical college admission scores.

BACKGROUND: Results of medical college admission tests in Austria demonstrate the slightly worse performance of women, and are the basis for discussions around fairness and a basic science knowledge gap among female applicants. PURPOSE: The purpose of this article was to investigate a basic science knowledge gap among female candidates of the admission test at the Medical University of Graz, and to evaluate whether the point of time of taking the examination has an influence on the test results. METHODS: Observational investigations of the results of the admission test at the Medical University of Graz were performed. A total of 3405 applicants were included in the study. Statistical analyses were performed by routine methods. RESULTS: Male Austrian applicants are invariably more successful than female Austrian applicants when they pass the admission test immediately after completing secondary education. When female as well as male candidates pass the admission test 1 year after completion of secondary education, the differences in the results are no longer statistically significant. CONCLUSIONS: A basic science knowledge gap in the Austrian applicants can be confirmed. The variable time can be interpreted as an opportunity for the reduction of a basic science knowledge gap.