Ventral striatal hypoactivation is associated with apathy but not diminished expression in patients with schizophrenia.

BACKGROUND: Negative symptoms of schizophrenia can be grouped in 2 dimensions: apathy and diminished expression. Increasing evidence suggests that negative symptoms are associated with altered neural activity of subcortical and cortical regions in the brain reward system. However, the neurobiological basis of the distinct symptom dimensions within negative symptoms is still poorly understood. The primary aim of our study was to examine the neural correlates of the negative symptom dimensions apathy and diminished expression during a reward processing task. METHODS: Patients with schizophrenia and healthy controls underwent event-related fMRI while performing a variant of the Monetary Incentive Delay Task. We assessed negative symptom dimensions using the Brief Negative Symptom Scale. RESULTS: We included 27 patients and 25 controls in our study. Both groups showed neural activation indicated by blood oxygen-level dependent signal in the ventral striatum during reward anticipation. Ventral striatal activation during reward anticipation showed a strong negative correlation with apathy. Importantly, this effect was not driven by cognitive ability, medication, depressive or positive symptoms. In contrast, no significant correlation with the diminished expression dimension was observed. LIMITATIONS: Although the results remain significant when controlling for chlorpromazine equivalents, we cannot fully exclude potential confounding effects of medication with atypical antipsychotics. CONCLUSION: The specific correlation of ventral striatal hypoactivation during reward anticipation with apathy demonstrates a differentiation of apathy and diminished expression on a neurobiological level and provides strong evidence for different pathophysiological mechanisms underlying these 2 negative symptom dimensions. Our findings contribute to a multilevel framework in which apathy and motivational impairment in patients with schizophrenia can be described on psychopathological, behavioural and neural levels.

The brief negative symptom scale: validation of the German translation and convergent validity with self-rated anhedonia and observer-rated apathy.

BACKGROUND: Negative symptoms are considered core symptoms of schizophrenia. The Brief Negative Symptom Scale (BNSS) was developed to measure this symptomatic dimension according to a current consensus definition. The present study examined the psychometric properties of the German version of the BNSS. To expand former findings on convergent validity, we employed the Temporal Experience Pleasure Scale (TEPS), a hedonic self-report that distinguishes between consummatory and anticipatory pleasure. Additionally, we addressed convergent validity with observer-rated assessment of apathy with the Apathy Evaluation Scale (AES), which was completed by the patient's primary nurse. METHODS: Data were collected from 75 in- and outpatients from the Psychiatric Hospital, University Zurich diagnosed with either schizophrenia or schizoaffective disorder. We assessed convergent and discriminant validity, internal consistency and inter-rater reliability. RESULTS: We largely replicated the findings of the original version showing good psychometric properties of the BNSS. In addition, the primary nurses evaluation correlated moderately with interview-based clinician rating. BNSS anhedonia items showed good convergent validity with the TEPS. CONCLUSIONS: Overall, the German BNSS shows good psychometric properties comparable to the original English version. Convergent validity extends beyond interview-based assessments of negative symptoms to self-rated anhedonia and observer-rated apathy.

Serum level of IP-10 increases predictive value of IL28B polymorphisms for spontaneous clearance of acute HCV infection.

BACKGROUND & AIMS: Single nucleotide polymorphisms (SNPs) in IL28B and serum levels of interferon γ inducible protein 10 (IP-10) predict outcomes of antiviral therapy in patients with chronic hepatitis C. We associated IL28B SNPs rs12979860 and rs8099917, along with serum levels of IP-10, with outcomes of patients with acute hepatitis C (AHC). METHODS: We studied 120 patients with AHC (64 male; 37 ± 16 years old) and 96 healthy individuals (controls). The IL28B SNPs rs12979860 and rs8099917 were detected using real-time polymerase chain reaction; serum concentrations of IP-10 were measured by enzyme-linked immunosorbent assays of 62 patients with AHC. RESULTS: Hepatitis C virus was cleared spontaneously from 59 patients (49.2%). The IL28B rs12979860 C/C genotype was more frequent among patients with AHC than controls (62.5% vs 39.6%; P < .001) and among patients with spontaneous clearance than those without (74.6% vs 51.7%; P = .02) (positive predictive value, 60.3%). Patients with IL28B rs12979860 C/C more frequently developed jaundice (53.2% vs 27.6%; P = .022) than carriers of the T allele. The median level of IP-10 was lower among patients with AHC and spontaneous clearance (764 [113-2470] pg/mL) than those without spontaneous clearance (1481 [141-4412] pg/mL; P = .006). Based on receiver operating characteristic analysis, 540 pg/mL IP-10 was set as the cutoff for patients most likely to have spontaneous clearance (positive predictive value, 71.4%; negative predictive value, 65.9%). Including data on IP-10 levels increased the ability of the IL28B rs12979860 C/C to identify patients most likely to have spontaneous clearance (83% of those who had an IP-10 level <540 pg/mL and 32% who had an IP-10 level >540 pg/mL) (P < .01). CONCLUSIONS: The combination of serum level of IP-10 and SNPs in IL28B can identify patients with AHC who are most likely to undergo spontaneous clearance and those in need of early antiviral therapy.

Peginterferon alfa-2a/ribavirin for 48 or 72 weeks in hepatitis C genotypes 1 and 4 patients with slow virologic response.

BACKGROUND & AIMS: This randomized multicenter trial evaluated individualization of treatment duration with peginterferon alfa-2a 180 microg/wk plus ribavirin 1000/1200 mg/day in patients with chronic hepatitis C genotype 1/4 based on the rapidity of virologic response (VR). METHODS: Patients with a rapid VR (RVR; undetectable hepatitis C virus [HCV]-RNA level (<50 IU/mL at week 4) were treated for 24 weeks, those with an early VR (EVR; no RVR but undetectable HCV-RNA level or >or=2-log(10) decrease at week 12) were randomized to 48 (group A) or 72 weeks of treatment (group B; peginterferon alfa-2a was reduced to 135 microg/wk after week 48). Patients without an EVR continued treatment until week 72 if they had undetectable HCV-RNA levels at week 24. The primary end point was relapse; sustained VR (SVR; undetectable HCV-RNA level after 24 weeks of follow-up evaluation) was a secondary end point. RESULTS: Of 551 genotype 1/4 patients starting treatment, 289 were randomized to group A (N = 139) or group B (N = 150). The relapse rate was 33.6% in group A (95% confidence interval [CI], 24.8%-43.4%) and 18.5% in group B (95% CI, 11.9%-27.6%; P = .0115 vs group A) and the SVR rate was 51.1% (95% CI, 42.5%-59.6%) and 58.6% (95% CI, 50.3%-66.6%; P > .1), respectively. The overall SVR rate was 50.4% (278 of 551; 95% CI, 46.2%-54.7%), including 115 of 150 patients with an RVR treated for 24 weeks and 4 of 78 patients without an EVR. CONCLUSIONS: Extending therapy with peginterferon alfa-2a/ribavirin to 72 weeks decreases the probability of relapse in patients with an EVR. If they can be maintained on extended-duration therapy, SVR rates also may improve.

How far to go in deconstructing negative symptoms? Behavioural and neural level evidence for the amotivation domain.

Negative symptoms in schizophrenia are conceptualised as loading onto two factors: amotivation and diminished expression, which relate to different behavioural and neural markers. This distinction has proven useful for understanding the cognitive, motivational and neural mechanisms involved in negative symptoms, and for the development of treatments. Recently, it has been advocated that an even finer distinction into five subdomains is needed to understand the mechanisms underlying negative symptoms, and to prevent masking specific treatment and intervention effects. However, it is currently unclear whether such a fine-grained approach offers additional insights grounded in theory. In the present work, we focused on the factor amotivation, which has been shown to selectively correlate with the propensity to discount rewards in the face of effort and with the activity in the ventral striatum during reward anticipation. In a reanalysis of these studies we explored whether subdomains of amotivation - avolition, asociality, anhedonia - showed preferential correlation with these previously identified behavioural and neural markers. We show that for both behavioural and neural markers, a fine-grained model with the three subdomains did not better explain the data than a model with the amotivation factor only. Moreover, none of the three subdomains correlated significantly more or less with the behavioural or neural markers. Thus, no additional information was gained on amotivation in schizophrenia by selectively looking at its three subdomains. Consequently, the two-factor solution currently remains a valid option for the study of negative symptoms and further research is needed for behavioural and neural validation of the five-factor model.

Clinical, behavioural and neural validation of the PANSS amotivation factor.

Negative symptoms in schizophrenia have been suggested to map onto two distinct factors - amotivation and diminished expression. Only recently, two-factor solutions for measuring negative symptoms have been proposed for the Positive and Negative Symptom Scale (PANSS), the most commonly used scale to assess the psychopathology of patients with schizophrenia. We aimed to validate the PANSS two-factor structure on a clinical, behavioural and neural level. For this multi-level validation, we reanalysed several datasets with patients for whom both the Brief Negative Symptom Assessment Scale (BNSS) and PANSS data were collected. We used a clinical dataset (n = 120) as well as behavioural data from an effort-based decision making task (n = 31) and functional neuroimaging data from a monetary incentive delay task (n = 41). Both tasks have previously been shown to be associated with BNSS amotivation. On the clinical level, the PANSS amotivation and diminished expression were highly correlated with their BNSS counterparts. On the behavioural level, we found that the PANSS amotivation factor but not the diminished expression factor specifically associated with willingness to invest effort to obtain a reward. On the neural level, PANSS amotivation was specifically related to reduced ventral striatal activation during reward anticipation. Our data confirm that the PANSS clearly allows distinguishing amotivation from diminished expression, as it relates selectively to specific aspects of behaviour and brain function. Our results will allow a re-analysis and sharing of existing datasets that used the PANSS to further substantiate the distinction between the two factors in neuroscientific studies and clinical trials.

Inflexible social inference in individuals with subclinical persecutory delusional tendencies.

It has been suspected that abnormalities in social inference (e.g., learning others' intentions) play a key role in the formation of persecutory delusions (PD). In this study, we examined the association between subclinical PD and social inference, testing the prediction that proneness to PD is related to altered social inference and beliefs about others' intentions. We included 151 participants scoring on opposite ends of Freeman's Paranoia Checklist (PCL). The participants performed a probabilistic advice-taking task with a dynamically changing social context (volatility) under one of two experimental frames. These frames differentially emphasised possible reasons behind unhelpful advice: (i) the adviser's possible intentions (dispositional frame) or (ii) the rules of the game (situational frame). Our design was thus 2 × 2 factorial (high vs. low delusional tendencies, dispositional vs. situational frame). We found significant group-by-frame interactions, indicating that in the situational frame high PCL scorers took advice less into account than low scorers. Additionally, high PCL scorers believed more frequently that incorrect advice was delivered intentionally and that such misleading behaviour was directed towards them personally. Overall, our results suggest that social inference in individuals with subclinical PD tendencies is shaped by negative prior beliefs about the intentions of others and is thus less sensitive to the attributional framing of adviser-related information. These findings may help future attempts of identifying individuals at risk for developing psychosis and understanding persecutory delusions in psychosis.

Peginterferon alfa-2a and ribavirin for 24 weeks in hepatitis C type 1 and 4 patients with rapid virological response.

BACKGROUND & AIMS: This analysis reports the rate of sustained virological response (SVR) in patients infected with hepatitis C virus (HCV) genotype 1 or 4 who were assigned to 24 weeks of treatment with pegylated interferon (peginterferon) alfa-2a 180 mug/wk plus ribavirin 1000/1200 mg/day after achieving a rapid virological response (RVR; HCV RNA level <50 IU/mL) at week 4 in a prospective trial investigating response-guided therapy. METHODS: Non-RVR patients with an early virological response were randomized to 48 or 72 weeks of therapy (this is a still-ongoing trial). RESULTS: A total of 150 of 516 patients (29%) had an RVR, 143 of whom completed 24 weeks of treatment. Younger patients, leaner patients, and those with an HCV RNA level

A randomized, prospective trial of ribavirin 400 mg/day versus 800 mg/day in combination with peginterferon alfa-2a in hepatitis C virus genotypes 2 and 3.

UNLABELLED: We compared the efficacy and tolerability of 24 weeks of treatment with ribavirin 800 mg/day (group A) or 400 mg/day (group B) plus peginterferon alfa-2a 180 mug/week in treatment-naive patients infected with hepatitis C virus (HCV) genotype 2 or 3. A total of 97 of 141 patients randomized to group A (68.8%, 95% confidence interval [CI] 60.5%-76.3%) and 90 of 141 patients randomized to group B (63.8; 95% CI 55.3%-71.7%) achieved a sustained virological response, defined as undetectable serum HCV RNA at the end of untreated follow-up (week 48). Among patients infected with genotype 3, the rate of sustained virological response was 67.5% (95% CI 58.4%-75.6%) in group A and 63.9% (95% CI 54.7%-72.4%) in group B, and among patients infected with genotype 2, the rate of sustained virological response was 77.8% (95% CI 54.2%-93.6%) in group A and 55.6% (95% CI 38.4%-83.7%) in group B. Relapse rates in the 2 treatment groups were similar (17% in group A and 20% in group B). The incidence of adverse events, laboratory abnormalities, and dose reductions was similar in the 2 treatment groups. CONCLUSION: The results suggest that when administered for 24 weeks with peginterferon alfa-2a, ribavirin doses of 400 and 800 mg/day produce equivalent outcomes in patients infected with HCV genotype 3.

[Insulin pump therapy in children, adolescents and adults, guidelines (Update 2019)]. / Insulinpumpentherapie bei Kindern, Jugendlichen und Erwachsenen (Update 2019).

This position statement is based on current evidence available on the safety and benefits of continuous subcutaneous insulin infusion therapy (CSII, pump therapy) in diabetes with an emphasis on the effects of CSII on glycemic control, hypoglycaemia rates, occurrence of ketoacidosis, quality of life and the use of insulin pump therapy in pregnancy. The current article represents the recommendations of the Austrian Diabetes Association for the clinical praxis of insulin pump treatment in children, adolescents and adults.

[CGM-Continuous Glucose Monitoring-Statement of the Austrian Diabetes Association (Update 2019)]. / Kontinuierliche Glukosemessung (CGM ­ Continuous Glucose Monitoring) bei Diabetes mellitus (Update 2019).

This position statement represents the recommendations of the Austrian Diabetes Association regarding the clinical diagnostic and therapeutic application, safety and benefits of continuous subcutaneous glucose monitoring systems in patients with diabetes, based on current evidence.

Cross-cultural Validation of the 5-Factor Structure of Negative Symptoms in Schizophrenia.

OBJECTIVE: Negative symptoms are currently viewed as having a 2-dimensional structure, with factors reflecting diminished expression (EXP) and motivation and pleasure (MAP). However, several factor-analytic studies suggest that the consensus around a 2-dimensional model is premature. The current study investigated and cross-culturally validated the factorial structure of BNSS-rated negative symptoms across a range of cultures and languages. METHOD: Participants included individuals diagnosed with a psychotic disorder who had been rated on the Brief Negative Symptom Scale (BNSS) from 5 cross-cultural samples, with a total N = 1691. First, exploratory factor analysis was used to extract up to 6 factors from the data. Next, confirmatory factor analysis evaluated the fit of 5 models: (1) a 1-factor model, 2) a 2-factor model with factors of MAP and EXP, 3) a 3-factor model with inner world, external, and alogia factors; 4) a 5-factor model with separate factors for blunted affect, alogia, anhedonia, avolition, and asociality, and 5) a hierarchical model with 2 second-order factors reflecting EXP and MAP, as well as 5 first-order factors reflecting the 5 aforementioned domains. RESULTS: Models with 4 factors or less were mediocre fits to the data. The 5-factor, 6-factor, and the hierarchical second-order 5-factor models provided excellent fit with an edge to the 5-factor model. The 5-factor structure demonstrated invariance across study samples. CONCLUSIONS: Findings support the validity of the 5-factor structure of BNSS-rated negative symptoms across diverse cultures and languages. These findings have important implications for the diagnosis, assessment, and treatment of negative symptoms.

Strict normoglycaemic blood glucose levels in the therapeutic management of patients within 12h after cardiac arrest might not be necessary.

AIM OF THE STUDY: The admission blood glucose level after cardiac arrest is predictive of outcome. However the blood glucose levels in the post-resuscitation period, that are optimal remains a matter of debate. We wanted to assess an association between blood glucose levels at 12h after restoration of spontaneous circulation and neurological recovery over 6 months. MATERIALS AND METHODS: A total of 234 patients from a multi-centre trial examining the effect of mild hypothermia on neurological outcome were included. According to the serum glucose level at 12h after restoration of spontaneous circulation, quartiles (Q) were generated: Median (range) glucose concentrations were for QI 100 (67-115 mg/dl), QII 130 (116-143 mg/dl), QIII 162 (144-193 mg/dl) and QIV 265 (194-464 mg/dl). RESULTS: In univariate analysis there was a strong non-linear association between blood glucose and good neurological outcome (odds ratio compared to QIV): QI 8.05 (3.03-21.4), QII 13.41 (4.9-36.67), QIII 1.88 (0.67-5.26). After adjustment for sex, age, "no-flow" and "low-flow" time, adrenaline (epinephrine) dose, history of coronary artery disease and myocardial infarction, and therapeutic hypothermia, this association still remained strong: QI 4.55 (1.28-16.12), QII 13.02 (3.29-49.9), QIII 1.37 (0.38-5.64). CONCLUSION: There is a strong non-linear association of survival with good neurological outcome and blood glucose levels 12h after cardiac arrest even after adjusting for potential confounders. Not only strict normoglycaemia, but also blood glucose levels from 116 to 143 mg/dl were correlated with survival and good neurological outcome, which might have an important therapeutic implication.

Combining actigraphy, ecological momentary assessment and neuroimaging to study apathy in patients with schizophrenia.

BACKGROUND: Apathy can be defined as a reduction of goal-directed behavior and is a strong predictor for poor functional outcome in schizophrenia. However, no objective measure of apathy has been identified and assessment is limited to retrospective interview-based ratings. Here we aimed to identify more precise objective readouts of apathy for translational research and clinical practice. METHODS: We employed a combined approach including interview-based ratings of the two negative symptom factors apathy and diminished expression, actigraphy based measures of spontaneous motor activity and the evaluation of daily activities using ecological momentary assessment. Furthermore, a functional magnetic resonance imaging task for reward anticipation was applied to investigate shared and divergent neural correlates of interview-based and behaviorally measured apathy. RESULTS: We found in 18 schizophrenia patients with high interview-based apathy levels that motor activity was negatively correlated with apathy but not with diminished expression. In contrast, measures of daily activities were not associated with apathy. Neural activation during reward anticipation revealed an association between hypoactivation of the ventral striatum and interview-based apathy as well as hypoactivation of the inferior frontal gyrus and motor activity level. CONCLUSIONS: Spontaneous motor activity is an objective readout of apathy, which was specific and not present for diminished expression. On a neural level, interview-based and objective measures of apathy showed divergent neural correlates in the cortical-striatal network, which suggests dissociable neural processes. Finally, motor activity provides a promising readout for quantifying apathy in both translational research and clinical practice.

Efficacy of peginterferon plus ribavirin in patients receiving opioid substitution therapy : Final results of the Austrian PegHope study.

BACKGROUND: Patients with a history of intravenous drug abuse included in an official opioid substitution program represent an important subgroup of patients with chronic hepatitis C. The objective of this study was to assess the efficacy of and adherence to treatment with peginterferon and ribavirin in Austrian patients on stable opioid substitution therapy (OST). METHODS: This prospective, multicenter, observational, non-interventional trial (clinicaltrials.gov identifier, NCT01416610) included treatment-naïve patients with chronic hepatitis C on OST. Treatment consisted of peginterferon alpha-2a (PEGASYS®, 180 µg/week) plus ribavirin (COPEGUS®, 1000/1200 mg/day in genotypes (GT) 1/4 and 800 mg/day in GT 2/3) for 24-72 weeks, according to GT and viral response. RESULTS: The intention-to-treat (ITT) population comprised 88 patients. Mean duration of therapy was 6.0 ± 2.8 months. Treatment was discontinued earlier than planned in 34 out of 88 patients (39%), mainly because of poor adherence or side effects of treatment. At the end of treatment 65/88 patients (74%) were PCR negative. During follow-up, 5 patients relapsed. Only 44/88 patients (50%) could be evaluated 24 weeks after the end of treatment. Sustained virologic response 24 weeks after end of therapy (SVR24) was documented in 39/88 patients (44%). If only patients were considered who finished treatment as planned and for whom results at follow-up week 24 were available, the SVR24 rate was 89% (32/36). CONCLUSION: Despite favorable prognostic factors, such as young age and a high proportion of GT3, SVR rates were low in this cohort of patients receiving OST, the main reason being poor adherence; however, in those patients completing treatment, the SVR rate was high.

Ventral Striatal Dysfunction and Symptom Expression in Individuals With Schizotypal Personality Traits and Early Psychosis.

Striatal abnormalities play a crucial role in the pathophysiology of schizophrenia. Growing evidence suggests an association between aberrant striatal activity during reward anticipation and symptom dimensions in schizophrenia. However, it is not clear whether this holds across the psychosis continuum. The aim of the present study was to investigate alterations of ventral striatal activation during reward anticipation and its relationship to symptom expression in persons with schizotypal personality traits (SPT) and first-episode psychosis. Twenty-six individuals with high SPT, 26 patients with non-affective first-episode psychosis (including 13 with brief psychotic disorder (FEP-BPD) and 13 with first-episode schizophrenia [FEP-SZ]) and 25 healthy controls underwent event-related functional magnetic resonance imaging while performing a variant of the Monetary Incentive Delay task. Ventral striatal activation was positively correlated with total symptom severity, in particular with levels of positive symptoms. This association was observed across the psychosis continuum and within each subgroup. Patients with FEP-SZ showed the strongest elevation of striatal activation during reward anticipation, although symptom levels did not differ between groups in the psychosis continuum. While our results provide evidence that variance in striatal activation is mainly explained by dimensional symptom expression, patients with schizophrenia show an additional dysregulation of striatal activation. Trans-diagnostic approaches are promising in order to disentangle dimensional and categorical neural mechanisms in the psychosis continuum.

Insulin resistance is unrelated to circulating retinol binding protein and protein C inhibitor.

CONTEXT: Recent data suggest that circulating retinol-binding protein (RBP) might be involved in the pathogenesis of insulin resistance. Moreover, protein C inhibitor (PCI), which specifically binds retinoic acid, was found to be increased in myocardial infarction survivors who are also insulin resistant. OBJECTIVE: The objective of this study was to investigate the association of insulin resistance with RBP factors and PCI active antigen. DESIGN AND SETTING: This was a clinical study. PATIENTS: Nondiabetic humans with high (IS; n = 20, 14 females, six males, aged 47.2 +/- 1.9 yr, body mass index 26 +/- 1 kg/m(2)) and low (IR; n = 20, 14 females, six males, aged 45.5 +/- 1.7 yr, body mass index 28 +/- 1 kg/m(2)) insulin-stimulated glucose-disposal (M) participated in this study. MAIN OUTCOME MEASURES: M was measured by 2-h hyperinsulinemic (40 mU.min(-1).m(-2))-isoglycemic clamp tests. Measurements of RBP were performed using a nephelometric method and validated using quantitative Western blotting. RESULTS: M (80-120 min) was higher in IS (10.9 +/- 0.6 mg.min(-1).kg(-1)) than IR (4.0 +/- 0.2; P < 10(-12)). Fasting plasma RBP concentrations were comparable between IS and IR measured by both nephelometry (IS: 4.4 +/- 0.3; IR: 4.6 +/- 0.3 mg/dl, P = 0.6) and quantitative Western blot (IS 7.9 +/- 0.5, IR 8.3 +/- 0.6 mg/dl; P = 0.6). Fasting plasma PCI active antigen was similar in both groups. Plasma RBP and PCI were not significantly related to M. RBP was positively correlated with uric acid (r = 0.488, P = 0.003), triglycerides (r = 0.592, P < 0.001), prealbumin (r = 0.63, P < 0.0001), and vitamin A (r = 0.75, P < 10(-6)). CONCLUSIONS: Our data demonstrate that healthy, insulin-resistant humans do not show altered plasma retinol binding factors, such as RBP and PCI. Both do not significantly correlate with insulin sensitivity. Thus, our findings do not support the hypothesis of insulin sensitivity modulation by proteins involved in retinol transport.

Severity of insulin resistance in critically ill medical patients.

Critical illness is characterized by a hypermetabolic state associated with increased mortality, which is partly ascribed to the occurrence of hyperglycemia caused by enhanced endogenous glucose production and insulin resistance (IR). Insulin resistance is well described in patients after surgery and trauma. However, it is less clearly quantified in critically ill medical patients. In this clinical cohort study, IR (M value) was quantified in 40 critically ill medical patients and 25 matched, healthy controls by isoglycemic hyperinsulinemic clamps after an overnight fast on the day after admission to a medical intensive care unit. Energy and substrate metabolism were measured by using indirect calorimetry in the patients before and during the clamp. The severity of illness was assessed by the acute physiology and chronic health evaluation (APACHE) III score. M values of critically ill medical patients were significantly lower compared with healthy controls (2.29 +/- 1.0 and 7.6 +/- 2.9 mg/kg per minute, respectively; P < .001) and were closely related to APACHE III scores (r = -0.43, P < .01), body mass index (r = -0.41, P < .01), and resting energy expenditure (r = 0.40, P < .05). The M value was not associated with age, basal glucose concentrations, and respiratory quotient, and it did not differ among patients with various admission diagnoses. In conclusion, insulin sensitivity was found to be reduced by 70% in critically ill medical patients. The severity of IR was associated with the severity of illness, body mass index, and resting energy expenditure, but not with substrate oxidation rates. In addition, the severity of IR did not vary among patients with different admission diagnoses.

Deficits in context-dependent adaptive coding of reward in schizophrenia.

Theoretical principles of information processing and empirical findings suggest that to efficiently represent all possible rewards in the natural environment, reward-sensitive neurons have to adapt their coding range dynamically to the current reward context. Adaptation ensures that the reward system is most sensitive for the most likely rewards, enabling the system to efficiently represent a potentially infinite range of reward information. A deficit in neural adaptation would prevent precise representation of rewards and could have detrimental effects for an organism's ability to optimally engage with its environment. In schizophrenia, reward processing is known to be impaired and has been linked to different symptom dimensions. However, despite the fundamental significance of coding reward adaptively, no study has elucidated whether adaptive reward processing is impaired in schizophrenia. We therefore studied patients with schizophrenia (n=27) and healthy controls (n=25), using functional magnetic resonance imaging in combination with a variant of the monetary incentive delay task. Compared with healthy controls, patients with schizophrenia showed less efficient neural adaptation to the current reward context, which leads to imprecise neural representation of reward. Importantly, the deficit correlated with total symptom severity. Our results suggest that some of the deficits in reward processing in schizophrenia might be due to inefficient neural adaptation to the current reward context. Furthermore, because adaptive coding is a ubiquitous feature of the brain, we believe that our findings provide an avenue in defining a general impairment in neural information processing underlying this debilitating disorder.

[CGM-Continuous Glucose Monitoring--Statement of the Austrian Diabetes Association]. / Kontinuierliche Glukosemessung (CGM - Continuous Glucose Monitoring) bei Diabetes mellitus.

This position statement represents the recommendations of the Austrian Diabetes Association regarding the clinical diagnostic and therapeutic application, safety and benefits of continuous subcutaneous glucose monitoring systems in patients with diabetes mellitus, based on current evidence.