False negativity to carbohydrate-deficient transferrin and drugs: a clinical case

Introduction: In this work we report on the possible effect of the medical therapy on CDT concentration in a chronic alcohol abuser, with known medical history (July 2007 – April 2012) and alcohol abuse confirmed by relatives. Case history: At the end of 2007, patient displayed the following laboratory results: AST 137 U/L, ALT 120 U/L, GGT 434 U/L, MCV 101 fL and CDT 3.3%. On December 2007, after double coronary artery bypass surgery, he began a pharmacological treatment with amlodipine, perindopril, atorvastatin, isosorbide mononitrate, carvedilol, ticlopidine and pantoprazole. In the next months, until may 2011, the patient resumed alcohol abuse, as confirmed by relatives; however, CDT values were repeatedly found negative (0.8% and 1.1%) despite elevated transaminases and GGT, concurrent elevated ethyl glucuronide concentration (> 50 mg/L) and blood alcohol concentration (> 1 g/L). Alcohol consumption still continued despite increasing disulfiram doses ordered by an Alcohol Rehab Center. On May 2011, the patient was transferred to a private medical center where he currently lives. Conclusions: This study suggests the possibility that a medical therapy including different drugs may hamper the identification of chronic alcohol abusers by CDT

Enhanced LDL oxidation in uremic patients: An additional mechanism for accelerated atherosclerosis?

Enhanced LDL oxidation in uremic patients: An additional mechanism for accelerated atherosclerosis? Since oxidized low-density lipoprotein (LDL) is more atherogenic than native LDL, LDL oxidation was investigated in uremic patients who often develop accelerated atherogenesis. Three groups of uremic patients were studied (10 on predialysis conservative therapy, 11 on repetitive hemodialysis, 13 on peritoneal dialysis) and compared with seventy matched controls. LDL oxidation was evaluated in all patients as: (i) the susceptibility to in vitro oxidation (by measuring the resistence to Cu++-induced formation of conjugated dienes), (ii) vitamin E concentration in LDL, and (iii) presence of plasma anti-oxidized LDL antibodies, expressed as the ratio anti-oxLDL/anti-nativeLDL antibodies. The lipid profile was studied in all patients. Vitamin E concentration did not differ between the various groups, although LDL from uremic patients appeared more susceptible to in vitro and in vivo oxidation (as demonstrated by an earlier generation of conjugated dienes and by the presence of an higher antibody ratio) compared to control subjects. Subclass analysis of the different patients revealed that peritoneal dialysis treatment ameliorated the oxidation markers. However, a prolonged dialytic treatment caused a decrease in vitamin E concentration in LDL and increased their susceptibility to oxidation

An rf-linac, FEL buncher

Abstract We describe a means of producing a train of 40 kA pulses of 3 ps duration as the drive beam for CLIC using an rf linac driven free electron laser (FEL) buncher. Potential debunching effects are discussed. Finally we describe a low energy test experiment

Improvement of insulin sensitivity in diabetic and non diabetic patients with chronic hepatitis C treated with direct antiviral agents

The increased incidence of type 2 diabetes mellitus among hepatitis C virus (HCV) infected patients is likely due to viral-induced insulin resistance (IR). Indeed, control of diabetes in these patients benefits of successful antiviral treatment; whether the same applies to subtler alterations of glucose metabolism is unknown. We aimed to fill this gap

“Real life use” of troponin in the emergency department: a survey of over 3000 cases

Introduction: The aim of this study was to identify clinical variables which may be independently associated with positivity of a cardiac troponin I (cTnI) assay in a large population of patients admitted to the emergency department (ED). Materials and methods: 3166 subjects, with at least two troponin I tests ordered within 6 hours in the ED, were studied. Patient data were statistically analyzed to identify clinical associations with increased values of Troponin I. Results: Although patients with diagnosis of acute coronary syndrome displayed troponin I values significantly higher than those of other groups, positivity to troponin I (> 40 ng/L) was also observed in patients with other clinical conditions. In multivariate analysis, age, elevated heart rate and electrocardiographyc changes were independently associated with troponin I positivity at admission. In the whole study population troponin I positivity exhibited high sensitivity and negative predictive value, counterbalanced by low specificity and limited positive predictive value. Conclusions: Troponin I positivity should be combined with history and clinical evaluation and cautiously interpreted in the ED, especially in patients exhibiting factors associated with higher troponin I levels such as older age, elevated heart rate or ECG changes

Mismatch Negativity and P3a Impairment through Different Phases of Schizophrenia and Their Association with Real-Life Functioning

Impairment in functioning since the onset of psychosis and further deterioration over time is a key aspect of subjects with schizophrenia (SCZ). Mismatch negativity (MMN) and P3a, indices of early attention processing that are often impaired in schizophrenia, might represent optimal electrophysiological candidate biomarkers of illness progression and poor outcome. However, contrasting findings are reported about the relationships between MMN-P3a and functioning. The study aimed to investigate in SCZ the influence of illness duration on MMN-P3a and the relationship of MMN-P3a with functioning. Pitch (p) and duration (d) MMN-P3a were investigated in 117 SCZ and 61 healthy controls (HCs). SCZ were divided into four illness duration groups: ≤ 5, 6 to 13, 14 to 18, and 19 to 32 years. p-MMN and d-MMN amplitude was reduced in SCZ compared to HCs, independently from illness duration, psychopathology, and neurocognitive deficits. p-MMN reduction was associated with lower “Work skills”. The p-P3a amplitude was reduced in the SCZ group with longest illness duration compared to HCs. No relationship between P3a and functioning was found. Our results suggested that MMN amplitude reduction might represent a biomarker of poor functioning in SCZ

The influence of autistic symptoms on social and non-social cognition and on real-life functioning in people with schizophrenia: Evidence from the Italian Network for Research on Psychoses multicenter study

BACKGROUND: Autism spectrum disorders (ASDs) and schizophrenia spectrum disorders (SSDs), although conceptualized as separate entities, may share some clinical and neurobiological features. ASD symptoms may have a relevant role in determining a more severe clinical presentation of schizophrenic disorder but their relationships with cognitive aspects and functional outcomes of the disease remain to be addressed in large samples of individuals. AIMS: To investigate the clinical, cognitive, and functional correlates of ASD symptoms in a large sample of people diagnosed with schizophrenia. METHODS: The severity of ASD symptoms was measured with the PANSS Autism Severity Scale (PAUSS) in 921 individuals recruited for the Italian Network for Research on Psychoses multicenter study. Based on the PAUSS scores, three groups of subjects were compared on a wide array of cognitive and functional measures. RESULTS: Subjects with more severe ASD symptoms showed a poorer performance in the processing speed (p\ua0=\ua00.010), attention (p\ua0=\ua00.011), verbal memory (p\ua0=\ua00.035), and social cognition (p\ua0=\ua00.001) domains, and an overall lower global cognitive composite score (p\ua0=\ua00.010). Subjects with more severe ASD symptoms also showed poorer functional capacity (p\ua0=\ua00.004), real-world interpersonal relationships (p\ua0<\ua00.001), and participation in community-living activities (p\ua0<\ua00.001). CONCLUSIONS: These findings strengthen the notion that ASD symptoms may have a relevant impact on different aspects of the disease, crucial to the life of people with schizophrenia. Prominent ASD symptoms may characterize a specific subpopulation of individuals with SSD

A multivariate approach to investigate the associations of electrophysiological indices with schizophrenia clinical and functional outcome

Abstract Background Different electrophysiological (EEG) indices have been investigated as possible biomarkers of schizophrenia. However, these indices have a very limited use in clinical practice, as their associations with clinical and functional outcomes remain unclear. This study aimed to investigate the associations of multiple EEG markers with clinical variables and functional outcomes in subjects with schizophrenia (SCZs). Methods Resting-state EEGs (frequency bands and microstates) and auditory event-related potentials (MMN-P3a and N100-P3b) were recorded in 113 SCZs and 57 healthy controls (HCs) at baseline. Illness- and functioning-related variables were assessed both at baseline and at 4-year follow-up in 61 SCZs. We generated a machine-learning classifier for each EEG parameter (frequency bands, microstates, N100-P300 task, and MMN-P3a task) to identify potential markers discriminating SCZs from HCs, and a global classifier. Associations of the classifiers’ decision scores with illness- and functioning-related variables at baseline and follow-up were then investigated. Results The global classifier discriminated SCZs from HCs with an accuracy of 75.4% and its decision scores significantly correlated with negative symptoms, depression, neurocognition, and real-life functioning at 4-year follow-up. Conclusions These results suggest that a combination of multiple EEG alterations is associated with poor functional outcomes and its clinical and cognitive determinants in SCZs. These findings need replication, possibly looking at different illness stages in order to implement EEG as a possible tool for the prediction of poor functional outcome

Hydrogen Peroxide Probes Directed to Different Cellular Compartments

Background: Controlled generation and removal of hydrogen peroxide play important roles in cellular redox homeostasis and signaling. We used a hydrogen peroxide biosensor HyPer, targeted to different compartments, to examine these processes in mammalian cells. Principal Findings: Reversible responses were observed to various redox perturbations and signaling events. HyPer expressed in HEK 293 cells was found to sense low micromolar levels of hydrogen peroxide. When targeted to various cellular compartments, HyPer occurred in the reduced state in the nucleus, cytosol, peroxisomes, mitochondrial intermembrane space and mitochondrial matrix, but low levels of the oxidized form of the biosensor were also observed in each of these compartments, consistent with a low peroxide tone in mammalian cells. In contrast, HyPer was mostly oxidized in the endoplasmic reticulum. Using this system, we characterized control of hydrogen peroxide in various cell systems, such as cells deficient in thioredoxin reductase, sulfhydryl oxidases or subjected to selenium deficiency. Generation of hydrogen peroxide could also be monitored in various compartments following signaling events. Conclusions: We found that HyPer can be used as a valuable tool to monitor hydrogen peroxide generated in different cellular compartments. The data also show that hydrogen peroxide generated in one compartment could translocate to other compartments. Our data provide information on compartmentalization, dynamics and homeostatic control of hydrogen peroxide in mammalian cells