Methodological characterization of the 2-keto [1-13C]isocaproate breath test to measure in vivo human mitochondrial function: application in alcoholic liver disease assessment

BACKGROUND: The 2-keto[1-13C]isocaproate oxidation measurement has been shown as a helpful tool in the in vivo assessment of liver mitochondrial function. METHODS: The aim of this work was to study the variability of the 2-keto[1-13C]isocaproate breath test in 24 healthy controls (8 men and 16 women) and to evaluate its clinical usefulness in 20 patients (14 men and 6 women) with liver disease (7 men with history of alcoholism). Breath test was performed by measuring 13CO2 enrichment in breath before and after the oral administration of the tracer and by using isotope ratio mass spectrometry. RESULTS: The intrasubject and intersubject variability of the percentage of tracer oxidized were 8 and 14%, respectively. The 2-keto[1-13C]isocaproate oxidation in women was faster (p = 0.004) and tended to be higher (p = 0.050) than in men. The percentage of oxidized tracer was lower in those patients with alcoholic liver disease than in healthy volunteers (p = 0.001) and in nonalcoholic patients (p = 0.003). CONCLUSIONS: The percentage of tracer oxidized appears as a convenient parameter to detect impairment in liver mitochondrial oxidation related to alcoholism by the 2-keto[1-13C]isocaproate breath test, establishing different cutoff values depending on gender.     

Activation of the human homologue of the Drosophila sina gene in apoptosis and tumor suppression.

Developmentally regulated genes in Drosophila, which are conserved through evolution, are potential candidates for key functions in biological processes such as cell cycle, programmed cell death, and cancer. We report cloning and characterization of the human homologue of the Drosophila seven in absentia gene (HUMSIAH), which codes for a 282 amino acids putative zinc finger protein. HUMSIAH is localized on human chromosome 16q12-q13. This gene is activated during the physiological program of cell death in the intestinal epithelium. Moreover, human cancer-derived cells selected for suppression of their tumorigenic phenotype exhibit constitutively elevated levels of HUMSIAH mRNA. A similar pattern of expression is also displayed by the p21waf1. These results suggest that mammalian seven in absentia gene, which is a target for activation by p53, may play a role in apoptosis and tumor suppression.     

Outcomes in spasticity after repetitive transcranial magnetic and transcranial direct current stimulations

Non-invasive brain stimulations mainly consist of repetitive transcranial magnetic stimulation and transcranial direct current stimulation. Repetitive transcranial magnetic stimulation exhib- its satisfactory outcomes in improving multiple sclerosis, stroke, spinal cord injury and cerebral palsy-induced spasticity. By contrast, transcranial direct current stimulation has only been studied in post-stroke spasticity. To better validate the efficacy of non-invasive brain stimulations in im- proving the spasticity post-stroke, more prospective cohort studies involving large sample sizes are needed.     

Effects of Expiratory Muscle Training and Air Stacking on Peak Cough Flow in Individuals with Parkinson’s Disease

The purpose of this study was to investigate the effects of air stacking (AS) and an expiratory muscle training (EMT) program to increase voluntary and reflex peak cough flow (PCF) in individuals with Parkinson’s disease. Participants were allocated to the control (n = 11), EMT (n = 11), or EMT + AS group (n = 11). All groups performed EMT (5 sets of 5 repetitions), 6 times a week for 2 months. The control group used a fixed resistance, EMT plus AS and EMT groups used a progressively increased resistance. The EMT plus AS group additionally performed 10 series of three to four lung insufflations using a manual resuscitator bag. Voluntary and reflex PCF, maximum expiratory pressure, and slow vital capacity were assessed before and after training. EMT plus AS was more beneficial than EMT alone for improving reflex and voluntary PCF. The effect of the EMT plus AS was greater for reflex PCF than for voluntary PCF.

     

Decreased spectral entropy modulation in patients with schizophrenia during a P300 task

Spectral entropy (SE), also known as Shannon entropy, is a useful parameter for quantifying the global regularity of the electroencephalographic (EEG) signal. Hence, it is of interest in the assessment of the electrophysiological correlates of cognitive processing in schizophrenia. However, to date, SE has been barely used in studies comparing resting EEG recordings between patients and controls. In this work, we compared SE between resting baseline [?250 0] ms and active task [150 550] ms windows of a P300 task in 31 patients with schizophrenia and 38 controls. Moreover, we also calculated the median frequency (MF) and relative power in each frequency band for these windows to assess the correlates of the possible SE differences. Controls showed a significant (p < 0.0029) SE decrease (i.e., meaning higher signal regularity) from baseline to the active task window at parietal and central electrode sites. This SE decrease from baseline to active conditions was significantly lower in patients. In controls, this SE decrease was accompanied by a statistically significant decrease in MF (i.e., a significant slowing of the EEG activity), not observed in patients. In this latter group, the difference in SE between resting baseline and active task windows was inversely correlated to positive and total symptoms scores, as measured with the positive and negative symptoms scale. Our data support the relevance of SE in the study of cerebral processing in schizophrenia.     

Timing of CMV‐specific effector memory T cells predicts viral replication and survival after allogeneic hematopoietic stem cell transplantation

The aim of this study was to characterize timing, kinetic, and magnitude of CMV‐specific immune response after hematopoietic stem cell transplantation (HSCT) and its ability to predict CMV replication and clinical outcomes. Using cell surface and intracellular cytokine staining by flow cytometry, CMV‐specific T‐cell response was measured in blood, while CMV viral load and chimerism were determined by real‐time PCR. Patients that reconstituted CMV‐specific T‐cell response within 6 weeks after Allo‐SCT showed a more robust immune response (CD8⁺: 0.7 cells/μl vs. 0.3/μl; P‐value = 0.01), less incidence of CMV replication (33% vs. 89.5%; P‐value = 0.007), reduced viral loads (1.81 log copies/ml vs. 0 copies/ml; P‐value = 0.04), and better overall survival (72%; CI: 0.53–0.96 vs. 42% CI: 0.24–0.71; P‐value = 0.07) than patients with a delayed immune reconstitution. Viremic patients had significantly higher transplant‐related mortality than nonviremic patients after 1 year (33% CI: 0.15–0.52 vs. 0% CI: 0.05–0.34; P‐value = 0.01). Risk factors independently associated with viral replication were receptor pretransplant CMV‐positive serostatus (P‐value = 0.02) and acquiring CMV‐specific T‐cell response after 6 weeks post‐transplantation (P‐value = 0.009). In conclusion, timing of acquiring a positive CMV‐specific T‐cell immune response after transplantation may identify patients with different risk for viral replication and different clinical outcomes, including survival.