Evaluation of the Beckman Coulter UniCel DxH 800, Beckman Coulter LH 780, and Abbott Diagnostics Cell-Dyn Sapphire hematology analyzers on adult specimens in a tertiary care hospital

We evaluated the new Beckman Coulter DxH 800 hematology analyzer (Beckman Coulter, Miami, FL) vs the Abbott Diagnostics Cell-Dyn Sapphire (Abbott Diagnostics, Santa Clara, CA) and Beckman Coulter LH 780 hematology analyzers using 430 adult specimens. The DxH 800 provided a CBC and differential that correlated well with those of the Sapphire and LH 780, with most parameters showing correlation coefficients (r) of more than 0.97. In the instrument vs 400-cell manual differential comparison, all 3 instruments showed similar and acceptable accuracy to the reference method except for nucleated RBC (NRBC) enumeration, in which the DxH 800 and Sapphire outperformed the LH 780. We also compared clinical efficiency by determining whether flagged specimens showed abnormalities on a peripheral blood smear as defined by International Council for Standardization in Haematology criteria. The efficiency, sensitivity, and specificity of the DxH 800 were 77.0%, 87.1%, and 73.0%, respectively, compared with the Sapphire at 75.8%, 93.5%, and 68.8%, respectively, and LH 780 at 66.1%, 93.5%, and 55.3%, respectively.     

Single dose of methylphenidate improves cognitive performance in multiple sclerosis patients with impaired attention process

BACKGROUND AND PURPOSE: Attention is one of the major cognitive domains adversely affected in multiple sclerosis (MS). The aim of the current study was to determine the effect of a single dose of methylphenidate on cognitive performance of MS patients with significant attention deficit. METHODS: In a double-blind placebo-controlled study design, 26 MS patients with impaired attention were randomly assigned to receive a single dose of 10 mg methylphenidate or placebo. Attention was assessed using the paced auditory serial addition test for 3 and 2 s (PASAT3' and PASAT2') at baseline and 1 h after drug/placebo administration. RESULTS: Methylphenidate significantly improved performance of both PASAT3' and PASAT2' tests by 22.8% and 25.6% respectively (p<0.001), while no significant changes were observed in placebo treated patients. CONCLUSION: Administration of a single dose of methylphenidate significantly improved attention in MS patients with considerable attention deficit.     

Hearing again with two ears: Recovery of spatial hearing after bilateral cochlear implantation

Bilateral cochlear implants (CI) offer a unique opportunity for the study of spatial hearing plasticity in humans. Here we studied the recovery of spatial hearing in two sequential bilateral CI recipients, adopting a longitudinal approach. Each recipient was tested in a sound-source identification task shortly after bilateral activation and at 1, 6, and 12 months follow-up. The results show fast recovery (1 month from CI activation) in the recipient who had substantial experience with auditory cues in adulthood. By contrast, the bilateral CI recipient who developed profound deafness in childhood, regained spatial hearing abilities only 12 months after CI activation. These findings provide the first direct evidence that recovery of auditory spatial abilities in bilateral CI recipients can occur shortly after activation of the two devices. In addition, they suggest that previous auditory experience can constrain the time course of this recovery.     

Late evening brain activation patterns and their relation to the internal biological time, melatonin, and homeostatic sleep debt

Sleep propensity increases sharply at night. Some evidence implicates the pineal hormone melatonin in this process. Using functional magnetic resonance imaging, brain activation during a visual search task was examined at 22:00 h (when endogenous melatonin levels normally increase). The relationships between brain activation, endogenous melatonin (measured in saliva), and self-reported fatigue were assessed. Finally, the effects of exogenous melatonin administered at 22:00 h were studied in a double blind, placebo-controlled crossover manner. We show that brain activation patterns as well as the response to exogenous melatonin significantly differ at night from those seen in afternoon hours. Thus, activation in the rostro-medial and lateral aspects of the occipital cortex and the thalamus diminished at 22:00 h. Activation in the right parietal cortex increased at night and correlated with individual fatigue levels, whereas exogenous melatonin given at 22:00 h reduced activation in this area. The right dorsolateral prefrontal cortex, an area considered to reflect homeostatic sleep debt, demonstrated increased activation at 22:00 h. Surprisingly, this increase correlated with endogenous melatonin. These results demonstrate and partially differentiate circadian effects (whether mediated by melatonin or not) and homeostatic sleep debt modulation of human brain activity associated with everyday fatigue at night.     

Gi and RGS proteins provide biochemical control of androgen receptor nuclear exclusion

Nuclear localization of androgen receptors (ARs) is essential for their activity. Melatonin induces AR nuclear exclusion via increase in cGMP, calcium, and protein kinase C (PKC) activation, presumably through G-protein(s). The effects of regulators of G-protein signaling (RGS) on AR localization were studied in AR-expressing PC3 cells. Gi-specific RGS10 inhibited melatonin but not cGMP-induced AR nuclear exclusion, independent of androgen. No evidence for Gq activation by melatonin was found. However, Gi/Gq-selective RGS4 inhibited AR nuclear exclusion downstream of PKC activation—an effect that was abrogated by constitutively active Gq. RGS10 and RGS4, but not RGS2, ablated the inhibitory effects of melatonin on AR reporter gene activity. For the first time, these data show regulation by Gi and Gi-specific RGS protein-mediated AR nuclear exclusion, which is potentially important in the treatment of AR-dependent cancers and neurodegenerative disorders. They also reveal a role for a Gq protein downstream of PKC activation in AR nuclear localization.     

Transcranial Magnetic Stimulation at M1 disrupts cognitive networks in schizophrenia

Transcranial Magnetic Stimulation (TMS) is rapidly gaining acceptance as a non-invasive probe into brain functionality. We utilize TMS to study the connectivity of a simple motor network in patients of schizophrenia (N=19), and in healthy control subjects (N=9). TMS was used in an externally paced finger tapping task, perturbing the internal network oscillations invoked by the finger motion as it keeps pace with a metronome. TMS perturbations were synchronized to the metronome and applied to the network at the level of the primary motor cortex (M1). Contrary to initial expectations, TMS did not affect the sensorimotor synchronization of subjects with schizophrenia or their tapping accuracy. TMS did cause extreme deviations in the finger's trajectory, and altered the timing perceptions of subjects with schizophrenia. Additionally, it invoked high-level deficiencies related to attention and volition in the form of lapses, implying that the connectivity between modules in the brain that underlie motor control, sensorimotor synchronization, timing perception and awareness of action, can be disrupted by TMS in subjects with schizophrenia, but not in healthy subjects. The ability to disrupt high level network functions with perturbations to the lower level of M1 supports models describing deficits in connectivity of distributed networks in the brains of schizophrenia patients. It also demonstrates the use of TMS to probe connectivity between components of such networks.