Early onset of treatment effects with oral risperidone

BACKGROUND: The dogma of a delayed onset of antipsychotic treatment effects has been maintained over the past decades. However, recent studies have challenged this concept. We therefore performed an analysis of the onset of antipsychotic treatment effects in a sample of acutely decompensated patients with schizophrenia. METHODS: In this observational study, 48 inpatients with acutely decompensated schizophrenia were offered antipsychotic treatment with oral risperidone. PANSS-ratings were obtained on day 0, day 1, day 3, day 7 and day 14. RESULTS: Significant effects of treatment were already present on day 1 and continued throughout the study. The PANSS positive subscore and the PANSS total score improved significantly more than the PANSS negative subscore. CONCLUSION: Our results are consistent with the growing number of studies suggesting an early onset of antipsychotic treatment effects. However, non-pharmacological effects of treatment also need to be taken into consideration

Peptide Fingerprinting of Alzheimer's Disease in Cerebrospinal Fluid: Identification and Prospective Evaluation of New Synaptic Biomarkers

<p><b>Background:</b> Today, dementias are diagnosed late in the course of disease. Future treatments have to start earlier in the disease process to avoid disability requiring new diagnostic tools. The objective of this study is to develop a new method for the differential diagnosis and identification of new biomarkers of Alzheimer's disease (AD) using capillary-electrophoresis coupled to mass-spectrometry (CE-MS) and to assess the potential of early diagnosis of AD.</p> <p><b>Methods and Findings:</b> Cerebrospinal fluid (CSF) of 159 out-patients of a memory-clinic at a University Hospital suffering from neurodegenerative disorders and 17 cognitively-healthy controls was used to create differential peptide pattern for dementias and prospective blinded-comparison of sensitivity and specificity for AD diagnosis against the Criterion standard in a naturalistic prospective sample of patients. Sensitivity and specificity of the new method compared to standard diagnostic procedures and identification of new putative biomarkers for AD was the main outcome measure. CE-MS was used to reliably detect 1104 low-molecular-weight peptides in CSF. Training-sets of patients with clinically secured sporadic Alzheimer's disease, frontotemporal dementia, and cognitively healthy controls allowed establishing discriminative biomarker pattern for diagnosis of AD. This pattern was already detectable in patients with mild cognitive impairment (MCI). The AD-pattern was tested in a prospective sample of patients (n = 100) and AD was diagnosed with a sensitivity of 87% and a specificity of 83%. Using CSF measurements of beta-amyloid1-42, total-tau, and phospho(181)-tau, AD-diagnosis had a sensitivity of 88% and a specificity of 67% in the same sample. Sequence analysis of the discriminating biomarkers identified fragments of synaptic proteins like proSAAS, apolipoprotein J, neurosecretory protein VGF, phospholemman, and chromogranin A.</p> <p><b>Conclusions:</b> The method may allow early differential diagnosis of various dementias using specific peptide fingerprints and identification of incipient AD in patients suffering from MCI. Identified biomarkers facilitate face validity for the use in AD diagnosis.</p&gt

Four ultra-short period eclipsing M-dwarf binaries in the WFCAM Transit Survey

We report on the discovery of four ultra-short period (P<0.18 days) eclipsing M-dwarf binaries in the WFCAM Transit Survey. Their orbital periods are significantly shorter than of any other known main-sequence binary system, and are all significantly below the sharp period cut-off at P~0.22 days as seen in binaries of earlier type stars. The shortest-period binary consists of two M4 type stars in a P=0.112 day orbit. The binaries are discovered as part of an extensive search for short-period eclipsing systems in over 260,000 stellar lightcurves, including over 10,000 M-dwarfs down to J=18 mag, yielding 25 binaries with P<0.23 days. In a popular paradigm, the evolution of short period binaries of cool main-sequence stars is driven by loss of angular momentum through magnetised winds. In this scheme, the observed P~0.22 day period cut-off is explained as being due to timescales that are too long for lower-mass binaries to decay into tighter orbits. Our discovery of low-mass binaries with significantly shorter orbits implies that either these timescales have been overestimated for M-dwarfs, e.g. due to a higher effective magnetic activity, or that the mechanism for forming these tight M-dwarf binaries is different from that of earlier type main-sequence stars.Comment: 22 pages, 17 figures, 3 tables Accepted for publication in MNRA

Wideband dynamic radio spectra of two ultra-cool dwarfs

A number of radio-loud ultra-cool dwarf (UCD ) stars exhibit both continuous broadband and highly polarized pulsed radio emission. In order to determine the nature of the emission and the physical characteristics in the source region, we have made multi-epoch, wideband spectral observations of TVLM 0513-46 and 2M 0746+20. We combine these observations with archival radio data to fully characterize both the temporal and spectral properties of the radio emission. The continuum spectral energy distribution can be well modeled using gyrosynchrotron emission from mildly relativistic electrons in a dipolar field. The pulsed emission exhibits a variety of time-variable characteristics, including frequency drifts, frequency cutoffs, and multiple pulses per period. For 2M 0746+20 we determine a pulse period consistent with previously determined values. We modeled locations of pulsed emission using an oblique rotating magnetospheric model with beamed electron-cyclotron maser ( ECM) sources. The bestfit models have narrow ECM beaming angles aligned with the local source magnetic field direction, except for one isolated burst from 2M 0746+20. For TVLM 0513-46, the best-fit rotation axis inclination is nearly orthogonal to the line of sight. For 2M0746+20 we found a good fit using a fixed inclination i = 36°, determined from optical observations. For both stars the ECM sources are located near feet of magnetic loops with radial extents 1.2Rs-2.7Rsand surface fields 2.2-2.5 kG. These results support recent suggestions that radio over-luminous UCDs have a global "weak field" non-axisymmetric magnetic topologies

Prime-boost immunization of rabbits with HIV-1 gp120 elicits potent neutralization activity against a primary viral isolate

<div><p>Development of a vaccine for HIV-1 requires a detailed understanding of the neutralizing antibody responses that can be experimentally elicited to difficult-to-neutralize primary isolates. Rabbits were immunized with the gp120 subunit of HIV-1 JR-CSF envelope (Env) using a DNA-prime protein-boost regimen. We analyzed five sera that showed potent autologous neutralizing activity (IC50s at ∼10³ to 10⁴ serum dilution) against pseudoviruses containing Env from the primary isolate JR-CSF but not from the related isolate JR-FL. Pseudoviruses were created by exchanging each variable and constant domain of JR-CSF gp120 with that of JR-FL or with mutations in putative N-glycosylation sites. The sera contained different neutralizing activities dependent on C3 and V5, C3 and V4, or V4 regions located on the glycan-rich outer domain of gp120. All sera showed enhanced neutralizing activity toward an Env variant that lacked a glycosylation site in V4. The JR-CSF gp120 epitopes recognized by the sera are generally distinct from those of several well characterized mAbs (targeting conserved sites on Env) or other type-specific responses (targeting V1, V2, or V3 variable regions). The activity of one serum requires specific glycans that are also important for 2G12 neutralization and this serum blocked the binding of 2G12 to gp120. Our findings show that different fine specificities can achieve potent neutralization of HIV-1, yet this strong activity does not result in improved breadth.</p> </div