Evaluation of a 2D UNet-Based Attenuation Correction Methodology for PET/MR Brain Studies

Journal of Digital Imaging - Deep learning (DL) strategies applied to magnetic resonance (MR) images in positron emission tomography (PET)/MR can provide synthetic attenuation correction (AC) maps,...     

New Fluorescent Probes Targeting the Mitochondrial-Located Translocator Protein 18 kDa (TSPO) as Activated Microglia Imaging Agents

Purpose  

To evaluate the utility of new Translocator protein 18 kDa (TSPO)-targeted fluorescent probes for in vivo molecular imaging of activated microglia.     

Corticotropin-Releasing Factor in the Norepinephrine Nucleus,Locus Coeruleus,Facilitates Behavioral Flexibility

Corticotropin-releasing factor (CRF), the stress-related neuropeptide, acts as a neurotransmitter in the brain norepinephrine nucleus, locus coeruleus (LC), to activate this system during stress. CRF shifts the mode of LC discharge from a phasic to a high tonic state that is thought to promote behavioral flexibility. To investigate this, the effects of CRF administered either intracerebroventricularly (30–300 ng, i.c.v.) or directly into the LC (intra-LC; 2–20 ng) were examined in a rat model of attentional set shifting. CRF differentially affected components of the task depending on dose and route of administration. Intracerebroventricular CRF impaired intradimensional set shifting, reversal learning, and extradimensional set shifting (EDS) at different doses. In contrast, intra-LC CRF did not impair any aspect of the task. The highest dose of CRF (20 ng) facilitated reversal learning and the lowest dose (2 ng) improved EDS. The dose–response relationship for CRF on EDS performance resembled an inverted U-shaped curve with the highest dose having no effect. Intra-LC CRF also elicited c-fos expression in prefrontal cortical neurons with an inverted U-shaped dose–response relationship. The number of c-fos profiles was positively correlated with EDS performance. Given that CRF excites LC neurons, the ability of intra-LC CRF to activate prefrontal cortical neurons and facilitate EDS is consistent with findings implicating LC-norepinephrine projections to medial prefrontal cortex in this process. Importantly, the results suggest that CRF release in the LC during stress facilitates shifting of attention between diverse stimuli in a dynamic environment so that the organism can adapt an optimal strategy for coping with the challenge.     

The long pentraxin 3 is a soluble and cell-associated component of the human semen

The long pentraxin 3 (PTX3) is a multifunctional soluble pattern recognition receptor, involved in several processes ranging from innate resistance and inflammation to clearance of apoptotic cells and organization of hyaluronic acid-rich extracellular matrices. PTX3 is also a novel marker in several pathological conditions of infectious, inflammatory, or autoimmune origin. This study was designed to assess whether PTX3 is expressed in the male reproductive tract and whether PTX3 interacts with human spermatozoa influencing their function. Here we show for the first time by immunohistochemistry that PTX3 is expressed in the male genital tract in perivascular connective tissue, in endothelial cells, in the interstitium, and in the cytoplasm of prostatic epithelial glandular cells; PTX3 was detectable in seminal plasma in variable levels, which correlated with the percentage of normal spermatozoa. Moreover, PTX3 binds to spermatozoa, in particular with immotile cells, localizing in the neck and in the subacrosomial region. Finally, recombinant PTX3 did not interfere with sperm motility.     

Comparative crossover, randomized, open-label bioequivalence study on the bioequivalence of two formulations of thioctic acid in healthy volunteers

An open-label, randomized, crossover single-dose study, using two periods and two sequences with a washout period of seven days was conducted to assess the comparative bioavailability of thioctic (alpha-lipoic) acid (ALA) 600 mg formulation and that of a reference formulation. Blood samples were collected up to +6 h post dosing, the plasma was separated, and thioctic acid concentrations were determined by high-performance liquid chromatographic method with single mass spectrometry detection (HPLC-MS) and a lower limit of quantification of 190.1 ng/ml. Mean values of the individual C(max) were 1338.6 +/- 751.8 ng/ml and 1215.8 +/- 560.5 ng/ml for the test and reference preparations, respectively. Mean +/- standard deviation (SD) total area under the curve up to the last measurable concentration (AUC(t)) was 3510.9 +/- 1088.6 ng x h/ml for the test formulation and 3563.5 +/- 1374.1 ng x h/ml for the reference formulation. Mean +/- SD total area under the curve (AUC(inf)) was 6925.6 +/- 4045.8 ng x h/ml for the test formulation and 7797.1 +/- 5963.1 ng x h/ml for the reference preparation. Terminal elimination half-life was 5.68 +/- 5.05 h for the test and 6.11 +/- 6.15 h for the reference formulations. Time of maximum concentration (t(max)) was 1.24 +/- 1.23 h for the test and 2.05 +/- 1.21 h for the reference formulations. Ninety percent confidence intervals were comprised within the bioequivalence acceptance criteria (80-125%) for all of the parameters analyzed except t(max). The comparison between males and females showed no significant difference for the two drug treatment.     

Cognitive behavioural therapy for weight gain associated with antipsychotic drugs

Schizophrenia patients with the deficit syndrome (DS) may represent a homogeneous subgroup. To increase the practicability of diagnosing the DS, Kirkpatrick et al. [Kirkpatrick, B., Buchanan, RW., Breier, A. Carpenter, WT., 1993. Case identification and stability of the deficit syndrome of schizophrenia. Psychiatry Res. 47, 47-56.] proposed the use of a 'proxy' case identification tool using standardized symptom ratings instead of the Schedule for the Deficit Syndrome (SDS) which requires an independent clinical assessment. The Proxy for the Deficit Syndrome (PDS) is based on the extraction of symptoms that are essentially equivalent or overlap substantially with the restricted affect and diminished emotional range on the SDS. Kirkpatrick et al. [Kirkpatrick, B., Buchanan, RW., Breier, A. Carpenter, WT., 1993. Case identification and stability of the deficit syndrome of schizophrenia. Psychiatry Res. 47, 47-56.] reported good sensitivity and specificity in a comparison of SDS and PDS assessments among 100 chronic schizophrenia outpatients. The present investigation involves the comparison of the deficit syndrome as assessed by the "gold standard" Schedule for the Deficit Syndrome with the ratings of the same symptoms embodied in the "proxy instrument" the PANSS, within the same group of 156 inpatients. Forty-four patients were assessed by the SDS to have the deficit syndrome. Patients with and without the DS, as defined by the SDS, did not differ for age, education, age at illness onset and duration of illness. The two main 'proxy' measures PDS1 and PDS2 discriminated across the SDS groups. The direct dichotomous comparison of the actual SDS and the 'proxy' derived PDS groups demonstrated good specificity (78.6% and 79.5%) and moderate to very good sensitivity (61.4% and 86.4%) and there was a moderately low rate of false positive cases (21.4% and 20.5%). For the two main 'proxy' measures (PDS1 and PDS2) kappas were .38 and .59, representing poor to good agreement. In our sample of rigorously diagnosed schizophrenia inpatients, the use of a 'proxy' case identification tool for the deficit syndrome would appear to be a viable alternative in identifying a subgroup of schizophrenia patients with the deficit syndrome when the use of the actual SDS is not feasible. Further study is indicated before the PDS as extracted from the PANSS can be used in lieu of the SDS for identifying patients with this syndrome.     

Breakdown kinetics of C-hydroxymethyl beta-dicarbonyl derivatives of carbon acids: implications in the bioconversion rate of C-phosphoryloxymethyl prodrugs of carbon acids

The kinetics of conversion of C-hydroxymethyl derivatives of pharmaceutically relevant beta-dicarbonyl carbon acids of two series, pyrazolidin-3,5-diones and inden-1,3-diones, and a model carbon acid back to the respective carbon acids were studied as a function of pH at 25 degrees C and an ionic strength of 0.15 M. This is a somewhat surprising reaction since it involves the facile breakdown of a carbon-carbon bond. The slopes of the pH-rate profiles for the dehydroxymethylation were approximately unity, which along with the lack of buffer catalysis, indicates a specific-base mechanism involving spontaneous breakdown of the oxymethyl anion. This breakdown generates the conjugate base of the respective carbon acids. Thus within a series, there exists a correlation between the second-order rate constant for dehydroxymethylation and the pK(a) of the corresponding carbon acid with a shorter conversion/dehydroxymethylation half-life (at all given pH values) with decreasing pK(a) of the parent carbon acid. The increasing acidity of the carbon acid affords an increase in the leaving group ability of the carbanion, and therefore facilitation of the rate-determining unimolecular carbon-carbon bond cleavage. Since the hydroxymethyl derivative is an intermediate in the bioconversion of C-phosphoryloxymethyl prodrugs of carbon acids, also under study, the relationship allows one to reasonably predict how facile the dehydroxymethylation would be for any new beta-dicarbonyl carbon acid.     

A proteomic view into infection of greyback canegrubs (<Emphasis Type="Italic">Dermolepida albohirtum</Emphasis>) by <Emphasis Type="Italic">Metarhizium anisopliae</Emphasis>

Metarhizium anisopliae is a naturally occurring cosmopolitan fungus infecting greyback canegrubs (Dermolepida albohirtum). The main molecular factors involved in the complex interactions occurring between the greyback canegrubs and M. anisopliae (FI-1045) were investigated by comparing the proteomes of healthy canegrubs, canegrubs infected with Metarhizium and fungus only. Differentially expressed proteins from the infected canegrubs were subjected to mass spectrometry to search for pathogenicity related proteins. Immune-related proteins of canegrubs identified in this study include cytoskeletal proteins (actin), cell communication proteins, proteases and peptidases. Fungal proteins identified include metalloproteins, acyl-CoA, cyclin proteins and chorismate mutase. Comparative proteome analysis provided a view into the cellular reactions triggered in the canegrub in response to the fungal infection at the onset of biological control.