Extramammary myofibroblastoma is genetically related to spindle cell lipoma

Extramammary-type myofibroblastoma is a rare, benign spindle cell lesion, strictly resembling the breast counterpart, but occurring in extramammary sites, mainly in the inguinal/groin area. In this paper, we describe an extramammary-type myofibroblastoma in the groin of a 37-year-old male patient. The tumor showed a typical morphological and immunophenotypical profile, including staining for both CD34 and desmin. Dual-color interphase florescent in situ hybridization analysis revealed losses of RB/13q14 and FKHR/13q14 loci within tumor cells. The chromosome 13 rearrangements associated with the loss of the 13q14 chromosomal region are typically seen in spindle cell lipoma, and have been previously recognized in mammary myofibroblastoma, providing strong evidence for a pathogenetic link between these lesions.     

Population pharmacokinetic modeling and optimal sampling strategy for Bayesian estimation of amikacin exposure in critically ill septic patients

Because the sepsis-induced pharmacokinetic (PK) modifications need to be considered in aminoglycoside dosing, the present study aimed to develop a population PK model for amikacin (AMK) in severe sepsis and to subsequently propose an optimal sampling strategy suitable for Bayesian estimation of the drug PK parameters. Concentration-time profiles for AMK were obtained from 88 critically ill septic patients during the first 24 hours of antibiotic treatment. The population PK model was developed using a nonlinear mixed effects modeling approach. Covariate analysis included demographic data, pathophysiological characteristics, and comedication. Optimal sampling times were selected based on a robust Bayesian design criterion. Taking into account clinical constraints, a two-point sampling approach was investigated. A two-compartment model with first-order elimination best fitted the AMK concentrations. Population PK estimates were 19.2 and 9.34 L for the central and peripheral volume of distribution and 4.31 and 2.21 L/h for the intercompartmental and total body clearance. Creatinine clearance estimated using the Cockcroft-Gault equation was retained in the final model. The two optimal sampling times were 1 hour and 6 hours after onset of the drug infusion. Predictive performance of individual Bayes estimates computed using the proposed optimal sampling strategy was reported: mean prediction errors were less than 5% and root mean square errors were less than 30%. The present study confirmed the significant influence of the creatinine clearance on the PK disposition of AMK during the first hours of treatment in critically ill septic patients. Based on the population estimates, an optimal sampling strategy suitable for Bayesian estimation of the drug PK parameters was developed, meeting the need of clinical practice.     

Structure of a Fe4O6-Heteraadamantane-Type Hexacation Stabilized by Chelating Organophosphine Oxide Ligands

Metal-containing heteraadamantanes are compounds of interest due to their spectroscopic and magnetic properties, which make them promising materials for non-linear optics and semiconductors. Herein we report the comprehensive structural characterization of a new coordination compound of the formula [(µ-OH′)₂(µ-OH″)₄(O = P(Ph₂)CH₂CH₂(Ph₂)P = O)₄{Fe(t-BuOH)}₄](PF₆)₄(Cl)₂ with the chelating ligand Ph₂P(O)-CH₂CH₂-P(O)Ph₂. The compound crystallizes as a polynuclear metal complex with the adamantane-like core [Fe₄O₆] in the space group I-43d of a cubic system. The single-crystal XRD analysis showed that the crystal contains one symmetrically independent octahedrally coordinated Fe atom in the oxidation state +3. The adamantine-like scaffold of the Fe complex is formed by hydroxy bridging oxygen atoms only. Hirshfeld surface analysis of the bridging oxygen atoms revealed two types of µ-OH groups, which differ in the degree of exposure and participation in long-range interactions. Additionally, the Hirshfeld surface analysis supported by the enrichment ratio calculations demonstrated the high propensity of the title complex to form C-H^…Cl, C-H^…F and C-H^…O interactions.     

Evaluation of the formalin test to assess the analgesic activity of diflunisal in the rat

The formalin test was evaluated to assess the analgesic activity of diflunisal in the rat. Fifty microliters of a 5% formalin solution was injected into the hindpaw of rats and two distinct nociceptive behaviors, i.e. flinching/shaking and licking/biting of the injected paw, were recorded over 120 min. The effect of factors such as age of the animal, time of injection (morning vs. afternoon), site of injection (right vs. left hind paw) were evaluated. Both nociceptive behaviors exhibited a biphasic time course. Rats weighing 210–220 grams showed a more intense response compared to older rats weighing 240–250 or 270–280 grams. The nociceptive behavior response was affected by the time of formalin injection and was more pronounced in the morning. Diflunisal (100 mg/kg, i.v. infusion over 3 min) caused a significant delay in the flinching/shaking response vs. time curve, whereas the licking/biting response was significantly inhibited. When carried out under carefully controlled conditions, the formalin test may be useful to study the analgesic effect of diflunisal in the rat. It seems to be less sensitive, however, than other commonly used nociceptive tests.     

Automated EEG source imaging: A retrospective,blinded clinical validation study

Objective

To evaluate the accuracy of automated EEG source imaging (ESI) in localizing epileptogenic zone.

Human leukocyte antigen variation and Parkinson's disease

A role for the immune system in the pathogenesis of Parkinson's Disease (PD) has previously been suggested. A recent genome-wide association (GWA) study identified an association between one single nucleotide polymorphism (SNP) in the human leucocyte antigen (HLA) region (HLA-DRA rs3129882) and PD in a population of American patients with European ancestry. In that study, the minor rs3129882 allele (G) was associated with an increased risk of PD under an additive model. Due to the increased likelihood of obtaining false positive results in GWA studies compared to studies conducted based on a hypothesis-driven approach, repeated validation of findings from GWA studies are necessary. Herein, we evaluated the association between rs3129882 and PD in three different Caucasian patient-control series (combined 1313 patients and 1305 controls) from the US, Ireland, and Poland. We observed no association (OR: 0.96, P = 0.50) between rs3129882 and PD when analyzing our data under an additive or dominant model. In contrast, when examined under a recessive model, the GG genotype was observed to be protective in the Irish (OR: 0.55, P = 0.008), Polish (OR: 0.67, P = 0.040) and combined (OR: 0.75, P = 0.006) patient-control series. In view of these diverging results, the exact role of genetic variation at the HLA region and susceptibility to PD remains to be resolved.