Frequency-domain analysis of fast oddball responses to visual stimuli: A feasibility study

Event-related potential responses to oddball stimuli, including the P300 component, have been proposed as a diagnostic tool for discerning psychiatric or higher-level neural disorders from malingering, for instance in cases of unexplained visual loss. For clinical use, short recording durations and easy statistical assessment are highly desirable. With this aim, we investigated the feasibility of recording oddball responses in a fast steady-state regime. We used gratings with two possible orientations in a rapid oddball paradigm with an inter-stimulus interval of 214 ms. Six consecutive presentations of one stimulus type (frequent) were followed by a single presentation of the other (infrequent) stimulus type. Subjects were attending to the rare stimulus type. The electroencephalographic recordings were analyzed in the frequency domain. All subjects produced significant harmonic responses related to the processing of the rare stimulus, demonstrating the feasibility of the technique, with the potential of reducing recording times substantially compared to conventional slow stimulation. We furthermore found that the regularity of the occurrence of infrequent stimuli, which is necessary for frequency-domain analysis, does not per se reduce the P300 responses, as would have been expected in the framework of some hypotheses regarding the role of the P300.     

Beneficial effect of a novel pentadecapeptide BPC 157 on gastric lesions induced by restraint stress,ethanol, indomethacin,and capsaicin neurotoxicity

Very recently, the integrity of capsaicin somatosensory neurons and their protection were suggested to be related to the activity in nociception of a newly discovered 15-amino acid peptide, BPC 157, shown to have strong beneficial effect on intestinal and liver lesions. Therefore, from this viewpoint, we have studied the gastroprotective effect of the pentadecapeptide BPC 157, on gastric lesions produced in rats by 96% ethanol, restraint stress, and indomethacin. The possible involvement of sensory neurons in the salutary actions of BPC 157 (10µg/kg, 10 ng/kg intraperitoneally) was studied with capsaicin, which has differential effects on sensory neurons: a high dose in adult (125 mg/kg subcutaneously, 3 months old) or administration (50 mg/kg subcutaneously) to neonatal animals (age of the 7 days) destroys sensory fibers, whereas a low dose (500µg/kg intraperitoneally) activates neurotransmitter release and protective effects on the mucosa. In the absence of capsaicin, BPC 157 protected gastric mucosa against ethanol, restraint, and indomethacin application. In the presence of neurotoxic doses of capsaicin, the negative influence of capsaicin on restraint, ethanol, or indomethacin lesions consistently affected salutary activity of BPC 157. However, BPC 157 protection was still evident in the capsaicin-treated rats (either treated as adults or as newborns) in all of these assays. Interestingly, after neonatal capsaicin treatment, a complete abolition of BPC gastroprotection was noted if BPC 157 was applied as a single nanogram-regimen, but the mucosal protection was fully reversed when the same dose was used daily. In line with the excitatory dose of capsaicin the beneficial effectiveness of BPC 157 appears to be increased as well. Taken together, these data provide evidence for complex synergistic interaction between the beneficial effectiveness of BPC 157 and peptidergic sensory afferent neuron activity.     

23S rRNA base pair 2057-2611 determines ketolide susceptibility and fitness cost of the macrolide resistance mutation 2058A-->G

The 23S rRNA A2058G alteration mediates macrolide, lincosamide, and streptogramin B resistance in the bacterial domain and determines the selectivity of macrolide antibiotics for eubacterial ribosomes, as opposed to eukaryotic ribosomes. However, this mutation is associated with a disparate resistance phenotype: It confers high-level resistance to ketolides in mycobacteria but only marginally affects ketolide susceptibility in streptococci. We used site-directed mutagenesis of nucleotides within domain V of 23S rRNA to study the molecular basis for this disparity. We show that mutational alteration of the polymorphic 2057-2611 base pair from A-U to G-C in isogenic mutants of Mycobacterium smegmatis significantly affects susceptibility to ketolides but does not influence susceptibility to other macrolide antibiotics. In addition, we provide evidence that the 2057-2611 polymorphism determines the fitness cost of the 23S rRNA A2058G resistance mutation. Supported by structural analysis, our results indicate that polymorphic nucleotides mediate the disparate phenotype of genotypically identical resistance mutations and provide an explanation for the large species differences in the epidemiology of defined drug resistance mutations.     

Surgery for fulminating colitis during pregnancy

Two cases of fulminating colitis presenting during pregnancy are described. In both cases, resectional surgery was performed. In the first case, cesarean section was combined with subtotal colectomy and ileostomy during the 32nd week of gestation. In the second case, cesarean section was performed during the 33rd week of gestation and proctocolectomy in the puerperium. In both cases, histopathologic examination showed colitis more consistent with Crohn's disease. It is concluded that if fulminating colitis appears during pregnancy it should be treated in the same manner as in the nonpregnant state.     

RV Fractional Area Change and TAPSE as Predictors of Severe Right Ventricular Dysfunction in Pulmonary Hypertension: A CMR Study

Background

The right ventricular ejection fraction (RVEF) is a surrogate marker of right ventricular function in pulmonary hypertension (PH), but its measurement is complicated and time consuming. The tricuspid annular plane systolic excursion (TAPSE) measures only the longitudinal component of RV contraction while the right ventricular fractional area change (RVFAC) takes into account both the longitudinal and the transversal components. The aim of our study was to evaluate the relationship between RVEF, RVFAC, and TAPSE according to hemodynamic severity in two groups of patients with PH: pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH).

Methods and Results

Fifty-four patients with PAH (n?=?15) and CTEPH (n?=?39) underwent right heart catheterization and cardiac magnetic resonance (CMR). The ventricular volumes and areas, TAPSE, and eccentricity index were measured. The RVFAC was more strongly correlated with the RVEF (r?=?0.81, p?<?0.0001) than the TAPSE (r?=?0.63, p?<?0.0001). RVEF?<?35% was better predicted by the RVFAC than the TAPSE (TAPSE: AUC?=?0.77 and RVFAC: AUC?=?0.91; p?=?0.042). In the group with the worse hemodynamic status, the RVFAC correlated much better with the RVEF than the TAPSE. There were no significant differences in the CMR data analyzed between the groups of PAH and CETPH patients.

Conclusions

The RVFAC is a good index to estimate RVEF in PH patients; even better than the TAPSE in patients with more severe hemodynamic profile, possibly for including the transversal component of right ventricular function in its measurement. Furthermore, RVFAC performance was similar in the two PH groups (PAH and CTEPH).

     

Vagotomy and gallbladder function

The effect of vagotomy on gallbladder function was investigated in a clinical and experimental study. In the clinical study both the size of the gallbladder and its capacity to respond to cholecystokinin were evaluated radiologically before and after vagotomy. In studies in the rabbit, both the immediate effect of vagotomy on the gallbladder and the effect of varying doses of cholecystokinin on gallbladder pressure were studied before and after vagotomy. In studies in the cat the long-term effect of vagotomy was studied with respect to the histology of the gallbladder and the composition of bile.The clinical investigation showed that vagotomy was followed by a significant increase in the volume of the gallbladder and that the effect of the cholecystokinin on the gallbladder remained unchanged after vagotomy. In experiments in the rabbit it was found that cholecystokinin in a dose of 1 unit/kg body weight exerted a somewhat lesser effect on gallbladder pressure after vagotomy than before, while after vagotomy a dose, approximately four times greater, resulted in a stronger gallbladder response. Further, the experiments showed that the chemical composition of the bile seemed to be altered after vagotomy, while the gallbladder remained histologically essentially unchanged.     

The dystrophin gene and cognitive function in the general population

The aim of our study is to investigate whether single-nucleotide dystrophin gene (DMD) variants associate with variability in cognitive functions in healthy populations. The study included 1240 participants from the Erasmus Rucphen family (ERF) study and 1464 individuals from the Rotterdam Study (RS). The participants whose exomes were sequenced and who were assessed for various cognitive traits were included in the analysis. To determine the association between DMD variants and cognitive ability, linear (mixed) modeling with adjustment for age, sex and education was used. Moreover, Sequence Kernel Association Test (SKAT) was used to test the overall association of the rare genetic variants present in the DMD with cognitive traits. Although no DMD variant surpassed the prespecified significance threshold (P<1 × 10⁻⁴), rs147546024:A>G showed strong association (β=1.786, P-value=2.56 × 10⁻⁴) with block-design test in the ERF study, while another variant rs1800273:G>A showed suggestive association (β=−0.465, P-value=0.002) with Mini-Mental State Examination test in the RS. Both variants are highly conserved, although rs147546024:A>G is an intronic variant, whereas rs1800273:G>A is a missense variant in the DMD which has a predicted damaging effect on the protein. Further gene-based analysis of DMD revealed suggestive association (P-values=0.087 and 0.074) with general cognitive ability in both cohorts. In conclusion, both single variant and gene-based analyses suggest the existence of variants in the DMD which may affect cognitive functioning in the general populations.