Motion Artifacts and Correction in Multipulse High-Frame Rate Contrast-Enhanced Ultrasound.

High-frame-rate (HFR) ultrasound (US) imaging and contrast-enhanced US (CEUS) are often implemented using multipulse transmissions, to enhance image quality. Multipulse approaches, however, suffer from degradation in the presence of motion, especially when coherent compounding and CEUS are combined. In this paper, we investigate this effect on the intensity of HFR CEUS in deep tissue imaging using simulations and in vivo contrast echocardiography (CE). The simulation results show that the motion artifact is much higher when the flow is in an axial direction than a lateral direction. Using a pulse repetition frequency suitable for cardiac imaging, a motion of 35 cm/s can cause as much as 28.5 dB decrease in image intensity, where compounding can contribute up to 18.7 dB of intensity decrease (11 angles). These motion effects are also demonstrated for in vivo cardiac HFR CE, where the large velocities of both the myocardium and the blood are present. Intensity reductions of 10.4 dB are readily visible in the chamber. Finally, we demonstrate how performing motion-correction before pulse inversion compounding greatly reduces such motion artifact and improve image signal-to-noise ratio and contrast.

Variability in circulating gas emboli after a same scuba diving exposure.

PURPOSE: A reduction in ambient pressure or decompression from scuba diving can result in ultrasound-detectable venous gas emboli (VGE). These environmental exposures carry a risk of decompression sickness (DCS) which is mitigated by adherence to decompression schedules; however, bubbles are routinely observed for dives well within these limits and significant inter-personal variability in DCS risk exists. Here, we assess the variability and evolution of VGE for 2 h post-dive using echocardiography, following a standardized pool dive in calm warm conditions. METHODS: 14 divers performed either one or two (with a 24 h interval) standardized scuba dives to 33 mfw (400 kPa) for 20 min of immersion time at NEMO 33 in Brussels, Belgium. Measurements were performed at 21, 56, 91 and 126 min post-dive: bubbles were counted for all 68 echocardiography recordings and the average over ten consecutive cardiac cycles taken as the bubble score. RESULTS: Significant inter-personal variability was demonstrated despite all divers following the same protocol in controlled pool conditions: in the detection or not of VGE, in the peak VGE score, as well as time to VGE peak. In addition, intra-personal differences in 2/3 of the consecutive day dives were seen (lower VGE counts or faster clearance). CONCLUSIONS: Since VGE evolution post-dive varies between people, more work is clearly needed to isolate contributing factors. In this respect, going toward a more continuous evaluation, or developing new means to detect decompression stress markers, may offer the ability to better assess dynamic correlations to other physiological parameters.

Poly (ADP-ribose) polymerase 1 mRNA levels strongly correlate with the prognosis of myelodysplastic syndromes.

Poly (ADP-ribose) polymerase 1 (PARP-1) has a central role in the repair of DNA breaks and is a promising treatment target in malignancy. We measured PARP1 mRNA levels by a SYBR-green-based PCR in the bone marrow of 74 patients with myelodysplastic syndrome (MDS) and correlated them to their demographic, hematologic and prognostic characteristics. The median PARP1 mRNA levels were correlated to the type of MDS (2008/2016 WHO classification, P=0.005) and to the IPSS score (P=0.002). A correlation was also found with the IPSS-R score (P=0.011) and the cytogenetic risk (P=0.008). In all cases, higher PARP1 levels were correlated with a higher risk category. Moreover, we found a significant survival disadvantage for patients with high PARP1 levels (median survival of 37.4 months versus 'not reached' for low PARP1 levels, P=0.0001, and a 5-year survival rate of 29.8 versus 88.9%, respectively). PARP1 mRNA levels were found to be the stronger predictor of survival in multivariate analysis. These correlations have never been reported in the past and may render PARP1 a prognostic factor to be incorporated in the current prognostic systems for MDS, also laying the basis for clinical trials evaluating PARP1 inhibitors in higher-risk MDS.

Heart rate variability and critical flicker fusion frequency changes during and after parachute jumping in experienced skydivers.

PURPOSE: The purpose of this study was (1) to further explore the heart rate dynamics and assess a potential cardiovascular risk in response to 4000 m jumps in experienced skydivers; (2) to assess whether there is an impact of such jumps on skydivers' cortical arousal or not, which may impact their decision making processes. METHOD: 18 experienced skydivers performed successive jumps from a plane at 4000 m of height. Heart rate dynamics and cortical arousal were assessed by the use of heart rate variability and Critical Flicker Fusion Frequency (CFFF), respectively. RESULTS: CFFF did not differ between the three measurement time points (p > 0.05). Mean heart rate increased during the jump (p < 0.001) and came back to pre-jump values after the jump (p < 0.001). Percentage of the differences of successive NN intervals greater than 50 ms (pNN50) decreased during the jump (p < 0.001) and kept lower values after the jump compared to pre-jump (p < 0.05). High-frequency power (HF) did not differ during the jump (p > 0.05) but decreased after the jump compared to both pre-jump (p < 0.01) and jump (p < 0.05). Sample entropy decreased during the jump (p < 0.001) and came back to pre-jump values after the jump (p > 0.05). CONCLUSION: These results confirm a vagal input reduction associated with a rise of the sympathetic tone during the jump and suggests that the experienced skydiver is not exposed to a high cardiovascular risk. This study also shows that environmental stresses induced by free fall could not hamper the perceptual vigilance of experienced skydivers.

Long term effects of recreational SCUBA diving on higher cognitive function.

We investigated long-term effects of SCUBA diving on cognitive function using a battery of neuropsychometric tests: the Simple Reaction Time (REA), Symbol Digit Substitution (SDS), Digit Span Backwards (DSB), and Hand-Eye Coordination tests (EYE). A group (n = 44) of experienced SCUBA divers with no history of decompression sickness was compared to non-diving control subjects (n = 37), as well as to professional boxers (n = 24), who are considered at higher risk of long term neurological damage. The REA was significantly shorter in SCUBA divers compared to the control subjects, and also more stable over the time course of the test. In contrast, the number of digits correctly memorized and reordered (DSB) was significantly lower for SCUBA divers compared to the control group. The results also showed that boxers performed significantly worse than the control group in three out of four tests (REA, DSB, EYE). While it may be concluded that accident-free SCUBA diving may have some long-term adverse effects on short-term memory, there is however, no evidence of general higher cognitive function deficiency.

Nitric oxide-related endothelial changes in breath-hold and scuba divers.

OBJECTIVE: Scuba and breath-hold divers are compared to investigate whether endothelial response changes are similar despite different exposure(s) to hyperoxia. DESIGN: 14 divers (nine scuba and five breath-holding) performed either one scuba dive (25m/25 minutes) or successive breath-hold dives at a depth of 20 meters, adding up to 25 minutes of immersion time in a diving pool. Flow-mediated dilation (FMD) was measured using echography. Peripheral post-occlusion reactive hyperemia (PORH) was assessed by digital plethysmography and plasmatic nitric oxide (NO) concentration using a nitrate/nitrite colorimetric assay kit. RESULTS: The FMD decreased in both groups. PORH was reduced in scuba divers but increased in breath-hold divers. No difference in circulating NO was observed for the scuba group. Opposingly, an increase in circulating NO was observed for the breath-hold group. CONCLUSION: Some cardiovascular effects can be explained by interaction between NO and superoxide anion during both types of diving ending to less NO availability and reducing FMD. The increased circulating NO in the breath-hold group can be caused by physical exercise. The opposite effects found between FMD and PORH in the breath-hold group can be assimilated to a greater responsiveness to circulating NO in small arteries than in large arteries.

Development of a reaction-limited model of dissolution: application to official dissolution tests experiments.

A reaction-limited model for drug dissolution is developed assuming that the reaction at the solid-liquid interface is controlling the rate of dissolution. The dissolution process is considered as a bidirectional chemical reaction of the undissolved drug species with the free solvent molecules, yielding the dissolved species of drug complex with solvent. This reaction was considered in either sink conditions, where it corresponds to the unidirectional case and the entire amount of the drug is dissolved, or reaching chemical equilibrium, which corresponds to saturation of the solution. The model equation was fitted successfully to dissolution data sets of naproxen and nitrofurantoin formulations measured in the paddle and basket apparatuses, respectively, under various experimental conditions. For comparative purposes these data were also analyzed using three functions based on the diffusion layer model. All functions failed to reveal the governing role of saturation solubility in the dissolution process associated with the diffusion layer model when the conditions for the valid estimation of saturation solubility, established theoretically in this study, were met by the experimental set up employed. Overall, the model developed provides an interesting alternative to the classic approaches of drug dissolution modeling, quantifying the case of reaction-limited dissolution of drugs.

L-2-Hydroxyglutaric aciduria presenting with severe autistic features.

L-2-Hydroxyglutaric aciduria (L-2-HGA) is an autosomal recessive neurometabolic disorder characterized by psychomotor delay, ataxia, macrocephaly and typical neuroradiological findings of subcortical leucoencephalopathy. Recently, the disease causing gene has been discovered (L2HGDH) encoding L-2-hydroxyglutarate dehydrogenase. We present a 3-year-old boy with L-2-HGA, who demonstrated macrocephaly, noted already in utero with ultrasound. Cranial MRI demonstrated diffuse subcortical encephalopathy with increased signal of the subcortical white matter. Subsequent metabolic screening revealed increased levels of L-2-HGA, and genomic DNA analysis demonstrated two missense mutations in L-2-HGDG. Patient's further motor development was mildly impaired, whilst his speech development was profoundly impaired (first words at the age of 2 years). Since the age of 2 years he started demonstrating autistic repetitive behaviors and movements, increasing aloofness to his environment and limitations in the variety of spontaneous activity (CARS score: 44/60-severe autism). Autism has not so far been described in L-2-HGA and may be considered as an additional feature of the phenotypic spectrum.

Poly-(ADP-ribose) polymerase-1 (Parp-1) binds in a sequence-specific manner at the Bcl-6 locus and contributes to the regulation of Bcl-6 transcription.

Bcl-6 is a transcription factor that is normally expressed in germinal centre B cells. It is essential for the formation of germinal centres and the production of high-affinity antibodies. Transcriptional downregulation of Bcl-6 occurs on terminal differentiation to plasma cells. Bcl-6 is highly expressed in B-cell non-Hodgkin's lymphoma and, in a subset of cases of diffuse large cell lymphoma, the mechanism of Bcl-6 overexpression involves interruption of normal transcriptional controls. Transcriptional control of Bcl-6 is, therefore, important for normal antibody responses and lymphomagenesis, but little is known of the cis-acting control elements. This report focuses on a region of mouse/human sequence homology in the first intron of Bcl-6, which is a candidate site for such a control element. We demonstrate that poly-(ADP-ribose) polymerase-1 (Parp-1) binds in vitro and in vivo to specific sequences in this region. We further show that PARP inhibitors, and Parp-1 knockdown by siRNA induce Bcl-6 mRNA expression in Bcl-6 expressing cell lines. We speculate that Parp-1 activation plays a role in switching off Bcl-6 transcription and subsequent B-cell exit from the germinal centre.

Retinoblastoma with an unusual presentation in a child with polydactyly. Clinical associations and genetic implications.

Retinoblastoma is the most common intraocular malignancy of childhood. It may rarely present with white spots on the iris and pseudohypopyon. We report a case of an 11-month old child with polydactyly with this presentation of retinoblastoma. There was no positive family history of the disease. Investigations included anterior segment examination under anaesthesia, fundoscopy with scleral indentation, A- and B-scan ultrasound and MRI examination of the head. This was a Reese Ellsworth group 5 retinoblastoma with an indication for enucleation. Pathology reports of the enucleated globe showed choroidal and ciliary body invasion. Therefore, subsequent chemotherapy treatment was undertaken. The retinoblastoma gene is located in the long arm of chromosome 13. Almost all familial and bilateral cases carry the abnormal gene. In unilateral isolated retinoblastomas--as in our case--most patients do not have a germinal mutation, however, only DNA analysis can safely exclude that. We also discuss possible factors having a link to both polydactyly and retinoblastoma.