Supersonic shear wave elastography of in vivo pig kidney: influence of blood pressure, urinary pressure and tissue anisotropy

The in vivo influence of renal anisotropy and of urinary and vascular pressure on elasticity values using ultrasonic supersonic shear wave elastography was studied in pigs. Experiments were conducted in agreement with the European Commission guidelines and directives of the French Research Ministry. Six kidneys in three pigs were studied in vivo. Elasticity of renal cortex and medulla was quantified through the shear modulus (μ) by using the supersonic shear imaging technique with an 8 MHz linear ultrasound probe. All measurements were done peroperatively both in the axis and perpendicular to the main axis of pyramids, in normal condition, after progressive increase of urinary pressure, and after renal artery and renal vein ligation. In normal conditions, cortical (C) and medullary (M) elasticity values were always higher when acquisitions were realized with the ultrasound main axis perpendicular to main pyramid axis (C_//: 7.7 ± 2.3 kPa; M_//: 8.7 ± 2.5 kPa) than parallel (C_⊥: 6.9 ± 1.4 kPa; M_⊥: 6.6 ± 2.3 kPa), demonstrating an effect of renal anisotropy. In renal cortex, two bands were separated, inner cortex showing higher elasticity values (IC_⊥: 8.1 ± 1.9 kPa) than outer cortex (OC_⊥: 6.9 ± 1.4 kPa). Renal artery and renal vein ligation induced a decrease and an increase of elasticity respectively. Parenchymal elasticity increased linearly with elevation of urinary pressure. Intrarenal elasticity values vary with tissue anisotropy and, with vascular and urinary pressure levels. These parameters have to be taken into account for interpretation of tissue changes. Separation of outer and inner cortex could be attributable to perfusion differences.     

Aromatic hydrocarbon receptor polymorphism: development of new methods to correlate genotype with phenotype.

Differential CYP1A1 inducibility, reflecting variations in aromatic hydrocarbon receptor (AHR) affinity among inbred mouse strains, is an important determinant of environmental toxicity. We took advantage of the Ahr polymorphism in C57BL/6 and DBA/2 mice to develop an oligonucleotide-hybridization screening approach for the rapid identification of DNA sequence differences between Ahr alleles. Oligonucleotides containing single-base changes at polymorphic sites were immobilized on a solid support and hybridized with C57BL/6 or DBA/2 AHR cDNA radiolabeled probes. The observed hybridization patterns demonstrate that this approach can be used to detect nucleotide differences in the Ahr coding region with very high accuracy. In parallel experiments, we used a yeast two-hybrid system to assess phenotypic differences in AHR function. AHR activation, as measured by beta-galactosidase reporter activity in Saccharomyces cerevisiae strain SFY526, was determined following treatment with varying doses of the AHR ligand beta-naphthoflavone (BNF). We found that the C57BL/6 AHR has about a 15-fold higher affinity for BNF than the DBA/2 AHR, in much better agreement with results reported for whole-animal studies than the values observed by in vitro ligand-binding assays. Using C57BL/6 and DBA/2 AHR chimeric proteins, we also confirmed the previously reported observation that an A375V change is principally responsible for the high- to low-affinity AHR phenotype. There has been no straightforward method to reliably and reproducibly phenotype large numbers of humans for CYP1A1 inducibility or AHR affinity. Screening human AHR cDNAs by oligonucleotide-hybridization and yeast two-hybrid methodologies will be invaluable for the rapid and unequivocal determination of changes in DNA sequence and receptor-ligand affinities associated with human AHR polymorphisms.     

Monte Carlo aided design of an improved well-type ionization chamber for low energy brachytherapy sources

The determination of the air kerma strength of a brachytherapy seed is necessary for effective treatment planning. Well-type ionization chambers are used on site at therapy clinics to determine the air kerma strength of seeds. In this work, an improved well-type ionization chamber for low energy, low dose rate brachytherapy sources is designed using Monte Carlo transport calculations to aid in the design process. The design improvements are the elimination of the air density induced over-response effect seen in other air-communicating chambers for low energy photon sources, and a larger signal strength (response or current) for 103Pd and 125I based seeds. A prototype well chamber based on the Monte Carlo aided design but using graphite coated acrylic walls rather than the design basis air equivalent plastic (C-552) walls was constructed and experimentally evaluated. The prototype chamber produced an 85% stronger signal when measuring a commonly used 103Pd seed and a 26% stronger signal when measuring a commonly used 125I seed when compared to another commonly used well chamber. The normalized PTP corrected chamber response is, at most, 1.3% and 2.4% over unity for air densities/pressures corresponding to an elevation of 3048 m (10000 feet) above sea level for the commonly used 103Pd and 125I based seeds respectively. Comparing calculated and measured chamber responses for common 103Pd and 125I based brachytherapy seeds show agreement within 0.6% and 0.2%, respectively. We conclude that Monte Carlo transport calculations accurately model the response of this new well chamber and in general can be used to predict the response of well chambers. The prototype chamber built in this work responds as predicted by the Monte Carlo calculations.     

Harassment in the workplace: clinic and psychopathological factors

Harassment may be either moral, physical or sexual. It is defined as a phenomenon that happens repeatedly. It is underestimated in professional environments and probably even more so in private life. Without referring to a pathological personality, harassers have common pathological traits.     

Genital human Papillomavirus infection in patients with autoimmune inflammatory diseases

Treatment advances achieved over the last few years have radically changed the management of patients with autoimmune inflammatory diseases requiring conventional or biological immunosuppressive therapy. These diseases and the drugs used to treat them increase the rate of infections, including genital infections due to the human Papillomavirus (HPV). Genital HPV infections have been extensively studied in organ transplant recipients, HIV-infected patients, and patients with congenital immune deficiencies. Although genital HPV infections usually manifest as benign lesions of the external genital organs (condylomata), they are associated with an increased risk of cancer. Very few data are available on genital HPV infections associated with autoimmune inflammatory diseases or their treatments. Here, we review the published information on this topic.     

Relationship between functional connectivity and sensory impairment: Red flag or red herring?

Resting-state functional magnetic resonance imaging (fMRI) can be used to study the functional connectivity in the somatosensory system. However, the relationship between sensory network connectivity, sensory deficits, and structural abnormality remains poorly understood. Previously, we investigated the motor network in children with congenital hemiparesis due to middle cerebral artery strokes (MCA, n = 6) or periventricular lesions (PL, n = 8). In the present study, we validate the use of interleaved resting-state data from blocked fMRI designs to investigate the somatosensory network in these patients. The approach was validated by assessing the predicted "crossed-over" connectivity between the cerebral cortex and the cerebellum. Furthermore, the impact on the volume of gray-matter (GM) in primary (S1) and secondary (S2) somatosensory cortex on functional connectivity measures was investigated. We were able to replicate the well-known "crossed-over" pattern of functional connectivity between cerebral and cerebellar cortex. The MCA group displayed more sensory deficit and significantly reduced functional connectivity in the lesioned S2 (but not in lesioned S1) when compared with the PL group. However, when accounting for GM volume loss, this difference disappeared. This study demonstrates the applicability of analyzing resting-state connectivity in patients with brain lesions. Reductions of functional connectivity within the somatosensory network were associated with sensory deficits, but were fully explained by the underlying GM damage.     

Integration of proprioceptive signals and attentional capacity during postural control are impaired but subject to improvement in dyslexic children

Children with developmental dyslexia suffer from delayed reading capabilities and may also exhibit attentional and sensori-motor deficits. The objective of this study was twofold. First, we aimed at investigating whether integration of proprioceptive signals in balance control was more impaired in dyslexic children when the attentional demand was varied. Secondly, we checked whether this effect was reduced significantly by using a specific treatment to improve eye control deficits and certain postural signs that are often linked to dyslexia (Quercia et al. in J Fr Ophtalmol 28:713–723, 2005, J Fr Ophtalmol 30:380–89, 2007). Thirty dyslexic and 51 treated dyslexic children (>3 months of treatment) were compared with 42 non-dyslexic children in several conditions (mean age: 136.2 ± 23.6, 132.2 ± 18.7 and 140.2 ± 25 months, respectively). Co-vibration of ankle muscles was effected in order to alter proprioceptive information originating from the ankle. In two vibration conditions, ankle muscles were either not vibrated or vibrated at 85 Hz without illusion of any movement. These two vibration conditions were combined with two attentional conditions. In the first such condition, children maintained balance while merely fixing their gaze on a point in front of them. In the second condition, they had to look for smaller or larger stars in a panel showing forty of each kind. Balance was assessed by means of a force plate. Results indicated that the mean velocity (i.e. the total length) of the center of pressure (CoP) displacement in the 85-Hz vibration condition increased significantly more (compared with no vibration) in the dyslexic and the treated dyslexic groups than in the control group, irrespective of the attention task. Interestingly, in the condition without vibration, the attentional performance of treated children was similar to that of the control group, whereas the attentional performance of the untreated dyslexic children was significantly impaired. Altogether, these results suggest that integration of proprioceptive signals in balance control and attentional capacity are impaired in dyslexic children. However, attention capacity during the control of stance could be improved significantly.     

Secretome from senescent melanoma engages the STAT3 pathway to favor reprogramming of naive melanoma towards a tumor-initiating cell phenotype

Here, we showed that the secretome of senescent melanoma cells drives basal melanoma cells towards a mesenchymal phenotype, with characteristic of stems illustrated by increased level of the prototype genes FN1, SNAIL, OCT4 and NANOG. This molecular reprogramming leads to an increase in the low-MITF and slow-growing cell population endowed with melanoma-initiating cell features. The secretome of senescent melanoma cells induces a panel of 52 genes, involved in cell movement and cell/cell interaction, among which AXL and ALDH1A3 have been implicated in melanoma development. We found that the secretome of senescent melanoma cells activates the STAT3 pathway and STAT3 inhibition prevents secretome effects, including the acquisition of tumorigenic properties. Collectively, the findings provide insights into how the secretome of melanoma cells entering senescence upon chemotherapy treatments increases the tumorigenicity of naïve melanoma cells by inducing, through STAT3 activation, a melanoma-initiating cell phenotype that could favor chemotherapy resistance and relapse.     

Assessment of reproducibility of thigh marker ranking during walking and landing tasks

The aim of this paper is to analyse the repeatability of marker deformation and marker ranking across subjects and motor tasks. A method based on the solidification of the thigh with optimized rototranslation was applied which used 26 markers placed on the left thigh. During five trials of landing and five trials of walking for eight participants, the deformation between the actual positions of the 26 markers and the recalled positions from solidification were calculated. Markers were then sorted and ranked from the most deformed to the least deformed. Like previous studies, marker deformation found in this paper is subject and movement-dependant. The reproducibility of the marker rankings was assessed using Kendall's coefficient of concordance. Results highlighted that the marker ranking was similar between the trials of landing and between the trials of walking. Moreover, for walking and landing the rankings were consistent across the eight subjects.