Antimicrobial susceptibility of Proteus mirabilis urinary tract isolates from 1999 to 2005 at Nîmes University Hospital

Aim of the studyTo analyse antimicrobial resistance trends of Proteus mirabilis urinary tract isolates from 1999 to 2005 at the Nîmes University hospital.Materials and methodsWe retrospectively collected non-duplicate urinary tract infections and colonization isolates from inpatients between 1 January 1999 and 31 December 2005.ResultsOne thousand and eight non-duplicate urinary tract isolates were studied, 63.1% were from females and the mean age was 76 years. The mean resistance rate was 59.0% for amoxicillin (AMX), 48.0% for piperacillin (PIP), 3.9% for cefotaxim, 33.9% for amoxicillin plus clavulanic acid (AMC) and 2.8% for piperacillin plus tazobactam (TZP). A significant increase in resistance was observed for AMC and TZP. The mean resistance rate was 35.0% for norfloxacin, 34.8% for ofloxacin and 23.5% for ciprofloxacin. No significant increase in resistance to fluoroquinolones was seen except for ciprofloxacin whereas a significant increase was observed for aminoglycosides. The mean rate resistance for cotrimoxazole was 33.2% with a significant decrease in the resistance during the study period.ConclusionP. mirabilis stilled sensitive to cefotaxim or ceftazidim and to TZP. The significant increase in the rate resistance to AMC and TZP could be explained by production of β-lactamases and in particular extended-spectrum β-lactamases. The increase in resistance observed for fluoroquinolones become a major concern. Amikacine was the most active aminoglycosides. These data suggested for the re-enforcement of the antimicrobial susceptibility surveillance in order to optimise the rational use of antibiotics.     

Improvement of radiological penumbra using intermediate energy photons (IEP) for stereotactic radiosurgery

Using efficient immobilization and dedicated beam collimation devices, stereotactic radiosurgery ensures highly conformal treatment of small tumours with limited microscopic extension. One contribution to normal tissue irradiation remains the radiological penumbra. This work aims at demonstrating that intermediate energy photons (IEP), above orthovoltage but below megavoltage, improve dose distribution for stereotactic radiosurgery for small irradiation field sizes due to a dramatic reduction of radiological penumbra. Two different simulation systems were used: (i) Monte Carlo simulation to investigate the dose distribution of monoenergetic IEP between 100 keV and 1 MeV in water phantom; (ii) the Pinnacle3 TPS including a virtual IEP unit to investigate the dosimetry benefit of treating with 11 non-coplanar beams a 2 cm tumour in the middle of a brain adjacent to a 1 mm critical structure. Radiological penumbrae below 300 microm are generated for field size below 2 x 2 cm2 using monoenergetic IEP beams between 200 and 400 keV. An 800 kV beam generated in a 0.5 mm tungsten target maximizes the photon intensity in this range. Pinnacle3 confirms the dramatic reduction in penumbra size. DVHs show for a constant dose distribution conformality, improved dose distribution homogeneity and better sparing of critical structures using a 800 kV beam compared to a 6 MV beam.     

Self-compassion,chronic age-related stressors,and diurnal cortisol secretion in older adulthood

Many older adults experience chronic age-related stressors (e.g., life regrets or health problems) that are difficult to control and can disturb cortisol regulation. Self-compassion may buffer adverse effects of these stressful experiences on diurnal cortisol secretion in older adulthood. To examine whether self-compassion could benefit older adults’ cortisol secretion in the context of chronic and largely uncontrollable age-related stressors, 233 community-dwelling older adults reported their levels of self-compassion, age-related stressors (regret intensity, physical health problems, and functional disability), and relevant covariates. Diurnal cortisol was measured over 3 days and the average area-under-the-curve and slope were calculated. Higher levels of self-compassion were associated with lower daily cortisol levels among older adults who reported higher levels of regret intensity, physical health problems, or functional disability (βs?<???.53, ps?<?.01), but not among their counterparts who reported lower levels of these age-related stressors (βs?<?.24, ps?>?.28). These results suggest that self-compassion may represent an important personal resource that could protect older adults from stress-related biological disturbances resulting from chronic and uncontrollable stressors.     

Radical fimbriectomy: a reasonable temporary risk-reducing surgery for selected women with a germ line mutation of BRCA 1 or 2 genes? Rationale and preliminary development

Objective

Bilateral salpingo-oophorectomy (BSO) is the gold standard prophylactic surgery for BRCA1 or 2 mutation carriers. However, due to the resulting early menopause and fertility desires, young women are reluctant to undergo this procedure. In view of the recent literature on ovarian carcinogenesis, we wish to report a novel conceptual surgical procedure we called “radical fimbriectomy.” This procedure is aimed to protect this subset of high-risk women from high-grade serous pelvic carcinoma, while preserving their ovarian function.

Methods

Women with BRCA mutation, who were scheduled for BSO, were informed of the procedure approved by our local review board. Radical fimbriectomy consists of removing all the tube and the fimbrio-ovarian junction, step immediately followed in this developmental phase by completion oophorectomy. Four methods of partial ovarian transsection were prospectively compared: sharp division, stapler, bipolar division and harmonic scalpel. Surgical safety and pathological alterations were assessed. All specimens underwent extensive pathological evaluation using both SEE-FIM protocol and serial sections.

Results

Fourteen women were enrolled in the study. Sharp and EndoGIA^® appeared to be the safest methods of ovarian resection providing the best specimen quality for pathological examination.

Conclusion

We believe this technique could be suggested to young mutation carriers reluctant to undergo BSO. This approach is preferable to no prophylactic surgery at all. However, until the safety and validity of this procedure is confirmed by a multi-institutional study, women who undergo radical fimbriectomy should continue to receive regular multimodal evaluation and be advised of the risks involved until they finally accept secondary castration.     

Non-Gaussian water diffusion in aging white matter

Age-associated white matter degeneration has been well documented and is likely an important mechanism contributing to cognitive decline in older adults. Recent work has explored a range of noninvasive neuroimaging procedures to differentially highlight alterations in the tissue microenvironment. Diffusional kurtosis imaging (DKI) is an extension of diffusion tensor imaging (DTI) that accounts for non-Gaussian water diffusion and can reflect alterations in the distribution and diffusion properties of tissue compartments. We used DKI to produce whole-brain voxel-based maps of mean, axial, and radial diffusional kurtoses, quantitative indices of the tissue microstructure's diffusional heterogeneity, in 111 participants ranging from the age of 33 to 91 years. As suggested from prior DTI studies, greater age was associated with alterations in white-matter tissue microstructure, which was reflected by a reduction in all 3 DKI metrics. Prominent effects were found in prefrontal and association white matter compared with relatively preserved primary motor and visual areas. Although DKI metrics co-varied with DTI metrics on a global level, DKI provided unique regional sensitivity to the effects of age not available with DTI. DKI metrics were additionally useful in combination with DTI metrics for the classification of regions according to their multivariate “diffusion footprint”, or pattern of relative age effect sizes. It is possible that the specific multivariate patterns of age-associated changes measured are representative of different types of microstructural pathology. These results suggest that DKI provides important complementary indices of brain microstructure for the study of brain aging and neurologic disease.     

Identification of medically important Candida and non-Candida yeast species by an oligonucleotide array

The incidence of yeast infections has increased in the recent decades, with Candida albicans still being the most common cause of infections. However, infections caused by less common yeasts have been widely reported in recent years. Based on the internal transcribed spacer 1 (ITS 1) and ITS 2 sequences of the rRNA genes, an oligonucleotide array was developed to identify 77 species of clinically relevant yeasts belonging to 16 genera. The ITS regions were amplified by PCR with a pair of fungus-specific primers, followed by hybridization of the digoxigenin-labeled PCR product to a panel of oligonucleotide probes immobilized on a nylon membrane for species identification. A collection of 452 yeast strains (419 target and 33 nontarget strains) was tested, and a sensitivity of 100% and a specificity of 97% were obtained by the array. The detection limit of the array was 10 pg of yeast genomic DNA per assay. In conclusion, yeast identification by the present method is highly reliable and can be used as an alternative to the conventional identification methods. The whole procedure can be finished within 24 h, starting from isolated colonies.     

Simultaneous Intracranial EEG-fMRI Shows Inter-Modality Correlation in Time-Resolved Connectivity Within Normal Areas but Not Within Epileptic Regions

For the first time in research in humans, we used simultaneous icEEG-fMRI to examine the link between connectivity in haemodynamic signals during the resting-state (rs) and connectivity derived from electrophysiological activity in terms of the inter-modal connectivity correlation (IMCC). We quantified IMCC in nine patients with drug-resistant epilepsy (i) within brain networks in ‘healthy’ non-involved cortical zones (NIZ) and (ii) within brain networks involved in generating seizures and interictal spikes (IZ1) or solely spikes (IZ2). Functional connectivity (h ² ) estimates for 10 min of resting-state data were obtained between each pair of electrodes within each clinical zone for both icEEG and fMRI. A sliding window approach allowed us to quantify the variability over time of h ² (vh ²) as an indicator of connectivity dynamics. We observe significant positive IMCC for h ² and vh ², for multiple bands in the NIZ only, with the strongest effect in the lower icEEG frequencies. Similarly, intra-modal h ² and vh ² were found to be differently modified as a function of different epileptic processes: compared to NIZ, \(h_{\text{BOLD}}^{2}\) was higher in IZ1, but lower in IZ2, while \(h_{\text{icEEG}}^{2}\) showed the inverse pattern. This corroborates previous observations of inter-modal connectivity discrepancies in pathological cortices, while providing the first direct invasive and simultaneous comparison in humans. We also studied time-resolved FC variability multimodally for the first time, finding that IZ1 shows both elevated internal \(h_{\text{BOLD}}^{2}\) and less rich dynamical variability, suggesting that its chronic role in epileptogenesis may be linked to greater homogeneity in self-sustaining pathological oscillatory states.     

Efficacy and safety of a quadruple combination Combivir + abacavir + efavirenz regimen in antiretroviral treatment-naive HIV-1-infected adults: La Francilienne

OBJECTIVE: To evaluate the safety and efficacy of a protease inhibitor sparing, quadruple therapy (Combivir + abacavir + efavirenz) in antiretroviral treatment-naive HIV-1-infected adults. DESIGN: Multicenter open-label pilot study. Clinical and biological assessments were performed at baseline and at weeks 2, 4, 8, 16, 24, 32, 40, 48. RESULTS: Thirty-one subjects enrolled with a median baseline viral load (VL) of 4.69 log10 copies/mL and CD4 cell count of 322 cells/mm3. At week 48, 90% (intention-to-treat [ITT] switch included) and 77% (ITT switch = failure) patients had a VL <50 copies/mL. These results were similar in the population (n = 13) with a VL >100,000 copies/mL at baseline. Combivir + abacavir + efavirenz demonstrated an early antiretroviral response: 58% of patients had plasma HIV-1 RNA <50 copies/mL at week 8. Using a modified assay, the percentage of patients with VL <5 copies/mL at week 48 was 55% (17/31) and 42% (13/31) using ITT (switch included) and ITT (switch = failure), respectively. Median VL decreased by -4.0 log10 copies/mL at week 48 (ITT). Median CD4+ cell count change from baseline at week 48 was +129 cells/mm3 (ITT). Most patients experienced at least one drug-related adverse event that was not considered treatment-limiting by the investigator. There were no cases of abacavir hypersensitivity reactions. CONCLUSIONS: Safety and efficacy results from this study demonstrated that the quadruple regimen Combivir/abacavir/efavirenz is generally safe and displays potent and durable antiretroviral activity in antiretroviral treatment-naive HIV-1-infected patients, offering a promising therapeutic option in a PI-sparing strategy.     

Migration through basement membrane modulates eosinophil expression of CD44

BACKGROUND: Tissue eosinophils express more membrane receptors and release more mediators than blood eosinophils, suggesting that migration from blood to tissue modulates eosinophil phenotype and functions. OBJECTIVE: We postulated that eosinophil passage through endothelial basement membrane, an important step of eosinophil migration into tissue, may be responsible for some of these changes. METHOD: We previously showed that 5-oxo-6, 8, 11, 14-eicosatetraenoic acid (5-oxo-ETE) in combination with IL-5 promotes eosinophil migration through Matrigel, a mouse tumour cell-derived basement membrane. Using this model, we evaluated the effect of trans-Matrigel migration on purified human blood eosinophil expressions of CD44, CD69 and HLA-DR that either increase or appear on activated eosinophils, and releases of peroxidase (EPO), leukotriene (LT) C(4) and granulocyte-monocyte colony stimulating factor (GM-CSF). RESULTS: IL-5, but not 5-oxo-ETE, increased eosinophil expression of CD44 and CD69. Migration of eosinophils through Matrigel significantly increased CD44 expression level over the one induced by IL-5 (P = 0.0001). Migration through Matrigel did not modify CD69 expression compared with the one obtained in the presence of IL-5 alone; however, incubation of eosinophils on Matrigel decreased IL-5-induced CD69 (P = 0.0001). Trans-Matrigel migration did not modify HLA-DR expression, nor EPO, LTC(4) and GM-CSF releases. CONCLUSION: These data show that in vitro trans-Matrigel migration and Matrigel contact modulate eosinophil membrane receptor expression. Consequently, they suggest that migration through basement membrane mediates changes in cell-surface phenotype observed on activated eosinophils and probably prepares them for interactions with tissue components and cells.