Modifications of the endosomal compartment in peripheral blood mononuclear cells and fibroblasts from Alzheimer's disease patients

Identification of blood-based biomarkers of Alzheimer''s disease (AD) remains a challenge. Neuropathological studies have identified enlarged endosomes in post-mortem brains as the earliest cellular change associated to AD. Here the presence of enlarged endosomes was investigated in peripheral blood mononuclear cells from 48 biologically defined AD patients (25 with mild cognitive impairment and 23 with dementia (AD-D)), and 23 age-matched healthy controls using immunocytochemistry and confocal microscopy. The volume and number of endosomes were not significantly different between AD and controls. However, the percentage of cells containing enlarged endosomes was significantly higher in the AD-D group as compared with controls. Furthermore, endosomal volumes significantly correlated to [C¹¹]PiB cortical index measured by positron emission tomography in the AD group, independently of the APOE genotype, but not to the levels of amyloid-beta, tau and phosphorylated tau measured in the cerebrospinal fluid. Importantly, we confirmed the presence of enlarged endosomes in fibroblasts from six unrelated AD-D patients as compared with five cognitively normal controls. This study is the first, to our knowledge, to report morphological alterations of the endosomal compartment in peripheral cells from AD patients correlated to amyloid load that will now be evaluated as a possible biomarker.     

Ambulatory Essure implant placement sterilization procedure for women: prospective study comparing general anesthesia versus hypnosis combined with sedation

Objective

Implant placement Essure™, sterilization procedure for women, were performed under hypnosedation (HYP) and compared to the operative anxiety and analgesia of 12 patients operated-on under general anesthesia (GA).

Study design

Prospective and comparative group study.

Patients and methods

Two groups of twelve patients were matched and compared based on the choice of anesthetic technique: hypnotics (HYP) with possible additional sedation by propofol and remifentanil or GA involving propofol, sevoflurane and remifentanil. The assessment of anxiety and pain based on a visual analogy scale (0–10) and use of analgesics were studied in the recovery room and at discharge of hospital. The statistical analysis relies on nonparametric tests for paired data (Wilcoxon test).

Results

All patients were operated. The two groups are statistically comparable. The preoperative anxiety before premedication is lower in the HYP group (p < 0.05). No conversion to general anaesthesia is necessary in the HYP group, but five patients were using sedatives drugs but doses are very low compared to general anaesthesia. The analgesic consumption was equivalent in both groups.

Conclusion

We conclude that hypnosedation is a valuable alternative to traditional anesthetic techniques for ambulatory Essure™ implant. The use of hypnotic tool is an interesting alternative for the management of patients during invasive medical procedures or surgical, providing psychological benefits to the patient.     

Effect of ribavirin and glucocorticoid treatment in a mouse model of human metapneumovirus infection

Human metapneumovirus (hMPV)-infected BALB/c mice were treated with ribavirin (40 mg/kg of body weight twice a day intraperitoneally), corticosterone (0.2 mg/ml in water), or both modalities. Ribavirin significantly decreased both hMPV replication in lungs (by 5 log10) and global pulmonary inflammation on day 5 postinfection, whereas glucocorticoids reduced only alveolar and interstitial inflammation, compared to controls.     

Epileptic seizure and migraine visual aura: revisiting migralepsy

INTRODUCTION: The term of "migralepsy" has been proposed to define migraine-triggered epileptic seizures. Although already reported in the literature for more than fifty years, a number of observations remain debatable because of possible confusion between migraine and epileptic seizure clinical manifestations, including hemifield visual hallucinations, digestive signs and severe headache. OBSERVATION: We report on the case of a young patient suffering from both diseases, in whom a visual aura preceded either migraine attacks or epileptic generalized tonic-clonic seizure. Subtle modification in the primitive visual hallucination, which suddenly contained colored figures and was accompanied by fear before a prolonged loss of contact, suggested a continuum between migraine aura and epileptic seizure in this patient. Brain MRI was normal and EEG showed some sharp waves in the right posterior area. CONCLUSION: The presence of a neurophysiological continuum between migrainous aura and epileptic seizure is supported by this observation of "migralepsy". Recent findings from genetic and epidemiological studies further support this link.     

Magnetic resonance imaging for diagnosis of early Alzheimer's disease

A major challenge for neuroimaging is to contribute to the early diagnosis of Alzheimer's disease (AD). In particular, magnetic resonance imaging (MRI) allows detecting different types of structural and functional abnormalities at an early stage of the disease. Anatomical MRI is the most widely used technique and provides local and global measures of atrophy. The recent diagnostic criteria of “mild cognitive impairment due to AD” include hippocampal atrophy, which is considered a marker of neuronal injury. Advanced image analysis techniques generate automatic and reproducible measures both in the hippocampus and throughout the whole brain. Recent modalities such as diffusion-tensor imaging and resting-state functional MRI provide additional measures that could contribute to the early diagnosis but require further validation.     

Genetic diversity in Cronartium quercuum f.sp. fusiforme on loblolly pines in southern U.S.

Twelve random amplified polymorphic DNA (RAPD) markers were used to study genetic variability in three populations of Cronartium quercuum f. sp. fusiforme, the causal agent of fusiform rust on pines. Most of the variability (94%) was found within populations while 6% of the total variability was attributable to frequency differences between populations. The frequency of three markers was significantly different between regions of origin on an east-west transect. Three markers were completely absent from one of the populations while present in the others, and one marker was fixed in the western population but polymorphic in the eastern and central populations. However, no significant differences were observed when the western population was omitted from the analysis. The results suggest that C. quercuum f. sp. fusiforme is a highly heterogeneous pathogen with little geographic differentiation and underscores the importance of considering the population structure of the pathogen in resistance breeding programs.     

Production of single- and double-strand breaks in plasmid DNA by ozone

Agarose gel electrophoresis and electron microscopy were used to determine the type of lesions produced in DNA by ozone. This strong oxidizing agent was found to relax, linearize, then degrade native plasmid (pAT153) DNA molecules in solution. Ozone, like ionizing radiation, thus produced DNA breakage. To ascertain this point, wild-type and radiosensitive strains of Escherichia coli were transfected with control or ozonated plasmid DNA, and the host cells were selected for antibiotic resistance. A significant reduction in the transforming ability of pAT153 was observed following ozonation. Mutants deficient in the repair of DNA single-strand breaks yielded less ampicillin- or tetracycline-resistant clones than repair-proficient strains. In E. coli, the same gene products are probably involved in the repair of both radiation- and ozone-induced DNA breaks.