27-Hydroxycholesterol Induces Aberrant Morphology and Synaptic Dysfunction in Hippocampal Neurons.

Hypercholesterolemia is a risk factor for neurodegenerative diseases, but how high blood cholesterol levels are linked to neurodegeneration is still unknown. Here, we show that an excess of the blood-brain barrier permeable cholesterol metabolite 27-hydroxycholesterol (27-OH) impairs neuronal morphology and reduces hippocampal spine density and the levels of the postsynaptic protein PSD95. Dendritic spines are the main postsynaptic elements of excitatory synapses and are crucial structures for memory and cognition. Furthermore, PSD95 has an essential function for synaptic maintenance and plasticity. PSD95 synthesis is controlled by the REST-miR124a-PTBP1 axis. Here, we report that high levels of 27-OH induce REST-miR124a-PTBP1 axis dysregulation in a possible RxRγ-dependent manner, suggesting that 27-OH reduces PSD95 levels through this mechanism. Our results reveal a possible molecular link between hypercholesterolemia and neurodegeneration. We discuss the possibility that reduction of 27-OH levels could be a useful strategy for preventing memory and cognitive decline in neurodegenerative disorders.

The transferability of blaOXA-23 gene in multidrug-resistant Acinetobacter baumannii isolates from Saudi Arabia and Egypt.

Carbapenem-resistant Acinetobacter spp. have been increasingly reported worldwide including Saudi Arabia and Egypt. We examined 64, non-repetitive, Acinetobacter baumannii isolates collected in 2013 and 2014 from four different medical centres (two from Saudi Arabia and two from Egypt). All the isolates were resistant to ceftazidime and ciprofloxacin. The intI1 harbouring blaGES-11 and aac-6'-1b was detected in 19% (n=12) of the isolates. ISAba1 over-expression of blaADC gene was observed in 65% (n=42) of isolates. Of all the isolates 19% (n=12) had ISAba1 upstream of the blaOXA-51-like gene, 69% (n=44) carried the blaOXA-23 gene within the Tn2006 structure, 8% (n=5) had blaOXA-24-like gene and 9% (n=6) harboured either blaVIM-2 or blaNDM-1 gene. Eighty nine percent (n=57) of isolates were resistant to imipenem and had an MIC of ≥8mg/L. Pulsed-field gel electrophoresis (PFGE) typing revealed the presence of 23 different PFGE. Three PFGE types were very widespread, ST236 (CC104) (PFGE type 1, n=15), ST208 (CC92) (PFGE type 2, n=10), ST884 (CC unassigned) (PFGE type 3, n=7) in and across all four medical centres. The blaOXA-23 gene was found to be present on a 60kb transferable plasmid in both PFGE type 1 and 2 but was absent in PFGE type 3. This is the first study to report on the emergence of ST236 in Saudi Arabia and Egypt, and spread of distinct carbapenem resistant A. baumannii clones belonging to ST884, ST945 and ST1096 in Saudi Arabia.

Effect of Head Tilt and Ocular Compensatory Mechanisms on Retinal Nerve Fiber Layer Measurements by Cirrus Spectral Domain and Spectralis Optical Coherence Tomography in Normal Subjects.

PURPOSE: To determine the effect of head tilt and ocular compensatory mechanisms on retinal nerve fiber layer (RNFL) thickness measurements using the Cirrus and Spectralis spectral-domain optical coherence tomography (OCT) in healthy eyes. Our secondary objective was to assess the visual influence on ocular compensatory mechanisms during head tilt. MATERIALS AND METHODS: This is a prospective, observational study. A single randomly selected eye was scanned undilated in 3 positions (baseline, right, and left tilt) using both machines. In addition, patching was also done for the contralateral eye during head tilt and RNFL measurements repeated. The paired t test was used to analyze effect on RNFL thickness. One-way repeated-measures analysis of variance was used to compare differences in RNFL measurements. RESULTS: In Cirrus OCT RNFL analysis, ipsilateral head tilt resulted in superior thinning and temporal thickening, whereas contralateral head tilt resulted in inferior thinning, nasal thickening, as well as temporal thickening (all P<0.05). Head tilt did not cause any significant change in RNFL thickness with Spectralis OCT (P>0.05). Patching the contralateral eye also did not alter Cirrus RNFL measurement errors due to head tilt. CONCLUSIONS: Head tilt can affect the measurement of the RNFL thickness in Cirrus OCT, and ocular compensatory mechanisms were not sufficient to prevent this. In contrast, Spectralis OCT RNFL thickness measurements were not affected by head tilt. Patching the contralateral eye during head tilt in Cirrus OCT also did not affect RNFL variability. The visual influence on ocular compensatory mechanisms during head tilt appears insignificant.