Surgical site infection after caesarean section. Space for post-discharge surveillance improvements and reliable comparisons

Surgical site infections (SSI) after caesarean section (CS) represent a substantial health system concern. Surveying SSI has been associated with a reduction in SSI incidence. We report the findings of three (2008, 2011 and 2013) regional active SSI surveillances after CS in community hospital of the Latium region determining the incidence of SSI. Each CS was surveyed for SSI occurrence by trained staff up to 30 post-operative days, and association of SSI with relevant characteristics was assessed using binomial logistic regression. A total of 3,685 CS were included in the study. A complete 30 day post-operation follow-up was achieved in over 94% of procedures. Overall 145 SSI were observed (3.9% cumulative incidence) of which 131 (90.3%) were superficial and 14 (9.7%) complex (deep or organ/space) SSI; overall 129 SSI (of which 89.9% superficial) were diagnosed post-discharge. Only higher NNIS score was significantly associated with SSI occurrence in the regression analysis. Our work provides the first regional data on CS-associated SSI incidence, highlighting the need for a post-discharge surveillance which should assure 30 days post-operation to not miss data on complex SSI, as well as being less labour intensive

Amyloid Precursor Protein Is Required for Normal Function of the Rod and Cone Pathways in the Mouse Retina

Amyloid precursor protein (APP) is a transmembrane glycoprotein frequently studied for its role in Alzheimer's disease. Our recent study in APP knockout (KO) mice identified an important role for APP in modulating normal neuronal development in the retina. However the role APP plays in the adult retina and whether it is required for vision is unknown. In this study we evaluated the role of APP in retinal function and morphology comparing adult wildtype (WT) and APP-KO mice. APP was expressed on neuronal cells of the inner retina, including horizontal, cone bipolar, amacrine and ganglion cells in WT mice. The function of the retina was assessed using the electroretinogram and although the rod photoreceptor responses were similar in APP-KO and WT mice, the post-photoreceptor, inner retinal responses of both the rod and cone pathways were reduced in APP-KO mice. These changes in inner retinal function did not translate to a substantial change in visual acuity as assessed using the optokinetic response or to changes in the gross cellular structure of the retina. These findings indicate that APP is not required for basic visual function, but that it is involved in modulating inner retinal circuitry

MeCP2 interacts with chromosomal microRNAs in brain

Although methyl CpG binding domain protein-2 (MeCP2) is commonly understood to function as a silencing factor at methylated DNA sequences, recent studies also show that MeCP2 can bind unmethylated sequences and coordinate gene activation. MeCP2 displays broad binding patterns throughout the genome, with high expression levels similar to histone H1 in neurons. Despite its significant presence in the brain, only subtle gene expression changes occur in the absence of MeCP2. This may reflect a more complex regulatory mechanism of MeCP2 to complement chromatin binding. Using an RNA immunoprecipitation of native chromatin technique, we identify MeCP2 interacting microRNAs in mouse primary cortical neurons. In addition, comparison with mRNA sequencing data from Mecp2-null mice suggests that differentially expressed genes may indeed be targeted by MeCP2-interacting microRNAs. These findings highlight the MeCP2 interaction with microRNAs that may modulate its binding with chromatin and regulate gene expression

Suppression of amyloid beta a11-immunoreactivity by vitamin C: possible role of heparan sulfate oligosaccharides derived from glypican-1 by ascorbate-induced, no-catalyzed degradation.

Amyloid beta is generated from the copper- and heparan sulfate (HS)-binding amyloid precursor protein (APP) by proteolytic processing. APP supports S-nitrosylation of the HS-proteoglycan glypican-1 (Gpc-1). In the presence of ascorbate there is NO-catalyzed release of anhydromannose (anMan)-containing oligosaccharides from Gpc-1-SNO. We have investigated whether these oligosaccharides interact with amyolid beta during APP processing and plaque formation. anMan-Immunoreactivity was detected in amyloid plaques of Alzheimer (AD) and APP transgenic (Tg2576) mouse brains by immunofluorescence microscopy. APP/APP degradation products detected by antibodies to the C-terminus of APP, but not amyolid beta oligomers detected by the anti-amyloid beta A11 antibody, colocalized with anMan-immunoreactivity in Tg2576 fibroblasts. A 50-55-kDa anionic, SDS-stable, anMan- and amyloid beta-immunoreactive species was obtained from Tg2576 fibroblasts using immunoprecipitation with anti-APP (C-terminal). anMan-Containing HS oligo- and disaccharide preparations modulated or suppressed A11-immunoreactivity and oligomerization of amyloid beta 42 peptide in an in vitro assay. A11 immunoreactivity increased in Tg2576 fibroblasts when Gpc-1 autoprocessing was inhibited by U18666A, and decreased when Gpc-1 autoprocessing was stimulated by ascorbate. Neither overexpression of Gpc-1 in Tg2576 fibroblasts nor addition of copper ion and NO-donor to hippocampal slices from 3xTg-AD mice affected A11 immunoreactivity levels. However, A11 immunoreactivity was greatly suppressed by the subsequent addition of ascorbate. We speculate that temporary interaction between the amyolid beta domain and small, anMan-containing oligosaccharides may preclude formation of toxic amyloid beta oligomers. A portion of the oligosaccharides co-secrete with the amyloid beta peptides and are deposited in plaques. These results support the notion that inadequate supply of vitamin C could contribute to late onset AD in humans

The amyloid precursor protein(APP)of Alzheimer's disease and its paralog APLP2 modulate the Cu/Zn-NO-catalyzed degradation of glypican-1 heparan sulfate In vivo.

Processing of the recycling proteoglycan glypican-1 involves the release of its heparan sulfate chains by copper ion- and nitric oxide-catalyzed ascorbate-triggered autodegradation. The Alzheimer disease amyloid precursor protein (APP) and its paralogue, the amyloid precursor-like protein 2 (APLP2), contain copper ion-, zinc ion-, and heparan sulfate-binding domains. We have investigated the possibility that APP and APLP2 regulate glypican-1 processing during endocytosis and recycling. By using cell-free biochemical experiments, confocal laser immunofluorescence microscopy, and flow cytometry of tissues and cells from wild-type and knock-out mice, we find that (a) APP and glypican-1 colocalize in perinuclear compartments of neuroblastoma cells, (b) ascorbate-triggered nitric oxidecatalyzed glypican-1 autodegradation is zinc ion-dependent in the same cells, (c) in cell-free experiments, APP but not APLP2 stimulates glypican-1 autodegradation in the presence of both Cu(II) and Zn(II) ions, whereas the Cu(I) form of APP and the Cu(II) and Cu(I) forms of APLP2 inhibit autodegradation, (d) in primary cortical neurons from APP or APLP2 knock-out mice, there is an increased nitric oxide-catalyzed degradation of heparan sulfate compared with brain tissue and neurons from wild-type mice, and (e) in growth-quiescent fibroblasts from APLP2 knock-out mice, but not from APP knock-out mice, there is also an increased heparan sulfate degradation. We propose that the rate of autoprocessing of glypican-1 is modulated by APP and APLP2 in neurons and by APLP2 in fibroblasts. These observation identify a functional relationship between the heparan sulfate and copper ion binding activities of APP/APLP2 in their modulation of the nitroxyl anion-catalyzed heparan sulfate degradation in glypican-1