Why do sub-Saharan Africans present late for HIV care in Switzerland?

OBJECTIVES: Late presentation (LP) to HIV care disproportionally affects individuals from sub-Saharan Africa (SSA). We explored the reasons for late presentation to care among this group of patients in the Swiss HIV Cohort Study. METHODS: The prevalence of LP was compared between patients from Western Europe (WE) and those from SSA enrolled between 2009 and 2012. Patients were asked about HIV testing, including access to testing and reasons for deferring it, during face-to-face interviews. RESULTS: The proportion of LP was 45.8% (435/950) among patients from WE, and 64.6% (126/195) among those from SSA (P < 0.001). Women from WE were slightly more likely to present late than men (52.6% versus 44.5%, respectively; P = 0.06), whereas there was no sex difference in patients from SSA (65.6% versus 63.2%, respectively; P = 0.73). Compared with late presenters from WE, those from SSA were more likely to be diagnosed during pregnancy (9.1% versus 0%, respectively; P < 0.001), but less likely to be tested by general practitioners (25.0% versus 44.6%, respectively; P = 0.001). Late presenters from SSA more frequently reported 'not knowing about anonymous testing possibilities' (46.4% versus 27.3%, respectively; P = 0.04) and 'fear about negative reaction in relatives' (39.3% versus 21.7%, respectively; P = 0.05) as reasons for late testing. Fear of being expelled from Switzerland was reported by 26.1% of late presenters from SSA. CONCLUSIONS: The majority of patients from SSA were late presenters, independent of sex or education level. Difficulties in accessing testing facilities, lack of knowledge about HIV testing and fear-related issues are important drivers for LP in this population.

Polymer Coatings of Cochlear Implant Electrode Surface - An Option for Improving Electrode-Nerve-Interface by Blocking Fibroblast Overgrowth.

Overgrowth of connective tissue and scar formation induced by the electrode array insertion increase the impedance and, thus, diminish the interactions between neural probes as like cochlear implants (CI) and the target tissue. Therefore, it is of great clinical interest to modify the carrier material of the electrodes to improve the electrode nerve interface for selective cell adhesion. On one side connective tissue growth needs to be reduced to avoid electrode array encapsulation, on the other side the carrier material should not compromise the interaction with neuronal cells. The present in vitro-study qualitatively and quantitatively characterises the interaction of fibroblasts, glial cells and spiral ganglion neurons (SGN) with ultrathin poly(N,N-dimethylacrylamide) (PDMAA), poly(2-ethyloxazoline) (PEtOx) and poly([2-methacryloyloxy)ethyl]trimethylammoniumchlorid) (PMTA) films immobilised onto glass surfaces using a photoreactive anchor layer. The layer thickness and hydrophilicity of the polymer films were characterised by ellipsometric and water contact angle measurement. Moreover the topography of the surfaces was investigated using atomic force microscopy (AFM). The neuronal and non-neuronal cells were dissociated from spiral ganglions of postnatal rats and cultivated for 48 h on top of the polymer coatings. Immunocytochemical staining of neuronal and intermediary filaments revealed that glial cells predominantly attached on PMTA films, but not on PDMAA and PEtOx monolayers. Hereby, strong survival rates and neurite outgrowth were only found on PMTA, whereas PDMAA and PEtOx coatings significantly reduced the SG neuron survival and neuritogenesis. As also shown by scanning electron microscopy (SEM) SGN strongly survived and retained their differentiated phenotype only on PMTA. In conclusion, survival and neuritogenesis of SGN may be associated with the extent of the glial cell growth. Since PMTA was the only of the polar polymers used in this study bearing a cationic charge, it can be assumed that this charge favours adhesion of both glial cells and SG neurons glial cells and SGN.

[Characterisation of the gene expression profiles in the inner ear and the colliculus inferior of normal and deafened rats by gene-array-technology]. / Charakterisierung der Genexpression im Innenohr und der Hörbahn hörender und ertaubter Ratten mittels Gene-Arrays.

BACKGROUND: The phenotype of deafness and its mechanisms are morphologically and electrophysiologically well characterised. However, the molecular mechanisms and the consequences of deafness are poorly understood. METHODS: In this study we investigated changes in gene expression profiles in subfractions of the cochlea and the colliculus inferior, a non-cochlear tissue, of normal and deafened (10 % Neomycin) rats using the gene-array-technology. RNA was prepared from modiolus (Mo) und sensorineural epithel/lateral wall (SnE/Lw) und Colliculus inferior (IC), reverse transcribed with gene specific primers, labeled with (32)P-dATP and hybridised with its complementary sequences of 1200 rat ESTs. RESULTS: Similar gene expression profiles were detected in Mo- and SnE/Lw in normal as well in deafened rats differing significantly from those found in IC. In deafened animals differences in mRNA levels were determined in IC for 8 genes, in Mo für 17 genes and in SnE/Lw for 25 genes in comparison to those of normal rats. By using gene-arrays many genes described in the literature previously could be detected. Otherwise most of the genes found in the cochlea are unknown. CONCLUSIONS: The gene-array-technology is a valuable tool in otological research for gene expression analysis and, therefore, for comprehensive understanding of molecular processes in the inner ear. Furthermore gene screening for candidate genes could be a big step ahead in developing therapies of diseases of the inner ear.

K(+) channel-blocking alkoxypsoralens inhibit the immune response of encephalitogenic T line cells and lymphocytes from Lewis rats challenged for experimental autoimmune encephalomyelitis.

Alkoxypsoralens, known as DNA photomodifying agents, have been shown to block voltage-dependent K(+) channels (Kv) as well as to alleviate functional deficits in certain multiple sclerosis (MS) patients in a manner similar to 4-aminopyridine. Since Kv channel blockers are known to inhibit T cell-mediated immune responses both in vitro and in vivo, we investigated the effects of three alkoxypsoralens, 5-methoxypsoralen (5-MOP), 8-methoxypsoralen (8-MOP), and 5,8-diethoxypsoralen (H37), on the following parameters: (1) whole-cell K(+) currents of encephalitogenic, myelin basic protein-specific memory T cell line cells (MBP-TCLC) derived from Lewis rats as measured by patch-clamp technique, (2) proliferation of MBP-TCLC and lymph node cells (LNC) from Lewis rats challenged for experimental autoimmune encephalomyelitis (EAE) by immunisation with spinal cord homogenate as measured by 3H-thymidine incorporation, (3) interferon-gamma (IFN-gamma) secretion of MBP-TCLC as measured by ELISA, and (4) IFN-gamma gene expression of LNC as measured by quantitative reverse transcription polymerase chain reaction (RT-PCR) with ELISA-detection. The examined alkoxypsoralens exhibited suppressive effects on the measured parameters with the same sequence of efficacy: H37>5-MOP>8-MOP. We, therefore, conclude that Kv channel-blocking alkoxypsoralens interfere with voltage-controlled signal transduction in lymphocytes and might thereby suppress immune responses in autoimmune diseases of the central nervous system and most likely also in other autoimmune disorders. Thus, alkoxypsoralens, especially the non-phototoxic substance H37, are new candidates for further studies on K(+) channel blocking immunosuppressive drugs. The agents may exert a dual beneficial effect on demyelinating diseases like MS, because they could attenuate the inflammatory process and improve axonal conductivity.

Epitope mapping of new monoclonal antibodies recognizing distinct human FcRII (CD32) isoforms.

The class II Fc gamma receptors are widely distributed on cells of the immune system. Nevertheless, the exact cell type distribution of the FcRII isoforms is still unclear because of the lack of appropriate antibodies that discriminate between the various isoforms. In this study we describe the generation and characterization of three monoclonal antibodies (MAbs) raised against recombinant human FcRIIb2 as well as a synthetic peptide (amino acids 30-39) of this receptor. Analyses of the isoform specificity of these antibodies using ELISA and Western blots revealed that the MAbs II1A5 (mIgG1) and ID2.7 (mIgM) are pan FcRII antibodies recognizing all known FcRII isoforms. In contrast, the MAb II8D2 (mIgG1) specifically reacts with FcRIIb but not with FcRIIa. The observed antibody reactivities could be confirmed by examination of the exact epitopes using overlapping 15-mer peptides spanning the entire FcRIIb2. So far these antibodies are the only ones described that detect FcRII in Western blots. Moreover, they can be used to analyze the cellular FcRII isoform distribution at the protein level, which was otherwise not possible.

Pharmacokinetics of ketoprofen enantiomers after different doses of the racemate.

The pharmacokinetics of the enantiomers of ketoprofen after oral administration of 12.5 mg, 25 mg and 50 mg and i.v. administration of 50 mg racemic ketoprofen to 24 healthy subjects were investigated. The AUC values of R- (r2 = 0.929) and S-ketoprofen (r2 = 0.930) were proportional to dose. The absolute bioavailability of the 50 mg oral dose was 84.5 (s.d. 20.6) % and 81.4 (18.0) % for R-ketoprofen and S-ketoprofen, respectively. With the exception of AUC values no dose dependent differences in pharmacokinetic parameters were observed. However, the R-enantiomer had higher AUC, lower clearance data and higher Cmax values than the S-form after oral administration. The results suggest that stereochemical and pharmacokinetic considerations cannot explain the lack of dose response observed with ketoprofen doses below 50 mg.