Disease-specific, neurosphere-derived cells as models for brain disorders

There is a pressing need for patient-derived cell models of brain diseases that are relevant and robust enough to produce the large quantities of cells required for molecular and functional analyses. We describe here a new cell model based on patient-derived cells from the human olfactory mucosa, the organ of smell, which regenerates throughout life from neural stem cells. Olfactory mucosa biopsies were obtained from healthy controls and patients with either schizophrenia, a neurodevelopmental psychiatric disorder, or Parkinson's disease, a neurodegenerative disease. Biopsies were dissociated and grown as neurospheres in defined medium. Neurosphere-derived cell lines were grown in serum-containing medium as adherent monolayers and stored frozen. By comparing 42 patient and control cell lines we demonstrated significant disease-specific alterations in gene expression, protein expression and cell function, including dysregulated neurodevelopmental pathways in schizophrenia and dysregulated mitochondrial function, oxidative stress and xenobiotic metabolism in Parkinson's disease. The study has identified new candidate genes and cell pathways for future investigation. Fibroblasts from schizophrenia patients did not show these differences. Olfactory neurosphere-derived cells have many advantages over embryonic stem cells and induced pluripotent stem cells as models for brain diseases. They do not require genetic reprogramming and they can be obtained from adults with complex genetic diseases. They will be useful for understanding disease aetiology, for diagnostics and for drug discovery

The effect of neuromuscular blockade on canine laparoscopic ovariectomy: A double-blinded, prospective clinical trial

The Effect of Neuromuscular Blockade on Canine Laparoscopic Ovariectomy: A Double-Blinded, Prospective Clinical Trial Bart Van Goethem, Diplomate ECVS, Sebastiaan Alexander van Nimwegen, PhD, Ies Akkerdaas, DVM, Joanna Claire Murrell, BVSc., PhD, Diplomate ECVAA, and Jolle Kirpensteijn, PhD, Diplomate ACVS & ECVS Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 108, 3584CM, Utrecht, The Netherlands Corresponding Author: Bart Van Goethem, Diplomate ECVS, Department of Small Animal Medicine and Clinical Biology, Faculty of Veterinary Medicine, Gent University, Gent, Belgium E-mail: [email protected] Submitted July 2010 Accepted November 2011 DOI:10.1111/j.1532-950X.2011.00962.x Objective: To evaluate the effect of neuromuscular blockade (NMB) on surgical time and various anesthetic variables during laparoscopic ovariectomy in dogs. Study Design: Prospective, double-blinded, randomized clinical trial. Animals: Female dogs (n = 40). Methods: Laparoscopic ovariectomy by bipolar electrocoagulation was performed by 1 surgeon using a standardized protocol, where 1 ovary was removed under NMB, and the other without NMB. Surgical and anesthetic (respiratory and circulatory) variables were recorded for predetermined procedural stages and were statistically evaluated. Results: Mean total surgical time was 25.1 ± 6.3 minutes (range, 16–47 minutes). With NMB, mean duration of surgical excision of the ovary (5.7 ± 2.3 minutes) was not significantly changed compared to ovariectomy without NMB (5.9 ± 1.9 minutes). Arterial blood pressure was the only recorded anesthetic variable that significantly changed under NMB (5% decrease). Occurrence of intraoperative complications did not differ. In obese dogs, total surgical time was increased by 22%. Other variables, including occurrence of intraoperative mesovarial bleeding did not influence surgical duration. Conclusions: NMB did not significantly improve laparoscopic ovariectomy times and except for a 5% decrease in arterial blood pressure did not change any of the evaluated anesthetic and surgical variables

The effect of neuromuscular blockade on canine laparoscopic ovariectomy: A double-blinded, prospective clinical trial

The Effect of Neuromuscular Blockade on Canine Laparoscopic Ovariectomy: A Double-Blinded, Prospective Clinical Trial Bart Van Goethem, Diplomate ECVS, Sebastiaan Alexander van Nimwegen, PhD, Ies Akkerdaas, DVM, Joanna Claire Murrell, BVSc., PhD, Diplomate ECVAA, and Jolle Kirpensteijn, PhD, Diplomate ACVS & ECVS Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 108, 3584CM, Utrecht, The Netherlands Corresponding Author: Bart Van Goethem, Diplomate ECVS, Department of Small Animal Medicine and Clinical Biology, Faculty of Veterinary Medicine, Gent University, Gent, Belgium E-mail: [email protected] Submitted July 2010 Accepted November 2011 DOI:10.1111/j.1532-950X.2011.00962.x Objective: To evaluate the effect of neuromuscular blockade (NMB) on surgical time and various anesthetic variables during laparoscopic ovariectomy in dogs. Study Design: Prospective, double-blinded, randomized clinical trial. Animals: Female dogs (n = 40). Methods: Laparoscopic ovariectomy by bipolar electrocoagulation was performed by 1 surgeon using a standardized protocol, where 1 ovary was removed under NMB, and the other without NMB. Surgical and anesthetic (respiratory and circulatory) variables were recorded for predetermined procedural stages and were statistically evaluated. Results: Mean total surgical time was 25.1 ± 6.3 minutes (range, 16–47 minutes). With NMB, mean duration of surgical excision of the ovary (5.7 ± 2.3 minutes) was not significantly changed compared to ovariectomy without NMB (5.9 ± 1.9 minutes). Arterial blood pressure was the only recorded anesthetic variable that significantly changed under NMB (5% decrease). Occurrence of intraoperative complications did not differ. In obese dogs, total surgical time was increased by 22%. Other variables, including occurrence of intraoperative mesovarial bleeding did not influence surgical duration. Conclusions: NMB did not significantly improve laparoscopic ovariectomy times and except for a 5% decrease in arterial blood pressure did not change any of the evaluated anesthetic and surgical variables

Deep sequencing reveals minor protease resistance mutations in patients failing a protease inhibitor regimen.

ArticleStandard genotypic antiretroviral resistance testing, performed by bulk sequencing, does not readily detect variants that comprise 500 copies/ml) of a first-line nonnucleoside reverse transcriptase inhibitor-based regimen, with at least the M184V mutation (lamivudine resistance), and second-line failure of a lopinavir/ritonavir (LPV/r)-based regimen. An amplicon-sequencing approach on the Roche 454 system was used. Six patients with viral loads of >90,000 copies/ml and one patient with a viral load of 520 copies/ml were included. Mutations not detectable by bulk sequencing during first- and second-line failure were detected by deep sequencing during second-line failure. Low-frequency variants (>0.5% of the sequence population) harboring major protease inhibitor resistance mutations were found in 5 of 7 patients despite poor adherence to the LPV/r-based regimen. In patients with intermittent adherence to a boosted PI regimen, deep sequencing may detect minority PI-resistant variants, which likely represent early events in resistance selection. In patients with poor or intermittent adherence, there may be low evolutionary impetus for such variants to reach fixation, explaining the low prevalence of PI resistance

Initial stages of structure formation on silicon electrodes investigated by photoelectron spectroscopy using synchrotron radiation and in situ atomic force microscopy

The surface condition of electrochemically H terminated Si is compared with the situation at the first photocurrent maximum in dilute acidic ammonium fluoride solution where the divalent dissolution converts into the four valent process. The first high spectral resolution photoelectron spectroscopy data using synchrotron radiation of electrochemically hydrogenated Si are presented. A combined electrochemistry UHV surface analysis system, attached to the U 49 2 beamline at the synchrotron Bessy II, is used for photoelectron spectroscopy PES of the electrochemically conditioned samples. We analyse the Si 2p, O 1s and F 1s core levels. A comparison of a density functional theory DFT calculation of the reaction sequence, proposed in the dissolution model of Gerischer and coworkers, with the PES results supports this model. The anodised sample is characterised by a residual H coverage of 0.35 monolayers ML evidenced by a surface core level shift, Si Fx species, F and a higher oxidised Si species. SiO2 is not found. Even on very well H terminated surfaces, we find residual Si OH complexes, fluoride and water. In situ AFM shows a roughening with a rms roughness parameter of 2.6 n

High resolution surface analysis of Si roughening in dilute ammonium fluoride solution

The initial stages of porous Si formation on Si 111 in dilute ammonium fluoride solution are analysed by photoelectron spectroscopy PES using synchrotron radiation. PES in the por Si formation regime shows no contradiction to a recent dissolution model. The contribution from a Si 2p surface core level shift shows that 0.4 ML of the surface is still H terminated after interruption of the conditioning process at the first photocurrent maximum. A higher oxidised species found with EB 103.2 eV is attributed to a precipitate, expected from the reaction mechanism and from theoretical calculations using density functional theory DFT . The roughening upon por Si formation is monitored by in situ AFM measurements. A RMS roughness parameter of 2.6 nm is calculated

Support networks before and after retirement

Changes in ones personal network can be expected to follow after retirement. A certain loss of relationships, for example with colleagues, is inevitable. How do people who are either about to retire or have recently done so react to this life event? Do they form new relationships or deepen their existing ones? Which type of relationships are most likely to be terminated? Is over benefiting or under benefiting in support a significant aspect in the termination of relationships? This article addresses these questions on how retirement affects support networks. The data were obtained from 50 men, interviewed before and after retirement. At