Acupuncture, Counseling, and Usual care for Depression (ACUDep): study protocol for a randomized controlled trial

Background: The evidence on the effect of acupuncture or counseling for depression is not conclusive yet is sufficient to warrant further research. Our aim is to conduct a full-scale RCT to determine the clinical and cost effectiveness of acupuncture and counseling compared to usual care alone. We will explore the experiences and perspectives of patients and practitioners. Methods/Design: Randomized controlled trial with three parallel arms: acupuncture plus usual care, counseling plus usual care, and usual care alone, in conjunction with a nested qualitative study using in-depth interviews with purposive samples of trial participants. Participants: Patients aged over 18 years diagnosed with depression or mood disorder by their GP and with a score of 20 or above on the Beck Depression Inventory (BDI-II). Randomization: Computer randomization by York Trials Unit to acupuncture, counseling, and usual care alone in proportions of 2:2:1, respectively, with secure allocation concealment. Interventions: Patients allocated to acupuncture and counseling groups receive the offer of up to 12 weekly sessions. Both interventions allow flexibility to address patient variation, yet are constrained within defined protocols. Acupuncture is based on traditional Chinese medicine and counseling is non-directive within the humanistic tradition. Outcome: The PHQ-9 is the primary outcome measure, collected at baseline, 3, 6, 9, and 12 months. Also measured is BDI-II, SF-36 Bodily pain subscale, and EQ-5D. Texted mood scores are collected weekly over the first 15 weeks. Health-related resource use is collected over 12 months. Analysis: The sample size target was for 640 participants, calculated for an effect size of 0.32 on the PHQ-9 when comparing acupuncture with counseling given 90% power, 5% significance, and 20% loss to follow-up. Analysis of covariance will be used on an intention-to-treat basis. Thematic analysis will be used for qualitative data. We will compare incremental cost-effectiveness of the three treatment options at 12 months. Discussion: Ethical approval was obtained in October 2009. There were six subsequent protocol amendments, the last of which was approved in January 2012. Recruitment of 755 participants took place over 18 months. Data collection will be completed by June 2012. No interim analyses have been conducted

Cytotoxicity of rhein, the active metabolite of sennoside laxatives, is reduced by multidrug resistance-associated protein 1

Anthranoid laxatives, belonging to the anthraquinones as do anthracyclines, possibly increase colorectal cancer risk. Anthracyclines interfere with topoisomerase II, intercalate DNA and are substrates for P-glycoprotein and multidrug resistance-associated protein 1. P-glycoprotein and multidrug resistance-associated protein 1 protect colonic epithelial cells against xenobiotics. The aim of this study was to analyse the interference of anthranoids with these natural defence mechanisms and the direct cytotoxicity of anthranoids in cancer cell lines expressing these mechanisms in varying combinations. A cytotoxicity profile of rhein, aloe emodin and danthron was established in related cell lines exhibiting different levels of topoisomerases, multidrug resistance-associated protein 1 and P-glycoprotein. Interaction of rhein with multidrug resistance-associated protein 1 was studied by carboxy fluorescein efflux and direct cytotoxicity by apoptosis induction. Rhein was less cytotoxic in the multidrug resistance-associated protein 1 overexpressing GLC4/ADR cell line compared to GLC4. Multidrug resistance-associated protein 1 inhibition with MK571 increased rhein cytotoxicity. Carboxy fluorescein efflux was blocked by rhein. No P-glycoprotein dependent rhein efflux was observed, nor was topoisomerase II responsible for reduced toxicity. Rhein induced apoptosis but did not intercalate DNA. Aloe emodin and danthron were no substrates for MDR mechanisms. Rhein is a substrate for multidrug resistance-associated protein 1 and induces apoptosis. It could therefore render the colonic epithelium sensitive to cytotoxic agents, apart from being toxic in itself

ICAR: endoscopic skull‐base surgery

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Molecular Cytogenetic Characterization of Multiple Intrachromosomal Rearrangements in Two Representatives of the Genus Turdus (Turdidae, Passeriformes)

Turdus rufiventris and Turdus albicollis, two songbirds belonging to the family Turdidae (Aves, Passeriformes) were studied by C-banding, 18S rDNA, as well as the use of whole chromosome probes derived from Gallus gallus (GGA) and Leucopternis albicollis (LAL). They showed very similar karyotypes, with 2n = 78 and the same pattern of distribution of heterochromatic blocks and hybridization patterns. However, the analysis of 18/28S rDNA has shown differences in the number of NOR-bearing chromosomes and ribosomal clusters. The hybridization pattern of GGA macrochromosomes was similar to the one found in songbirds studied by Fluorescent in situ hybridization, with fission of GGA 1 and GGA 4 chromosomes. In contrast, LAL chromosome paintings revealed a complex pattern of intrachromosomal rearrangements (paracentric and pericentric inversions) on chromosome 2, which corresponds to GGA1q. The first inversion changed the chromosomal morphology and the second and third inversions changed the order of chromosome segments. Karyotype analysis in Turdus revealed that this genus has derived characteristics in relation to the putative avian ancestral karyotype, highlighting the importance of using new tools for analysis of chromosomal evolution in birds, such as the probes derived from L. albicollis, which make it possible to identify intrachromosomal rearrangements not visible with the use of GGA chromosome painting solely

The molecular basis of chromosome orthologies and sex chromosomal differentiation in palaeognathous birds

Palaeognathous birds (Struthioniformes and Tinamiformes) have morphologically conserved karyotypes and less differentiated ZW sex chromosomes. To delineate interspecific chromosome orthologies in palaeognathous birds we conducted comparative chromosome painting with chicken (Gallus gallus, GGA) chromosome 1-9 and Z chromosome paints (GGA1-9 and GGAZ) for emu, double-wattled cassowary, ostrich, greater rhea, lesser rhea and elegant crested tinamou. All six species showed the same painting patterns: each probe was hybridized to a single pair of chromosomes with the exception that the GGA4 was hybridized to the fourth largest chromosome and a single pair of microchromosomes. The GGAZ was also hybridized to the entire region of the W chromosome, indicating that extensive homology remains between the Z and W chromosomes on the molecular level. Comparative FISH mapping of four Z- and/or W-linked markers, the ACO1/IREBP, ZOV3 and CHD1 genes and the EE0.6 sequence, revealed the presence of a small deletion in the proximal region of the long arm of the W chromosome in greater rhea and lesser rhea. These results suggest that the karyotypes and sex chromosomes of palaeognathous birds are highly conserved not only morphologically, but also at the molecular level; moreover, palaeognathous birds appear to retain the ancestral lineage of avian karyotypes