Differentiated effects of the multimodal antidepressant vortioxetine on sleep architecture: Part 1, a pharmacokinetic/pharmacodynamic comparison with paroxetine in healthy men

We compared the effect of vortioxetine, paroxetine and placebo after three days of dosing on sleep architecture. This was a randomised, double-blind, four-way crossover, placebo-controlled, multiple-dose study in 24 healthy young men. Subjects received 20mg vortioxetine, 40mg vortioxetine, 20mg paroxetine or placebo for three consecutive days in four different periods with at least three weeks between them. Polysomnography and blood sampling for pharmacokinetic analysis were performed on the pre-dose night and nights 1 and 3 of dosing in each period. Plasma concentrations of vortioxetine and paroxetine during the polysomnography measurement were used to estimate SERT occupancies using published relationships in healthy subjects. All three active treatments significantly increased REM onset latency and decreased time spent in REM sleep. In the pharmacokinetic/pharmacodynamics analysis significant relationships were found between REM onset latency and time spent in REM sleep and vortioxetine/paroxetine exposure. The relation between REM suppression parameters and SERT occupancy was significantly different between vortioxetine and paroxetine, despite the same SERT occupancy. This indicates that vortioxetine has a different clinical pharmacological profile from paroxetine, which may explain the differences in adverse effect profile of the two drugs, for instance the lower incidence of nausea, weight gain and sexual dysfunction with vortioxetine

A tandem duplication within the fibrillin 1 gene is associated with the mouse tight skin mutation.

Mice carrying the Tight skin (Tsk) mutation have thickened skin and visceral fibrosis resulting from an accumulation of extracellular matrix molecules. These and other connective tissue abnormalities have made Tskl + mice models for scleroderma, hereditary emphysema, and myocardial hypertrophy. Previously we localized Tsk to mouse chromosome 2 in a region syntenic with human chromosome 15. The microfibrillar glycoprotein gene, fibrillin 1 (FBN1), on human chromosome 15q, provided a candidate for the Tsk mutation. We now demonstrate that the Tsk chromosome harbors a 30- to 40-kb genomic duplication within the Fbn1 gene that results in a larger than normal in-frame Fbn1 transcript. These findings provide hypotheses to explain some of the phenotypic characteristics of Tskl + mice and the lethality of Tsk/Tsk embryos

“You Come Back to the Same Ole Shit:” A Qualitative Study of Smoking Cessation Barriers among Women Living with HIV: Implications for Intervention Development

Although tobacco use among women living with HIV (WLWH) is decreasing, the prevalence is more than double that of women in the general population and remains an important health behavior to target among WLWH. Few smoking cessation interventions specifically focus on the unique social and medical needs of women living with HIV (WLWH). Thus, the investigative team engaged WLWH (N=18) in qualitative focus groups to: 1) understand barriers and facilitators to smoking cessation; and 2) inform intervention structure and content priorities. Participants identified salient reasons for smoking and barriers to smoking cessation, which included coping mechanisms for life stressors, HIV-related stress, HIV-related stigma, and social isolation. Further, WLWH highlighted the importance of long-term smoking cessation support, peer support, mental health content, religion/spirituality, and targeted risk messaging in smoking cessation intervention development. Study findings provide concrete, operational strategies for future use in a theory-based smoking cessation intervention, and underscore the importance of formative research to inform smoking cessation interventions for WLWH

The gene coding for variant hepatic nuclear factor 1 ( Tcf-2 ), maps between the Edp-1 and Erba genes on mouse Chromosome 11

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46992/1/335_2004_Article_BF00352466.pd

The Use of a Compression Device as an Alternative to Hand-Sewn and Stapled Colorectal Anastomoses: Is Three a Crowd?

BackgroundThe NiTi CAR™ 27 is a newer device that uses compression to create an anastomosis. An analysis of this device in the creation of colorectal anastomoses in humans has yet to be reported in the USA.MethodsA non-randomized, prospective pilot study of the NiTi CAR™ 27 device in patients undergoing a left-sided colectomy between March 2008 and August 2009 was performed.ResultsTwenty-three patients (9 men and 14 women) underwent a left-sided colectomy and compression anastomosis with the CAR™ 27 device. Minor morbidities, 3 of 23 (13%) patients, included one small postoperative abscess requiring antibiotics alone and two postoperative anastomotic strictures requiring balloon dilation. Major morbidities, 1 of 23 (4%) patients, included a partial anastomotic dehiscence/leak requiring surgical dismantling of the anastomosis and diversion.ConclusionThe CAR™ 27 device shows promise as a safe and effective alternative for the creation of colorectal anastomoses. However, studies in a larger patient population are warranted to demonstrate equivalence of this device

Neurofibromatosis type 1 gene product (neurofibromin) associates with microtubules

The neurofibromatosis type 1 (NF1) gene was recently identified by positional cloning and found to encode a protein with structural and functional homology to mammalian and yeast GTPase-activating proteins (GAPs). Using antibodies directed against the NF1 gene product, a protein of ∼250kDa was identified and termed neurofibromin. Double-indirect immunofluorescent labeling with anti-neurofibromin and anti-tubulin antibodies demonstrates that neurofibromin associates with cytoplasmic microtubules. Immunoblotting of microtubule-enriched cytoplasmic fractions, using antibodies generated against neurofibromin, shows that neurofibromin copurifies with microtubules. When portions of neurofibromin are expressed in Sf9 insect cells they associate with polymerized microtubules; furthermore, the critical residues for this interaction reside within the GAP-related domain of neurofibromin. The unexpected association of neurofibromin with microtubules suggests that neurofibromin is involved in microtubule-mediated intracellullar signal transduction pathways.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45544/1/11188_2005_Article_BF01233074.pd

Mouse Chromosome 11

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46996/1/335_2004_Article_BF00648429.pd

Mouse Chromosome 3

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46995/1/335_2004_Article_BF00648421.pd