When, where, and why should we look for vestibular dysfunction in people with diabetes mellitus?

The biochemistry of diabetes mellitus results in multi-system tissue compromise that reduces functional mobility and interferes with disease management. Sensory system compromise, such as peripheral neuropathy and retinopathy, are specific examples of tissue compromise detrimental to functional mobility. There is lack of clarity regarding if, when, and where parallel changes in the peripheral vestibular system, an additional essential sensory system for functional mobility, occur as a result of diabetes. Given the systemic nature of diabetes and the plasticity of the vestibular system, there is even less clarity regarding if potential vestibular system changes impact functional mobility in a meaningful fashion. This commentary will provide insight as to when we should employ diagnostic vestibular function tests in people with diabetes, where in the periphery we should look, and why testing may or may not matter. The commentary concludes with recommendations for future research and clinical care

Hanoi Revisited

TB

Guidelines of the American Society of Mammalogists for the use of wild mammals in research

Guidelines for use of wild mammal species are updated from the American Society of Mammalogists (ASM) 2007 publication. These revised guidelines cover current professional techniques and regulations involving mammals used in research and teaching. They incorporate additional resources, summaries of procedures, and reporting requirements not contained in earlier publications. Included are details on marking, housing, trapping, and collecting mammals. It is recommended that institutional animal care and use committees (IACUCs), regulatory agencies, and investigators use these guidelines as a resource for protocols involving wild mammals. These guidelines were prepared and approved by the ASM, working with experienced professional veterinarians and IACUCs, whose collective expertise provides a broad and comprehensive understanding of the biology of nondomesticated mammals in their natural environments. The most current version of these guidelines and any subsequent modifications are available at the ASM Animal Care and Use Committee page of the ASM Web site (http://mammalsociety.org/committees/index.asp).American Society of Mammalogist

Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation.

GWAS have identified a breast cancer susceptibility locus on 2q35. Here we report the fine mapping of this locus using data from 101,943 subjects from 50 case-control studies. We genotype 276 SNPs using the 'iCOGS' genotyping array and impute genotypes for a further 1,284 using 1000 Genomes Project data. All but two, strongly correlated SNPs (rs4442975 G/T and rs6721996 G/A) are excluded as candidate causal variants at odds against >100:1. The best functional candidate, rs4442975, is associated with oestrogen receptor positive (ER+) disease with an odds ratio (OR) in Europeans of 0.85 (95% confidence interval=0.84-0.87; P=1.7 × 10(-43)) per t-allele. This SNP flanks a transcriptional enhancer that physically interacts with the promoter of IGFBP5 (encoding insulin-like growth factor-binding protein 5) and displays allele-specific gene expression, FOXA1 binding and chromatin looping. Evidence suggests that the g-allele confers increased breast cancer susceptibility through relative downregulation of IGFBP5, a gene with known roles in breast cell biology

PenQuest Volume 2, Number 1

Table of Contents for this Volume: Untitled by Janet Collins Untitled by Judy Gozdur Last Hour of Light by Susan Reed Untitled by Judy Godzur Untitled by Rick Wagner Untitled by Carol Groover Untitled by R. Wagner Only in the Portico by Linda Banicki Untitled by Helen Hagadorn Private Place, Pubic Place by David Reed Untitled by Tammy Hutchinson Untitled by Tammy Hutchinson Madison Knights by Susan Reed Untitled by Sissy Crabtree The Price by Sandra Coleman Untitled by Ann Harrington Invasion of Privacy by Mark Touchton Untitled by Bruce Warner Untitled by Tom Schifanella Untitled by Tammy Hutchinson Bloodwork by Laura Jo Last Untitled by David Whitsett Burial Instructions by Bill Slaughter Untitled by S. Trevett PenQuest Interview: Joe Haldeman by David Reed Her Name Came from the Sea by Richard L. Ewart Untitled by V. Williams In the Woodshed by R. E. Mallery Untitled by Modesta Matthews Untitled by David Olson Illumination by E. Allen Tilley Untitled by Joseph Avanzini Everywoman by Laura Jo Last Untitled by Beth Goeckel Believe Me by Donna Kaluzniak Untitled by Judy Gozdur Untitled by Judy Gozdur Unicorn by David Reed Untitled by Susan Reed untitled by Paul Cramer Unititled by Lucinda Halsema The Violin by Richard L. Ewart Untitled by Maria Barry Untitled by Roger Whitt Jr. Haiku by Lori Nasrallah Rhymer’s Revolt by R. E. Mallery Untitled by Valerie William

Antiretroviral penetration into the CNS and incidence of AIDS-defining neurologic conditions

Objective: The link between CNS penetration of antiretrovirals and AIDS-defining neurologic disorders remains largely unknown. Methods: HIV-infected, antiretroviral therapy-naive individuals in the HIV-CAUSAL Collaboration who started an antiretroviral regimen were classified according to the CNS Penetration Effectiveness (CPE) score of their initial regimen into low (,8), medium (8-9), or high (.9) CPE score. We estimated "intention-to-treat" hazard ratios of 4 neuroAIDS conditions for baseline regimens with high and medium CPE scores compared with regimens with a low score. We used inverse probability weighting to adjust for potential bias due to infrequent follow-up. Results: A total of 61,938 individuals were followed for a median (interquartile range) of 37 (18, 70) months. During follow-up, there were 235 cases of HIV dementia, 169 cases of toxoplasmosis, 128 cases of cryptococcal meningitis, and 141 cases of progressive multifocal leukoencephalopathy. The hazard ratio (95% confidence interval) for initiating a combined antiretroviral therapy regimen with a high vs low CPE score was 1.74 (1.15, 2.65) for HIV dementia, 0.90 (0.50, 1.62) for toxoplasmosis, 1.13 (0.61, 2.11) for cryptococcal meningitis, and 1.32 (0.71, 2.47) for progressive multifocal leukoencephalopathy. The respective hazard ratios (95% confidence intervals) for a medium vs low CPE score were 1.01 (0.73, 1.39), 0.80 (0.56, 1.15), 1.08 (0.73, 1.62), and 1.08 (0.73, 1.58). Conclusions: We estimated that initiation of a combined antiretroviral therapy regimen with a high CPE score increases the risk of HIV dementia, but not of other neuroAIDS conditions