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We report a high-quality draft of the genome sequence of the grey, short-tailed opossum (Monodelphis domestica). As the first metatherian ('marsupial') species to be sequenced, the opossum provides a unique perspective on the organization and evolution of mammalian genomes. Distinctive features of the opossum chromosomes provide support for recent theories about genome evolution and function, including a strong influence of biased gene conversion on nucleotide sequence composition, and a relationship between chromosomal characteristics and X chromosome inactivation. Comparison of opossum and eutherian genomes also reveals a sharp difference in evolutionary innovation between protein-coding and non-coding functional elements. True innovation in protein-coding genes seems to be relatively rare, with lineage-specific differences being largely due to diversification and rapid turnover in gene families involved in environmental interactions. In contrast, about 20% of eutherian conserved non-coding elements (CNEs) are recent inventions that postdate the divergence of Eutheria and Metatheria. A substantial proportion of these eutherian-specific CNEs arose from sequence inserted by transposable elements, pointing to transposons as a major creative force in the evolution of mammalian gene regulation.

Badke MB, Shea TA, Miedaner JA, Grove CR. Outcomes after rehabilitation for adults with balance dysfunction. Arch Phys Med Rehabil 2004;85:227–33. Objectives To assess balance, dynamic gait, and dynamic visual acuity outcomes after a vestibular and balance rehabilitation program and to determine which variables were significantly associated with improved balance and ambulation. Design Retrospective case series. Setting Outpatient setting at a tertiary care facility. Participants Twenty patients who were seen for vestibular and balance therapy between July 1999 and June 2000. Interventions A customized exercise program was developed for each patient according to the results of the assessment and included the following interventions, as indicated: gaze stabilization, balance and gait training, and habituation exercises. Main outcome measures The Dynamic Gait Index (DGI), Berg Balance Scale (BBS), Dynamic Visual Acuity Test (DVAT), and computerized posturography (Sensory Organization Test [SOT]). Results The mean change scores for the DGI showed significant improvement for both patients with peripheral vestibular dysfunction and patients with central balance disorders. For the central balance disorders group, the BBS score also showed significant improvement. No difference was noted for pretherapy and posttherapy SOT scores between groups. The total group appeared to show an average improvement of more than 2 lines on the visual acuity chart on the clinical DVAT. Patients who were 66 years or older were 1.5 times more likely to score less than 20 on the DGI, and those whose pretherapy vertical dynamic visual acuity was 20/80 or worse were 1.3 times more likely to score less than 20 on the DGI. Conclusions Patients showed functional improvements in balance, visual acuity, and gait stability after balance and vestibular physical therapy. Age and pretherapy vertical dynamic visual acuity score influenced dynamic gait outcome after a balance rehabilitation program.

Objective To assess dizziness handicap and postural recovery in 17 patients undergoing a vestibular ablative procedure. Study design Outcomes were compared between nine patients who underwent selective vestibular neurectomy and eight patients who underwent a transmastoid labyrinthectomy. Setting Patients underwent ablative procedures at a tertiary care facility. Methods Patients were tested with posturography (sensory organization test [SOT]) and the Dizziness Handicap Inventory (DHI) before and 4 to 5 weeks after their procedure. Results The mean change scores for each of the DHI subscales and the total DHI score showed significant improvement for the labyrinthectomy group. For the neurectomy group, only the emotional DHI subscale change score showed significant improvement. No difference was noted between preprocedure and postprocedure SOT scores for either group. The results indicated that the largest proportion of significant correlations existed between DHI and the somatosensory and vestibular subtests of platform posturography. In regression analyses, a model with age (p = 0.04) and vestibular score (p = 0.001) fitted the data well and explained 52.9% of the variance. Persons who were less than 69 years old were three times more likely to report persistent episodes of dizziness after the ablative procedure, and those who had neurectomies were 2.3 times more likely to report episodes of dizziness than those who underwent transmastoid labyrinthectomy. Conclusion Dizziness handicap after an ablative procedure is influenced by the type of procedure (labyrinthectomy versus neurectomy), age, and preoperative vestibular score on the SOT. Preoperative vestibular SOT score is highly associated with the emotional, physical, and functional domains of perceived handicap and quality of life after the surgery.

Background Declining cognition is a risk factor for falls among older adults. The extent to which impaired judgment in performance of daily activities increases fall risk is unclear. Objective The aim of this study was to determine whether engagement in mobility activities in a risky manner explains the association between declining cognition and rate of falls. Design This study was a secondary analysis of baseline and prospective data from older adults enrolled in the intervention arm of a randomized clinical trial. Methods Two hundred forty-five community-dwelling older adults (79% female; mean age=79 years, SD=8.0) who were at risk for falls received physical, cognitive, and functional evaluations. Cognition was assessed with the Short Portable Mental Status Questionnaire (SPMSQ). Using interview and in-home assessment data, physical therapists determined whether participants were at risk for falls when performing mobility-related activities of daily living (ADL) and instrumental ADL (IADL). Falls were measured prospectively for 1 year using monthly falls diaries. Results Declining cognition was associated with increased number of mobility activities designated as risky (1.5% of mobility activities performed in a risky manner per SPMSQ point) and with increased rate of falls (rate ratio=1.16 for each unit change in SPMSQ score). Risky performance of mobility activities mediated the relationship between cognition and rate of falls. Limitations Risk assessment was based on the clinical judgment of experienced physical therapists. Cognition was measured with a relatively insensitive instrument, and only selected mobility activities were evaluated. Conclusions Engagement in mobility ADL and IADL tasks in a risky manner emerged as a link between declining cognition and increased number of falls, suggesting a mechanism through which the rate of falls may increase. Specifically, declining cognition is associated with performance of mobility activities in an unsafe manner, thereby increasing the risk for falls.

This retrospective study was undertaken to assess balance recovery and dizziness handicap in 32 patients after a vestibular and balance rehabilitation program. Outcomes were compared between 12 patients with peripheral vestibular disorders and 20 patients with central or mixed balance disorders. The patients were tested with posturography (sensory organization test [SOT]) and the Dizziness Handicap Inventory (DHI) before and after their therapy program. The vestibular SOT, composite SOT, and functional DHI scores obtained before and after exercise were significantly improved in both the peripheral and central groups. The visual SOT mean scores obtained before and after therapy were significantly different only for the group with central or mixed vestibular disorders. Changes in SOT scores were not directly correlated with changes in DHI scores. Outcome measures of vestibular rehabilitation protocols confirmed objective and subjective improvement of balance and dizziness handicap in patients with peripheral and central vestibular disorders.

Herpes simplex virus 2 is an important human pathogen as the causative agent of genital herpes, neonatal herpes, and increased risk of HIV acquisition and transmission. Nevertheless, the only genomic sequence that has been completed is the attenuated HSV-2 HG52 laboratory strain. In this study we defined the genomic sequence of the HSV-2 SD90e low passage clinical isolate and a plaque-purified derivative, SD90-3P. We found minimal sequence differences between SD90e and SD90-3P. However, in comparisons with the HSV-2 HG52 reference genome sequence, the SD90e genome ORFs contained numerous point mutations, 13 insertions/deletions (indels), and 9 short compensatory frameshifts. The indels were true sequence differences, but the compensatory frameshifts were likely sequence errors in the original HG52 sequence. Because HG52 virus is less virulent than other HSV-2 strains and may not be representative of wildtype HSV-2 strains, we propose that the HSV-2 SD90e genome serve as the new HSV-2 reference genome.