Ashtanga-Based Yoga Therapy Increases the Sensory Contribution to Postural Stability in Visually-Impaired Persons at Risk for Falls as Measured by the Wii Balance Board: A Pilot Randomized Controlled Trial

Objective

Persons with visual impairment (VI) are at greater risk for falls due to irreparable damage to visual sensory input contributing to balance. Targeted training may significantly improve postural stability by strengthening the remaining sensory systems. Here, we evaluate the Ashtanga-based Yoga Therapy (AYT) program as a multi-sensory behavioral intervention to develop postural stability in VI.

Design

A randomized, waitlist-controlled, single-blind clinical trial

Methods

The trial was conducted between October 2012 and December 2013. Twenty-one legally blind participants were randomized to an 8-week AYT program (n = 11, mean (SD) age = 55(17)) or waitlist control (n=10, mean (SD) age = 55(10)). AYT subjects convened for one group session at a local yoga studio with an instructor and two individual home-based practice sessions per week for a total of 8 weeks. Subjects completed outcome measures at baseline and post-8 weeks of AYT. The primary outcome, absolute Center of Pressure (COP), was derived from the Wii Balance Board (WBB), a standalone posturography device, in 4 sensory conditions: firm surface, eyes open (EO); firm surface, eyes closed (EC); foam surface, EO; and foam surface, EC. Stabilization Indices (SI) were computed from COP measures to determine the relative visual (SI_firm, SI_foam), somatosensory (SI_EO, SI_EC) and vestibular (SI_V, i.e., Foam_EC vs. Firm_EO) contributions to balance. This study was not powered to detect between group differences, so significance of pre-post changes was assessed by paired samples t-tests within each group.

Results

Groups were equivalent at baseline (all p > 0.05). In the AYT group, absolute COP significantly increased in the Foam_EO (t(8) = -3.66, p = 0.01) and Foam_EC (t(8) = -3.90, p = 0.01) conditions. Relative somatosensory SI_EO (t(8) = -2.42, p = 0.04) and SI_EC (t(8) = -3.96, p = 0.01), and vestibular SI_V (t(8) = -2.47, p = 0.04) contributions to balance increased significantly. As expected, no significant changes from EO to EC conditions were found indicating an absence of visual dependency in VI. No significant pre-post changes were observed in the control group (all p > 0.05).

Conclusions

These preliminary results establish the potential for AYT training to develop the remaining somatosensory and vestibular responses used to optimize postural stability in a VI population.

Trial Registration

www.ClinicalTrials.gov NCT01366677     

Assessing telomeric DNA content in pediatric cancers using whole-genome sequencing data

Background

Telomeres are the protective arrays of tandem TTAGGG sequence and associated proteins at the termini of chromosomes. Telomeres shorten at each cell division due to the end-replication problem and are maintained above a critical threshold in malignant cancer cells to prevent cellular senescence or apoptosis. With the recent advances in massive parallel sequencing, assessing telomere content in the context of other cancer genomic aberrations becomes an attractive possibility. We present the first comprehensive analysis of telomeric DNA content change in tumors using whole-genome sequencing data from 235 pediatric cancers.

Results

To measure telomeric DNA content, we counted telomeric reads containing TTAGGGx4 or CCCTAAx4 and normalized to the average genomic coverage. Changes in telomeric DNA content in tumor genomes were clustered using a Bayesian Information Criterion to determine loss, no change, or gain. Using this approach, we found that the pattern of telomeric DNA alteration varies dramatically across the landscape of pediatric malignancies: telomere gain was found in 32% of solid tumors, 4% of brain tumors and 0% of hematopoietic malignancies. The results were validated by three independent experimental approaches and reveal significant association of telomere gain with the frequency of somatic sequence mutations and structural variations.

Conclusions

Telomere DNA content measurement using whole-genome sequencing data is a reliable approach that can generate useful insights into the landscape of the cancer genome. Measuring the change in telomeric DNA during malignant progression is likely to be a useful metric when considering telomeres in the context of the whole genome.     

Temperature-induced changes in fatty acid composition of myelinated and non-myelinated axon phospholipids

The olfactory (non-myelinated) and trigeminal (myelinated) nerve axons of garfish show changes in phospholipid fatty acid composition when these fish are acclimated to temperatures ranging from 11 to 35 degrees C. Myelinated and non-myelinated nerve axons show similar changes in the percent saturated, percent 16-carbon, percent 18-carbon, and percent 20-carbon-and-greater unsaturated fatty acids. The observed changes in phospholipid fatty acid composition fit a linear regression model suggesting a gradual change in axonal phospholipid fatty acid composition with temperature. The temperature-induced changes in garfish nerve phospholipid fatty acid composition are consistent with the general observation of increased saturated fatty acid residues in plasma membrane phospholipids of organisms acclimated to higher environmental temperatures. The garfish data are similar to data previously obtained for goldfish tissues and Tetrahymena.     

Clinical and pathological characteristics of Chinese patients with BRCA related breast cancer

Breast cancers related to BRCA mutations are associated with particular biological features. Here we report the clinical and pathological characteristics of breast cancer in Chinese women with and without BRCA mutations and of carriers of BRCA1 mutations compared to BRCA2 mutations. Two hundred and 26 high-risk Hong Kong Chinese women were tested for BRCA mutations, medical information was obtained from medical records, and risk and demographic information was obtained from personal interviews. In this cohort, 28 (12.4%) women were BRCA mutation carriers and among these carriers, 39.3% were BRCA1 and 60.7% were BRCA2 mutations. Mutation carriers were more likely to have a familial history of breast and ovarian cancer, high-grade cancers, and triple negative (TN) cancers. Prevalence of TN was 48.3% in BRCA carriers and 25.6% in non-carriers and was 67.7% in BRCA1 and 35.3% in BRCA2 carriers. Estrogen receptor (ER) negative cancer was significantly associated with BRCA1 mutations, especially in those under 40 years of age. BRCA-related breast cancer in this Chinese population is associated with family history and adverse pathological/prognostic features, with BRCA2 mutations being more prevalent but BRCA1 carriers having more aggressive and TN cancers. Compared to Caucasian populations, prevalence of BRCA2 mutations and TN cancer in BRCA2 mutation carriers in Chinese population are elevated.     

Recombination and Chromosome Segregation during the Single Division Meiosis in SPO12–1 and SPO13–1 Diploids

This paper reports a study of chromosome segregation and recombination during sporulation of spo12–1 and spo13–1 diploid strains of S. cerevisiae. These strains undergo a single division to form asci containing two diploid or near-diploid spores. The segregation of centromere-linked markers in the two-spored (dyad) products indicates that the division is generally equational. However, in a small percentage of the spo12–1 and spo13–1 cells, it appears that a meiosis I-like division occurs. Aberrant segregation of the MAT locus on chromosome III, yielding a monosomic and a trisomic spore pair, occurs in 12% of all dyads. The segregation patterns of markers at various distances from their centromeres and several pairs of markers on the same chromosome indicate that recombination takes place in both strains at nearly standard meiotic levels.     

MMP-13 selective α-sulfone hydroxamates: a survey of P1' heterocyclic amide isosteres

Seeking compounds preferentially potent and selective for MMP-13, we reported in the preceding Letter on a series of hydroxamic acids with a flexible benzamide tail groups.^1a Here, we replace the amide moiety with non-hydrolyzable heterocycles in an effort to improve half-life. We identify a hydroxamate tetrazole 4e that spares MMP-1 and -14, shows >400-fold selectivity versus MMP-8 and >600-fold selectivity versus MMP-2, and has a 4.8 h half-life in rats. X-ray data (1.9 Å) for tetrazole 4c is presented.     

CREST maps somatic structural variation in cancer genomes with base-pair resolution

We developed 'clipping reveals structure' (CREST), an algorithm that uses next-generation sequencing reads with partial alignments to a reference genome to directly map structural variations at the nucleotide level of resolution. Application of CREST to whole-genome sequencing data from five pediatric T-lineage acute lymphoblastic leukemias (T-ALLs) and a human melanoma cell line, COLO-829, identified 160 somatic structural variations. Experimental validation exceeded 80%, demonstrating that CREST had a high predictive accuracy.