313 research outputs found

    Multiplexed DNA Sequence Capture of Mitochondrial Genomes Using PCR Products

    Get PDF
    BACKGROUND: To utilize the power of high-throughput sequencers, target enrichment methods have been developed. The majority of these require reagents and equipment that are only available from commercial vendors and are not suitable for the targets that are a few kilobases in length. METHODOLOGY/PRINCIPAL FINDINGS: We describe a novel and economical method in which custom made long-range PCR products are used to capture complete human mitochondrial genomes from complex DNA mixtures. We use the method to capture 46 complete mitochondrial genomes in parallel and we sequence them on a single lane of an Illumina GA(II) instrument. CONCLUSIONS/SIGNIFICANCE: This method is economical and simple and particularly suitable for targets that can be amplified by PCR and do not contain highly repetitive sequences such as mtDNA. It has applications in population genetics and forensics, as well as studies of ancient DNA

    Cold-induced vasoconstriction at forearm and hand skin sites: the effect of age

    Get PDF
    During mild cold exposure, elderly are at risk of hypothermia. In humans, glabrous skin at the hands is well adapted as a heat exchanger. Evidence exists that elderly show equal vasoconstriction due to local cooling at the ventral forearm, yet no age effects on vasoconstriction at hand skin have been studied. Here, we tested the hypotheses that at hand sites (a) elderly show equal vasoconstriction due to local cooling and (b) elderly show reduced response to noradrenergic stimuli. Skin perfusion and mean arterial pressure were measured in 16 young adults (Y: 18–28 years) and 16 elderly (E: 68–78 years). To study the effect of local vasoconstriction mechanisms local sympathetic nerve terminals were blocked by bretylium (BR). Baseline local skin temperature was clamped at 33°C. Next, local temperature was reduced to 24°C. After 15 min of local cooling, noradrenalin (NA) was administered to study the effect of neural vasoconstriction mechanisms. No significant age effect was observed in vasoconstriction due to local cooling at BR sites. After NA, vasoconstriction at the forearm showed a significant age effect; however, no significant age effect was found at the hand sites. [Change in CVC (% from baseline): Forearm Y: −76 ± 3 vs. E: −60 ± 5 (P < 0.01), dorsal hand Y: −74 ± 4 vs. E: −72 ± 4 (n.s.), ventral hand Y: −80 ± 7 vs. E: −70 ± 11 (n.s.)]. In conclusion, in contrast to results from the ventral forearm, elderly did not show a blunted response to local cooling and noradrenalin at hand skin sites. This indicates that at hand skin the noradrenergic mechanism of vasoconstriction is maintained with age

    Logopenic and nonfluent variants of primary progressive aphasia are differentiated by acoustic measures of speech production

    Get PDF
    Differentiation of logopenic (lvPPA) and nonfluent/agrammatic (nfvPPA) variants of Primary Progressive Aphasia is important yet remains challenging since it hinges on expert based evaluation of speech and language production. In this study acoustic measures of speech in conjunction with voxel-based morphometry were used to determine the success of the measures as an adjunct to diagnosis and to explore the neural basis of apraxia of speech in nfvPPA. Forty-one patients (21 lvPPA, 20 nfvPPA) were recruited from a consecutive sample with suspected frontotemporal dementia. Patients were diagnosed using the current gold-standard of expert perceptual judgment, based on presence/absence of particular speech features during speaking tasks. Seventeen healthy age-matched adults served as controls. MRI scans were available for 11 control and 37 PPA cases; 23 of the PPA cases underwent amyloid ligand PET imaging. Measures, corresponding to perceptual features of apraxia of speech, were periods of silence during reading and relative vowel duration and intensity in polysyllable word repetition. Discriminant function analyses revealed that a measure of relative vowel duration differentiated nfvPPA cases from both control and lvPPA cases (r2 = 0.47) with 88% agreement with expert judgment of presence of apraxia of speech in nfvPPA cases. VBM analysis showed that relative vowel duration covaried with grey matter intensity in areas critical for speech motor planning and programming: precentral gyrus, supplementary motor area and inferior frontal gyrus bilaterally, only affected in the nfvPPA group. This bilateral involvement of frontal speech networks in nfvPPA potentially affects access to compensatory mechanisms involving right hemisphere homologues. Measures of silences during reading also discriminated the PPA and control groups, but did not increase predictive accuracy. Findings suggest that a measure of relative vowel duration from of a polysyllable word repetition task may be sufficient for detecting most cases of apraxia of speech and distinguishing between nfvPPA and lvPPA

    Perceived barriers to integrated care in rheumatoid arthritis: views of recipients and providers of care in an inner-city setting

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>A number of recent reports published in the UK have put the quality of care of adults with Rheumatoid Arthritis (RA) centre stage. These documents set high standards for health care professionals and commissioning bodies that need to be implemented into routine clinical practice. We therefore have obtained the views of recipients and providers of care in inner city settings as to what they perceive are the barriers to providing integrated care.</p> <p>Methods</p> <p>We conducted focus groups and face to face interviews between 2005-8 with 79 participants (patients, carers, specialist medical and nursing outpatient staff and general practitioners (GPs)) working in or attending three hospitals and three primary care trusts (PCT).</p> <p>Results</p> <p>Three barriers were identified that stood in the way of seamless integrated care in RA from the perspective of patients, carers, specialists and GPs: (i) early referral (e.g. 'gate keeper's role of GPs); (ii) limitations of ongoing care for established RA (e.g. lack of consultation time in secondary care) and (iii) management of acute flares (e.g. pressure on overbooked clinics).</p> <p>Conclusion</p> <p>This timely study of the multi-perspective views of recipients and providers of care was conducted during the time of publications of many important reports in the United Kingdom (UK) that highlighted key components in the provision of high quality care for adults with RA. To achieve seamless care across primary and secondary care requires organisational changes, greater personal and professional collaboration and GP education about RA.</p

    Effects of supervised exercise training on lower-limb cutaneous microvascular reactivity in adults with venous ulcers

    Get PDF
    Purpose: To investigate the effects of a 12-week supervised exercise programme on lower-limb cutaneous microvascular reactivity in adults with venous leg ulceration. Methods: Thirty-eight adults with unilateral venous ulceration who were being treated with lower-limb compression therapy (58% male; mean age 65 years; median ulcer size 5 cm2) were randomly allocated to exercise or control groups. Exercise participants (n=18) were invited to attend thrice weekly sessions of lower-limb aerobic and resistance exercise for 12 weeks. Cutaneous microvascular reactivity was assessed in the gaiter region of ulcerated and non-ulcerated legs at baseline and 3 months using laser Doppler fluxmetry coupled with iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP). Cutaneous vascular conductance (CVC) was calculated as laser Doppler flux (AU)/mean arterial pressure (mmHg). Results: Thirty-seven participants completed follow-up assessments. Median class attendance was 36 (range 2 to 36). Analyses of covariance revealed greater peak CVC responses to ACh in the exercise group at 3 months in both the ulcerated (adjusted difference = 0.944 AU/mmHg; 95% CI 0.504 to 1.384) and non-ulcerated (adjusted difference = 0.596 AU/mmHg; 95% CI 0.028 to 1.164) legs. Peak CVC responses to SNP were also greater in the exercise group at 3 months in the ulcerated leg (adjusted difference = 0.882 AU/mmHg; 95% CI 0.274 to 1.491), but not the non-ulcerated leg (adjusted difference = 0.392 AU/mmHg; 95% CI -0.377 to 1.161). Conclusion: Supervised exercise training improves lower-limb cutaneous microvascular reactivity in adults with venous leg ulceration. Keywords Randomized controlled trial; Exercise; Ulceration; Vascular function; Laser Doppler fluxmetry; Iontophoresi

    Pain relief is associated with decreasing postural sway in patients with non-specific low back pain

    Get PDF
    Background Increased postural sway is well documented in patients suffering from non-specific low back pain, whereby a linear relationship between higher pain intensities and increasing postural sway has been described. No investigation has been conducted to evaluate whether this relationship is maintained if pain levels change in adults with non-specific low back pain. Methods Thirty-eight patients with non-specific low back pain and a matching number of healthy controls were enrolled. Postural sway was measured by three identical static bipedal standing tasks of 90 sec duration with eyes closed in narrow stance on a firm surface. The perceived pain intensity was assessed by a numeric rating scale (NRS-11). The patients received three manual interventions (e.g. manipulation, mobilization or soft tissue techniques) at 3-4 day intervals, postural sway measures were obtained at each occasion. Results A clinically relevant decrease of four NRS scores in associated with manual interventions correlated with a significant decrease in postural sway. In contrast, if no clinically relevant change in intensity occurred ([less than or equal to]1 level), postural sway remained similar compared to baseline. The postural sway measures obtained at follow-up sessions 2 and 3 associated with specific NRS level showed no significant differences compared to reference values for the same pain score. Conclusions Alterations in self-reported pain intensities are closely related to changes in postural sway. The previously reported linear relationship between the two variables is maintained as pain levels change. Pain interference appears responsible for the altered sway in pain sufferers. This underlines the clinical use of sway measures as an objective monitoring tool during treatment or rehabilitation
    corecore