Passage and concentration-dependent effects of Indomethacin on tendon derived cells

<p>Abstract</p> <p>Background</p> <p>Non-steroidal anti-inflammatory drugs (NSAID) are commonly used in the treatment of tendinopathies such as tendonitis and tendinosis. Despite this, little is known of their direct actions on tendon-derived cells. As NSAIDs have been shown to delay healing in a number of mesenchymal tissues we have investigated the direct effects of indomethacin on the proliferation of tendon-derived cells.</p> <p>Results and Discussion</p> <p>The results obtained were dependent on both the type of cells used and the method of measurement. When measured using the Alamar blue assay, a common method for the measurement of cell proliferation and viability, no effect of indomethacin was seen regardless of cell source. It is likely that this lack of effect was due to a paucity of mitochondrial enzymes in tendon cells.</p> <p>However, when cell number was assessed using the methylene blue assay, which is a simple nuclear staining technique, an Indomethacin-induced inhibition of proliferation was seen in primary cells but not in secondary subcultures.</p> <p>Conclusion</p> <p>These results suggest that firstly, care must be taken when deciding on methodology used to investigate tendon-derived cells as these cells have a quite different metabolism to other mesenchymal derive cells. Secondly, Indomethacin can inhibit the proliferation of primary tendon derived cells and that secondary subculture selects for a population of cells that is unresponsive to this drug.</p

Determining the Effects of Transcranial Direct Current Stimulation on Tinnitus, Depression, and Anxiety: A Systematic Review

(1) Background: Tinnitus is the awareness of a sound in the absence of an external source. It affects around 10–15% of people, a significant proportion of whom also experience symptoms such as depression or anxiety that negatively affect their quality of life. Transcranial direct current stimulation (tDCS) is a technique involving constant low-intensity direct current delivered via scalp electrodes. It is a potential treatment option for tinnitus, as well as tinnitus-related conditions such as depression and anxiety. This systematic review estimates the effects of tDCS on outcomes relevant to tinnitus. In addition, it sheds light on the relationship between stimulation parameters and the effect of tDCS on these outcomes; (2) Methods: Exhaustive searches of electronic databases were conducted. Randomised controlled trials were included if they reported at least one of the following outcomes: tinnitus symptom severity, anxiety, or depression. Where available, data on quality of life, adverse effects, and neurophysiological changes were also reviewed. GRADE was used to assess the certainty in the estimate; (3) Results: Meta-analyses revealed a statistically significant reduction in tinnitus (moderate certainty) and depression (low certainty)-but not anxiety-following active tDCS compared to sham control. Network meta-analyses revealed potential optimal stimulation parameters; (4) Conclusions: The evidence synthesised in this review suggests tDCS has the potential to reduce symptom severity in tinnitus and depression. It further narrows down the number of potentially optimal stimulation parameters

Pharyngeal electrical stimulation for treatment of dysphagia in subacute stroke

Background and Purpose: Dysphagia is common after stroke, associated with increased death and dependency, and treatment options are limited. Pharyngeal electric stimulation (PES) is a novel treatment for poststroke dysphagia that has shown promise in 3 pilot randomized controlled trials. Methods: We randomly assigned 162 patients with a recent ischemic or hemorrhagic stroke and dysphagia, defined as a penetration aspiration score (PAS) of ≥3 on video fluoroscopy, to PES or sham treatment given on 3 consecutive days. The primary outcome was swallowing safety, assessed using the PAS, at 2 weeks. Secondary outcomes included dysphagia severity, function, quality of life, and serious adverse events at 6 and 12 weeks. Results: In randomized patients, the mean age was 74 years, male 58%, ischemic stroke 89%, and PAS 4.8. The mean treatment current was 14.8 (7.9) mA and duration 9.9 (1.2) minutes per session. On the basis of previous data, 45 patients (58.4%) randomized to PES seemed to receive suboptimal stimulation. The PAS at 2 weeks, adjusted for baseline, did not differ between the randomized groups: PES 3.7 (2.0) versus sham 3.6 (1.9), P=0.60. Similarly, the secondary outcomes did not differ, including clinical swallowing and functional outcome. No serious adverse device-related events occurred. Conclusions: In patients with subacute stroke and dysphagia, PES was safe but did not improve dysphagia. Undertreatment of patients receiving PES may have contributed to the neutral result. Clinical Trial Registration: URL: http://www.controlled-trials.com. Unique identifier: ISRCTN25681641

Presidential History

News release announces the Presidential History of the University of Dayton

Tissue specific characteristics of cells isolated from human and rat tendons and ligaments

<p>Abstract</p> <p>Background</p> <p>Tendon and ligament injuries are common and costly in terms of surgery and rehabilitation. This might be improved by using tissue engineered constructs to accelerate the repair process; a method used successfully for skin wound healing and cartilage repair. Progress in this field has however been limited; possibly due to an over-simplistic choice of donor cell. For tissue engineering purposes it is often assumed that all tendon and ligament cells are similar despite their differing roles and biomechanics. To clarify this, we have characterised cells from various tendons and ligaments of human and rat origin in terms of proliferation, response to dexamethasone and cell surface marker expression.</p> <p>Methods</p> <p>Cells isolated from tendons by collagenase digestion were plated out in DMEM containing 10% fetal calf serum, penicillin/streptomycin and ultraglutamine. Cell number and collagen accumulation were by determined methylene blue and Sirius red staining respectively. Expression of cell surface markers was established by flow cytometry.</p> <p>Results</p> <p>In the CFU-f assay, human PT-derived cells produced more and bigger colonies suggesting the presence of more progenitor cells with a higher proliferative capacity. Dexamethasone had no effect on colony number in ACL or PT cells but 10 nM dexamethasone increased colony size in ACL cultures whereas higher concentrations decreased colony size in both ACL and PT cultures. In secondary subcultures, dexamethasone had no significant effect on PT cultures whereas a stimulation was seen at low concentrations in the ACL cultures and an inhibition at higher concentrations. Collagen accumulation was inhibited with increasing doses in both ACL and PT cultures. This differential response was also seen in rat-derived cells with similar differences being seen between Achilles, Patellar and tail tendon cells. Cell surface marker expression was also source dependent; CD90 was expressed at higher levels by PT cells and in both humans and rats whereas D7fib was expressed at lower levels by PT cells in humans.</p> <p>Conclusion</p> <p>These data show that tendon & ligament cells from different sources possess intrinsic differences in terms of their growth, dexamethasone responsiveness and cell surface marker expression. This suggests that for tissue engineering purposes the cell source must be carefully considered to maximise their efficacy.</p

Superheated Microdrops as Cold Dark Matter Detectors

It is shown that under realistic background considerations, an improvement in Cold Dark Matter sensitivity of several orders of magnitude is expected from a detector based on superheated liquid droplets. Such devices are totally insensitive to minimum ionizing radiation while responsive to nuclear recoils of energies ~ few keV. They operate on the same principle as the bubble chamber, but offer unattended, continuous, and safe operation at room temperature and atmospheric pressure.Comment: 15 pgs, 4 figures include

The effectiveness and cost-effectiveness of assistive technology and telecare for independent living in dementia: a randomised controlled trial

OBJECTIVES: The use of assistive technology and telecare (ATT) has been promoted to manage risks associated with independent living in people with dementia but with little evidence for effectiveness. METHODS: Participants were randomly assigned to receive an ATT assessment followed by installation of all appropriate ATT devices or limited control of appropriate ATT. The primary outcomes were time to institutionalisation and cost-effectiveness. Key secondary outcomes were number of incidents involving risks to safety, burden and stress in family caregivers and quality of life. RESULTS: Participants were assigned to receive full ATT (248 participants) or the limited control (247 participants). After adjusting for baseline imbalance of activities of daily living score, HR for median pre-institutionalisation survival was 0.84; 95% CI, 0.63 to 1.12; P = 0.20. There were no significant differences between arms in health and social care (mean -£909; 95% CI, -£5,336 to £3,345, P = 0.678) and societal costs (mean -£3,545; 95% CI, -£13,914 to £6,581, P = 0.499). ATT group members had reduced participant-rated quality-adjusted life years (QALYs) at 104 weeks (mean - 0.105; 95% CI, -0.204 to -0.007, P = 0.037) but did not differ in QALYs derived from proxy-reported EQ-5D. DISCUSSION: Fidelity of the intervention was low in terms of matching ATT assessment, recommendations and installation. This, however, reflects current practice within adult social care in England. CONCLUSIONS: Time living independently outside a care home was not significantly longer in participants who received full ATT and ATT was not cost-effective. Participants with full ATT attained fewer QALYs based on participant-reported EQ-5D than controls at 104 weeks

The impact of assistive technology on burden and psychological well-being in informal caregivers of people with dementia (ATTILA Study)

INTRODUCTION: Assistive technology and telecare (ATT) may alleviate psychological burden in informal caregivers of people with dementia. This study assessed the impact of ATT on informal caregivers’ burden and psychological well‐being. METHODS: Individuals with dementia and their informal caregivers were recruited to a randomized‐controlled trial assessing effectiveness of ATT. Caregivers were allocated to two groups according to their cared‐for person's randomization to a full or basic package of ATT and were assessed on caregiver burden, state anxiety, and depression. Caregivers’ data from three assessments over 6 months of the trial were analyzed. RESULTS: No significant between‐ or within‐group differences at any time point on caregivers’ burden, anxiety, and depression levels were found. DISCUSSION: Full ATT for people with dementia did not impact caregivers’ psychological outcomes compared to basic ATT. The length of follow up was restricted to 6 months