The Alzheimer's and Music Therapy (ALMUTH) study is the first randomised controlled trial (RCT) design with 12 months of active non-pharmacological therapy (NPT) implementing music therapy (MT) and ...physical activity (PA) for participants with Alzheimer's disease (AD). The aim of the present article is to retrospectively examine the inclusion of mild-to-moderate Alzheimer's Disease patients into the main ALMUTH study protocol and to determine if continued inclusion of AD patients is warranted.
The randomised pilot trial was conducted as a parallel three-arm RCT, reflecting the experimental design of the ALMUTH study. The trial was conducted in Bergen, Norway, and randomisation (1:1:1) was performed by an external researcher. The study was open label and the experimental design features two active NPTs: MT and PA, and a passive control (no intervention, CON) in Norwegian speaking patients with AD who still live at home and could provide informed consent. Sessions were offered once per week (up to 90 min) up to 40 sessions over 12 months. Baseline and follow-up tests included a full neuropsychological test battery and three magnetic resonance imaging (MRI) measurements (structural, functional, and diffusion weighted imaging). Feasibility outcomes were assessed and were determined as feasible if they met the target criteria.
Eighteen participants with a diagnosis of mild-to-moderate AD were screened, randomised, and tested once at baseline and once after 12-months. Participants were divided into three groups: MT (n = 6), PA (n = 6), and CON (n = 6). Results of the study revealed that the ALMUTH protocol in patients with AD was not feasible. The adherence to the study protocol was poor (50% attended sessions), with attrition and retention rates at 50%. The recruitment was costly and there were difficulties acquiring participants who met the inclusion criteria. Issues with study fidelity and problems raised by staff were taken into consideration for the updated study protocol. No adverse events were reported by the patients or their caregivers.
The pilot trial was not deemed feasible in patients with mild-to-moderate AD. To mitigate this, the ALMUTH study has expanded the recruitment criteria to include participants with milder forms of memory impairment (pre-AD) in addition to expanding the neuropsychological test battery. The ALMUTH study is currently ongoing through 2023.
Norsk Forskningsråd (NFR) funded. Regional Committees for Medical and Health Research Ethics (REC-WEST: reference number 2018/206).
gov: NCT03444181 (registered retrospectively 23 February 2018, https://clinicaltrials.gov/ct2/show/NCT03444181 ).
Purpose
The purpose of this study was to evaluate the effects of 16 weeks combined aerobic and resistance training, twice a week, on the physical performance in women treated for gynecological ...cancer.
Methods
Sixty women (56.9 ± 13.3 years) who had completed curative treatment for gynecological cancer were divided into two groups: a physical training group (PT) (
n
= 29) or a control group (C) (
n
= 31). The PT group performed two sessions of combined aerobic and resistance training weekly for 16 weeks. Peak oxygen consumption (V̇O
2peak
) and one repetition maximum (1RM) of leg press, leg extension, and chest press were measured before group assignment, after 16 weeks and at the 1-year follow-up.
Results
A significant increase in V̇O
2peak
(ml min
−1
kg
−1
) (29.7 ± 8.0 vs. 31.3 ± 8.3,
p
= .009), leg press (kg) (113.0 ± 27.3 vs. 116.7 ± 29.2,
p
= .047), leg extension (kg) (44.2 ± 10.1 vs. 48.0 ± 10.6,
p
< .001), and chest press (kg) (24.5 ± 7.5 vs. 26.9 ± 8.2,
p
= .001) was seen in the PT group from pre- to post-measurement. The PT group maintained the improved aerobic condition and muscle strength 1 year after the training intervention. In the C group, there were no significant differences between pre- and post-measurements, but a significant decrease (28.2 ± 7.5 vs. 27.0 ± 7.3,
p
= .040) in the V̇O
2peak
from post to 1-year follow-up measurements.
Conclusions
Combined aerobic and resistance training twice a week in 16 weeks improves V̇O
2peak
and maximal strength in women treated for gynecological cancer. The training effects were sustained after 1 year in the PT group.
Photodetection (PD) and photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA)–induced protoporphyrin IX (PPIX) accumulation are approaches to detect and treat dysplasia and early cancer in the ...gastrointestinal tract and in the urinary bladder. Because ALA-induced PPIX production is limited, we synthesized ALA ester hydrochlorides 3–22 and tested them in two different in vitro models (gastrointestinal tract: HT29–CCD18; urinary bladder: J82–UROTSA). PPIX accumulation after incubation with 0.12 mmol/L for 3 h and PPIX accumulation as a function of different incubation times were measured using flow cytometry. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays were performed to check cellular dark toxicity. Phototoxicity after irradiation was tested. ALA nonafluorohexylester hydrochloride 11, ALA thiohexylester hydrochloride 13 and ALA dibenzyldiester dihydrochloride 19 induced appreciably increased PPIX levels and showed improved phototoxicity compared with the references ALA hydrochloride 1, ALA hexylester hydrochloride 3 and ALA benzylester hydrochloride 4. Thus, the new compounds 11, 13 and 19 are promising compounds for PD and PDT.
Hyperinflammation contributes to lung injury and subsequent acute respiratory distress syndrome (ARDS) with high mortality in patients with severe coronavirus disease 2019 (COVID-19). To understand ...the underlying mechanisms involved in lung pathology, we investigated the role of the lung-specific immune response. We profiled immune cells in bronchoalveolar lavage fluid and blood collected from COVID-19 patients with severe disease and bacterial pneumonia patients not associated with viral infection. By tracking T cell clones across tissues, we identified clonally expanded tissue-resident memory-like Th17 cells (Trm17 cells) in the lungs even after viral clearance. These Trm17 cells were characterized by a a potentially pathogenic cytokine expression profile of
and
(GM-CSF). Interactome analysis suggests that Trm17 cells can interact with lung macrophages and cytotoxic CD8
T cells, which have been associated with disease severity and lung damage. High IL-17A and GM-CSF protein levels in the serum of COVID-19 patients were associated with a more severe clinical course. Collectively, our study suggests that pulmonary Trm17 cells are one potential orchestrator of the hyperinflammation in severe COVID-19.
Single-mode waveguides for GRAVITY Perrin, G.; Jocou, L.; Perraut, K. ...
Astronomy and astrophysics (Berlin),
01/2024, Volume:
681
Journal Article
Peer reviewed
Open access
The second generation Very Large Telescope Interferometer (VLTI) instrument GRAVITY is a two-field infrared interferometer operating in the
K
band between 1.97 and 2.43 µm with either the four 8 m or ...the four 1.8 m telescopes of the Very Large Telescope (VLT). Beams collected by the telescopes are corrected with adaptive optics systems and the fringes are stabilized with a fringe-tracking system. A metrology system allows the measurement of internal path lengths in order to achieve high-accuracy astrometry. High sensitivity and high interferometric accuracy are achieved thanks to (i) correction of the turbulent phase, (ii) the use of low-noise detectors, and (iii) the optimization of photometric and coherence throughput. Beam combination and most of the beam transport are performed with single-mode waveguides in vacuum and at low temperature. In this paper, we present the functions and performance achieved with weakly birefringent standard single-mode fiber systems in GRAVITY. Fibered differential delay lines (FDDLs) are used to dynamically compensate for up to 6 mm of delay between the science and reference targets. Fibered polarization rotators allow us to align polarizations in the instrument and make the single-mode beam combiner close to polarization neutral. The single-mode fiber system exhibits very low birefringence (less than 23°), very low attenuation (3.6–7 dB km
−1
across the
K
band), and optimized differential dispersion (less than 2.04 µrad cm
2
at zero extension of the FDDLs). As a consequence, the typical fringe contrast losses due to the single-mode fibers are 6% to 10% in the lowest-resolution mode and 5% in the medium- and high-resolution modes of the instrument for a photometric throughput of the fiber chain of the order of 90%. There is no equivalent of this fiber system to route and modally filter beams with delay and polarization control in any other
K
-band beamcombiner.
Photodynamic diagnosis (PDD) and photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA)–induced protoporphyrin IX (PPIX) is an interesting approach to detect and treat dysplasia and early ...cancers in the gastrointestinal tract. Because of low lipophilicity resulting in poor penetration across cell membranes, high doses of ALA should be administered in order to reach clinically relevant levels of PPIX. One way of increasing PPIX accumulation is derivatization of ALA into a more lipophilic molecule. In our in vitro study, different esterifications of ALA were investigated to analyze the effects on PPIX accumulation in human adenocarcinoma cell lines. For systematic analysis of cell type–specific PPIX accumulation, three human adenocarcinoma cell lines (SW480, HT29 and CaCo2) and a fibroblast cell line (CCD18) were tested. 3-(4,5-Dimethylthiazole-2-yl)-2,5-biphenyl tetrazolium bromide (MTT) assays were performed to ensure that the ALA esters showed no cellular dark toxicity. Different concentrations (ranging from 0.012 to 0.6 mmol/L, 3 h) and incubation times (5, 10, 30, 180 min; 0.12 mmol/L) were examined. PPIX accumulation was measured using flow cytometry. ALA esters, especially ALA-hexylester and ALA-benzylester, induced significant higher PPIX levels in adenocarcinoma cell lines when compared with ALA and may be promising candidates for PDT and PDD.
Single-mode waveguides for GRAVITY Perraut, K.; Jocou, L.; Berger, J. P. ...
Astronomy and astrophysics (Berlin),
06/2018, Volume:
614
Journal Article
Peer reviewed
Open access
Context.
Within the framework of the second-generation instrumentation of the Very Large Telescope Interferometer of the European Southern Observatory we have developed the four-telescope beam ...combiner in integrated optics.
Aims.
We optimized the performance of such beam combiners, for the first time in the near-infrared
K
band, for the GRAVITY instrument dedicated to the study of the close environment of the galactic centre black hole by precision narrow-angle astrometry and interferometric imaging.
Methods.
We optimized the design of the integrated optics chip and the manufacturing technology as well, to fulfil the very demanding throughput specification. We also designed an integrated optics assembly able to operate at 200 K in the GRAVITY cryostat to reduce thermal emission.
Results.
We manufactured about 50 beam combiners by silica-on-silicon etching technology. We glued the best combiners to single-mode fluoride fibre arrays that inject the VLTI light into the integrated optics beam combiners. The final integrated optics assemblies have been fully characterized in the laboratory and through on-site calibrations: their global throughput over the
K
band is higher than 55% and the instrumental contrast reaches more than 95% in polarized light, which is well within the GRAVITY specifications.
Conclusions.
While integrated optics technology is known to be mature enough to provide efficient and reliable beam combiners for astronomical interferometry in the
H
band, we managed to successfully extend it to the longest wavelengths of the
K
band and to manufacture the most complex integrated optics beam combiner in this specific spectral band.
Ultraviolet signals in birds are special Hausmann, Franziska; Arnold, Kathryn E.; Marshall, N. Justin ...
Proceedings of the Royal Society. B, Biological sciences,
01/2003, Volume:
270, Issue:
1510
Journal Article
Peer reviewed
Open access
Recent behavioural experiments have shown that birds use ultraviolet (UV)-reflective and fluorescent plumage as cues in mate choice. It remains controversial, however, whether such UV signals play a ...special role in sexual communication, or whether they are part of general plumage coloration. We use a comparative approach to test for a general association between sexual signalling and either UV-reflective or fluorescent plumage. Among the species surveyed, 72% have UV colours and there is a significant positive association between UV reflectance and courtship displays. Among parrots (Psittaciformes), 68% of surveyed species have fluorescent plumage, and again there is a strong positive association between courtship displays and fluorescence. These associations are not artefacts of the plumage used in courtship displays, being generally more 'colourful' because there is no association between display and colours lacking UV reflectance or fluorescence. Equally, these associations are not phylogenetic artefacts because all results remain unchanged when families or genera, rather than species, are used as independent data points. We also find that, in parrots, fluorescent plumage is usually found adjacent to UV-reflective plumage. Using a simple visual model to examine one parrot, the budgerigar Melopsittacus undulatus, we show that the juxtaposition of UV-reflective and fluorescent plumage leads to a 25-fold increase in chromatic contrast to the budgerigar's visual system. Taken together, these results suggest that signals based on UV contrast are of special importance in the context of active sexual displays. We review briefly six hypotheses on why this may be the case: suitability for short-range signalling; high contrast with backgrounds; invisibility to predators; exploitation of pre-existing sensory biases; advertisement of feather structure; and amplification of behavioural signals.
Photodynamic diagnosis and especially therapy after sensitization with 5-aminolevulinic acid (ALA) is hampered by limitations of uptake and distribution of ALA due to its hydrophilic nature. Chemical ...modification of ALA into its more lipophilic esters seems to be promising to overcome these problems. The aim of the present study was to investigate the comparative kinetics of protoporphyrin IX (PPIX) fluorescence in rat colonic tissue after topical application of ALA and its esterified derivatives, ALA-hexylester (h-ALA), ALA-methylester (m-ALA) and ALA-benzylester (b-ALA). Fluorescence intensity induced by PPIX in normal colonic tissue was quantified using fluorescence microscopy at 1, 2, 4, 6 and 8 h after sensitization. Mucosa exhibited higher fluorescence levels compared to the underlying submucosa or smooth muscle. Peak fluorescence intensities were seen 4 h after local sensitization with 86.0 mol ml(-1) ALA (513 +/- 0.57 counts per pixel), 6.6 mol ml(-1) m-ALA (508 +/- 35.50) and 4.8 mol ml(-1) h-ALA (532 +/- 128.80), and 6 h after sensitization with 4.6 mol ml(-1) b-ALA (468 +/- 190.27). A 13-18 times lower concentration of ALA esters was required for fluorescence intensities reached with ALA alone. A similar degree of the fluorescence ratio between mucosa and muscularis (5-6:1) was detected for ALA and its derivatives. The time point of the maximum value of this ratio was consistent with peak fluorescence levels for ALA and each ALA-ester. The clinical feasibility and the advantages of topical ALA ester-based fluorescence for detection of malignant and premalignant lesions need further investigations.
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