| 231. |
- Chuang, YF, et al.
(författare)
-
Use of diuretics is associated with reduced risk of Alzheimer's disease: the Cache County Study
- 2014
-
Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580. ; 35:11, s. 2429-35
-
Tidskriftsartikel (refereegranskat)abstract
- Although the use of antihypertensive medications has been associated with reduced risk of Alzheimer's disease (AD), it remains unclear which class provides the most benefit. The Cache County Study of Memory Health and Aging is a prospective longitudinal cohort study of dementing illnesses among the elderly population of Cache County, Utah. Using waves I to IV data of the Cache County Study, 3417 participants had a mean of 7.1 years of follow-up. Time-varying use of antihypertensive medications including different class of diuretics, angiotensin converting enzyme inhibitors, β-blockers, and calcium channel blockers was used to predict the incidence of AD using Cox proportional hazards analyses. During follow-up, 325 AD cases were ascertained with a total of 23,590 person-years. Use of any antihypertensive medication was associated with lower incidence of AD (adjusted hazard ratio [aHR], 0.77; 95% confidence interval [CI], 0.61-0.97). Among different classes of antihypertensive medications, thiazide (aHR, 0.7; 95% CI, 0.53-0.93), and potassium-sparing diuretics (aHR, 0.69; 95% CI, 0.48-0.99) were associated with the greatest reduction of AD risk. Thiazide and potassium-sparing diuretics were associated with decreased risk of AD. The inverse association of potassium-sparing diuretics confirms an earlier finding in this cohort, now with longer follow-up, and merits further investigation
|
|
| 232. |
- Condurache, C. I., et al.
(författare)
-
Screening for high hip fracture risk does not impact on falls risk: a post hoc analysis from the SCOOP study
- 2020
-
Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 31:3, s. 457-464
-
Tidskriftsartikel (refereegranskat)abstract
- A reduction in hip fracture incidence following population screening might reflect the effectiveness of anti-osteoporosis therapy, behaviour change to reduce falls, or both. This post hoc analysis demonstrates that identifying high hip fracture risk by FRAX was not associated with any alteration in falls risk. Introduction To investigate whether effectiveness of an osteoporosis screening programme to reduce hip fractures was mediated by modification of falls risk in the screening arm. Methods The SCOOP study recruited 12,483 women aged 70-85 years, individually randomised to a control (n = 6250) or screening (n = 6233) arm; in the latter, osteoporosis treatment was recommended to women at high risk of hip fracture, while the control arm received usual care. Falls were captured by self-reported questionnaire. We determined the influence of baseline risk factors on future falls, and then examined for differences in falls risk between the randomisation groups, particularly in those at high fracture risk. Results Women sustaining one or more falls were slightly older at baseline than those remaining falls free during follow-up (mean difference 0.70 years, 95%CI 0.55-0.85, p < 0.001). A higher FRAX 10-year probability of hip fracture was associated with increased likelihood of falling, with fall risk increasing by 1-2% for every 1% increase in hip fracture probability. However, falls risk factors were well balanced between the study arms and, importantly, there was no evidence of a difference in falls occurrence. In particular, there was no evidence of interaction (p = 0.18) between baseline FRAX hip fracture probabilities and falls risk in the two arms, consistent with no impact of screening on falls in women informed to be at high risk of hip fracture. Conclusion Effectiveness of screening for high FRAX hip fracture probability to reduce hip fracture risk was not mediated by a reduction in falls.
|
|
| 233. |
|
|
| 234. |
- Docking, TR, et al.
(författare)
-
A clinical transcriptome approach to patient stratification and therapy selection in acute myeloid leukemia
- 2021
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 2474-
-
Tidskriftsartikel (refereegranskat)abstract
- As more clinically-relevant genomic features of myeloid malignancies are revealed, it has become clear that targeted clinical genetic testing is inadequate for risk stratification. Here, we develop and validate a clinical transcriptome-based assay for stratification of acute myeloid leukemia (AML). Comparison of ribonucleic acid sequencing (RNA-Seq) to whole genome and exome sequencing reveals that a standalone RNA-Seq assay offers the greatest diagnostic return, enabling identification of expressed gene fusions, single nucleotide and short insertion/deletion variants, and whole-transcriptome expression information. Expression data from 154 AML patients are used to develop a novel AML prognostic score, which is strongly associated with patient outcomes across 620 patients from three independent cohorts, and 42 patients from a prospective cohort. When combined with molecular risk guidelines, the risk score allows for the re-stratification of 22.1 to 25.3% of AML patients from three independent cohorts into correct risk groups. Within the adverse-risk subgroup, we identify a subset of patients characterized by dysregulated integrin signaling and RUNX1 or TP53 mutation. We show that these patients may benefit from therapy with inhibitors of focal adhesion kinase, encoded by PTK2, demonstrating additional utility of transcriptome-based testing for therapy selection in myeloid malignancy.
|
|
| 235. |
- Elsayed, Mohamed Hammad, et al.
(författare)
-
Overcoming small-bandgap charge recombination in visible and NIR-light-driven hydrogen evolution by engineering the polymer photocatalyst structure
- 2024
-
Ingår i: Nature Communications. - 2041-1723. ; 15:1
-
Tidskriftsartikel (refereegranskat)abstract
- Designing an organic polymer photocatalyst for efficient hydrogen evolution with visible and near-infrared (NIR) light activity is still a major challenge. Unlike the common behavior of gradually increasing the charge recombination while shrinking the bandgap, we present here a series of polymer nanoparticles (Pdots) based on ITIC and BTIC units with different π-linkers between the acceptor-donor-acceptor (A-D-A) repeated moieties of the polymer. These polymers act as an efficient single polymer photocatalyst for H2 evolution under both visible and NIR light, without combining or hybridizing with other materials. Importantly, the difluorothiophene (ThF) π-linker facilitates the charge transfer between acceptors of different repeated moieties (A-D-A-(π-Linker)-A-D-A), leading to the enhancement of charge separation between D and A. As a result, the PITIC-ThF Pdots exhibit superior hydrogen evolution rates of 279 µmol/h and 20.5 µmol/h with visible (>420 nm) and NIR (>780 nm) light irradiation, respectively. Furthermore, PITIC-ThF Pdots exhibit a promising apparent quantum yield (AQY) at 700 nm (4.76%).
|
|
| 236. |
- Emerson, FJ, et al.
(författare)
-
The chromatin factors SET-26 and HCF-1 oppose the histone deacetylase HDA-1 in longevity and gene regulation in C. elegans
- 2023
-
Ingår i: bioRxiv : the preprint server for biology. - : Cold Spring Harbor Laboratory.
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- SET-26, HCF-1, and HDA-1 are highly conserved chromatin factors with key roles in development and aging. Here we present mechanistic insights into how these factors regulate gene expression and modulate longevity inC. elegans. We show that SET-26 and HCF-1 cooperate to regulate a common set of genes, and both antagonize the histone deacetylase HDA-1 to limit longevity. We propose a model in which SET-26 recruits HCF-1 to chromatin in somatic cells, where they stabilize each other at the promoters of a subset of genes, particularly mitochondrial function genes, and regulate their expression. HDA-1 opposes SET-26 and HCF-1 on the regulation of a subset of their common target genes and in longevity. Our findings suggest that SET-26, HCF-1, and HDA-1 comprise a mechanism to fine-tune gene expression and longevity and likely have important implications for the mechanistic understanding of how these factors function in diverse organisms, particularly in aging biology.
|
|
| 237. |
|
|
| 238. |
|
|
| 239. |
- Götlind, Yu-Yuan Chiu, 1964, et al.
(författare)
-
Interplay between Th1 and Th17 effector T cell pathways in the pathogenesis of spontaneous colitis and colon cancer in the Gai2-deficient mouse
- 2013
-
Ingår i: International Immunology. - Oxford, United Kingdom : Oxford University Press. - 0953-8178 .- 1460-2377. ; 25:1, s. 35-44
-
Tidskriftsartikel (refereegranskat)abstract
- Gαi2-deficient mice spontaneously develop colitis. Using xMAP technology and RT-PCR, we investigated cytokine/chemokine profiles during histologically defined phases of disease: (i) no/mild, (ii) moderate, (iii) severe colitis without dysplasia/cancer and (iv) severe colitis with dysplasia/cancer, compared with age-matched wild-type (WT) littermates. Colonic dysplasia was observed in 4/11 mice and cancer in 1/11 mice with severe colitis. The histology correlated with progressive increases in colon weight/cm and spleen weight, and decreased thymus weight, all more advanced in mice with dysplasia/cancer. IL-1β, IL-6, IL-12p40, IL-17, TNF-α, CCL2 and CXCL1 protein levels in colons, but not small intestines increased with colitis progression and were significantly increased in mice with moderate and severe colitis compared with WT mice, irrespective of the absence/presence of dysplasia/cancer. CCL5 did not change during colitis progression. Colonic IL-17 transcription increased 40- to 70-fold in all stages of colitis, whereas IFN-γ mRNA was gradually up-regulated 12- to 55-fold with colitis progression, and further to 62-fold in mice with dysplasia/cancer. IL-27 mRNA increased 4- to 15-fold during the course of colitis, and colonic IL-21 transcription increased 3-fold in mice with severe colitis, both irrespective of the absence/presence of dysplasia/cancer. FoxP3 transcription was significantly enhanced (3.5-fold) in mice with moderate and severe colitis, but not in mice with dysplasia/cancer, compared with WT mice. Constrained correspondence analysis demonstrated an association between increased protein levels of TNF-α, CCL2, IL-1β, IL-6 and CXCL1 and dysplasia/cancer. In conclusion, colonic responses are dominated by a mixed T(h)1/T(h)17 phenotype, with increasing T(h)1 cytokine transcription with progression of colitis in Gαi2(-/-) mice.
|
|
| 240. |
|
|
