Can motor decline be a modifiable marker of clinical progression in subjective cognitive decline? A national prospective cohort study.

OBJECTIVES: Subjective cognitive decline represents a critical stage for preventing mild cognitive impairment and dementia, but the links between clinical progression in the subjective cognitive decline stage and various motor functions remain inconclusive. This cohort study aimed to elucidate the independent and joint associations between the clinical progression of subjective cognitive decline and motor functions. METHODS: We enrolled 4880 community-dwelling elderly participants from a national cohort and used Cox proportional hazard regression model and restricted cubic spline models to explore the longitudinal associations between motor functions (gait, strength, balance, and endurance) and the clinical progression of subjective cognitive decline. RESULTS: During 5-years follow-up, 1239 participants experienced clinical progression. After adjusting for demographics, vascular burden, body components, and polypharmacy, gait speed [hazard ratios (HRs)= 0.96, 95% confidence interval (CI) 0.94-0.99], chair stand test (HRs=1.02, 95%CI 1.01-1.03), and endurance limitation in jogging 1 kilometer (HRs=1.18, 95%CI 1.04-1.34) were significantly associated with clinical progression. Among all participants, individuals characterized by poor upper- and lower-body strength, as well as those with slow pace and reduced endurance, faced the highest risk of cognitive impairment. CONCLUSIONS: This study emphasizes the potential of gait speed, muscle strength, and endurance as non-cognitive indicators of clinical progression in subjective cognitive decline. Understanding their combined effectiveness may reveal primary physiological mechanisms contributing to the dual decline of motor and cognition.

Self-reported practices, competence and difficulties towards palliative care among nurses: A cross-sectional study.

OBJECTIVE: Nurses' palliative care practice ability is the key to evaluating the quality of palliative care. This study aimed to identify the current situation of palliative care practices, competence and difficulties among nurses and determine whether difficulties play a mediating role between practices and competence. METHODS: A cross-sectional study was conducted. The online survey comprised demographics, the Palliative Care Self-Reported Practices Scale, the Palliative Care Nursing Self-competence Scale and the Palliative Care Difficulties Scale. Data were analysed by using descriptive statistics, univariate analysis, linear regression and mediation analysis. RESULTS: A total of 284 questionnaires were included for statistical analysis. The mean scores for practices, competence and difficulties were 67.81 (SD = 13.60), 124.28 (41.21) and 44.32 (12.68), respectively. There was a correlation between practices, competence and difficulties (p < 0.01). Competence and difficulties were independent predictors of practices (R2 adj  = 0.384, p < 0.001). Furthermore, difficulties mediated the relationship between practices and competence (b = 0.052, 95% confidence interval: 0.008-0.155). CONCLUSIONS: Continuous efforts should be made to enhance nurses' practices, competence and problem-solving abilities in palliative care. This study suggested further targeted education programmes, especially in special symptom management, interagency and multidisciplinary communication.

Activation of TGR5 promotes mitochondrial biogenesis in human aortic endothelial cells.

Impairment of mitochondrial biogenesis has been associated with vascular pathophysiology. The G-protein-coupled receptor (TGR5) is an important mediator of bile acid signaling and glucose metabolism. However, the effects of TGR5 on mitochondrial biogenesis in endothelial cells remain elusive. In this study, we found that activation of TGR5 using its specific agonist taurolithocholic acid (TLCA) promoted the expression of PGC-1α, a master regulator of mitochondrial biogenesis in human aortic endothelial cells (HAECs). Additionally, activation of TGR5 increased the expression of PGC-1α target genes, such as NRF1 and TFAM. Indeed, we found that TLCA treatment promoted mitochondrial biogenesis by increasing mitochondrial mass, mitochondrial-to-nuclear DNA (mtDNA/nDNA), COX-Ⅰ expression, and cytochrome c oxidase activity in HAECs. Notably, our results displayed that activation of TGR5 resulted in a functional gain in mitochondria by increasing the rate of respiration and ATP production. Mechanistically, we found that TLCA treatment activated the transcriptional factor CREB by inducing the phosphorylation of CREB at Ser133. Using the PKA/CREB inhibitor H89 abolished the effects of TLCA on PGC-1α, NRF1 and TFAM expression as well as the increase in mtDNA/nDNA and ATP production. These findings suggest that activation of TGR5 promoted mitochondrial biogenesis in endothelial cells, which is mediated by the CREB/PGC-1α signaling pathway.

Benefits and Challenges with Applying Unique Molecular Identifiers in Next Generation Sequencing to Detect Low Frequency Mutations.

Indexing individual template molecules with a unique identifier (UID) before PCR and deep sequencing is promising for detecting low frequency mutations, as true mutations could be distinguished from PCR errors or sequencing errors based on consensus among reads sharing same index. In an effort to develop a robust assay to detect from urine low-abundant bladder cancer cells carrying well-documented mutations, we have tested the idea first on a set of mock templates, with wild type and known mutants mixed at defined ratios. We have measured the combined error rate for PCR and Illumina sequencing at each nucleotide position of three exons, and demonstrated the power of a UID in distinguishing and correcting errors. In addition, we have demonstrated that PCR sampling bias, rather than PCR errors, challenges the UID-deep sequencing method in faithfully detecting low frequency mutation.

Early detection biomarkers for ovarian cancer.

Despite the widespread use of conventional and contemporary methods to detect ovarian cancer development, ovarian cancer remains a common and commonly fatal gynecological malignancy. The identification and validation of early detection biomarkers highly specific to ovarian cancer, which would permit development of minimally invasive screening methods for detecting early onset of the disease, are urgently needed. Current practices for early detection of ovarian cancer include transvaginal ultrasonography, biomarker analysis, or a combination of both. In this paper we review recent research on novel and robust biomarkers for early detection of ovarian cancer and provide specific details on their contributions to tumorigenesis. Promising biomarkers for early detection of ovarian cancer include KLK6/7, GSTT1, PRSS8, FOLR1, ALDH1, and miRNAs.

Combinatorial marking of cells and organelles with reconstituted fluorescent proteins.

Expression of GFP and other fluorescent proteins depends on cis-regulatory elements. Because these elements rarely direct expression to specific cell types, GFP production cannot always be sufficiently limited. Here we show that reconstitution of GFP, YFP, and CFP previously split into two polypeptides yields fluorescent products when coexpressed in C. elegans. Because this reconstitution involves two components, it can confirm cellular coexpression and identify cells expressing a previously uncharacterized promoter. By choosing promoters whose expression patterns overlap for a single cell type, we can produce animals with fluorescence only in those cells. Furthermore, when one partial GFP polypeptide is fused with a subcellularly localized protein or peptide, this restricted expression leads to the fluorescent marking of cellular components in a subset of cells.