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1.
Eur J Ageing ; 19(4): 1571-1585, 2022 12.
Article in English | MEDLINE | ID: mdl-36506680

ABSTRACT

Meeting the needs of acute geriatric patients is often challenging, and although evidence shows that older patients need tailored care, it is still unclear which interventions are most appropriate. The objective of this study is to systematically evaluate the hospital-wide acute geriatric models compared with conventional pathways. The design of the study includes hospital-wide geriatric-specific models characterized by components including patient-centered care, frequent medical review, early rehabilitation, early discharge planning, prepared environment, and follow-up after discharge. Primary and secondary outcomes were considered, including functional decline, activities of daily living (ADL), length-of-stay (LoS), discharge destination, mortality, costs, and readmission. A systematic review and meta-analysis were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A total of 20 studies reporting on 15 trials and acutely admitted patients with an average age of 79, complex conditions and comorbidities to acute geriatric-specific pathways (N = 13,595) were included. Geriatric-specific models were associated with lower costs (weighted mean difference, WMD = - $174.98, 95% CI = -$332.14 to - $17.82; P = 0.03), and shorter LoS (WMD = - 1.11, 95% CI = - 1.39 to - 0.83; P < 0.001). No differences were found in functional decline, ADL, mortality, case fatalities, discharge destination, or readmissions. Geriatric-specific models are valuable for improving patient and system-level outcomes. Although several interventions had positive results, further research is recommended to study hospital-wide geriatric-specific models. Supplementary Information: The online version contains supplementary material available at 10.1007/s10433-022-00743-w.

2.
Nat Commun ; 13(1): 1618, 2022 03 25.
Article in English | MEDLINE | ID: mdl-35338148

ABSTRACT

Loss of expression or activity of the tumor suppressor PTEN acts similarly to an activating mutation in the oncogene PIK3CA in elevating intracellular levels of phosphatidylinositol (3,4,5)-trisphosphate (PIP3), inducing signaling by AKT and other pro-tumorigenic signaling proteins. Here, we analyze sequence data for 34,129 colorectal cancer (CRC) patients, capturing 3,434 PTEN mutations. We identify specific patterns of PTEN mutation associated with microsatellite stability/instability (MSS/MSI), tumor mutational burden (TMB), patient age, and tumor location. Within groups separated by MSS/MSI status, this identifies distinct profiles of nucleotide hotspots, and suggests differing profiles of protein-damaging effects of mutations. Moreover, discrete categories of PTEN mutations display non-identical patterns of co-occurrence with mutations in other genes important in CRC pathogenesis, including KRAS, APC, TP53, and PIK3CA. These data provide context for clinical targeting of proteins upstream and downstream of PTEN in distinct CRC cohorts.


Subject(s)
Colorectal Neoplasms , PTEN Phosphohydrolase , Class I Phosphatidylinositol 3-Kinases/genetics , Colorectal Neoplasms/pathology , DNA Mutational Analysis , Humans , Microsatellite Instability , Mutation , PTEN Phosphohydrolase/genetics , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/metabolism
3.
Chemistry ; 16(21): 6187-92, 2010 Jun 01.
Article in English | MEDLINE | ID: mdl-20432413

ABSTRACT

We have developed an analytical assay to detect the enzymatic activity of acetylcholine esterase and alkaline phosphatase based on the generation of quantum dots by enzymatic products. Acetylcholine esterase converts acetylthiocholine into thiocholine. The latter enhances the rate of decomposition of sodium thiosulfate into H(2)S, which in the presence of cadmium sulfate yields CdS quantum dots showing a time dependent exponential growth, typical of autocatalytic processes. This assay was also applied to detect acetylcholine esterase inhibitors. Alkaline phosphatase hydrolyzes thiophosphate and yields H(2)S, which instantly reacts with Cd(2+) to give CdS quantum dots. The formation of CdS quantum dots in both reactions was followed by fluorescence spectroscopy and showed dependence on the concentration of enzyme and substrate.


Subject(s)
Acetylcholinesterase/metabolism , Alkaline Phosphatase/metabolism , Quantum Dots , Biocatalysis , Cadmium Compounds/chemistry , Hydrogen Sulfide/metabolism , Sulfates/chemistry
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