WATCHFUL OBSERVATION VERSUS EARLY AORTIC VALVE REPLACEMENT FOR SYMPTOMATIC PATIENTS WITH LOW-GRADIENT SEVERE AORTIC STENOSIS AND PRESERVED EJECTION FRACTION

Brief Communications Arising: arising from X. Dong, B. Milholland & J. Vijg Nature 538, 257–259 (2016); doi:10.1038/nature19793. Comments by: Beer, J.A.A. de, Bardoutsos, A. & Janssen, F. (2017)

Cancer-Associated Splicing Variant of Tumor Suppressor AIMP2/p38: Pathological Implication in Tumorigenesis

Although ARS-interacting multifunctional protein 2 (AIMP2, also named as MSC p38) was first found as a component for a macromolecular tRNA synthetase complex, it was recently discovered to dissociate from the complex and work as a potent tumor suppressor. Upon DNA damage, AIMP2 promotes apoptosis through the protective interaction with p53. However, it was not demonstrated whether AIMP2 was indeed pathologically linked to human cancer. In this work, we found that a splicing variant of AIMP2 lacking exon 2 (AIMP2-DX2) is highly expressed by alternative splicing in human lung cancer cells and patient's tissues. AIMP2-DX2 compromised pro-apoptotic activity of normal AIMP2 through the competitive binding to p53. The cells with higher level of AIMP2-DX2 showed higher propensity to form anchorage-independent colonies and increased resistance to cell death. Mice constitutively expressing this variant showed increased susceptibility to carcinogen-induced lung tumorigenesis. The expression ratio of AIMP2-DX2 to normal AIMP2 was increased according to lung cancer stage and showed a positive correlation with the survival of patients. Thus, this work identified an oncogenic splicing variant of a tumor suppressor, AIMP2/p38, and suggests its potential for anti-cancer target

Phase II Study of Low-dose Paclitaxel and Cisplatin as a Second-line Therapy after 5-Fluorouracil/Platinum Chemotherapy in Gastric Cancer

This study was performed to evaluate the efficacy and toxicity of low-dose paclitaxel/cisplatin chemotherapy in patients with metastatic or recurrent gastric cancer that had failed 5-fluorouracil/platinum-based chemotherapy. Thirty-two patients with documented progression on or within 6 months after discontinuing 5-fluorouracil/platinum-based chemotherapy were enrolled. As a second-line treatment, paclitaxel (145 mg/m2) and cisplatin (60 mg/m2) was administered on day 1 every 3 weeks. Among 32 patients enrolled, 8 (25%) responded partially to paclitaxel/cisplatin, 8 (25%) had stable disease, and 14 (44%) had progressive disease. Two patients (6%) were not evaluable. The median time to progression (TTP) and overall survival for all patients were 2.9 months and 9.1 months, respectively. The most common hematologic toxicity was anemia (47%). Grade 3 neutropenia developed in three patients (9%), but no other grade 3/4 hematologic toxicity occurred. The most common non-hematologic toxicities were emesis (31%) and peripheral neuropathy (38%). Three cases (9%) of grade 3/4 emesis and 2 cases (6%) of grade 3 peripheral neuropathy developed. In conclusion, low-dose paclitaxel and cisplatin chemotherapy showed moderate activity with favorable toxicity profiles. However, relatively short TTP of this regimen warrants the development of more effective paclitaxel-based regimens other than combination with cisplatin in these patients as second-line therapies

Trajectories of Life Satisfaction and their Predictors among Korean Older Adults

Abstract Background Among older adults, life satisfaction (LS) correlates with health, mortality, and successful ageing. As various potential threats to LS tend to increase with advancing years, patterns of age-related changes in LS among older adults remain inconsistent. This study aimed to identify LS trajectories in older adults and the characteristics of individuals who experience them. Methods Large-scale, nationally representative, longitudinal data collected from 2005 to 2013 were analyzed for this study. The outcome measure was a summary of multidimensional domains influencing LS: health, finance, housing, neighbor relationships, and family relationships. Latent class growth models and logistic regression models were used to identify trajectory groups and their predictors, respectively. Results Within 3517 individuals aged 65 or older, five trajectories were identified across eight follow-up years: “low-stable” (TG1; n = 282; 8%), “middle-stable” (TG2; n = 1146; 32.6%), “improving” (TG3; n = 75; 2.1%), “upper middle-stable” (TG4; n = 1653; 47%), and “high” (TG5; n = 361; 10.3%). High trajectory individuals more frequently had higher education, financial security, good physical health, and good mental health than those in the stable, but less satisfied, groups. Similarly, compared to the largest group (upper middle-stable trajectory), individuals in the low-stable or middle-stable trajectory group not only had poorer physical and mental health but were more likely to be living alone, financially stressed, and residing in urban locations. Individuals with improving trajectory were younger and in poorer mental health at baseline compared to the upper middle-stable trajectory group. Conclusion Life satisfaction in the older follows distinct trajectories. For older adults, trajectories are stable over time and predictable, in part, from individual characteristics. Knowledge of these patterns is important for effective policy and program development

Trajectories of Life Satisfaction and their Predictors among Korean Older Adults

Abstract Background Among older adults, life satisfaction (LS) correlates with health, mortality, and successful ageing. As various potential threats to LS tend to increase with advancing years, patterns of age-related changes in LS among older adults remain inconsistent. This study aimed to identify LS trajectories in older adults and the characteristics of individuals who experience them. Methods Large-scale, nationally representative, longitudinal data collected from 2005 to 2013 were analyzed for this study. The outcome measure was a summary of multidimensional domains influencing LS: health, finance, housing, neighbor relationships, and family relationships. Latent class growth models and logistic regression models were used to identify trajectory groups and their predictors, respectively. Results Within 3517 individuals aged 65 or older, five trajectories were identified across eight follow-up years: “low-stable” (TG1; n = 282; 8%), “middle-stable” (TG2; n = 1146; 32.6%), “improving” (TG3; n = 75; 2.1%), “upper middle-stable” (TG4; n = 1653; 47%), and “high” (TG5; n = 361; 10.3%). High trajectory individuals more frequently had higher education, financial security, good physical health, and good mental health than those in the stable, but less satisfied, groups. Similarly, compared to the largest group (upper middle-stable trajectory), individuals in the low-stable or middle-stable trajectory group not only had poorer physical and mental health but were more likely to be living alone, financially stressed, and residing in urban locations. Individuals with improving trajectory were younger and in poorer mental health at baseline compared to the upper middle-stable trajectory group. Conclusion Life satisfaction in the older follows distinct trajectories. For older adults, trajectories are stable over time and predictable, in part, from individual characteristics. Knowledge of these patterns is important for effective policy and program development