This study examined the association between dietary patterns and the development of frailty during 4-, 8-, 12-year follow-up periods in the population-based Taiwan Study. We used the data of an ...elderly population aged 53 years and over (n = 3486) from four waves of the Taiwan Longitudinal Study on Aging. Frailty was identified by using the modified Fried criteria and the values were summed to derive a frailty score. We applied reduced rank regression to determine dietary patterns, which were divided into tertiles (healthy, general, and unhealthy dietary pattern). We used multinomial logistic regression models to assess the association between dietary patterns and the risk of frailty. The healthy dietary pattern was characterized by a higher intake of antioxidant drinks (tea), energy-rich foods (carbohydrates, e.g., rice, noodles), protein-rich foods (fish, meat, seafood, and eggs), and phytonutrient-rich foods (fruit and dark green vegetables). Compared with the healthy pattern, the unhealthy dietary pattern showed significant cross-sectional, short-term, medium-term, and long-term associations with a higher prevalence of frailty (odds ratios (OR) 2.74; 95% confidence interval (CI) 1.94–3.87, OR 2.55; 95% CI 1.67–3.88, OR 1.66; 95% CI 1.07–2.57, and OR 2.35; 95% CI 1.27–4.34, respectively). Our findings support recommendations to increase the intake of antioxidant drinks, energy-rich foods, protein-rich foods, and phytonutrient-rich foods, which were associated with a non-frail status. This healthy dietary pattern can help prevent frailty over time in elderly people.
OBJECTIVES: To examine the combined effect of healthy behaviors on the development of functional disability in an elderly cohort.
DESIGN: Prospective cohort study.
SETTING: Taiwan Longitudinal Study ...in Aging from 1989, 1993, 1996, 1999, and 2003.
PARTICIPANTS: A national sample of 1,940 men and 1,247 women aged 60 and older without functional disability at baseline.
MEASUREMENTS: Functional disability was defined as difficulty with activities of daily living: taking a bath or walking 200 to 300 m. Time to functional disability was the age at midpoint between the first occurrence of disability onset in the survey year and prior survey year. Considering that the onset of disability is probably a precursor of death, for those who died without disability, time to disability onset was set at the midpoint between the last follow‐up and death year. Four healthy behaviors were measured: not smoking, moderate alcohol consumption, regular exercise, and sleeping 6 to 8 hours per day. A Cox proportional hazards model with time‐dependent covariates was used to analyze the association between age at the first functional disability and prior healthy behavior, after controlling for sex, time‐varying disease status, marital status, and education.
RESULTS: Healthy behaviors were linked to the onset of functional disability. Participants who performed one or more healthy behaviors were 15% to 75% less likely to be disabled than those who performed none.
CONCLUSION: In the population studied, healthy behaviors were associated with lower incidence of functional disability. As the number of healthy behaviors increased, the likelihood of disability decreased.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Among patients with chronic obstructive pulmonary disease (COPD), some have features of both asthma and COPD-a condition categorized as asthma-COPD overlap (ACO). Our aim was to determine whether ...asthma- or COPD-related microRNAs (miRNAs) play a role in the pathogenesis of ACO.
A total of 22 healthy subjects and 27 patients with ACO were enrolled. We selected 6 miRNAs that were found to correlate with COPD and asthma. The expression of miRNAs and target genes was analyzed using quantitative reverse-transcriptase polymerase chain reaction. Cell apoptosis and intracellular reactive oxygen species production were evaluated using flow cytometry. In vitro human monocytic THP-1 cells and primary normal human bronchial epithelial (NHBE) cells under stimuli with cigarette smoke extract (CSE) or ovalbumin (OVA) allergen or both were used to verify the clinical findings.
We identified the upregulation of miR-125b-5p in patients with ACO and in THP-1 cells stimulated with CSE plus OVA allergen. We selected 16 genes related to the miR-125b-5p pathway and found that IL6R and TRIAP1 were both downregulated in patients with ACO and in THP-1 cells stimulated with CSE plus OVA. The percentage of late apoptotic cells increased in the THP-1 cell culture model when stimulated with CSE plus OVA, and the effect was reversed by transfection with miR-125b-5p small interfering RNA (siRNA). The percentage of reactive oxygen species-producing cells increased in the NHBE cell culture model when stimulated with CSE plus OVA, and the effect was reversed by transfection with miR-125b-5p siRNA. In NHBE cells, siRNA transfection reversed the upregulation of STAT3 under CSE+OVA stimulation.
Our study revealed that upregulation of miR-125b-5p in patients with ACO mediated late apoptosis in THP-1 cells and oxidative stress in NHBE cells via targeting IL6R and TRIAP1. STAT3 expression was also regulated by miR-125b-5p.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The current coronavirus disease 2019 (COVID-19) pandemic has caused significant challenges throughout the world and a rapid, reliable diagnostic test is in high demand. Real-time reverse ...transcription polymerase chain reaction (RT-PCR) was one of the most quickly established methods of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection and is considered to be the gold standard. In this report, we share our experience of using two different testing platforms: the cobas 6800 SARS-CoV-2 test, an automated system that was recently granted Emergency Use Authorization by the FDA, and a laboratory-developed test based on the protocol from the Taiwan Centers for Disease Control (CDC). There was an overall 96.2% agreement between the two platforms. However, the positive agreement between the two platforms was only 80.0%. We found 3 instances of discordance between the two systems and this emphasized the need for timely diagnosis with a reliable testing platform.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Controversy exists in previous studies on macrophage M1/M2 polarization in chronic obstructive pulmonary disease (COPD). We hypothesized that formyl peptide receptor (FPR), a marker of efferocytosis ...and mediator of M1/M2 polarization, may be involved in the development of COPD.
We examined FPR 1/2/3 expressions of blood M1/M2a monocyte, neutrophil, natural killer (NK) cell, NK T cell, T helper (Th) cell, and T cytotoxic (Tc) cell by flowcytometry method in 40 patients with cigarette smoking-related COPD and 16 healthy non-smokers. Serum levels of five FPR ligands were measured by ELISA method.
The COPD patients had lower M2a percentage and higher percentages of NK, NK T, Th, and Tc cells than the healthy non-smokers. FPR2 expressions on Th/Tc cells, FPR3 expressions of M1, M2a, NK, NK T, Th, and Tc cells, and serum annexin A1 (an endogenous FPR2 ligand) levels were all decreased in the COPD patients as compared with that in the healthy non-smokers. FPR1 expression on neutrophil was increased in the COPD patient with a high MMRC dyspnea scale, while FPR2 expression on neutrophil and annexin A1 were both decreased in the COPD patients with a history of frequent moderate exacerbation (≥ 2 events in the past 1 year). In 10 COPD patients whose blood samples were collected again after 1-year treatment, M2a percentage, FPR3 expressions of M1/NK/Th cells, FPR2 expression on Th cell, and FPR1 expression on neutrophil were all reversed to normal, in parallel with partial improvement in small airway dysfunction.
Our findings provide evidence for defective FPR2/3 and annexin A1 expressions that, associated with decreased M2a polarization, might be involved in the development of cigarette smoking induced persistent airflow limitation in COPD.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Nontuberculous mycobacterial lung disease (NTM-LD) prevalence has been increasing over the recent decades. Numerous host factors are associated with NTM-LD development, including susceptible ...phenotypes such as ciliary defect and lung structural change, pulmonary clearance defect with poor clearance of secretions, and immune suppression. Specifically, regarding the susceptible host phenotypes without clear pathogenesis, a slender body, pectus excavatum, and postmenopausal female status are common. Also, decreased host immunity to NTM, especially T helper 1 cell responses is frequently observed. Even so, the underlying mechanisms remain unclear and relevant large-scale studies are lacking. Infections due to host genetics associated defects are mostly untreatable but rare in Asia, particularly Taiwan. Nevertheless, some risks for NTM-LD are controllable over disease progression. We suggest that clinicians first manage host factors and deal with the controllable characteristics of NTM-LD, followed by optimizing anti-NTM treatment. Further researches focusing on NTM-LD pathogenesis, especially the host–NTM interaction may advance understanding the nature of the disease and develop efficient therapeutic regimens.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Sepsis-induced immune dysfunction ranging from cytokines storm to immunoparalysis impacts outcomes. Monitoring immune dysfunction enables better risk stratification and mortality prediction and is ...mandatory before widely application of immunoadjuvant therapies. We aimed to develop and validate a scoring system according to patients' immune dysfunction status for 28-day mortality prediction.
A prospective observational study from a cohort of adult sepsis patients admitted to ICU between August 2013 and June 2016 at Kaohsiung Chang Gung Memorial Hospital in Taiwan. We evaluated immune dysfunction status through measurement of baseline plasma Cytokine levels, Monocyte human leukocyte-DR expression by flow cytometry, and stimulated immune response using post LPS stimulated cytokine elevation ratio. An immune dysfunction score was created for 28-day mortality prediction and was validated.
A total of 151 patients were enrolled. Data of the first consecutive 106 septic patients comprised the training cohort, and of other 45 patients comprised the validation cohort. Among the 106 patients, 21 died and 85 were still alive on day 28 after ICU admission. (mortality rate, 19.8%). Independent predictive factors revealed via multivariate logistic regression analysis included segmented neutrophil-to-monocyte ratio, granulocyte-colony stimulating factor, interleukin-10, and monocyte human leukocyte antigen-antigen D-related levels, all of which were selected to construct the score, which predicted 28-day mortality with area under the curve of 0.853 and 0.789 in the training and validation cohorts, respectively.
The immune dysfunction scoring system developed here included plasma granulocyte-colony stimulating factor level, interleukin-10 level, serum segmented neutrophil-to-monocyte ratio, and monocyte human leukocyte antigen-antigen D-related expression appears valid and reproducible for predicting 28-day mortality.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Autophagy is a catabolic process that recycles damaged organelles and acts as a pro-survival mechanism, but little is known about autophagy dysfunction and epigenetic regulation in patients with ...obstructive sleep apnea (OSA).
Protein/gene expressions and DNA methylation levels of the autophagy-related genes (ATG) were examined in blood leukocytes from 64 patients with treatment-naïve OSA and 24 subjects with primary snoring (PS).
LC3B protein expression of blood monocytes, and ATG5 protein expression of blood neutrophils were decreased in OSA patients versus PS subjects, while p62 protein expression of cytotoxic T cell was increased, particularly in those with nocturia. ATG5, ULK1, and BECN1 gene expressions of peripheral blood mononuclear cells were decreased in OSA patients versus PS subjects. LC3B gene promoter regions were hypermethylated in OSA patients, particularly in those with excessive daytime sleepiness, while ATG5 gene promoter regions were hypermethylated in those with morning headache or memory impairment. LC3B protein expression of blood monocytes and DNA methylation levels of the LC3B gene promoter region were negatively and positively correlated with apnea hyponea index, respectively. In vitro intermittent hypoxia with re-oxygenation exposure to human THP-1/HUVEC cell lines resulted in LC3B/ATG5/ULK1/BECN1 down-regulations and p62 up-regulation along with increased apoptosis and oxidative stress, while rapamycin and umbilical cord-mesenchymal stem cell treatment reversed these abnormalities through de-methylation of the ATG5 gene promoter.
Impaired autophagy activity in OSA patients was regulated by aberrant DNA methylation, correlated with clinical phenotypes, and contributed to increased cell apoptosis and oxidative stress. Autophagy enhancers may be novel therapeutics for OSA-related neurocognitive dysfunction.
Liver metastasis has been found to affect outcome in prostate cancer and colorectal cancer, but its role in lung cancer is unclear. The current study aimed to evaluate the impact of de novo liver ...metastasis (DLM) on stage IV non-small cell lung cancer (NSCLC) outcomes and to examine whether tyrosine kinase inhibitors (TKI) reverse poor prognosis in patients with DLM and epidermal growth factor receptor (EGFR)-mutant NSCLC. Among 1392 newly diagnosed NSCLC patients, 490 patients with stage IV disease treated between November 2010 and March 2014 at Kaohsiung Chang Gung Memorial Hospital were included. Patients were divided into two groups according to DLM status. There were 75 patients in the DLM group and 415 patients in the non-DLM group. The DLM group included more patients with bone metastasis, fewer patients with a lymphocyte-to-monocyte ratio (LMR) > 3.1, and fewer patients with pleural metastasis. In the DLM group, Eastern Cooperative Oncology Group performance status 3-4 and LMR ≦3.1 were associated with poor outcome. In patients without DLM, overall survival (OS) was longer in patients with EGFR-mutant NSCLC than in those without (20.2 vs. 7.3 months, p < 0.001). Among DLM patients, OS was similar between the EGFR-mutant and wild-type EGFR tumor subgroups (11.9 vs. 7.7 months, p = 0.155). We found that DLM was a significant poor prognostic factor in the EGFR-mutant patients treated with EGFR-TKIs, whereas DLM did not affect the prognosis of EGFR-wild-type patients.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
The aim of the study was to assess programmed death‐ligand‐1 (PD‐L1) expression in different histological types and gene mutation status of patients with non‐small cell lung cancer ...(NSCLC).
Methods
A total of 4062 pathology‐confirmed lung cancer patients were retrospectively screened at Kaohsiung Chang Gung Memorial Hospital from November 2010 to June 2017. There were 699 NSCLC patients with confirmed PD‐L1 expression level retrospectively enrolled for analysis.
Results
There was a trend of higher PD‐L1 expression in squamous cell carcinoma and adenosquamous cell carcinoma than in adenocarcinoma (p = 063). Significant higher PD‐L1 expression in EGFR wild‐type was noted (p < 0.001). No significant differences in PD‐L1 expression were found between ALK wild‐ and mutant types, but there seem was a trend of high PD‐L1 level noted in ALK mutation patients (p = 0.069). In EGFR mutation patients, a higher time to treatment failure (TTF) duration was observed in no PD‐L1 expression (p = 0.011). Longer tumor tissue storage time correlated with lower PD‐L1 expression in lung cancer (p < 0.001 for linear trend).
Conclusions
There were a trend or significant differences in PD‐L1 expression between different histological types in NSCLC, different EGFR and ALK status, and different tumor tissue storage time. A higher survival benefit was observed in no PD‐L1 expression than with PD‐L1 expression in adenocarcinoma, EGFR and ALK mutation patients. We recommend that PD‐L1 assay should be performed as early as possible if tissue is available.
A trend or significant differences in PD‐L1 expression between different histologic types in NSCLC, different EGFR status, and different ALK status, and different tumor tissue storage time. A higher survival benefit (TTF or OS) was observed in no PD‐L1 expression than with PD‐L1 expression in adenocarcinoma, EGFR mutation, and ALK mutation patients. PD‐L1 assay should be performed as early as possible if tissue is available.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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