Dual decline in subjective gait speed and domain-specific cognition is associated with higher risk of incident dementia in older Japanese adults: A 15-year age-specific cohort study.

OBJECTIVES: Dual decline in gait speed and cognition has been found to have higher dementia risk than no decline or pure decline. However, evidence from the Asian population is lacking. Therefore, we aimed to investigate the association of dual decline from age 65 to 70 years with late-life dementia in older Japanese adults with different personal characteristics. METHODS: Data were collected from an age-specific cohort study conducted in 482 Japanese 65-year-old adults. We investigated participant demographics, medical histories, lifestyles, subjective gait speed, and cognition at both 64/65 and 70/71 years old, and confirmed dementia until age of 85 years. Cox proportion hazard models were used to estimate the risk of dementia, with adjustments for covariates, and death was treated as a competing risk. RESULTS: After a mean follow-up period of 12.5-years, 111 participants developed dementia. Older adults with dual decline are more likely to have hyperlipidemia, diabetes, and smoking habits. And we found that dual decline in gait speed and domain-specific cognition was associated with a higher risk of dementia compared with no decline in most cognitive tests, with the highest risk observed for gait speed combined with memory (sub-distribution hazard ratio:3.89, 95 %, confidence intervals: [1.68-9.01]). However, significant differences only existed in men after stratification by sex. CONCLUSIONS: A dual decline in subjective gait speed and cognition may serve as a robust predictor of dementia over a decade prior to its onset, particularly in men. These findings highlighted the importance of screening for dual decline at an early age.

Construction of an EMT-related lncRNA prognostic signature for lung adenocarcinoma and functional verification of its hub gene LINC01615.

BACKGROUND: The epithelial-mesenchymal transition (EMT) plays a vital role in the progression of lung adenocarcinoma (LUAD). Long non-coding RNAs (lncRNAs) participate in the EMT process as an important regulatory factor and have the potential to serve as prognostic biomarkers. We aimed to construct a novel lncRNA prognostic signature for LUAD based on EMT-related lncRNAs, identify EMT-related hub lncRNA, and investigate its biological functions. METHODS: RNA-seq data, clinical and survival information were obtained from The Cancer Genome Atlas database. The EMT-related lncRNA prognostic signature (EMTscore) was constructed using the Least Absolute Shrinkage and Selection Operator Cox regression analysis. The efficiency of EMTscore in predicting the prognosis of LUAD was evaluated through the area under the time-dependent receiver operating characteristic (ROC) curves. The hub lncRNA of the prognostic signature was selected using a co-expression network map, and its effects on cell proliferation and metastasis were explored by in vitro experiments. RESULTS: We constructed a prognostic signature (EMTscore) containing 8 tumor-high expressed lncRNAs. The EMTscore performed well in predicting overall survival rates with AUC values of 0.708 at 5 years in the training set. EMTscore could independently predict the survival of LUAD, with HR = 4.011 (95% CI 2.430-6.622) in the multivariate Cox regression. Importantly, we identified LINC01615 as the hub lncRNA in the EMTscore and revealed that LINC01615 enhanced the proliferation, migration, and EMT of lung cancer cells. CONCLUSIONS: A new EMT-related lncRNA prognostic signature named EMTscore was developed, and LINC01615 was identified as the hub lncRNA of EMTscore. The hub lncRNA LINC01615 had an oncogenic biological function in LUAD.

Temporal change in the association between life satisfaction and functional decline with gender differences: an age-specific prospective cohort study.

BACKGROUND: Although life satisfaction (LS) has been shown to predict mortality, research studying the relationship between LS and functional decline is scarce. This study examined the association between LS and functional decline across four time points in young-old Japanese adults. METHODS: We analysed 1,899 community-dwelling 65-year-olds in this age-specific cohort study conducted between 2000 and 2005. The Life Satisfaction Index K was used to evaluate LS and was classified into quartiles. Functional decline was determined using the Japanese Long-Term Care Insurance (LTCI) system: 1) mild disability; 2) severe disability; 3) all-cause mortality; 4) mild or severe disability; 5) severe disability or death; 6) mild or severe disability, or death. Adjusted hazard ratios (HR) with 95% confidence intervals (CI) were calculated using the Cox proportional hazard model. The analyses were conducted in the 8th, 10th, 12th, and 14th years to assess the effect of LS on functional decline across time points. RESULTS: The impact of LS gradually weakened over time. In the 8th year (aged 72-73), a higher LS was associated with a lower risk of mild or severe disability among the women participants (adjusted HR [95% CI] = 0.30 [0.11-0.81]). However, the effect disappeared gradually (adjusted HR [95% CI] = 0.55 [0.27-1.14]) in the 10th year (aged 74-75), 0.72 (0.41-1.26) in the 12th year (aged 76-77), and 0.68 (0.41-1.14) in the 14th year (aged 78-79). This trend continued in severe disability or death (adjusted HR [95% CI] = 0.24 [0.06-0.70], 0.31 [0.11-0.76], 0.57 [0.28-1.14], and 0.60 [0.32-1.12]) and mild or severe disability, or death (adjusted HR [95% CI] = 0.30 [0.14-0.68], 0.46 [0.24-0.87], 0.67 [0.41-1.10], and 0.65 [0.42-1.02]) in the 8th, 10th, 12th, and 14th years, respectively. No statistically significant association was found among men at any time points or in any classification of outcomes. CONCLUSIONS: Higher LS scores in 65-year-old women were associated with a lower risk for functional decline in any combination of mild disability, severe disability, or death. Additionally, the effect of LS was observed to weaken over time. TRIAL REGISTRATION: This is not an intervention survey and does not require registration.

Changes in social activities and the occurrence and persistence of depressive symptoms: Do type and combination of social activities make a difference?

OBJECTIVE: We aimed to explore the association between changes in social activities and the occurrence/persistence of depressive symptoms and investigate the difference in effect sizes among the types and combinations of social activities. METHODS: The study adopted a valid 15-item Geriatric Depression Scale to assess depressive symptoms in 2480 community-dwelling adults aged 64/65 years. Changes in social-related, learning, and personal activities were classified into four categories: continued low frequency (CLF), increased frequency (IF), decreased frequency (DF), and continued regular frequency (CRF)1. Relative ratios (RRs) and 95% confidence intervals (95% CI) were calculated using a modified Poisson regression model. RESULTS: Those without depressive symptoms at baseline and who engaged in social-related (RRIF = 0.56 (0.39, 0.81), RRCRF = 0.55 (0.41, 0.74)), learning (RRIF = 0.63 (0.44, 0.89), RRCRF = 0.62 (0.46, 0.85)), and personal activities (RRIF = 0.37 (0.24, 0.57), RRCRF = 0.41 (0.30, 0.56)) at IF or CRF were less likely to develop depressive symptoms. Those with depressive symptoms at baseline, engaging in personal activities at IF (RR=0.67 (0.51, 0.87)) and CRF (RR= 0.80 (0.65-1.00)) were less likely to have persistent depressive symptoms. Participation in all three activities consistently at a regular frequency was inversely associated with the occurrence/persistence of depressive symptoms. CONCLUSIONS: The effect of personal activities was more manifest in preventing depressive symptoms than the other two kinds, regardless of depressive symptoms at baseline. Regularly engaging in a combination of all three activities at baseline and follow-up was associated with the occurrence and persistence of depressive symptoms.

Changes in behavioral activities and transition of depressive symptoms among younger-old community-dwelling adults during 6 years: An age-specific prospective cohort study.

OBJECTIVE: Regular engagement in behavioral activities plays a crucial role against depressive symptoms in older adults. This study aims to explore the relationship between behavioral activities and the temporal evolution of depressive symptoms. METHODS: We included community-dwelling Japanese adults aged 64 or 65 years with and without depressive symptoms enrolled in the New Integrated Suburban Seniority Investigation (NISSIN) project. Depressive symptoms at baseline and follow-up were assessed using the 15-item Geriatric Depression Scale. Behavioral activities were measured by self-reported questions. Risk ratios and 95% confidence intervals were calculated using modified Poisson regression, adjusting for relevant sociodemographic variables and health-related confounders. RESULTS: During the 6 year follow-up period, 139 (10.1%) without depressive symptoms at baseline developed such symptoms over time, while 174 (51.6%) with depressive symptoms improved to the point of these symptoms being absent. The participants without depressive symptoms at baseline and those who engaged in social activity or daily walking at a continued regular frequency (CRF) or an increased frequency (IF) and exercise habits at CRF were the least likely to have depressive symptoms onset at follow-up. There was no significant difference between the changes in behavioral activities and the improvement of depressive symptoms after controlling for confounders. Participants engaging in a greater variety of behavioral activities at CRF were less likely to experience a new onset of depressive symptoms. CONCLUSIONS: Consistent and regular participation in one or more behavioral activities was significantly associated with the onset of depressive symptoms in Japanese community-dwelling older adults.

Recent developments in mesoporous polydopamine-derived nanoplatforms for cancer theranostics.

Polydopamine (PDA), which is derived from marine mussels, has excellent potential in early diagnosis of diseases and targeted drug delivery owing to its good biocompatibility, biodegradability, and photothermal conversion. However, when used as a solid nanoparticle, the application of traditional PDA is restricted because of the low drug-loading and encapsulation efficiencies of hydrophobic drugs. Nevertheless, the emergence of mesoporous materials broaden our horizon. Mesoporous polydopamine (MPDA) has the characteristics of a porous structure, simple preparation process, low cost, high specific surface area, high light-to-heat conversion efficiency, and excellent biocompatibility, and therefore has gained considerable interest. This review provides an overview of the preparation methods and the latest applications of MPDA-based nanodrug delivery systems (chemotherapy combined with radiotherapy, photothermal therapy combined with chemotherapy, photothermal therapy combined with immunotherapy, photothermal therapy combined with photodynamic/chemodynamic therapy, and cancer theranostics). This review is expected to shed light on the multi-strategy antitumor therapy applications of MPDA-based nanodrug delivery systems.

Early kidney injury predicts disease progression in patients with COVID-19: a cohort study.

BACKGROUND: The receptor of severe respiratory syndrome coronavirus 2 (SARS-CoV-2), angiotensin-converting enzyme 2, is more abundant in kidney than in lung tissue, suggesting that kidney might be another important target organ for SARS-CoV-2. However, our understanding of kidney injury caused by Coronavirus Disease 2019 (COVID-19) is limited. This study aimed to explore the association between kidney injury and disease progression in patients with COVID-19. METHODS: A retrospective cohort study was designed by including 2630 patients with confirmed COVID-19 from Huoshenshan Hospital (Wuhan, China) from 1 February to 13 April 2020. Kidney function indexes and other clinical information were extracted from the electronic medical record system. Associations between kidney function indexes and disease progression were analyzed using Cox proportional-hazards regression and generalized linear mixed model. RESULTS: We found that estimated glomerular filtration rate (eGFR) and creatinine clearance (Ccr) decreased in 22.0% and 24.0% of patients with COVID-19, respectively. Proteinuria was detected in 15.0% patients and hematuria was detected in 8.1% of patients. Hematuria (HR 2.38, 95% CI 1.50-3.78), proteinuria (HR 2.16, 95% CI 1.33-3.51), elevated baseline serum creatinine (HR 2.84, 95% CI 1.92-4.21) and blood urea nitrogen (HR 3.54, 95% CI 2.36-5.31), and decrease baseline eGFR (HR 1.58, 95% CI 1.07-2.34) were found to be independent risk factors for disease progression after adjusted confounders. Generalized linear mixed model analysis showed that the dynamic trajectories of uric acid was significantly related to disease progression. CONCLUSION: There was a high proportion of early kidney function injury in COVID-19 patients on admission. Early kidney injury could help clinicians to identify patients with poor prognosis at an early stage.

Fasting plasma glucose and glucose fluctuation are associated with COVID-19 prognosis regardless of pre-existing diabetes.

AIMS: We aimed to investigate the role of Fasting Plasma Glucose (FPG) and glucose fluctuation in the prognosis of COVID-19 patients stratified by pre-existing diabetes. METHODS: The associations of FPG and glucose fluctuation indexes with prognosis of COVID-19 in 2,642 patients were investigated by multivariate Cox regression analysis. The primary outcome was in-hospital mortality; the secondary outcome was disease progression. The longitudinal changes of FPG over time were analyzed by the latent growth curve model in COVID-19 patients stratified by diabetes and severity of COVID-19. RESULTS: We found FPG as an independent prognostic factor of overall survival after adjustment for age, sex, diabetes and severity of COVID-19 at admission (HR: 1.15, 95% CI: 1.06-1.25, P = 1.02 × 10-3). Multivariate logistic regression analysis indicated that the standard deviation of blood glucose (SDBG) and largest amplitude of glycemic excursions (LAGE) were also independent risk factors of COVID-19 progression (P = 0.03 and 0.04, respectively). The growth trajectory of FPG over the first 3 days of hospitalization was steeper in patients with critical COVID-19 in comparison to moderate patients. CONCLUSIONS: Hyperglycemia and glucose fluctuation were adverse prognostic factors of COVID-19 regardless of pre-existing diabetes. This stresses the importance of glycemic control in addition to other therapeutic management.

Inflammation characteristics and anti-inflammation treatment with tocilizumab of severe/critical COVID-19 patients: A retrospective cohort study.

The efficacy of tocilizumab on the prognosis of severe/critical COVID-19 patients is still controversial so far. We aimed to delineate the inflammation characteristics of severe/critical COVID-19 patients and determine the impact of tocilizumab on hospital mortality. Here, we performed a retrospective cohort study which enrolled 727 severe or critical inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Huoshenshan Hospital (Wuhan, China), among which 50 patients received tocilizumab. This study confirmed that most recovered patients manifested relatively normal inflammation levels at admission, whereas most of the deceased cases presented visibly severe inflammation at admission and even progressed into extremely aggravated inflammation before their deaths, proved by some extremely high concentrations of interleukin-6, procalcitonin, C-reactive protein and neutrophil count. Moreover, based on the Cox proportional-hazards models before or after propensity score matching, we demonstrated that tocilizumab treatment could lessen mortality by gradually alleviating excessive inflammation and meanwhile continuously enhancing the levels of lymphocytes within 14 days for severe/critical COVID-19 patients, indicating potential effectiveness for treating COVID-19.

Risk stratification scores for hospitalization duration and disease progression in moderate and severe patients with COVID-19.

BACKGROUND: During outbreak of Coronavirus Disease 2019 (COVID-19), healthcare providers are facing critical clinical decisions based on the prognosis of patients. Decision support tools of risk stratification are needed to predict outcomes in patients with different clinical types of COVID-19. METHODS: This retrospective cohort study recruited 2425 patients with moderate or severe COVID-19. A logistic regression model was used to select and estimate the factors independently associated with outcomes. Simplified risk stratification score systems were constructed to predict outcomes in moderate and severe patients with COVID-19, and their performances were evaluated by discrimination and calibration. RESULTS: We constructed two risk stratification score systems, named as STPCAL (including significant factors in the prediction model: number of clinical symptoms, the maximum body temperature during hospitalization, platelet count, C-reactive protein, albumin and lactate dehydrogenase) and TRPNCLP (including maximum body temperature during hospitalization, history of respiratory diseases, platelet count, neutrophil-to-lymphocyte ratio, creatinine, lactate dehydrogenase, and prothrombin time), to predict hospitalization duration for moderate patients and disease progression for severe patients, respectively. According to STPCAL score, moderate patients were classified into three risk categories for a longer hospital duration: low (Score 0-1, median = 8 days, with less than 20.0% probabilities), intermediate (Score 2-6, median = 13 days, with 30.0-78.9% probabilities), high (Score 7-9, median = 19 days, with more than 86.5% probabilities). Severe patients were stratified into three risk categories for disease progression: low risk (Score 0-5, with less than 12.7% probabilities), intermediate risk (Score 6-11, with 18.6-69.1% probabilities), and high risk (Score 12-16, with more than 77.9% probabilities) by TRPNCLP score. The two risk scores performed well with good discrimination and calibration. CONCLUSIONS: Two easy-to-use risk stratification score systems were built to predict the outcomes in COVID-19 patients with different clinical types. Identifying high risk patients with longer stay or poor prognosis could assist healthcare providers in triaging patients when allocating limited healthcare during COVID-19 outbreak.

Modern urbanization has reshaped the bacterial microbiome profiles of house dust in domestic environments.

BACKGROUND: The prevalence of allergy and other common chronic diseases is higher in developed than developing countries, and higher in urban than rural regions. Urbanization through its modification of environmental microbiomes may play a predominant role in the development of these conditions. However, no studies have been conducted to compare the microbiome in house dust among areas with different urbanization levels. METHODS: House dust from Xinxiang rural area (XR, n = 74), Xinxiang urban area (XU, n = 33), and Zhengzhou urban area (ZU, n = 32) in central China, and from Australia (AU, n = 58 [with pets AUP, n = 15, without pets AUNP, n = 43]) were collected during a summer season in China and Australia. High-throughput sequencing of 16S rDNA was employed to profile house dust bacterial communities. RESULTS: Settled dust collected in China was dominant with 2 bacterial phyla: Proteobacteria and Actinobacteria, while floor dust collected in Australia had a higher proportion of phylum Proteobacteria, Firmicutes, and Actinobacteria. XR dust samples presented higher bacterial richness and diversity compared with XU or ZU samples. Urbanization level (r2 = 0.741 P < 0.001) had a significant correlation with the distribution of house dust bacterial community. At the genus level, there was a positive correlation (r coefficient > 0.5) between urbanization level and bacterial genera Streptococcus, Bartonella, Staphylococcus, Pseudomonas, Acinetobacter, Bacteroides, Corynebacterium_1 , and Enhydrobacter and a negative correlation (r coefficient < -0.5) with Rhodanobacter. CONCLUSION: There was a significant difference in house dust microbiota among different urbanization areas. The areas with a lower urbanization level presented higher dust-borne bacterial richness and diversity. Modern urbanization has a significant influence on the bacterial microbiome profiles of indoor dust.

House dust microbiome and human health risks.

People spend a lot of time indoors and the indoor microbiome is a major part of the environment that we are exposed to. However, awareness of the exposure to the indoor microbiome and its health effects remains poor. Outdoor environment (soil and air), indoor sources (ventilation, dampness and building materials), human occupants, and pets compose the indoor microbial community. It has been estimated that up to 500-1000 different species can be present in house dust. House dust is a major source and reservoir of indoor microbiome, which influences human microbiome and determines health and disease. Herein, we review the origins and the components of the fungal and bacterial communities in house dust and their possible effect on human health, in particular on allergic disorders, intestinal microbiome, and immune responses. We expect to lay a solid foundation for the further study on the mechanisms of how the house dust microbes interact with the host microbiome and the human immune system.

An asymmetric approach to bicyclo[2.2.1]heptane-1-carboxylates via a formal [4 + 2] cycloaddition reaction enabled by organocatalysis.

An organocatalytic formal [4 + 2] cycloaddition reaction has been realized that permits rapid access to a wide range of bicyclo[2.2.1]heptane-1-carboxylates in a highly enantioselective manner from simple starting materials under mild and operationally simple conditions.