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1.
Am J Pathol ; 194(6): 1078-1089, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38417697

ABSTRACT

Ferroptosis is a new form of cell death characterized by iron-dependent lipid peroxidation. Whether ferroptosis is involved in retinal microvascular dysfunction under diabetic condition is not known. Herein, the expression of ferroptosis-related genes in patients with proliferative diabetic retinopathy and in diabetic mice was determined with quantitative RT-PCR. Reactive oxygen species, iron content, lipid peroxidation products, and ferroptosis-associated proteins in the cultured human retinal microvascular endothelial cells (HRMECs) and in the retina of diabetic mice were examined. The association of ferroptosis with the functions of endothelial cells in vitro was evaluated. After administration of ferroptosis-specific inhibitor, Fer-1, the retinal microvasculature in diabetic mice was assessed. Characteristic changes of ferroptosis-associated markers, including glutathione peroxidase 4, ferritin heavy chain 1, long-chain acyl-CoA synthetase 4, transferrin receptor protein 1, and cyclooxygenase-2, were detected in the retinal fibrovascular membrane of patients with proliferative diabetic retinopathy, cultured HRMECs, and the retina of diabetic mice. Elevated levels of reactive oxygen species, lipid peroxidation, and iron content were found in the retina of diabetic mice and in cultured HRMECs. Ferroptosis was found to be associated with HRMEC dysfunction under high-glucose condition. Inhibition of ferroptosis with specific inhibitor Fer-1 in diabetic mice significantly reduced the severity of retinal microvasculopathy. Ferroptosis contributes to microvascular dysfunction in diabetic retinopathy, and inhibition of ferroptosis might be a promising strategy for the therapy of early-stage diabetic retinopathy.


Subject(s)
Diabetic Retinopathy , Ferroptosis , Reactive Oxygen Species , Diabetic Retinopathy/pathology , Diabetic Retinopathy/metabolism , Animals , Humans , Mice , Male , Reactive Oxygen Species/metabolism , Endothelial Cells/metabolism , Endothelial Cells/pathology , Diabetes Mellitus, Experimental/pathology , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/metabolism , Lipid Peroxidation , Mice, Inbred C57BL , Microvessels/pathology , Microvessels/metabolism , Iron/metabolism , Retinal Vessels/metabolism , Retinal Vessels/pathology
2.
Redox Biol ; 70: 103064, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38320455

ABSTRACT

Amyloid-beta (Aß) is a key factor in the onset and progression of Alzheimer's disease (AD). Selenium (Se) compounds show promise in AD treatment. Here, we revealed that selenoprotein K (SELENOK), a selenoprotein involved in immune regulation and potentially related to AD pathology, plays a critical role in microglial immune response, migration, and phagocytosis. In vivo and in vitro studies corroborated that SELENOK deficiency inhibits microglial Aß phagocytosis, exacerbating cognitive deficits in 5xFAD mice, which are reversed by SELENOK overexpression. Mechanistically, SELENOK is involved in CD36 palmitoylation through DHHC6, regulating CD36 localization to microglial plasma membranes and thus impacting Aß phagocytosis. CD36 palmitoylation was reduced in the brains of patients and mice with AD. Se supplementation promoted SELENOK expression and CD36 palmitoylation, enhancing microglial Aß phagocytosis and mitigating AD progression. We have identified the regulatory mechanisms from Se-dependent selenoproteins to Aß pathology, providing novel insights into potential therapeutic strategies involving Se and selenoproteins.


Subject(s)
Alzheimer Disease , CD36 Antigens , Microglia , Selenoproteins , Animals , Humans , Mice , Alzheimer Disease/genetics , Alzheimer Disease/metabolism , Amyloid beta-Peptides/metabolism , Disease Models, Animal , Lipoylation , Mice, Transgenic , Microglia/metabolism , Phagocytosis , Selenoproteins/genetics , Selenoproteins/metabolism , CD36 Antigens/metabolism
3.
ACS Appl Mater Interfaces ; 15(31): 37554-37562, 2023 Aug 09.
Article in English | MEDLINE | ID: mdl-37522843

ABSTRACT

Mg3(Sb1-xBix)2 alloy has been extensively studied in the last 5 years due to its exceptional thermoelectric (TE) performance. The absence of accurate force field for inorganic alloy compounds presents great challenges for computational studies. Here, we explore the atomic microstructure, thermal, and elastic properties of the Mg3(Sb1-xBix)2 alloy at different solution concentrations through atomic simulations with a highly accurate machine learning interatomic potential (ML-IAP). We find atomic local ordering in the optimized structure with the Bi-Bi pair inclined to join adjacent layers and Sb-Sb pair preferring to stay within the same layer. The thermal conductivity changes with the solution concentrations can be correctly predicted through ML-IAP-based molecular dynamics simulations. Spectral thermal conductance analysis shows that the continuous movement of low-frequency peak to high frequency is responsible for the reduction of the thermal conductivity upon alloying. Elastic calculations reveal that similar to the thermal conductivity, solid solution alloying can reduce the overall elastic properties at both Mg3Sb2 and Mg3Bi2 ends, while anisotropic behavior is clearly observed with linear interpolation relationship upon alloying along the interlayer direction and nonlinearity along the intralayer direction. Although the atomic local ordering shows little effects on the properties of the Mg3(Sb1-xBix)2 alloy with only two alloying elements, it possesses potential important impacts on multiprincipal element inorganic TE alloys. This work provides a recipe for computational studies on the TE alloy systems and thus can accelerate the discovery and optimization of TE materials with high TE performance.

4.
Metallomics ; 15(4)2023 04 03.
Article in English | MEDLINE | ID: mdl-36921994

ABSTRACT

Selenoprotein K (SELENOK) is one of the endoplasmic reticulum (ER) proteins that mainly functions in the regulation of ER stress, calcium flux, and antioxidant defense. Reactive oxygen species (ROS) is one of the key indicators of ferroptosis, and SELENOK inhibition could disrupt ROS balance, and consequently might cause ferroptosis. However, there are no previous studies about the mechanism of SELENOK in ferroptosis by regulating ROS. In this study, we report the effect of SELENOK inhibition on cell proliferation, viability, iron recycling-associated proteins, ROS, antioxidant enzymes, and lipid peroxidation of cervical cancer cells (HeLa cells). The results showed that ROS levels and iron-dependent lipid peroxidation were significantly enhanced, whereas cell viability and proliferation were significantly downregulated, and resulted in marked reductions in tumor size after SELENOK knockdown. SELENOK knockdown also caused steep decreases in glutathione peroxidase 4/glutathione levels and deterioration in ROS scavenging ability, and exacerbated ferroptosis in HeLa cells. Our findings elucidated that SELENOK knockdown could shrink tumor size by regulating ferroptosis, which might provide a theoretical basis for treating cervical cancer.


Subject(s)
Ferroptosis , Uterine Cervical Neoplasms , Female , Humans , Reactive Oxygen Species/metabolism , Antioxidants , HeLa Cells , Iron/metabolism
5.
J Agric Food Chem ; 71(3): 1607-1619, 2023 Jan 25.
Article in English | MEDLINE | ID: mdl-36635091

ABSTRACT

Selenium, a trace element associated with memory impairment and glucose metabolism, mainly exerts its function through selenoproteins. SELENOM is a selenoprotein located in the endoplasmic reticulum (ER) lumen. Our study demonstrates for the first time that SELENOM knockout decreases synaptic plasticity and causes memory impairment in 10-month-old mice. In addition, SELENOM knockout causes hyperglycaemia and disturbs glucose metabolism, which is essential for synapse formation and transmission in the brain. Further research reveals that SELENOM knockout leads to inhibition of the brain insulin signaling pathway [phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR/p70 S6 kinase pathway], which may impair synaptic plasticity in mice. High-fat diet (HFD) feeding suppresses the brain insulin signaling pathway in SELENOM knockout mice and leads to earlier onset of cognitive impairment at 5 months of age. In general, our study demonstrates that SELENOM knockout induces synaptic deficits via the brain insulin signaling pathway, thus leading to cognitive dysfunction in mice. These data strongly suggest that SELENOM plays a vital role in brain glucose metabolism and contributes substantially to synaptic plasticity.


Subject(s)
Cognitive Dysfunction , Glucose , Animals , Mice , Brain/metabolism , Cognitive Dysfunction/genetics , Cognitive Dysfunction/metabolism , Diet, High-Fat , Glucose/metabolism , Insulin/metabolism , Mice, Inbred C57BL , Mice, Knockout , Phosphatidylinositol 3-Kinases/metabolism , Selenoproteins/metabolism
6.
Exp Eye Res ; 227: 109378, 2023 02.
Article in English | MEDLINE | ID: mdl-36603796

ABSTRACT

HuR (also known as ELAV1), a ubiquitous RNA-binding protein, is implicated in the pathogenesis of diverse diseases via the mechanism of post-transcriptional regulation. Whether it is involved in pathological angiogenesis in oxygen-induced retinopathy is not clear. In this study, we detected HuR expression was increased in the retina of mouse model of oxygen-induced retinopathy (OIR) as well as in vascular endothelial cells exposed to hypoxia. With gain-of-function and loss-of-function studies using adenovirus infection, we found HuR over-expression promoted while HuR knockdown inhibited the migration, proliferation and tube formation of vascular endothelial cells. Moreover, HuR regulated the expression of VEGFA in vascular endothelial cells. We also found the retinal pathological angiogenesis in mouse OIR model was greatly reduced with HuR knockdown using recombinant AAV expressing HuR specific shRNA which was administered by intravitreal injection. The results of this study suggest HuR is involved in pathological angiogenesis via regulating angiogenic behaviors of endothelial cells, providing a potential target for the treatment of retinopathy of prematurity.


Subject(s)
ELAV-Like Protein 1 , Oxygen , Retinal Neovascularization , Animals , Mice , Disease Models, Animal , Down-Regulation , Endothelial Cells/metabolism , Mice, Inbred C57BL , Neovascularization, Pathologic/metabolism , Oxygen/toxicity , Oxygen/metabolism , Retina/metabolism , Retinal Neovascularization/metabolism , ELAV-Like Protein 1/metabolism
7.
Exp Eye Res ; 226: 109347, 2023 01.
Article in English | MEDLINE | ID: mdl-36502924

ABSTRACT

Retinopathy of prematurity (ROP) is a vision-threatening ocular disease that occurs in premature infants, but the underlying mechanism is still unclear. Since oxidative stress has been well documented in the ROP development, we aimed to investigate whether ferroptosis, a new type of cell death characterized by lipid peroxidation and iron overload, is also involved in ROP. We detected the lipid peroxidation, oxidative stress and the expression of ferroptosis markers in the retina of mouse model of oxygen-induced retinopathy. After ferroptosis inhibitor, ferrostatin-1, was administered by intravitreal injection, ferroptosis marker, lipid peroxidation, retinal vasculature and glial cell activation were examined. We found decreased expression of SLC7A11 and GPX4, increased expression of FTH1 and TFRC, as well as increase of lipid peroxidation in the retina of OIR mice. Ferrostatin-1 administration significantly reduced lipid peroxidation, and also reversed the change of ferroptosis marker. Neovascular area and avascular area were suppressed and the pathological vasculature changes including acellular vessels and ghost pericytes were decreased. Microglial cell and Müller cell activation was not evidently influenced by ferrostatin-1 treatment. Our findings suggest that ferroptosis is involved in the pathological angiogenesis and might be a promising target for ROP therapy.


Subject(s)
Ferroptosis , Neovascularization, Pathologic , Retinopathy of Prematurity , Animals , Humans , Infant, Newborn , Mice , Ferroptosis/drug effects , Ferroptosis/physiology , Neovascularization, Pathologic/drug therapy , Neovascularization, Pathologic/pathology , Oxygen/toxicity , Retinopathy of Prematurity/drug therapy , Retinopathy of Prematurity/pathology , Oxidative Stress
8.
BMC Health Serv Res ; 22(1): 260, 2022 Feb 25.
Article in English | MEDLINE | ID: mdl-35216586

ABSTRACT

BACKGROUND: Diabetic retinopathy (DR) has become a leading cause of global blindness as a microvascular complication of diabetes. Regular screening of diabetic retinopathy is strongly recommended for people with diabetes so that timely treatment can be provided to reduce the incidence of visual impairment. However, DR screening is not well carried out due to lack of eye care facilities, especially in the rural areas of China. Artificial intelligence (AI) based DR screening has emerged as a novel strategy and show promising diagnostic performance in sensitivity and specificity, relieving the pressure of the shortage of facilities and ophthalmologists because of its quick and accurate diagnosis. In this study, we estimated the cost-effectiveness of AI screening for DR in rural China based on Markov model, providing evidence for extending use of AI screening for DR. METHODS: We estimated the cost-effectiveness of AI screening and compared it with ophthalmologist screening in which fundus images are evaluated by ophthalmologists. We developed a Markov model-based hybrid decision tree to analyze the costs, effectiveness and incremental cost-effectiveness ratio (ICER) of AI screening strategies relative to no screening strategies and ophthalmologist screening strategies (dominated) over 35 years (mean life expectancy of diabetes patients in rural China). The analysis was conducted from the health system perspective (included direct medical costs) and societal perspective (included medical and nonmedical costs). Effectiveness was analyzed with quality-adjusted life years (QALYs). The robustness of results was estimated by performing one-way sensitivity analysis and probabilistic analysis. RESULTS: From the health system perspective, AI screening and ophthalmologist screening had incremental costs of $180.19 and $215.05 but more quality-adjusted life years (QALYs) compared with no screening. AI screening had an ICER of $1,107.63. From the societal perspective which considers all direct and indirect costs, AI screening had an ICER of $10,347.12 compared with no screening, below the cost-effective threshold (1-3 times per capita GDP of Chinese in 2019). CONCLUSIONS: Our analysis demonstrates that AI-based screening is more cost-effective compared with conventional ophthalmologist screening and holds great promise to be an alternative approach for DR screening in the rural area of China.


Subject(s)
Diabetes Mellitus , Diabetic Retinopathy , Artificial Intelligence , China/epidemiology , Cost-Benefit Analysis , Diabetic Retinopathy/diagnosis , Humans , Mass Screening , Quality-Adjusted Life Years
9.
Invest Ophthalmol Vis Sci ; 62(12): 1, 2021 09 02.
Article in English | MEDLINE | ID: mdl-34473190

ABSTRACT

Purpose: HIV infection is associated with a variety of ocular surface diseases. Understanding the difference of the ocular microbiota between HIV-infected and healthy individuals as well as the influence of antiretroviral therapy will help to investigate the pathogenesis of these conditions. Methods: A cross-sectional study was conducted on subjects including HIV-negative individuals, untreated HIV-infected individuals, and HIV-infected individuals with antiretroviral therapy. Conjunctival microbiota was assessed by bacterial 16S rRNA sequencing of the samples obtained from the conjunctival swab. Results: The microbial richness in ocular surface was similar in HIV-negative, untreated HIV-positive, and highly active antiretroviral therapy (HAART) subjects. The bacterial compositions were similar in the two HIV infection groups but were significantly different from the HIV-negative group. HAART changed the beta diversity of bacterial community as determined by Shannon index. CD4+ T cell count had no significant influence on the diversity of ocular microbiota in HIV-infected individuals. Conclusions: The data revealed the compositional and structural difference in conjunctival microbial community in subjects with and without HIV infection, indicating that HIV infection or its treatment, may contribute to ocular surface dysbiosis.


Subject(s)
Anti-Retroviral Agents/therapeutic use , Antiretroviral Therapy, Highly Active/methods , Bacteria/genetics , Conjunctiva/microbiology , Gastrointestinal Microbiome/physiology , HIV Infections/drug therapy , RNA, Ribosomal, 16S/genetics , Adult , Bacteria/metabolism , Conjunctiva/pathology , Cross-Sectional Studies , DNA, Viral/analysis , Female , Follow-Up Studies , HIV , HIV Infections/virology , Humans , Male , Middle Aged , RNA, Ribosomal, 16S/metabolism
10.
Biochem Med (Zagreb) ; 31(2): 020709, 2021 Jun 15.
Article in English | MEDLINE | ID: mdl-34140832

ABSTRACT

INTRODUCTION: The prognostic value of D-dimer (DD) in sepsis remains controversial. This study aimed to investigate the performance of DD for predicting sepsis mortality in the hospital and for identifying its potential correlates. MATERIALS AND METHODS: The clinical and laboratory data of adult sepsis patients were extracted from the Medical Information Mart for Intensive Care III (MIMIC III, v1.4) database using the structured query language (SQL). The database contains critical illness admitted to the intensive care unit at Beth Israel Deaconess Medical Center between June 2001 and October 2012. The association between DD and mortality was investigated with receiver operating characteristic (ROC) curve, restricted cubic spline and logistic regression analysis. Subgroup analysis was also used for identifying DD correlates. RESULTS: The study population consisted of 358 sepsis patients. Those who died during hospital stay (N = 160) had significantly higher DD values than those who survived (N = 198). The area under the ROC curve (AUC) of DD was 0.59 (P < 0.010). In subgroup analysis, white blood cell (WBC) count > 18 x109/L and vasopressor therapy significantly decreased DD diagnostic performance. Categorical DD value was independently associated with hospital mortality after sequential organ failure score (SOFA) and blood lactate adjustment. Restricted cubic spline analysis revealed a U-shape relationship between DD and in-hospital mortality. DISCUSSION: We conclude that the accuracy of DD for predicting in-hospital sepsis mortality depends on WBC count and vasopressor therapy. Both low and extremely elevated DD values are associated with higher risk of death.


Subject(s)
Fibrin Fibrinogen Degradation Products/metabolism , Hospital Mortality , Intensive Care Units , Sepsis/blood , Sepsis/mortality , Adult , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Retrospective Studies
11.
Transl Cancer Res ; 10(4): 1856-1862, 2021 Apr.
Article in English | MEDLINE | ID: mdl-35116507

ABSTRACT

BACKGROUND: Circulating microRNAs are novel diagnostic markers for various types of cancer. Several studies have investigated the diagnostic accuracy of circulating miR-126 for malignant pleural mesothelioma (MPM), but the results varied. Therefore, we performed a systematic review and meta-analysis to investigate the diagnostic value of circulating miR-126 for MPM. METHODS: The PubMed database was searched to identify potentially eligible studies published before October 2020. The studies investigating the diagnostic value of circulating miR-126 for MPM were included in a systematic review and meta-analysis. A bivariate model was used to pool eligible studies' sensitivity and specificity. The revised tool for the quality assessment of diagnostic accuracy studies (QUADAS-2) was used to assess eligible studies' quality. RESULTS: Four studies with 156 MPM patients and 459 controls were included in this systematic review and meta-analysis. The pooled diagnostic sensitivity and specificity of circulating miR-126 for MPM were 0.71 and 0.69, respectively. A high risk of bias was observed in the domains of patient selection, index test, and flow and timing. CONCLUSIONS: Circulating miR-126 has limited value for diagnosing MPM. Considering that the available studies have a high risk of bias, further rigorous studies are needed to assess the diagnostic value of circulating miR-126 for MPM.

12.
Ann Transl Med ; 7(20): 554, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31807535

ABSTRACT

BACKGROUND: Several studies have investigated the diagnostic accuracy of serum lactate dehydrogenase (LDH) to pleural fluid adenosine deaminase ratio (cancer ratio, CR) for malignant pleural effusion (MPE), but the results were various. Therefore, we performed this systematic review and meta-analysis to ascertain the diagnostic accuracy of CR for MPE. METHODS: The PubMed and EMBASE databases were searched up to 7 June, 2019 to identify publications concerning diagnostic accuracy of CR for MPE. The sensitivities and specificities of CR in included studies were pooled with a bivariate model. A summary receiver operating characteristic (sROC) curve was used to estimate the global diagnostic accuracy of CR. Quality of the included studies was assessed with the revised tool for the quality assessment of diagnostic accuracy studies (QUADAS-2). RESULTS: Finally, five studies with 596 MPE patients and 863 benign pleural effusion (BPE) patients were included in this systematic review and meta-analysis. The pooled sensitivity and specificity of CR were 0.97 (95% CI: 0.92-0.99) and 0.89 (0.69-0.97), respectively. The area under sROC curve was 0.98 (95% CI: 0.97-0.99). The major design weaknesses of the included studies were patients selection and partial verification bias. CONCLUSIONS: CR has high diagnostic accuracy for MPE. Considering the design weaknesses of available studies, further studies with rigorous design are needed to further validate the findings of this meta-analysis.

13.
Clin Chim Acta ; 498: 62-67, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31419411

ABSTRACT

BACKGROUND: The prognostic value of red blood cell distribution width (RDW) in critical illness remains controversial. The aim of this study was to investigate the prognostic value of on-admission RDW for in-hospital and 4-year mortality in adults with critical illness. METHODS: This is a retrospective cohort study from the Medical Information Mart for Intensive Care III (MIMIC III) database (version 1.4). Patients admitted to the intensive care unit (ICU) for the first time were included. Their on-admission RDW and severity scores were extracted with the Structured Query Language (SQL). The patients were categorized into a training set and a validation set. The relation of RDW to in-hospital and 4-year all-cause mortality was analyzed using receiver operating characteristic (ROC) curve, Kaplan-Meier curve, Cox model, net reclassification index (NRI), integrated discriminatory index (IDI) and nomogram. RESULTS: A total of 36,532 patients (21,090 in training and 15,442 in validation set) were included in this study. Increased RDW was significantly associated with higher in-hospital and 4-year mortality. The prognostic value of RDW for 4-year mortality was independent of conventional severity scores. Using conventional severity scores as covariates the continuous NRI and IDI of RDW for in-hospital mortality were around 0.3-0.5 and 0.01-0.03, respectively. For 4-year mortality the NRI was around 0.2-0.3 and IDIs was around 0.03-0.08. CONCLUSIONS: Admission RDW predicts both in-hospital and 4-year mortality in adult patients with critical illness admitted in the ICU, and can provide additional prognostic values beyond conventional clinical severity scores.


Subject(s)
Critical Illness , Diagnostic Techniques and Procedures/mortality , Erythrocyte Indices , Adult , Aged , Databases, Factual , Female , Humans , Intensive Care Units , Male , Middle Aged , Mortality , Prognosis , Retrospective Studies , Severity of Illness Index
14.
BMJ Open ; 9(8): e027287, 2019 08 01.
Article in English | MEDLINE | ID: mdl-31375609

ABSTRACT

INTRODUCTION: Serum and fluid laboratory markers are valuable for exploring the aetiologies of pleural effusion (PE) because of their relative non-invasiveness, low cost, objective result and short turnaround time. The diagnostic accuracy of these potential markers needs to be rigorously evaluated before their widespread application in clinical practice. Here, we plan to perform a Study Investigating Markers in PLeural Effusion (SIMPLE). METHODS AND ANALYSIS: This is a prospective and double-blind clinical trial which is being performed at the Affiliated Hospital of Inner Mongolia Medical University, China. Adult patients admitted for the evaluation of aetiology of PE from September 2018 to July 2021 will be enrolled after informed consent. Pleural fluid and serum specimens will be collected and stored at -80°C for the laboratory analysis. The final diagnosis will be concurred with further imaging, microbiology, cytology and biopsy if needed. The results of investigated laboratory markers will be unknown to the clinicians who will make diagnosis and the clinical diagnoses will be unknown to the laboratory technicians who will determine markers. The diagnostic accuracy of investigated markers will be assessed using receiver operating characteristics (ROC) curve analysis, multivariable logistic regression model, decision curve analysis (DCA), net reclassification index (NRI) and integrated discriminatory index (IDI). ETHICS AND DISSEMINATION: The study is approved by the Ethic Committee of the Affiliated Hospital of Inner Mongolia Medical University (NO: 2018011). The results of SIMPLE will be submitted to international scientific peer-reviewed journals or conferences in laboratory medicine or respiratory medicine, thoracic diseases. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR1800017449); Pre-results.


Subject(s)
Biomarkers/metabolism , Pleural Effusion/diagnosis , Biopsy , Double-Blind Method , Humans , Pleural Effusion/metabolism , Prospective Studies , ROC Curve , Reproducibility of Results
15.
Clin Chim Acta ; 487: 112-116, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30218659

ABSTRACT

BACKGROUND: Although some underpowered studies have proven that increased red blood cell distribution width (RDW) may be associated with short-term prognosis of sepsis, the long-term prognostic value of RDW remains largely unknown. METHODS: This retrospective observational study was based on the Medical Information Mart for Intensive Care III (MIMIC III), a large critical care database. Baseline RDW and conventional disease severity scores were extracted along with data on 4-year mortality, of adult patients with severe sepsis upon first admission to the intensive care unit (ICU). The prognostic value of RDW was analyzed with Kapan-Meier cure, Cox model, receiver operating characteristic (ROC) curve analysis, net reclassification index (NRI) and integrated discriminatory index (IDI). RESULTS: A total of 4264 subjects were included. The area under ROC curve of RDW for predicting 4-year mortality was 0.64 (95% CI: 0.63-0.66). In multivariable Cox model, increased RDW was independently associated with all-cause mortality, irrespective of anemia. With conventional severity scores as reference, RDW had continuous NRI comprised between 0.18 and 0.20, and IDI comprised between 0.30 and 0.40. CONCLUSION: RDW values significantly predicts long-term all-cause mortality in critically ill patients with severe sepsis beyond conventional severity scores.


Subject(s)
Intensive Care Units , Sepsis/blood , Aged , Aged, 80 and over , Discriminant Analysis , Erythrocyte Indices , Female , Humans , Male , Middle Aged , ROC Curve , Retrospective Studies , Sepsis/diagnosis , Treatment Outcome
16.
Huan Jing Ke Xue ; 37(6): 2131-2140, 2016 Jun 08.
Article in Chinese | MEDLINE | ID: mdl-29964878

ABSTRACT

The concentrations of 16 organochlorine pesticides (OCPs) in 7 water samples collected from different sites of water source areas of Guangdong and Guangxi were detected by SPE-GC-MS, and then the pollution characteristics were analyzed. This study established species sensitivity distribution(SSD) curves with BurrⅢ distribution model. In the meantime, HC5 values were calculated by BurrliOZ software, which were used to evaluate the toxicity effects of OCPs towards aquatic organisms. Finally, margin of safety concentration values were calculated to assess the ecological risk. The results showed that the concentration of OCPs varied from 6.64 to 34.19 ng·L-1, with a mean value of 16.76 ng·L-1, while HCHs and DDTs contributed a lot. HCHs were predominately originated from lindane, which is a component in household insecticide, while DDTs were from dicofol contamination or historical residues. Vertebrates could stand severer toxicity in comparison with invertebrates. α-endosulfan showed a greater toxicity towards aquatic plants and microorganisms than others, while p, p'-DDT turned out to be the most hazardous pollutant to vertebrates and invertebrates among the 16 OCPs studied. Generally speaking, OCPs in study areas didn't show conspicuous ecological risks towards aquatic organisms, DDTs and α-endosulfan, however, are still worth paying close attention due to their high potential risks.


Subject(s)
Environmental Monitoring , Hydrocarbons, Chlorinated/toxicity , Pesticides/toxicity , Water Pollutants, Chemical/toxicity , Animals , China , DDT , Ecotoxicology , Hexachlorocyclohexane , Risk Assessment , Toxicity Tests , Water
17.
NeuroRehabilitation ; 30(4): 267-75, 2012.
Article in English | MEDLINE | ID: mdl-22672940

ABSTRACT

OBJECTIVE: This investigation examined the demographic characteristics along with 3 measures of motor function in determining outcomes in activities of daily living (ADL) after distributed constraint-induced therapy (dCIT). METHODS: The study recruited 69 stroke patients who received 3 weeks of dCIT for 2 hours daily, 5 days a week. The self-reported outcome measures for daily function were the Motor Activity Log (MAL) including the amount of use (AOU) and quality of movement (QOM), Nottingham Extended Activities of Daily Living Questionnaire (NEADL), and the Stroke Impact Scale (SIS). Age, sex, onset, side of stroke, Fugl-Meyer assessment (FMA), Wolf Motor Function Test (WMFT), and Action Research Arm Test (ARAT) were the potential predictors. RESULTS: The ARAT grasp-grip-pinch score was the most dominant predictor for MAL-AOU and NEADL (P< 0.05), and the ARAT total score for the subscore of the ADL/instrumental ADL section of the SIS (P< 0.05). The FMA wrist-hand score was a significant predictor for MAL-QOM (P< 0.05). Age was the only demographic factor that significantly predicted NEADL performance (P< 0.05). CONCLUSION: Among the 3 commonly used measures of motor function after stroke, ARAT was the strongest determinant in predicting MAL-AOU, MAL-QOM, and SIS-ADL/instrumental ADL after dCIT.


Subject(s)
Activities of Daily Living , Disability Evaluation , Movement/physiology , Stroke Rehabilitation , Stroke/physiopathology , Aged , Exercise Therapy , Female , Hand Strength/physiology , Humans , Male , Middle Aged , Predictive Value of Tests , Regression Analysis , Surveys and Questionnaires , Treatment Outcome
18.
Alzheimer Dis Assoc Disord ; 26(2): 135-9, 2012.
Article in English | MEDLINE | ID: mdl-21617520

ABSTRACT

The aims of this study were to identify subsyndromes of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer disease (AD), and to investigate whether the apolipoprotein E (ApoE) gene confers a risk of distinct BPSD subsyndromes. BPSD of 96 patients with AD were assessed using the Neuropsychiatric Inventory. Factor analysis with principal component analysis and varimax rotation was used to construct the BPSD subsyndromes. ApoE genotypes were determined using the TaqMan technology. The results showed that the 5 subsyndromes can be determined, including: agitation/aggression-delusion, euphoria-disinhibition, depression-apathy, hallucination-nighttime behavior, and appetite. ApoE ε4 carriers had higher factor scores in the agitation/aggression-delusion subsyndrome. We demonstrated that ApoE ε4 confers a higher risk for the subsyndrome of agitation/aggression delusion in AD.


Subject(s)
Alzheimer Disease/genetics , Apolipoproteins E/genetics , Behavioral Symptoms/genetics , Polymorphism, Genetic , Aged , Aged, 80 and over , Alzheimer Disease/psychology , Behavioral Symptoms/physiopathology , Female , Humans , Male , Middle Aged , Neuropsychological Tests , Psychomotor Agitation/psychology
19.
J Rehabil Med ; 44(1): 58-64, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22124733

ABSTRACT

OBJECTIVE: To validate the dimensionality, hierarchical properties, and reliability of the Frenchay Activities Index. DESIGN: Self-report survey of patients with stroke. PATIENTS: A total of 127 patients provided 254 observations before and after treatments. METHODS: Multidimensional Rasch model was conducted. RESULTS: The 2-factor model showed the significantly smallest deviance and fitted the data best among 6 possible models. The 2-factor structure was stable before and after treatments, after the rating scale was revised from 4 points to 3 points. Differential item functioning relevant to the time since stroke was detected for 2 tasks. The item difficulty hierarchy of the 2 domains was determined. The correlation between the 2 domains was 0.58. The scale demonstrated acceptable ceiling and floor effects. The overall person (separation) reliability was 0.99. The reliabilities for the 2 domains were 0.81 and 0.73. CONCLUSION: The Frenchay Activities Index is a useful 2-dimensional scale for evaluating daily functions in stroke patients. The item difficulty hierarchy and significant differential item functioning related to the time since stroke might reflect the changes in the recovery course after stroke. The Frenchay Activities Index could be improved by adding items to capture patients with high and low levels of daily activities in domestic chores.


Subject(s)
Activities of Daily Living , Severity of Illness Index , Stroke Rehabilitation , Female , Humans , Male , Reproducibility of Results
20.
Nagoya J Med Sci ; 71(3-4): 115-26, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19994724

ABSTRACT

A 6-month, twice weekly, well-rounded exercise program (47 sessions in total) comprised of a combination of aerobic, resistance and flexibility training was provided for institutionalized older adults aged 60 to 93. We analyzed the data of 18 older adults who could stand and had attended more than 10% of the classes (mean participation rate: 54%) to examine changes in activities of daily living (ADL), physical fitness tests and depressive moods. The mean (+/- standard deviation, range) age of the participants was 71.3 (+/- 15.6, 60-93) in men and 85.9 (+/- 5.8, 72-93) in women. Significant improvement in ADL of the hand manipulation domain and borderline significant improvement in ADL of the mobility domain were observed (McNemar test p = 0.011 and 0.072, respectively). A 6-minute walk distance increased significantly from 151.6 m to 236.6 m (p = 0.01, paired t-test), and the result of the Soda Pop test, which tests hand-eye coordination, also improved significantly from 35.2 sec to 25.3 sec (p = 0.01, paired t-test). These findings suggest that such a program could be effective in improving the ADL and physical fitness of the elderly.


Subject(s)
Activities of Daily Living , Depression/prevention & control , Exercise , Physical Fitness , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Muscle Strength , Nursing Homes
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