The rising prevalence of smokers in the community, specifically psychiatric patients, necessitates smoking cessation as an important strategy for reducing the harmful effects of tobacco. This study ...aims to compare the profiles of depressed and non-depressed smokers and evaluate how psychiatric symptoms influence respiratory symptoms. A cross-sectional survey was administered to 276 non-depressed adult smokers in the community and 69 adult smokers who had been formally diagnosed with depression in the outpatient clinic of a University Hospital in Singapore. Participants were administered questionnaires on smoking attitudes and perceptions, psychiatric symptoms, and respiratory symptoms. Correlations and multiple regression analyses were conducted. The mean age of smokers in the study was 35.32 ± 13.05 years. Smokers in the community and psychiatric samples were largely similar on all of the sociodemographic factors, except that fewer depressed people were employed (χ² = 8.35,
< 0.01). Smokers with depression also reported more attempts to quit smoking (χ² = 7.14,
< 0.05), higher mean depressive, anxiety, and stress symptom (DASS) scores (t = -10.04,
< 0.01), and endorsed more respiratory symptoms than smokers in the community (t = -2.40,
< 0.05). The DASS scores, number of cigarettes smoked daily, years of smoking, general perception of smokers getting heart disease, and presence of lung disease were positively and significantly correlated with respiratory symptoms. On multiple regression, only anxiety symptoms (β = 0.26, p < 0.05) and the presence of lung disease (β = 0.22, p < 0.001) were significantly correlated with respiratory symptoms. Depressed smokers reported greater difficulty in quitting tobacco use, and they perceived more severe respiratory symptoms compared to non-depressed counterparts. Anxiety symptoms were positively associated with the severity of respiratory symptoms. Smoking cessation campaigns need to specifically target psychological symptoms in smokers and focus more psychoeducation on the risk of cardiovascular disease in the middle-aged population.
Cell-free DNA (cfDNA) in human plasma is a class of biomarkers with many current and potential future diagnostic applications. Recent studies have shown that cfDNA molecules are not randomly ...fragmented and possess information related to their tissues of origin. Pathologies causing death of cells from particular tissues result in perturbations in the relative distribution of DNA from the affected tissues. Such tissue-of-origin analysis is particularly useful in the development of liquid biopsies for cancer. It is therefore of value to accurately determine the relative contributions of the tissues to the plasma DNA pool in a simultaneous manner. In this work, we report that in open chromatin regions, cfDNA molecules show characteristic fragmentation patterns reflected by sequencing coverage imbalance and differentially phased fragment end signals. The latter refers to differences in the read densities of sequences corresponding to the orientation of the upstream and downstream ends of cfDNA molecules in relation to the reference genome. Such cfDNA fragmentation patterns preferentially occur in tissue-specific open chromatin regions where the corresponding tissues contributed DNA into the plasma. Quantitative analyses of such signals allow measurement of the relative contributions of various tissues toward the plasma DNA pool. These findings were validated by plasma DNA sequencing data obtained from pregnant women, organ transplantation recipients, and cancer patients. Orientation-aware plasma DNA fragmentation analysis therefore has potential diagnostic applications in noninvasive prenatal testing, organ transplantation monitoring, and cancer liquid biopsy.
Significance We used massively parallel sequencing to study the size profiles of plasma DNA samples at single-base resolution and in a genome-wide manner. We used chromosome arm-level z -score ...analysis (CAZA) to identify tumor-derived plasma DNA for studying their specific size profiles. We showed that populations of aberrantly short and long DNA molecules existed in the plasma of patients with hepatocellular carcinoma. The short ones preferentially carried the tumor-associated copy number aberrations. We further showed that there were elevated amounts of mitochondrial DNA in the plasma of hepatocellular carcinoma patients. Such molecules were much shorter than the nuclear DNA in plasma. These findings have shed light on fundamental biological characteristics of plasma DNA and related diagnostic applications for cancer.
The analysis of tumor-derived circulating cell-free DNA opens up new possibilities for performing liquid biopsies for the assessment of solid tumors. Although its clinical potential has been increasingly recognized, many aspects of the biological characteristics of tumor-derived cell-free DNA remain unclear. With respect to the size profile of such plasma DNA molecules, a number of studies reported the finding of increased integrity of tumor-derived plasma DNA, whereas others found evidence to suggest that plasma DNA molecules released by tumors might be shorter. Here, we performed a detailed analysis of the size profiles of plasma DNA in 90 patients with hepatocellular carcinoma, 67 with chronic hepatitis B, 36 with hepatitis B-associated cirrhosis, and 32 healthy controls. We used massively parallel sequencing to achieve plasma DNA size measurement at single-base resolution and in a genome-wide manner. Tumor-derived plasma DNA molecules were further identified with the use of chromosome arm-level z -score analysis (CAZA), which facilitated the studying of their specific size profiles. We showed that populations of aberrantly short and long DNA molecules existed in the plasma of patients with hepatocellular carcinoma. The short ones preferentially carried the tumor-associated copy number aberrations. We further showed that there were elevated amounts of plasma mitochondrial DNA in the plasma of hepatocellular carcinoma patients. Such molecules were much shorter than the nuclear DNA in plasma. These results have improved our understanding of the size profile of tumor-derived circulating cell-free DNA and might further enhance our ability to use plasma DNA as a molecular diagnostic tool.
It is uncertain whether aspirin therapy should be continued after endoscopic hemostatic therapy in patients who develop peptic ulcer bleeding while receiving low-dose aspirin.
To test that continuing ...aspirin therapy with proton-pump inhibitors after endoscopic control of ulcer bleeding was not inferior to stopping aspirin therapy, in terms of recurrent ulcer bleeding in adults with cardiovascular or cerebrovascular diseases.
A parallel randomized, placebo-controlled noninferiority trial, in which both patients and clinicians were blinded to treatment assignment, was conducted from 2003 to 2006 by using computer-generated numbers in concealed envelopes. (ClinicalTrials.gov registration number: NCT00153725)
A tertiary endoscopy center.
Low-dose aspirin recipients with peptic ulcer bleeding.
78 patients received aspirin, 80 mg/d, and 78 received placebo for 8 weeks immediately after endoscopic therapy. All patients received a 72-hour infusion of pantoprazole followed by oral pantoprazole. All patients completed follow-up.
The primary end point was recurrent ulcer bleeding within 30 days confirmed by endoscopy. Secondary end points were all-cause and specific-cause mortality in 8 weeks.
156 patients were included in an intention-to-treat analysis. Three patients withdrew from the trial before finishing follow-up. Recurrent ulcer bleeding within 30 days was 10.3% in the aspirin group and 5.4% in the placebo group (difference, 4.9 percentage points 95% CI, -3.6 to 13.4 percentage points). Patients who received aspirin had lower all-cause mortality rates than patients who received placebo (1.3% vs. 12.9%; difference, 11.6 percentage points CI, 3.7 to 19.5 percentage points). Patients in the aspirin group had lower mortality rates attributable to cardiovascular, cerebrovascular, or gastrointestinal complications than patients in the placebo group (1.3% vs. 10.3%; difference, 9 percentage points CI, 1.7 to 16.3 percentage points).
The sample size is relatively small, and only low-dose aspirin, 80 mg, was used. Two patients with recurrent bleeding in the placebo group did not have further endoscopy.
Among low-dose aspirin recipients who had peptic ulcer bleeding, continuous aspirin therapy may increase the risk for recurrent bleeding but potentially reduces mortality rates. Larger trials are needed to confirm these findings.
Vascularization is critical for the survival of engineered tissues in vitro and in vivo. In vivo, angiogenesis involves endothelial cell proliferation and sprouting followed by connection of extended ...cellular processes and subsequent lumen propagation through vacuole fusion. We mimicked this process in engineering an organized capillary network anchored by an artery and a vein. The network was generated by inducing directed capillary sprouting from vascular explants on micropatterned substrates containing thymosin β4-hydrogel. The capillary outgrowths connected between the parent explants by day 21, a process that was accelerated to 14 d by application of soluble VEGF and hepatocyte growth factor. Confocal microscopy and transmission electron microscopy indicated the presence of tubules with lumens formed by endothelial cells expressing CD31, VE-cadherin, and von Willebrand factor. Cardiac tissues engineered around the resulting vasculature exhibited improved functional properties, cell striations, and cell–cell junctions compared with tissues without prevascularization. This approach uniquely allows easy removal of the vasculature from the microfabricated substrate and easy seeding of the tissue specific cell types in the parenchymal space.
Cell-free DNA in plasma has been used for noninvasive prenatal testing and cancer liquid biopsy. The physical properties of cell-free DNA fragments in plasma, such as fragment sizes and ends, have ...attracted much recent interest, leading to the emerging field of cell-free DNA fragmentomics. However, one aspect of plasma DNA fragmentomics as to whether double-stranded plasma molecules might carry single-stranded ends, termed a jagged end in this study, remains underexplored. We have developed two approaches for investigating the presence of jagged ends in a plasma DNA pool. These approaches utilized DNA end repair to introduce differential methylation signals between the original sequence and the jagged ends, depending on whether unmethylated or methylated cytosines were used in the DNA end-repair procedure. The majority of plasma DNA molecules (87.8%) were found to bear jagged ends. The jaggedness varied according to plasma DNA fragment sizes and appeared to be in association with nucleosomal patterns. In the plasma of pregnant women, the jaggedness of fetal DNA molecules was higher than that of the maternal counterparts. The jaggedness of plasma DNA correlated with the fetal DNA fraction. Similarly, in the plasma of cancer patients, tumor-derived DNA molecules in patients with hepatocellular carcinoma showed an elevated jaggedness compared with nontumoral DNA. In mouse models, knocking out of the
gene reduced jaggedness, whereas knocking out of the
gene enhanced jaggedness. Hence, plasma DNA jagged ends represent an intrinsic property of plasma DNA and provide a link between nuclease activities and the fragmentation of plasma DNA.
Tribological coatings with low coefficients of friction are in high demand by various industries since they can improve machine efficiency and have an environmental impact. A self-lubricating ...Ni-P-MoS2 composite coating has been successfully deposited on a mild steel substrate by electrodeposition. The effects of MoS2 on the tribological coatings have been investigated. Compared to a pure Ni-P coating, the Ni-P-MoS2 composite coating exhibited a dramatic reduction in friction coefficient against a bearing steel ball from 0.45 to 0.05. Examination and analysis of the worn surfaces and wear debris, the composite coating showed minimum wear and oxidation compared to the severe wear and oxidation observed in the pure Ni-P coating. The evolution of MoS2 particles in sliding wear has been elucidated.
•Successfully electrodeposited a super lubricated Ni-P-MoS2 coating.•Composite coatings may extend the application of MoS2 to humid atmosphere.•MoS2 contents have a strong influence on friction.
Abstract The aim of this study was to engineer a biomaterial capable of supporting vascularization in vitro and in vivo . We covalently immobilized vascular endothelial growth factor (VEGF) and ...Angiopoietin-1 (Ang1) onto three-dimensional porous collagen scaffolds using 1-ethyl-3-3-dimethylaminopropylcarbodiimide hydrochloride (EDC) chemistry. Over both 3 and 7 days in vitro , seeded endothelial cells (ECs) had increased proliferation on scaffolds with immobilized VEGF and/or Ang1 compared to unmodified scaffolds and soluble growth factor controls. Notably, the group with co-immobilized VEGF and Ang1 showed significantly higher cell number ( P = 0.0079), higher overall lactate production rate ( P = 0.0044) and higher overall glucose consumption rate ( P = 0.0034) at Day 3, compared to its corresponding soluble control for which growth factors were added to culture medium. By Day 7, hematoxylin and eosin, live/dead, CD31, and von Willebrand factor staining all showed improved tube formation by ECs when cultivated on scaffolds with co-immobilized growth factors. Interestingly, scaffolds with co-immobilized VEGF and Ang1 showed increased EC infiltration in the chorioallantoic membrane (CAM) assay, compared to scaffolds with independently immobilized VEGF/Ang1. This study presents an alternative method for promoting the formation of vascular structures, via covalent immobilization of angiogenic growth factors that are more stable than soluble ones and have a localized effect.
Abstract Vascularization of engineered tissues in vitro and in vivo remains a key problem in translation of engineered tissues to clinical practice. Growth factor signalling can be prolonged by ...covalent tethering, thus we hypothesized that covalent immobilization of vascular endothelial growth factor (VEGF-165) to a porous collagen scaffold will enable rapid vascularization in vivo . Covalent immobilization may be preferred over controlled release or cell transfection if the effects are desired within the biomaterial rather than the surrounding tissue. Scaffolds were prepared with 14.5 ± 1.4 ng (Low) or 97.2 ± 8.0 ng (High) immobilized VEGF, or left untreated (control), and used to replace a full right ventricular free wall defect in rat hearts. In addition to rapid vascularization, an effective cardiac patch should exhibit neither thinning nor dilatation upon implantation. In vitro , VEGF enhanced the growth of endothelial and bone marrow cells seeded onto scaffolds. In vivo , High VEGF patches had greater blood vessel density ( p < 0.01) than control at Day 7 and 28 due to increased cell recruitment and proliferation ( p < 0.05 vs. control). At Day 28, VEGF-treated patches were significantly thicker ( p < 0.05) than control, and thickness correlated positively with neovascularization ( r = 0.67, p = 0.023). Importantly, angiogenesis in VEGF scaffolds contributed to improved cell survival and tissue formation.
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