Adherence to COVID-19 measures and the associated factors: evidence from a two-wave longitudinal study in Singapore.

BACKGROUND: At the onset of the Coronavirus disease (COVID-19) pandemic when pharmaceutical interventions were not readily available, governments relied on public health mandates and social distancing measures to counter rising infection rates. In order to address the dearth of longitudinal studies, this study sought to identify factors associated with continued adherence to COVID-19 preventive behaviours in Singapore. METHODS: Data were from a two-wave longitudinal cohort study; baseline study was conducted from May 2020 to June 2021 and follow-up study from October 2021 to September 2022. Participants (n = 858) were Singapore residents, aged 18 and above, and able to speak English, Chinese or Malay. Weighted multivariable logistic regressions were conducted to identify factors associated with adherence to the COVID-19 measures. RESULTS: Adherence rates of 'avoid dining out', 'crowded places', 'people with flu symptoms' and 'small group gatherings' at baseline were 39.41%, 60.82%, 79.82%, and 44.82% respectively. All measures had a decrease in adherence rates across the two-waves. Older age groups were associated with greater adherence to 'avoid dining out' and 'avoid crowded places'. Having high trust in local public health experts was associated with greater adherence to 'avoid crowded places' and 'avoid people with flu symptoms'. Fear of family and friends getting infected with COVID-19 was associated with 'avoid dining out' and 'avoid crowded places'. CONCLUSIONS: Soft interventions like nudges can be implemented at crowded places to remind the public of the ease of transmitting the virus to their loved ones. Increasing media presence of public health experts can be a viable alternative to improve adherence.

A modified transactional model of stress and coping on depressive symptoms among informal caregivers of persons with dementia.

Informal caregivers are crucial to the care of persons with dementia (PWD), but their role is often reported as challenging. This study aims to examine caregiver stress and depressive symptoms among informal caregivers of PWD using a modified transactional stress and coping model. Path analysis was conducted among a sample of informal caregivers of PWD in Singapore (n = 281) using information on functional dependence and memory and behavioral problems of PWD, and self-reported measurements on caregivers' knowledge of dementia, perceived positive aspects of caregiving, social support, coping patterns, caregiving self-efficacy, caregiving burden and depressive symptoms. The initial model reflecting our assumptions for the transactional stress and coping model showed a poor fit (model 1 - CFI = 0.858, TLI = 0.665, RMSEA = 0.118). Logical modifications were made until sufficient model fit was achieved (model 2 - CFI = 0.987, TLI = 0.955, RMSEA = 0.043). We then removed the insignificant paths in model 2 and obtained our final model (model 3 - CFI = 0.990, TLI = 0.974, RMSEA = 0.033). The final model supported our hypotheses, with some adjustments. This study advances our understanding of caregiver distress by modifying the transactional stress and coping model, including (1) the key role of caregiver self-efficacy in the primary appraisal process, (2) the dynamic assessment of coping resources across all stages of the model, and (3) the importance of coping patterns. Future studies could explore the generalizability of these findings.

Diabetes Self-Care Behaviors in Singapore and Their Associations With Patients' Characteristics and Health Literacy.

PURPOSE: The purpose of this study was to examine the relationship between self-management behaviors (eg, healthy eating, being active, medication taking, glucose monitoring, feet check), sociodemographic factors, disease-related characteristics, and health literacy among patients with type 2 diabetes in Singapore. METHODS: Data were analyzed from a nationwide survey conducted between 2019 and 2020 (n = 387). Self-management behaviors were assessed using the Dietary Approaches to Stop Hypertension questionnaire, the Global Physical Activity Questionnaire, and a diabetes care questionnaire. A linear regression model was generated to examine the association of healthy eating with the variables of interest (sociodemographic factors, disease-related characteristics, and health literacy), and logistic regression models were generated to investigate the significant correlates of the remaining self-care behaviors. RESULTS: Regression models showed that the 5 self-care behaviors have different correlates. Nonetheless, compared to individuals aged 50 to 64 years, those aged 65 years and above were less likely to be active, adhere to their medication prescription, and check their feet. Individuals with a higher number of diabetes-related complications were less likely to be sufficiently active but more likely to monitor their glucose level and check their feet. Moreover, individuals with poor health literacy were more likely to eat healthily and be sufficiently active. CONCLUSIONS: Programs related to self-care behaviors can be tailored to specific demographics to improve their uptake in the population. Furthermore, encouraging comprehensive self-care behaviors in those aged 65 years and above is crucial for effective diabetes management.

Proenkephalin Improves Cardio-Renal Risk Prediction in Acute Coronary Syndromes: The KID-ACS Score.

BACKGROUND AND AIMS: Circulating proenkephalin (PENK) is a stable endogenous polypeptide with fast response to glomerular dysfunction and tubular damage. This study examined the predictive value of PENK for renal outcomes and mortality in patients with acute coronary syndromes (ACS). METHODS: Proenkephalin was measured in plasma in a prospective multicentre ACS cohort from Switzerland (n=4787) and in validation cohorts from the UK (n=1141), Czechia (n=927), and Germany (n=220). A biomarker-enhanced risk score (KID-ACS score) for simultaneous prediction of in-hospital acute kidney injury (AKI) and 30-day mortality was derived and externally validated. RESULTS: On multivariable adjustment for established risk factors, circulating PENK remained associated with in-hospital AKI (per log2 increase: adjusted odds ratio [OR] 1.53, 95% confidence interval [CI] 1.13-2.09, P=0.007) and 30-day mortality (adjusted hazard ratio [HR] 2.73, 95% CI 1.85-4.02, P<0.001). The KID-ACS score integrates PENK and showed an area under the receiver operating characteristic curve (AUC) of 0.72 (95% CI 0.68-0.76) for in-hospital AKI, and of 0.91 (95% CI 0.87-0.95) for 30-day mortality in the derivation cohort. Upon external validation, KID-ACS achieved similarly high performance for in-hospital AKI (Zurich: AUC 0.73, 95% CI 0.70-0.77; Czechia: AUC 0.75, 95% CI 0.68-0.81; Germany: AUC 0.71, 95% CI 0.55-0.87) and 30-day mortality (UK: AUC 0.87, 95% CI 0.83-0.91; Czechia: AUC 0.91, 95% CI 0.87-0.94; Germany: AUC 0.96, 95% CI 0.92-1.00) outperforming the CA-AKI score and the GRACE 2.0 score, respectively. CONCLUSIONS: Circulating PENK offers incremental value for predicting in-hospital AKI and mortality in ACS. The simple 6-item KID-ACS risk score integrates PENK and provides a novel tool for simultaneous assessment of renal and mortality risk in patients with ACS.

Tourmaline triggered biofilm transformation: Boosting ultrafiltration efficiency and fouling resistance.

Ultralow pressure filtration system, which integrates the dual functionalities of biofilm degradation and membrane filtration, has gained significant attention in water treatment due to its superior contaminant removal efficiency. However, it is a challenge to mitigate membrane biofouling while maintaining the high activity of biofilm. This study presents a novel ceramic-based ultrafiltration membrane functionalized with tourmaline nanoparticles to address this challenge. The incorporation of tourmaline nanoparticles enables the release of nutrient elements and the generation of an electric field, which enhances the biofilm activity on the membrane surface and simultaneously alleviates intrapore biofouling. The tourmaline-modified ceramic membrane (TCM) demonstrated a significant antifouling effect, with a substantial increase in water flux by 60 %. Additionally, the TCM achieved high removal efficiencies for contaminants (48.78 % in TOC, 22.28 % in UV254, and 24.42 % in TN) after 30 days of continuous operation. The fouling resistance by various constituents in natural water was individually analyzed using model compounds. The TCM with improved electronegativity and hydrophilicity exhibited superior resistance to irreversible fouling through increased electrostatic repulsion and reduced adhesion to foulants. Comprehensive characterizations and analyses, including interfacial interaction energies, redox reaction processes, and biofilm evolutions, demonstrated that the TCM can release nutrient elements to facilitate the development of functional microbial community within the biofilm, and generate reactive oxygen species (ROS) on the membrane surface to the degrade contaminants and mitigate membrane biofouling. The electric field generated by tourmaline nanoparticles can promote electron transfer in the Fe(III)/Fe(II) cycle, ensuring a stable and sustainable generation of ROS and bactericidal negative ions. These synergistic functions enhance contaminant removal and reduce irreversible fouling of the TCM. This study provides fundamental insights into the role of tourmaline-modified surfaces in enhancing membrane filtration performance and fouling resistance, inspiring the development of high-performance, anti-fouling membranes.

Supramolecular assembly of Polydopamine@Fe nanoparticles with near-infrared light-accelerated cascade catalysis applied for synergistic photothermal-enhanced chemodynamic therapy.

Chemodynamic therapy (CDT) via Fenton-like reaction is greatly attractive owing to its capability to generate highly cytotoxic •OH radicals from tumoral hydrogen peroxide (H2O2). However, the antitumor efficacy of CDT is often challenged by the relatively low radical generation efficiency and the high levels of antioxidative glutathione (GSH) in tumor microenvironment. Herein, an innovative photothermal Fenton-like catalyst, Fe-chelated polydopamine (PDA@Fe) nanoparticle, with excellent GSH-depleting capability is constructed via one-step molecular assembly strategy for dual-modal imaging-guided synergetic photothermal-enhanced chemodynamic therapy. Fe(III) ions in PDA@Fe nanoparticles can consume the GSH overexpressed in tumor microenvironment to avoid the potential •OH consumption, while the as-produced Fe(II) ions subsequently convert tumoral H2O2 into cytotoxic •OH radicals through the Fenton reaction. Notably, PDA@Fe nanoparticles demonstrate excellent near-infrared light absorption that results in superior photothermal conversion ability, which further boosts above-mentioned cascade catalysis to yield more •OH radicals for enhanced CDT. Taken together with T1-weighted magnetic resonance imaging (MRI) contrast enhancement (r1 = 8.13 mM-1 s-1) and strong photoacoustic (PA) imaging signal of PDA@Fe nanoparticles, this design finally realizes the synergistic photothermal-chemodynamic therapy. Overall, this work offers a new promising paradigm to effectively accommodate both imaging and therapy functions in one well-defined framework for personalized precision disease treatment.

Suppression of RCAN1 alleviated lipid accumulation and mitochondrial fission in diabetic cardiomyopathy.

BACKGROUND: Although metabolic disturbance is a characteristic of diabetic cardiomyopathy (DbCM), the detailed pathogenesis of DbCM remains unknown. METHODS: We used a heart transplantation (HTx) cohort to explore the effect of diabetes mellitus on heart failure (HF) progression dependent of myocardium. Microscopic and ultramicroscopic pathology were used to depict the pathological features of human myocardium of DbCM. We performed targeted metabolomics to characterize the metabolic phenotype of human DbCM. Transcriptomics data were analyzed and weighted gene co-expression network analysis was performed to explore the potential upstream regulator for metabolic remodeling of DbCM. In vivo and in vitro experiments were further conducted to demonstrate the therapeutic effects and molecular mechanisms. RESULTS: DbCM promoted the progression of HF and increased death or HF-rehospitalization after HTx. Lipid accumulation and mitochondrial fission were the obvious pathological features of DbCM myocardium. The concentrations of C14:0-CoA and C16:1-CoA were significantly increased in the myocardium, and they were positively correlated with the accelerated HF progression and RCAN1 expression in DbCM patients. Knockdown of RCAN1 improved cardiac dysfunction, lipid accumulation, and mitochondrial fission in db/db mice. In vitro studies showed that RCAN1 knockdown improved mitochondrial dysfunction in DbCM cardiomyocytes via the RCAN1-p-Drp1 Ser616 axis. CONCLUSIONS: Diabetes is associated with faster progression of HF and causes poor prognosis after HTx, accompanied by metabolic remodeling in the myocardium. Accumulation of long chain acyl-CoA in the myocardium is the metabolic hallmark of human DbCM and is associated with more rapid disease progression for DbCM patients. Upregulation of RCAN1 in the myocardium is associated with the metabolic signatures of DbCM and RCAN1 is a potential therapeutic target for DbCM.

Promising dawn in the management of pulmonary hypertension: The mystery veil of gut microbiota.

The gut microbiota is a complex community of microorganisms inhabiting the intestinal tract, which plays a vital role in human health. It is intricately involved in the metabolism, and it also affects diverse physiological processes. The gut-lung axis is a bidirectional pathway between the gastrointestinal tract and the lungs. Recent research has shown that the gut microbiome plays a crucial role in immune response regulation in the lungs and the development of lung diseases. In this review, we present the interrelated factors concerning gut microbiota and the associated metabolites in pulmonary hypertension (PH), a lethal disease characterized by elevated pulmonary vascular pressure and resistance. Our research team explored the role of gut-microbiota-derived metabolites in cardiovascular diseases and established the correlation between metabolites such as putrescine, succinate, trimethylamine N-oxide (TMAO), and N, N, N-trimethyl-5-aminovaleric acid with the diseases. Furthermore, we found that specific metabolites, such as TMAO and betaine, have significant clinical value in PH, suggesting their potential as biomarkers in disease management. In detailing the interplay between the gut microbiota, their metabolites, and PH, we underscored the potential therapeutic approaches modulating this microbiota. Ultimately, we endeavor to alleviate the substantial socioeconomic burden associated with this disease. This review presents a unique exploratory analysis of the link between gut microbiota and PH, intending to propel further investigations in the gut-lung axis.

Cu-chelated polydopamine nanozymes with laccase-like activity for photothermal catalytic degradation of dyes.

The industrial applications of enzymes are usually hindered by the high production cost, intricate reusability, and low stability in terms of thermal, pH, salt, and storage. Therefore, the de novo design of nanozymes that possess the enzyme mimicking biocatalytic functions sheds new light on this field. Here, we propose a facile one-pot synthesis approach to construct Cu-chelated polydopamine nanozymes (PDA-Cu NPs) that can not only catalyze the chromogenic reaction of 2,4-dichlorophenol (2,4-DP) and 4-aminoantipyrine (4-AP), but also present enhanced photothermal catalytic degradation for typical textile dyes. Compared with natural laccase, the designed mimic has higher affinity to the substrate of 2,4-DP with Km of 0.13 mM. Interestingly, PDA-Cu nanoparticles are stable under extreme conditions (temperature, ionic strength, storage), are reusable for 6 cycles with 97 % activity, and exhibit superior substrate universality. Furthermore, PDA-Cu nanozymes show a remarkable acceleration of the catalytic degradation of dyes, malachite green (MG) and methylene blue (MB), under near-infrared (NIR) laser irradiation. These findings offer a promising paradigm on developing novel nanozymes for biomedicine, catalysis, and environmental engineering.

The relationship between therapeutic alliance, frequency of consultation and uptake of telemedicine among patients seeking treatment for early psychosis: A moderated mediation model.

Background: Telehealth services ensure the delivery of healthcare services to a wider range of consumers through online platforms. Nonetheless, the acceptance and uptake of telehealth remain elusive. This study aims to understand the (a) uptake and (b) acceptability of telemedicine, (c) if therapeutic alliance mediates the relationship between the frequency of consultations with clinicians and the uptake of telemedicine in patients with early psychosis, and (d) role of education in moderating the relationship between therapeutic alliance and the uptake of telemedicine for their mental healthcare. Methods: A convenience sample of outpatients (n = 109) seeking treatment for early psychosis and their care providers (n = 106) were recruited from a tertiary psychiatric care centre. Sociodemographic and clinical characteristics, therapeutic alliance (Working Alliance Inventory), and telemedicine use were captured through self-administered surveys. The moderated mediation analysis was performed using PROCESS macro 3.4.1 with therapeutic alliance and level of education as the mediating and moderating factors, respectively. Results: The acceptance of telemedicine was high (possibly will use: 47.7%; definitely will use: 26.6%) whilst the uptake was low (11%). Therapeutic alliance mediated the relationship between the frequency of consultation and the uptake of telemedicine (ß: 0.326; CI: 0.042, 0.637). This effect was moderated by the level of education (ß: -0.058; p < 0.05). Conclusion: Therapeutic alliance mediates the relationship between the frequency of consultations and the uptake of telemedicine services with the level of education moderating this mediation. Focusing on the patients with lower education to improve their telemedicine knowledge and therapeutic alliance might increase the uptake.

The protective role of resilience and social support against burnout during the COVID-19 pandemic.

Background: The COVID-19 pandemic brought on a range of stressors in homes and workplaces. With no sign of ending after one year, burnout was a concern. Resilience has been known to shield against the effects of stress. While often thought of as an individual trait, previous studies have shown social support to improve resilience. The study aimed to examine the extent of burnout in the Singapore population and whether social support and resilience cushioned the impact of COVID-19 related stressors a year into the pandemic. Methods: Participants were 858 Singapore residents who participated in a larger study between October 2021 and September 2022. The Copenhagen Burnout Inventory provided Work-and Personal-related burnout scores. Multivariable linear regression was used to identify demographic variables associated with burnout. Path analysis revealed the associations between COVID-19 stressors, social support, resilience and burnout. Results: 22 and 19% of the sample reported work and personal burnout respectively, with younger adults being more burnt out than older adults. Higher stress was associated with higher burnout and higher social support was associated with lower burnout. Path analysis revealed that the relationship between social support and burnout was partially accounted for by increased resilience. Conclusion: Managing altered work arrangements, career expectations, and increased responsibilities at home may contribute to greater levels of burnout in the younger adults. Increased employer support and targeted interventions could mitigate the impact of these stressors. The study also highlighted the importance of maintaining social connections even while physically distancing.

Renal function alters the association of lipoprotein(a) with cardiovascular outcomes in patients undergoing percutaneous coronary intervention: a prospective cohort study.

Background and hypothesis: Lipoprotein(a) [Lp(a)] and renal dysfunction are both independent risk factors for cardiovascular disease. However, it remains unclear whether renal function mediates the association between Lp(a) and cardiovascular outcomes in patients undergoing percutaneous coronary intervention (PCI). Methods: From a large prospective cohort study, 10 435 eligible patients undergoing PCI from January 2013 to December 2013 were included in our analysis. Patients were stratified into three renal function groups according to their baseline estimated glomerular filtration rate (eGFR) (<60; 60-90; ≥90 ml/min/1.73 m2). The primary endpoint was a composite of all-cause death, nonfatal MI, ischemic stroke, and unplanned revascularization [major adverse cardiac and cerebrovascular events (MACCE)]. Results: Over a median follow-up of 5.1 years, a total of 2144 MACCE events occurred. After multivariable adjustment, either eGFR <60 ml/min/1.73 m2 or elevated Lp(a) conferred a significantly higher MACCE risk. Higher Lp(a) was significantly associated with an increased risk of MACCE in patients with eGFR <60 ml/min/1.73 m2. However, this association was weakened in subjects with only mild renal impairment and diminished in those with normal renal function. A significant interaction for MACCE between renal categories and Lp(a) was observed (P = 0.026). Patients with concomitant Lp(a) ≥30 mg/dl and eGFR <60 ml/min/1.73 m2 experienced worse cardiovascular outcomes compared with those without. Conclusion: The significant association between Lp(a) and cardiovascular outcomes was mediated by renal function in patients undergoing PCI. Lp(a)-associated risk was more pronounced in patients with worse renal function, suggesting close monitoring and aggressive management are needed in this population.

Public awareness of war on diabetes campaign and its association with behavioural outcomes.

The War on Diabetes campaign was launched in 2016, encouraging Singapore residents to engage in regular exercise, adopt healthy dietary habits and screen for early detection of diabetes. This study aims to examine campaign awareness and its associations with sedentary behaviour, dietary habits and identifying diabetes. Data were obtained from the nationwide Knowledge, Attitudes and Practices study on diabetes in Singapore. A total of 2895 participants responded to a single question assessing campaign awareness. The Dietary Approaches to Stop Hypertension (DASH) diet screener assessed dietary habits, and the Global Physical Activity Questionnaire (GPAQ) measured sedentary behaviour. Recognition of diabetes was established using a vignette depicting a person with diabetes mellitus. Logistic and linear regression models were used to measure the associations. Most participants were 18- to 34-years old (29.9%) and females (51.6%). About 57.4% identified the campaign. Campaign awareness exhibited positive associations with identifying diabetes based on the vignette [odds ratio (OR): 1.5; 95% confidence interval (CI): 1.1-2.2; P = 0.022], lower odds of sedentary behaviour ≥7 h/day (OR: 0.7; CI: 0.5-0.9; P = 0.018) and higher DASH scores (ß = 1.3; P < 0.001). The study recognized early significant associations between the behavioural outcomes and the campaign, emphasizing the need for ongoing campaign sustainability and evaluation of its long-term impact on population health.

Study of electronic biofeedback combined with nursing intervention in the treatment of vascular cognitive impairment-no dementia.

OBJECTIVE: To investigate the effects of electronic biofeedback combined with nursing intervention and conventional drug treatment on cognitive function in patients with vascular cognitive impairment-no dementia (VCIND). METHODS: A total of 102 patients with VCIND treated in the Department of Neurology from January 2021 to May 2022 were enrolled and divided into the routine treatment group and biofeedback group according to different treatment methods. The routine treatment group was given conventional drug therapy and nursing intervention; for the biofeedback group, electronic biofeedback therapy was added, based on the routine treatment group. The Montreal Cognitive Assessment, (MoCA), Alzheimer's Disease Assessment Scale-Cognitive Subscale, (ADAS-cog), and Hamilton Depression Scale (HAMD) were checked before treatment, 2 weeks after treatment, and 3 months after treatment. RESULTS: At 3 months of treatment, the scores of the MoCA and ADAS-cog scales in the biofeedback group were better than those in the routine treatment group, while no difference was detected in the HAMD scores before and after treatment and between the two groups. CONCLUSION: Electronic biofeedback therapy for VCIND can significantly improve the MoCA score, reduce the ADAS-cog score and improve the cognitive level of patients and can be used as a complementary treatment for VCIND.

The significance of dynamic monitoring plasma TMAO level in pulmonary arterial hypertension - a cohort study.

BACKGROUND: Gut microbiota assumes an essential role in the development and progression of pulmonary arterial hypertension (PAH). Trimethylamine N-oxide (TMAO), a gut microbiota-dependent metabolite, is correlated with the prognosis of patients with PAH. However, the correlation between changes in TMAO (ΔTMAO) and the prognosis of PAH remains elusive. OBJECTIVES: To investigate the association between ΔTMAO and prognosis of PAH, and explore whether dynamic assessment of TMAO level was superior to measurement at a single time point in predicting prognosis. DESIGN: Single-center cohort study. METHODS: Consecutive patients diagnosed with PAH and had at least two TMAO measurements taken from May 2019 to June 2020 were eligible. The outcome events of this study were defined as adverse clinical events. RESULTS: A total of 117 patients with PAH who had two TMAO measurements and follow-up were included in this study. Patients with ΔTMAO ⩾1.082 µmol/L had over four times increased risk of adverse clinical events than their counterparts after adjusting for confounders [hazard ratio (HR) 4.050, 95% confidence interval (CI): 1.468-11.174; p = 0.007]. Patients with constant high TMAO levels at both time points had the highest risk of adverse clinical events compared with patients with constant low TMAO levels (HR 3.717, 95% CI: 1.627-8.492; p = 0.002). ΔTMAO was also associated with changes in parameters reflecting PAH severity (p < 0.05). CONCLUSION: Changes in TMAO were independently correlated with prognosis in patients with PAH, irrespective of baseline level of TMAO. ΔTMAO also correlated with alteration in disease severity. Repeated assessment of TMAO level contributes to better identification of patients with increased risk of adverse clinical events.

Circulating acetylcholine serves as a potential biomarker role in pulmonary hypertension.

BACKGROUND: An increased acetylcholine (ACh) level in the right ventricle tissue of pulmonary hypertension (PH) was revealed, which indicated the important role of ACh in disease pathogenesis. However, the relationship between plasma ACh levels and disease conditions and patients' prognosis has not been investigated. We aimed to explore the association between plasma ACh levels and the prognosis of patients with PH. We also discussed the feasibility of plasma ACh as a biomarker, which may contribute to the management of PH patients in the future. METHODS: Patients with confirmed PH in Fuwai Hospital from April 2019 to August 2020 were enrolled. The primary clinical outcome in this study was defined as a composite outcome, including death/lung transplantation, heart failure, and worsening of symptoms. Fasting plasma was collected to detect the ACh levels. The association between ACh levels and patients' prognosis was explored. RESULTS: Finally, four hundred and eight patients with PH were enrolled and followed for a mean period of 2.5 years. Patients in the high ACh group had worse World Health Organization Functional Class (WHO-FC), lower 6-minute walk distance (6 MWD), and higher N-terminal pro-brain natriuretic peptide (NT-proBNP). Notably, echocardiographic and hemodynamic parameters in the high metabolite group also suggested a worse disease condition compared with the low ACh group. After adjusting for confounders, compared with low ACh patients, those with high metabolite levels still have worse prognoses characterized as elevated risk of mortality, heart failure, and symptoms worsening. CONCLUSION: High circulating ACh levels were associated with severe PH conditions and poor prognosis, which might serve as a potential biomarker in PH.

Baseline high-sensitivity C-reactive protein and glycosylated hemoglobinA1c predict adverse outcomes in patients with chronic coronary syndromes undergoing percutaneous coronary intervention.

Introduction: This study explored the ability of high-sensitivity C-reactive protein (hs-CRP) and glycosylated hemoglobin A1c (HbA1c) to predict adverse cardiac and cerebrovascular outcomes in patients with chronic coronary syndromes (CCS) undergoing percutaneous coronary intervention (PCI). Methods: In total, 4083 consecutive patients with CCS undergoing PCI were investigated throughout 2013 at a single center. The primary endpoint was all-cause death at the 5-year follow-up. Hs-CRP and HbA1c data were collected on admission. Results: The highest quartile of hs-CRP had a significantly increased the risk of all-cause death, with an adjusted HR of 1.747 (95 % CI 1.066-2.863), while, there was no difference in all-cause death among the groups of HbA1c after adjustment, with an adjusted HR of 1.383 (95 % CI 0.716-2.674). The highest quartiles for hs-CRP and HbA1c in the study population had a significantly increased risk of major adverse cardiac and cerebrovascular events (MACCE), with an adjusted hazard ratios (HR) of 1.263 (95 % confidence intervals [CI] 1.032-1.545) for hs-CRP and an adjusted HR of 1.417 (95 % CI 1.091-1.840) for HbA1c. Remarkably, the incidence of all-cause death and that of MACCE were significantly increased when both hs-CRP and HbA1c were elevated (HR 1.971, 95 % CI 1.079-3.601, P = 0.027 and HR 1.560, 95 % CI 1.191-2.042), P = 0.001, respectively). Addition of hs-CRP and HbA1c to conventional risk factors significantly improved prediction of the risk of all cause death (net reclassification index 0.492, P < 0.001; integrated discrimination improvement 0.007, P = 0.011) and MACCE (net reclassification index 0.160, P < 0.001; integrated discrimination improvement 0.006, P < 0.001). Conclusions: Hs-CRP and HbA1c can serve as independent predictors of MACCE in patients with CCS undergoing PCI. Furthermore, a combination of hs-CRP and HbA1c could predict all cause death and MACCE better than each component individually.

Prognostic significance of inflammation in patients with coronary artery disease at low residual inflammatory risk.

Patients with coronary artery disease (CAD) at low residual inflammatory risk are often overlooked in research and practice. This study examined the associations between fourteen inflammatory indicators and all-cause mortality in 5,339 CAD patients with baseline high-sensitivity C-reactive protein (hsCRP) <2 mg/L who received percutaneous coronary intervention and statin and aspirin therapy. The median follow-up time was 2.1 years. Neutrophil-derived systemic inflammatory response index (SIRI) yielded the strongest and most robust association with all-cause mortality among all indicators. Lower hsCRP remained to be associated with a lower risk of all-cause mortality. A newly developed comprehensive inflammation score (CIS) showed better predictive performance than other indicators, which was validated by an independent external cohort. In conclusion, neutrophil-derived indicators, particularly SIRI, strongly predicted all-cause mortality independent of hsCRP in CAD patients at low residual inflammatory risk. CIS may help identify individuals with inflammation burdens that cannot be explained by hsCRP alone.

Defect-Mediated Atomic Layer Etching Processes on Cl-Si(100): An Atomistic Insight.

Defects play a significant role in atomic layer etching (ALE) processes; however, a fundamental understanding at the atomic level is still lacking. To bridge this knowledge gap, this study investigated the role of point defects in the laser-induced ALE of Cl-Si(100) using density functional theory (DFT) and real-time time-dependent DFT calculations. In the calculations, both the pristine surface and the defective surface were considered for comparative analysis. The key finding is the enhanced desorption of SiCl molecules, facilitated by point defects under laser pulse irradiation. The presence of point defects was found to effectively reduce both the desorption energy barrier and the laser intensity threshold required for desorption. Additionally, extra defective levels within the band gap were observed through the density-of-state diagram. Based on these findings, a defect-mediated etching regime was proposed to elucidate the layer-by-layer etching process. This study provides atomistic insight into understanding the role of defects in laser-induced ALE processes. The presence of point defects can enhance the etching selectivity between the topmost layer and the underlying layers, thereby contributing to highly efficient and damage-free etching processes through the defect-mediated etching mechanism.

HIV gp120/Tat protein-induced epithelial-mesenchymal transition promotes the progression of cervical lesions.

BACKGROUND: Human immunodeficiency virus (HIV) infection is associated with an elevated incidence of cervical cancer, and accelerated disease progression, but the underlying mechanisms are not well understood. This study aimed to investigate the relationship between HIV infection and epithelial-mesenchymal transition (EMT) in cervical cancer. METHODS: Tissue samples from HIV-positive and negative patients with cervical intraepithelial neoplasia (CIN) and cervical cancer were analyzed for EMT-related proteins. Human cervical cancer SiHa cells were treated with HIV Tat and gp120 proteins to test their effects on EMT, migration, and invasion. RESULTS: HIV-positive patients had lower E-cadherin and cytokeratin, and higher N-cadherin and vimentin levels than HIV-negative patients. HIV Tat and gp120 proteins induced EMT, migration, and invasion in SiHa cells. Transcriptome sequencing analysis revealed that, compared to the control group, the protein-treated group showed upregulation of 22 genes and downregulation of 77 genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed the involvement of the Wnt signaling pathway in EMT. Further analysis of gene expression related to this pathway revealed upregulation of DVL1, TCF7, KRT17, and VMAC, while GSK3ß, SFRP2, and CDH1 were downregulated. Immunofluorescence assay demonstrated that HIVgp120 and Tat proteins treatment induced elevated ß-catenin expression with nuclear accumulation in SiHa cells. CONCLUSIONS: The treatment of SiHa cells with HIV Tat and gp120 proteins induces EMT and activates the Wnt/ß-catenin pathway, suggesting that the Wnt/ß-catenin pathway may play a crucial role in promoting EMT progression in cervical lesion tissues of HIV-infected patients.