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Introduction: The main alkaloid component in cigarettes is nicotine. Cotinine, a metabolite of nicotine, is capable of causing dependence effects through endless mechanisms modulated by the ion channel nicotinic acetylcholine receptors nAChRs. Nicotine and cotinine can also cause damage to blood vessels through a chronic inflammatory process mediated by the Ligand-Tie2 Angiopoietin Receptor system. Hypoxic conditions that occur due to vascular inflammation cause a decrease in the concentration of nitric oxide (NO). This study aimed to evaluate the relationship between NO levels and cotinine through the expression of nAChRs that mediate the nicotine dependence mechanism and Tie2 (Tyrosine Kinase 2) expression., Methods: A cross-sectional study was conducted with 200 participants grouped into two groups based on their smoking status: 100 smokers and 100 non-smokers. All participants were men aged 20-40 years with no history of cardiovascular disease, diabetes mellitus, or dyslipidemia, and were not currently on medication. According to the parameters used, all blood samples were taken from peripheral blood for analysis using the ELISA kit or Colorimetric Assay Kit., Results: Cigarette consumption increases blood cotinine concentrations in smokers and causes dependence by modulating nAChRs. The study indicates an emerging cycle regarding nicotine-cotinine consumption and nAChRs expression. In addition, the data in this study showed a significant relationship (p<0.001) regarding the cycle formed with decreased NO levels as a result of damage caused by Tie2-mediated inflammation., Conclusions: There is a relationship between NO levels and cotinine through nAChRs, which mediate the nicotine dependence mechanism and Tie2 expression., Competing Interests: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors declare that they have no competing interests, financial or otherwise, related to the current work. All authors report that since the initial planning of the work, study materials and medical writing for this research were funded by the Ministry of Research, Technology, and Higher Education of the Republic of Indonesia., (© 2024 Kumboyono K. et al.)

Introduction: Ascorbic acid and calcitriol were frequently utilized in conjunction as therapy during the COVID-19 pandemic, and individuals with minor symptoms had notable improvements. There have been a few studies, often with conflicting findings, that examine the use of them for endothelium restoration and numerous clinical trial studies that failed to establish the efficacy. The aim of this study was to find the efficacy of ascorbic acid compared to calcitriol on the inflammatory markers monocyte chemoattractant protein-1 (MCP-1), nitric oxide (NO), and superoxide dismutase (SOD), as protective agents which play an important role in the early stages of atherosclerosis formation. This study was an experimental in vivo study., Methods: The total of 24 male Rattus norvegicus strain Wistar rats were divided into 4 groups, namely: control/normal group (N), atherosclerosis group (DL) given atherogenic diet, atherosclerosis group given atherogenic diet and ascorbic acid (DLC), and atherosclerosis group given atherogenic diet and calcitriol (DLD) treatment for 30 days., Results: Ascorbic acid and calcitriol treatment was significantly effective ( P <0.05) in lowering expression of MCP-1 and increasing NO and SOD level. Calcitriol was superior to ascorbic acid in increasing SOD ( P <0.05). There was no significant difference between ascorbic acid and calcitriol in decreasing MCP-1 and increasing NO ( P >0.05)., Discussion: Both treatments could reduce MCP-1, and increase NO and SOD by increasing antioxidants. In this study calcitriol was superior to ascorbic acid in increasing SOD, but not NO and decreasing MCP-1. According to the theory, it was found that calcitriol through nuclear factor erythroid 2-related factor 2 (Nrf2) causes a direct increase in the amount of SOD. Nrf2 is an emerging regulator of cellular resistance to oxidants., Conclusion: Ascorbic acid and calcitriol treatment was able to reduce MCP-1 and increase NO and SOD in atherosclerosis rat. Calcitriol was significantly superior in increasing SOD levels compared to ascorbic acid., Competing Interests: The authors declare no conflicts of interest in this work., (© 2023 Heriansyah et al.)

Purpose: Smoking is a significant risk factor in developing cardiovascular disease pathogenesis through oxidative stress and inflammation mechanisms. This study used cotinine as a biomarker of nicotine exposure levels in the body, which was associated with levels of Interleukin-6 (IL-6) and Superoxide Dismutase (SOD) as markers of oxidative stress and vascular inflammation. The research aimed to analyze the effect of cotinine levels on the expression of IL-6 and SOD., Methods: This study used a cross-sectional design on 200 subjects, consisting 100 smokers and 100 non-smokers. Cotinine levels, IL-6 expression, and SOD were measured from the blood serum of each subject using the Enzyme-Linked Immunosorbent Assay (ELISA) method. Then the data were analyzed using Generalized Structured Component Analysis (GSCA)., Results: There was a significant effect of cotinine levels on the reduction of SOD mediated by IL-6 (CR = 4.006). Cotinine levels also increased IL-6 mediated by SOD (CR = 4.292). The structural model shows that higher cotinine levels will increase IL-6 expression, and conversely, SOD expression will decrease., Conclusion: High cotinine levels cause an increase in the inflammatory process and oxidative stress in the vasculature of smokers, which is characterized by high IL-6 expression and low SOD expression., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Kumboyono et al.)

Background: Tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and monocyte chemoattractant protein-1 (MCP-1) are early phase cytokines often encountered when the body is exposed to severe acute respiratory syndrome-associated-coronavirus-2. TNF-α, IL-1β, and MCP-1 are pro-inflammatory cytokines critical in the defence response against systemic infection and injury. Therefore, TNF-α, IL-1β, and MCP-1 are the most aggressive responses to viral infections in the acute phase, so they can be used to determine the survival of coronavirus disease 2019 (COVID-19) patients., Purpose: The study aimed to determine the levels of TNF-α, IL-1β, and MCP-1 as predictors of survival for COVID-19 patients., Patients and Methods: A prospective cohort study was conducted on confirmed COVID-19 by a reverse-transcriptase-polymerase-chain-reaction (RT-PCR) in 84 adults admitted to the hospital in Indonesia. TNF-α, IL-1β, and MCP-1 level were measured from serum subjects using the enzyme-linked immunosorbent assay., Results: The results from logistic regression modelling of the survival status of COVID-19 patients based on TNF-α, IL-1β, and MCP-1 levels were significant (p-value=0.024). The predictors of all cytokines had P Wald <0.05, so the three cytokines could be used simultaneously to predict the survival status of COVID-19 patients. MCP-1 has the most dominant risk relative value (2.76; 95% CI; 2.53-4.68) compared to TNF-α and IL-1β in predicting patient survival., Conclusion: TNF-α, IL-1β, and MCP-1 as markers of acute systemic inflammatory cytokines can be measured at the beginning of hospitalisation of COVID-19 patients for early diagnosis of disease severity so that healthcare professionals can determine clinical guidance needs for therapeutic programs., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Kumboyono et al.)

Objective: This study aims to determine the protective cardiovascular effect of aerobic exercise training by measuring cluster of differentiation 146 (CD146), circulating endothelial cell (CEC), and high-density lipoprotein-cholesterol (HDL-C) levels in adults., Methods: This study was an experimental pre-post-test without a control group. Forty-five participants were divided into three groups based on aerobic exercise training intensity: low, moderate, and high. Whole blood samples were measured for HDL-C levels. In addition, CEC was isolated from Peripheral Blood Mononuclear Cells (PBMC) samples, then identified by CD146 marker using flow cytometry., Results: CEC percentage and HDL-C increase after aerobic exercise training. There was a significant difference in CEC percentage between the intensity groups. However, there was no difference in HDL-C levels., Conclusion: Aerobic exercise training can protect cardiovascular health by stimulating CEC mobilization, identified by CD146. In addition, an HDL-C level increase also contributes to cardiovascular protection by decreasing inflammation levels, inhibiting low-density lipoprotein-cholesterol oxidation, improving endothelial regeneration capabilities, and lowering blood glucose., (© 2022 [The Author/The Authors].)

Introduction: Endothelial Progenitor Cells (EPCs) are part of hematopoietic stem cells that differentiate into endothelial cells during their blood vessels' maturation process. The role of EPCs is widely known to contribute to repair of the vascular wall when endothelial dysfunction occurs. However, various risk factors for cardiovascular disease (CVD) influence EPC performance, leading to endothelial dysfunction. One EPC dysfunction is decreased amount of EPC mobilization to the injured tissue. EPC dysfunction reduces the angiogenetic function of EPCs. The vital maturation process that the EPCs must pass is the late phase. The dysfunction of late EPCs is known as senescence. This study aimed to identify and compare senescence of late EPCs, through CD62E and CD41 markers, in non-smokers and smokers as a risk factor for CVD., Methods: EPC collection was from peripheral mononuclear cells (PBMCs) in non-smokers (n=30) and smokers (n=31). The EPCs were then marked by CD62E/CD41 and senescence β-galactosidase assay using FACS. Identification of senescence cells was based on fluorescence with DAPI., Results: Positive percentage of late EPCs in non-smokers was not significantly different from that in smokers (p=0.014). The number of senescent late EPCs in smokers was higher than in non-smokers (p<0.0001)., Conclusions: Endothelial progenitor cells that experienced senescence in the smokers showed EPC dysfunction, which resulted in decreased cell angiogenic function. Further research is needed to explain the mechanism of re-endothelialization failure in EPC dysfunction due to smoking., Competing Interests: The authors have each completed and submitted an ICMJE form for disclosure of potential conflicts of interest. The authors declare that they have no competing interests, financial or otherwise, related to the current work. All the authors declare that the study materials and medical writing for this research were funded by the Ministry of Research, Technology, and Higher Education of the Republic of Indonesia and that they received support from the Ministry of Research, Technology, and Higher Education of the Republic of Indonesia in the past 36 months., (© 2021 Kumboyono K. et al.)

Introduction: Smoking can cause vascular damage in the form of an inflammatory reaction characterized by endothelial activation. Endothelial activation forms a pathological adaptation pattern so that it can induce the atherogenesis process. Several markers, such as E-selectin, platelet-derived micro particles (PMPs) and hematopoietic stem cell (HSC) can identify the activation of endothelial in circulating blood. Therefore, the deviation of vascular adaptation due to smoking can be detected early through the feedback mechanism between E-selectin, PMPs, and HSC., Purpose: This study aims to analyze the initial picture of the negative impact of smoking on vascular adaptation by measuring E-selectin, PMPs, and HSC in the peripheral blood circulation. Participant criteria and methods: Peripheral blood samples (5 mL) were taken from each participant, both the smoking group (n = 30) and the non-smoker group (n = 31) to obtain peripheral blood mononuclear cells (PBMNC). PBMNC was isolated using ficoll-based gradient centrifugation. The flow cytometry assay method used to measure the E-selectin, PMPs and hematopoietic stem cells., Results: The mean of circulating E-selectin in smokers was higher than that of non-smokers. On the other hand, the average number of PMPs and HSCs in smokers was lower than non-smokers., Conclusion: Smoking increases the risk of accelerated vascular block formation, as indicated by an increase in the amount of circulating E-selectin. The increase in E-selectin in the blood vessels mediates the increased adhesion of PMPs in the vascular area so that the number of circulating PMPs in smokers decreases. The decrease in circulating PMPs decreases the signal of vascular repair, which is characterized by a decline in the number of HSCs., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Kumboyono et al.)

Background: Family's ability to care for children with avoidant restrictive food intake disorder (ARFID) is a central indicator in preventing the children from worse nutritional disorders. Environmental factor, child factor, caregiving behavioral systems, and beliefs can improve the family's ability to care for children. The aim of this research was to analyze the effect of environmental factor, child factor, caregiving behavioral systems, and beliefs on the family's ability to care for children with ARFID. Design and Methods: This cross-sectional research was carried out on 245 families with children suffering from ARFID in Malang Regency, in the working area of the Health Office of Malang Regency. The population of this research was families with children suffering from ARFID within the working area of the Health Office of Malang Regency. The research sample size was computed using the rule of thumb in structural equation modeling (SEM), the sample size used was 245. Results: Results showed that the family's ability to care for children with ARFID was highly influenced by the caregiver's belief (t = 21.796; β = 0.713). Caregiver's belief became a dominant factor in the promotion of the family's ability to care for children with ARFID. A caregiver's belief was influenced by his/her behavior. Conclusions: It was concluded that the caregiver's belief serves as a primary factor in the promotion of the family's ability to care for children with ARFID. A caregiver's behavior holds a prominent role in influencing his/her belief in providing care for children suffering from ARFID., (©Copyright: the Author(s).)

Background: The pathomechanism of CVD is a complex and multifactorial process. The primary mechanism of CVD is atherosclerosis. Inflammation in atherogenesis raises the risk of hypoxia, which will activate hypoxia-inducible factor-1α (HIF1A). Also, together with lipoprotein-associated phospholipase A2 (Lp-PLA2), an inflammatory mediator for atherogenesis., Purpose: This study aims to measure the hypoxia-inducible factor-1α (HIF1A) expression and its correlation to Lp-PLA2 expression at low-risk, intermediate, and high-risk CVD populations., Patients and Methods: The study used a correlational analysis method with a total sampling technique in 160 individuals in the risk population. The atherosclerosis risk group was analyzed using the Framingham Risk Score and categorized into low, intermediate, and high-risk groups. Venous blood samples taken from respondents were measured using the ELISA method with Lp-PLA2 and HIF-1α as parameters. Data were analyzed using normality test, homogeneity test, one-way ANOVA, post hoc-Tukey HSD, and Pearson correlation., Results: The concentration of HIF1A had a very strong correlation with Lp-PLA2 expression, both in the low-risk group (r = 0.512), intermediate (r = 0.512), and high (r = 0.715) (P <0.05). However, the concentrations of Lp-PLA2 did not match the FRS., Conclusion: HIF1A expression increased with increasing risk, while Lp-PLA2 expression decreased with increasing risk of atherosclerosis based on the FRS category. There is a significant correlation between HIF1A expression and Lp-PLA2 expression based on FRS., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Heriansyah et al.)

Objectives: This study aimed to identify predictors of promotive behaviours in mothers of Indonesian children with avoidant restrictive food intake disorder (ARFID)., Methods: A cross-sectional descriptive survey was administered to 245 mothers who were caring for children with ARFID. Data were collected with a self-administered questionnaire. For descriptive data analysis, independent t-test, Mann-Whitney U test, one-way analysis of variance, Kruskal-Wallis, and multiple linear regression were employed., Results: The factors related to promotive behaviours in these mothers were embodied in mutual parenting, especially in terms of childcare ( p  = 0.001 < 0.05) and interaction with children ( p  = 0.001 < 0.05. Additionally, multiple linear regression showed that mutual parenting remained at the communication domain, with children as the primary predictor (β 0.401, p 0.001), where the number of children (β -0.201, p  = 0.008) influenced the promotive behaviours., Conclusions: This study found that the number of children and mutual parenting in interacting with children were key factors that influenced promotive behaviours in mothers of children with ARFID. We suggest that nursing interventions can potentially improve promotive behaviours in this population., (© 2019 The Authors.)

IntroductionAcute Coronary Syndrome (ACS) is a life-threatening condition. Immediate and proper treatment will decrease mortality rate. Patient awareness on ACS is still lacking and as the consequence, ACS patients do not seek immediate help.ProblemThe patients' efforts to get rid of ACS symptoms., Methods: The study was a descriptive, qualitative study in which a semi-structured, in-depth interview became the instrument. The respondents were 34 participants (including 17 ACS patients and 17 family caregivers). Data analysis was done by triangulation of data sources., Results: Three themes were obtained, namely: (1) prefer traditional and self-treatment, for example (a) traditional medicine, (b) taking non-prescription drugs to overcome ACS symptoms, and (c) spontaneous action; (2) using available health resources and facilities that consisted of (a) getting initial treatment at home by nurses, (b) visiting a health center to take care of the symptoms, and (c) using non-ambulance service to visit the health centers; and (3) expectations on health care services to patients composed by sub-themes such as (a) the expectation to get information that supports the healing, and (b) the caring attitude of the heath professional., Conclusions: The results showed that in the prehospital setting when experiencing ACS symptoms, the patients try to overcome the symptoms independently. However, as the symptoms get worse, they utilize health facilities in different ways. At the time of obtaining health services, patients are satisfied with health professionals who show caring attitudes, explain the results of the examination, and provide health education on health care efforts. Thus, to prevent mortality and morbidity, it is important for a health professional to educate the public about ACS, including topics about ACS healthy lifestyles and potential threats if it is too late to get treatment. Furthermore, it is also important for the government to implement prehospital emergency services nation-wide. KumboyonoK, RefialdinataJ, WihastutiTA, RachmawatiSD, AzizAN. Health-seeking behavior of patients with Acute Coronary Syndrome and their family caregivers. Prehosp Disaster Med. 2018;33(6):614-620.