Background: Silybum marianum, as well as known milk thistle, has long been recognized for its hepatoprotective effects, primarily attributed to its active flavonolignan complex, silymarin (an extract from water hyacinth fruit). While the pharmacological effects of silymarin have been studied, research on bioactive peptides derived from Silybum marianum remains limited. Aim: To evaluate the toxicity effects of silybum marianum peptides Marerials and Method: This study aimed to evaluate the potential toxicity of Silybum marianum peptide in mice through a 14-day oral administration experiment. Twenty adult male C57BL/6 mice were divided into two groups: the experimental group received 200 mg/kg of Silybum marianum peptide daily, while the control group received an equivalent volume of saline solution. Physiological and biochemical parameters, including body weight, fasting blood glucose levels, liver and spleen wet weights, as well as alanine aminotransferase (ALT) enzyme activity, were assessed to determine potential toxic effects. This exploration aims to shed light on the toxicological effects of silybum marianum peptide in mice, providing insights into its potential benefits and challenges. Results: Results indicated no significant differences between the experimental and control groups in terms of body weight, blood glucose levels, or major organ wet weights. Additionally, ALT enzyme activity remained unaffected, suggesting no detectable liver toxicity. Throughout the study, no abnormal behaviors, physical changes, or mortality were observed in the test subjects. Mice in both the silybum marianum peptide and control groups exhibited shiny and soft fur, normal activity, and regular food consumption. These findings indicate that Silybum marianum peptide exhibits good safety and low biological toxicity under the tested conditions, supporting its potential use as a safe dietary supplement or therapeutic agent. Conclusion At the designated dosage, silybum marianum peptide demonstrated good safety and low biological toxicity.

Leptin, an adipose tissue-derived hormone, has exhibited the potent hepatotoxic effects. However, the underlying molecular mechanisms are not fully understood. In this study, we have elucidated the mechanisms by which leptin exerts cytotoxic effects in hepatocytes, particularly focusing on the role of interleukin-1β (IL-1β) signaling. Leptin significantly induced maturation and secretion of IL-1β in cultured rat hepatocytes. Interestingly, inhibition of IL-1β signaling by pretreatment with an IL-1 receptor antagonist (IL-1Ra) or gene silencing of type I IL-1 receptor (IL-1R1) markedly abrogated leptin-induced cell cycle arrest. The critical role of IL-1β signaling in leptin-induced cell cycle arrest is mediated via upregulation of p16, which acts as an inhibitor of cyclin-dependent kinase. In addition, leptin-induced apoptotic cell death was relieved by inhibition of IL-1β signaling, as determined by annexin V/7-AAD binding assay. Mechanistically, IL-1β signaling contributes to apoptotic cell death and cell cycle arrest by suppressing AKT and activation of p38 mitogen-activated protein kinase (p38MAPK) signaling pathways. Involvement of IL-1β signaling in cytotoxic effect of leptin was further confirmed in vivo using hepatocyte specific IL-1R1 knock out (IL-1R1 KO) mice. Essentially similar results were obtained in vivo, where leptin administration caused the upregulation of apoptotic markers, dephosphorylation of AKT, and p38MAPK activation were observed in wild type mice liver without significant effects in the livers of IL-1R1 KO mice. Taken together, these results demonstrate that IL-1β signaling critically contributes to leptin-induced cell cycle arrest and apoptosis, at least in part, by modulating p38MAPK and AKT signaling pathways.

Purpose: The aim of this study was to evaluate the influence of different cone-beam computed tomography (CBCT) acquisition protocols on reducing the effective radiation dose while maintaining image quality. Materials and Methods: The effective dose emitted by a CBCT device was calculated using thermoluminescent dosimeters placed in a Rando Alderson phantom. Image quality was assessed by 3 experienced evaluators. The relation-ship between image quality and confidence was evaluated using the Fisher exact test, and the agreement among raters was assessed using the kappa test. Multiple linear regression analysis was performed to investigate whether the technical parameters could predict the effective dose. P-values<0.05 were considered to indicate statistical significance. Results: The optimized protocol (3 mA, 99 kVp, and 450 projection images) demonstrated good image quality and a lower effective dose for radiation-sensitive organs. Image quality and confidence had consistent values for all structures (P<0.05). Multiple linear regression analysis resulted in a statistically significant model. The milliamperage (b = 0.504; t = 3.406; P = 0.027), kilovoltage peak (b = 0.589; t = 3.979; P = 0.016) and number of projection images (b = 0.557; t = 3.762; P = 0.020) were predictors of the effective dose. Conclusion Optimized CBCT acquisition protocols can significantly reduce the effective radiation dose while maintaining acceptable image quality by adjusting the milliamperage and projection images.

Problem: Novel vaccines were developed in an unprecedentedly short time in response to the global coronavirus disease (COVID-19) pandemic, which triggered concerns about the safety profiles of the new vaccines. This paper describes the actions and outcomes of three major adverse events of special interest (AESIs) reported in the World Health Organization’s (WHO’s) Western Pacific Region: anaphylaxis, thrombosis with thrombocytopenia syndrome (TTS) and post-vaccination death. Context: During the large-scale introduction of various novel COVID-19 vaccines, robust monitoring of and response to COVID-19 vaccine safety events were critical. Action: We developed and disseminated information sheets about anaphylaxis and TTS; provided tailor-made training for anaphylaxis monitoring and response, webinars about TTS and AESIs, and an algorithm to support decision-making about AESIs following immunization; as well as provided country-specific technical support for causality assessments, including for possible vaccination-related deaths. Outcome: Each major vaccine event and situation of high concern was responded to appropriately and in a timely manner with comprehensive technical support from WHO. Our support activities have not only strengthened countries’ capacities for vaccine safety surveillance and response, but also enabled countries to decrease the negative impact of these events on their immunization programmes and maintain the confidence of health-care professionals and the general population through proactive delivery of risk communications. Discussion: This paper summarizes selected, major AESIs following COVID-19 vaccination and responses made by WHO’s Regional Office for the Western Pacific to support countries. The examples of responses to vaccine safety events during the pandemic and unprecedented mass vaccination campaigns could be useful for countries to adopt, where applicable, to enhance their preparation for activities related to monitoring vaccine safety.

The speed at which new vaccines against coronavirus disease (COVID-19) were developed and rolled out as part of the global response to the pandemic was unprecedented. This report summarizes COVID-19 vaccine-related safety data in the World Health Organization Western Pacific Region. Data for 1 March 2021 to 31 March 2022 from 36 out of 37 countries and areas in the Western Pacific Region are presented. More than 732 million doses of eight COVID-19 vaccines were administered; reporting rates of adverse events following immunization (AEFIs) and serious AEFIs were 130.1 and 5.6 per 100 000 doses administered, respectively. Anaphylaxis, thrombosis with thrombocytopenia syndrome, and myocarditis/pericarditis were the most frequent COVID-19 adverse events of special interest (AESIs) reported. The reported rates of AESIs in the Western Pacific Region were within the range of expected or background rates. Vaccine benefits far outweigh the risk of reported serious adverse reactions and serious outcomes of COVID-19. Continued AEFI surveillance is recommended to better understand and ensure the safety profiles of novel COVID-19 vaccines.

Objective: Routine immunization coverage in Papua New Guinea has decreased in the past 5 years. This persistently low routine immunization coverage has resulted in low population immunity and frequent outbreaks of vaccine-preventable disease across the country. We describe the use of a catch-up programme to improve routine immunization during the coronavirus disease pandemic in Papua New Guinea during 2020–2022. Methods: In June 2020, 13 provinces of Papua New Guinea were selected to undergo a vaccination catch-up programme, with technical support from the World Health Organization (WHO) and the United Nations Children’s Fund. Twelve provinces received financial and logistic support through the Accelerated Immunization and Health Systems Strengthening programme, and one received support from WHO. All stakeholders were involved in planning and implementing the catch-up programme. Results: Between July 2020 and June 2022, about 340 health facilities conducted catch-up activities. The highest number of children aged under 1 year were vaccinated in 2022 (n = 33 652 for third dose of pentavalent vaccine). The national coverage of routine immunization (including the catch-up vaccinations) increased between 2019 and 2020 – by 5% for the third dose of pentavalent vaccine, 11% for the measles-rubella vaccine and 16% for the inactivated poliovirus vaccine. The coverage declined slightly in 2021 before increasing again in 2022. Discussion: The catch-up programme was an instrumental tool to improve routine immunization coverage between 2020 and 2022 and during the pandemic in Papua New Guinea. With appropriate technical and logistic support, including financial and human resources, catch-up programmes can strengthen routine immunization coverage across the country.

Introduction: During the Coronavirus Disease-2019 (COVID-19) pandemic, online learning has become an important strategy in the implementation of nursing education, in order to prevent the SARS-CoV-2 transmission in the education sector. This study aimed to assess: (i) the correlation between self-efficacy and psychological distress; (ii) the correlation between self-efficacy and online learning readiness; and (iii) the correlation between psychological distress and online learning readiness among nursing students in Indonesia. Methods: The cross-sectional study was conducted from October until December 2020, and involved 500 nursing students from 3 universities in Yogyakarta, Indonesia who were recruited using consecutive sampling methods. The instruments used in this study were: 1) the 10-item Kessler Psychological Distress Scale (K-10) to assess the psychological distress, 2) Online Learning Self-Efficacy Scale (OLSES) to assess online learning self-efficacy, and 3) Student Online Learning Readiness (SOLR) to assess online learning readiness. Spearman’s rank test was used to analyze the correlation between online learning self-efficacy, psychological distress, and online learning readiness. Results: Most of the nursing students (70.6%) had psychological distress ranging from mild to severe distress. The self-efficacy had an inverse correlation with psychological distress (Rho=-0.488, p=0.001). Contrarily, self-efficacy was positively correlated with online learning readiness (Rho=0.708, P=0.001). Psychological distress was inversely correlated with online learning readiness (Rho=-0.423, p=0.001). Conclusion: Online learning self-efficacy and psychological distress are significantly correlated with online learning readiness. Strategies to increase self-efficacy and ameliorates psychological distress, such as appropriate online learning training, adequate technical assistance, and psychological support were required to improve students’ online learning readiness.

Introduction: Personal preventive behaviors was cited as effective strategy to prevent the SARS-CoV-2 transmissions. When vaccine become available, preventive behavior must still be implemented to significantly decreased the COVID-19 infection risk in the emergence of novel SARS-CoV-2 variants of concern with immune escape phenotype. The Health Belief Model (HBM) is the most widely recognized behaviour theory, but its capacity to predict the preventive behaviours have been inconsistent. This study aimed to assess predictors adherence to COVID-19 preventive behaviour among nursing students based on HBM during the second wave of COVID-19 in Indonesia. Methods: An online cross-sectional study was conducted from May to September 2021. Undergraduate nursing students (n=1,413) from 10 universities in Indonesia was recruited using consecutive sampling. Online self-administered questionnaire was used to collect the data. Binary logistic regression was employed to analyse the association between sociodemographic and HBM construct with adherence to preventive behaviors. Results: Most of the students (n=804; 56.9 %) had poor adherence to COVID-19 preventive behaviors, and poor physical distancing identified as the most dominant non-adherence type (n=774; 54.8 %). First year students (AOR=1.313; 95%CI: 1.020-1.690), low perceived susceptibility (AOR=1.530; 95%CI: 1.193-1.962), low perceived severity (AOR= 1.756; 95%CI: 1.337- 2.307), low perceived effectiveness (AOR=1.910; 95%CI: 1.315-2.777), and low self-efficacy (AOR=4.795; 95%CI: 3.566-6.447) significantly associated with poor adherence (p<0.05). Nagelkerke R square value was 0.313 suggesting that the whole model explained 31.3% of variance in adherence. Conclusion: Intervention that targeting health belief model could be useful to increased adherence level to COVID-19 preventive measures among nursing students.

There is a lack of evidence regarding the use of betel quid (BQ) and its potential contribution to oral cancer. Limited attention has been directed towards investigating the involvement of BQ-derived organic acids in the modulation of metabolic-epigenomic pathways associated with oral cancer initiation and progression. We employed novel protocol for preparing saliva-amalgamated BQ filtrate (SABFI) that mimics the oral cavity environment. SABFI and saliva control were further purified by an in-house developed vertical tube gel electrophoresis tool. The purified SABFI was then subjected to liquid chromatography-high resolution mass spectrometry analysis to identify the presence of organic acids. Profiling of SABFI showed a pool of prominent organic acids such as citric acid. malic acid, fumaric acid, 2-methylcitric acid, 2-hydroxyglutarate, cis-aconitic acid, succinic acid, 2-hydroxyglutaric acid lactone, tartaric acid and β-ketoglutaric acid. SABFI showed anti-proliferative and early apoptosis effects in oral cancer cells. Molecular docking and molecular dynamics simulations predicted that SABFI-derived organic acids as potential inhibitors of the epigenetic demethylase enzyme, Ten-Eleven Translocation-2 (TET2). By binding to the active site of α-ketoglutarate, a known substrate of TET2, these organic acids are likely to act as competitive inhibitors. This study reports a novel approach to study SABFI-derived organic acids that could mimic the chemical composition of BQ in the oral cavity. These SABFI-derived organic acids projected as inhibitors of TET2 and could be explored for their role oral cancer.

Background: and Purpose Vestibular schwannoma (VS) is the most common type of tumor found in the cerebellopontine angle that accounts for 8% of all intracranial tumors. VS management is currently a challenge due to the unpredictable nature of the tumor. Few studies have compared the results and complications of various therapeutic approaches to VS. Therefore, as a treatment option for VSs smaller than 25 mm, we conducted a systematic review to compare Gamma Knife radiosurgery (GKRS) with conventional surgery. Methods: Literature searches were conducted of four online databases (PubMed, Google Scholar, Cochrane, and ScienceDirect) using the following keyword search: (“vestibular schwannoma” OR “acoustic neuroma”) AND (“gamma knife” OR “gamma knife radiosurgery”) AND (“resection” OR “open surgery”) AND (“hearing preservation” OR “facial nerve” OR “tumor growth”). Results: We identified six retrospective cohort studies, five of which were of fair-to-good quality. All studies showed that GKRS was superior to surgery in hearing preservation. Two studies indicated that surgery was superior to GKRS in maintaining tumor control, one indicated that GKRS was superior, and the remainder indicated that there was no significant difference in maintaining tumor control between GKRS and microsurgery. Conclusions Based on the three outcomes chosen for this review, GKRS was superior to microsurgery in small VS.