In Vitro Neutralisation Sensitivity of Gold (I) and Bismuth (III) Thiolates against Human Immunodeficiency Virus Type 1 virus-like particles

Human immunodeficiency virus type 1 (HIV-1) infects immune cells, causing one to experience immunodeficiency. The high prevalence of HIV-1 infections around the globe makes them the major public health issue. Anti-retroviral drugs (ARVs) are prescribed as treatment for HIV-1 infected individuals, yet the choices of effective ARVs become limited due to the rise of drug resistance. Therefore, the first objective of this study is to identify possible binding target of gold thiolates, specifically as entry inhibitors, through in silico analysis; and the second objective is to unveil potential anti-HIV-1 activities of gold thiolates as well as bismuth thiolates (hereon define as AAu and Bis complexes) against viral replication and viral entry. Physical binding abilities of complexes to HIV-1 viral proteins were screened using ELISA assay. Complexes were added to recombinant viral proteins, but no interaction was found between the complexes and the recombinant proteins tested. In spite of that, AAu and Bis complexes exhibited in vitro anti-HIV-1 activities in bioassays that involves the use of virus-like particles (VLPs). HIV-1 VLPs were produced from transient transfection of HEK293T cells with HIV-1 encoding luciferase reporter vectors and Env-expressing plasmids. By exposing HEK293T cells to treatments before or after transfection, AAu3, AAu2, Bis2, and Bis3 resulted in reduced level of viral protein expressed and/or decreased viral infectivity, thus suggesting their effects against viral replication with the following mechanisms of actions: (1) AAu2 and AAu3 disrupts the formation of functional VLPs; and (2) Bis2 and Bis3 affect the overall viral protein expression. In addition to viral replication, inhibitory effects of AAu and Bis complexes against the entry of HIV-1 VLPs were evaluated by treating VLPs before infecting Cf2Th.CD4.CCR5 cells that are permissive to infections of HIV-1 virions and VLPs. All complexes demonstrated significant neutralising activities against HIV-1 strains (strain BG505.W6M.C2, JR-FL, WTO.33, ZM197 and CM246.c1) with IC50 values ranged between 0.6 µg/mL and 6.13 µg/mL. The neutralising properties of AAu complexes were supported by the in silico docking studies that revealed their potential interacting site on HIV-1 Env trimer. AAu1 – 3 bind similarly to inner domain of Env trimer, demonstrating binding affinities from -7.34 kcal/mol to -7.62 kcal/mol. The interacting site shared among AAu complexes lies within the interface of gp120 and gp41 subunits, a site that play major role in regulating subunit gp120-gp41 association and CD4-gp120 association. Based on the in vitro neutralisation assays and docking studies, AAu and Bis complexes are suggested as potential entry inhibitors due to their significant neutralizing activities against HIV-1 VLPs, more notably AAu with a proposed mechanism in which the conformational shifting of Env is intervened

A study on cyberbullying among visually impaired youth in Malaysia: prevalence and its associated factors

Technological advances have revolutionised the way we communicate, especially with the influx of social networking sites used primarily by young people. However, a worldwide phenomenon, cyberbullying, is a cause of concern for youth advocates who are up to date with technology. Malaysian visually impaired youth are vulnerable to cyberbullying, but the aspect has been poorly studied in Malaysia. This is a mixed method sequential study with two phases. Phase 1 uses quantitative methods to investigate the prevalence rate of cyberbullying from the perspectives of victims, perpetrators, and bystanders among Malaysian visually impaired youth as well as the technological exposure, self-efficacy, and social support associated with cyberbullying experiences and if social support acted as a mediator between variables. For Phase 2, qualitative focus groups were used to collect data on how participants experience cyberbullying with regards technological exposure, self-efficacy, and social support. 199 Malaysian visually impaired youths (Mean = 17.81; S.D.= 1.641) participated in this mixed-method cross-sectional study (Phase 1) with Braille paper-and-pen and voice-over online surveys. Data were analysed using the Statistical Package for the Social Sciences (SPSS) and Partial Least Squares Structural Equation Modeling (PLS-SEM) to test the proposed research hypotheses. For phase 1, the results revealed that of the 188 participants, 47.2% are cybervictims, 10.6% are cyberperpetrators, and 50.3% are cyberbystanders. Social support from teachers is the most important factor negatively influencing cyberbullying experiences, followed by empathic and defending self-efficacy. Results also showed that defending self-efficacy was positively related to social support from family and friends and social support from teachers. Indirect mediating relationships were investigated and found that social support from teachers mediated the relationship between defending self-efficacy and cyberbullying experiences, as well as empathic self-efficacy and cyberbullying experiences. For Phase 2, the research objective was to explore how participants experience cyberbullying with regards technological exposure, self-efficacy, and social support and data were analysed using NVivo software. Phase 2 qualitative findings supported the quantitative results and provided the rich details in the three themes which emerged: (1) Technological exposure, (2) Self-efficacy, and (3) Social support. To raise awareness of cyberbullying, an educational programme can be considered that focuses on raising awareness of cyberbystanders. Implementing educational programmes on the importance of support from school counsellors and teachers should be considered to teach students skills such as coping mechanisms for cyberbullying to reduce the incidence of cyberbullying. In addition, implementation of law and regulation by the government is relatively important and should be drawn attention to, in order to decrease the likelihood of cyberbullying incidents

Natural bioactive compounds targeting DNA methyltransferase enzymes in cancer: Mechanisms insights and efficiencies

The regulation of gene expression is fundamental to health and life and is essentially carried out at the promoter region of the DNA of each gene. Depending on the molecular context, this region may be accessible or non-accessible (possibility of integration of RNA polymerase or not at this region). Among enzymes that control this process, DNA methyltransferase enzymes (DNMTs), are responsible for DNA demethylation at the CpG islands, particularly at the promoter regions, to regulate transcription. The aberrant activity of these enzymes, i.e. their abnormal expression or activity, can result in the repression or overactivation of gene expression. Consequently, this can generate cellular dysregulation leading to instability and tumor development. Several reports highlighted the involvement of DNMTs in human cancers. The inhibition or activation of DNMTs is a promising therapeutic approach in many human cancers. In the present work, we provide a comprehensive and critical summary of natural bioactive molecules as primary inhibitors of DNMTs in human cancers. The active compounds hold the potential to be developed as anti-cancer epidrugs targeting DNMTs

ChatGPT in psychiatry: promises and pitfalls

ChatGPT has become a hot topic of discussion since its release in November 2022. The number of publications on the potential applications of ChatGPT in various fields is on the rise. However, viewpoints on the use of ChatGPT in psychiatry are lacking. This article aims to address this gap by examining the promises and pitfalls of using ChatGPT in psychiatric practice. While ChatGPT offers several opportunities, further research is warranted, as the use of chatbots like ChatGPT raises various technical and ethical concerns. Some practical ways of addressing the challenges for the use of ChatGPT in psychiatry are also discussed

A systematic review on the silica fibre thermoluminescence dosimeters for medical applications

Silica fibre thermoluminescence (TL) dosimeters have demonstrated versatility in medical and industrial, offering high spatial resolution, sensitivity, water resistance, and insensitivity to electromagnetic fields. A systematic review focusing on the medical applications of silica fibre TLDs is conducted, highlighting the potential of these materials in medical radiation dosimetry. Despite some limitations, such as non-linearity at low energies and relatively high signal fading, silica fibre TL dosimeters have shown excellent TL performance. However, their application in clinical practice is yet to be established since the TL responses for a wide range of doses and energies are not accurately certified yet

Carbon nanotube–graphene-based nanofluids: a comprehensive review on the role of thermal conductivity and its solar energy applications

Nowadays, nanofluids are considered as excellent working fluids with good thermophysical properties for augmenting the heat transfer in solar systems. Consisting of single-phase nanopowder, metal oxide-based nanofluids exhibit either a good thermal network or good physicochemical properties. Allotropes of carbon (e.g., carbon nanotubes; CNTs and graphene) have their own set of distinct structural and thermal properties to enhance the thermophysical properties of base fluids (e.g., water, ethylene glycol, etc.). For working fluids, researchers tried to optimize the preparation methodology in which a two-step method has been preferred due to the synergistic involvement of solid (i.e., particulate) and liquid (i.e., base fluid) phase. Also, several research groups have discussed the thermal behavior of different nanofluids with the help of correlations. A combination of MgO and CNTs has also been studied thoroughly to distinguish the effect of temperature and concentration of solid phase on the thermal conductivity of nanofluid. Further, CNT/graphene-based nanofluids serve a critical role in improving the thermal performance of solar collectors, solar stills, solar ponds, and solar cookers. It can also be utilized to reduce the surface temperature of solar cells in photo voltaic thermal (PV/T) systems which in turn increases the electrical efficiency of these systems. The present work illustrates a detailed review on the CNT/graphene-based nanofluids and their structural features for different solar energy applications

Kenaf-based activated carbon: A sustainable solution for high-performance aqueous symmetric supercapacitors

This study presents an innovative method for synthesizing activated carbon with an exceptionally high surface area (3359 m2 g-1) using kenaf fiber-based biochar through chemical activation. The achieved specific surface area surpasses activated carbon derived from other reported fiber-based precursors. The resulting activated carbon was investigated as electrodes for supercapacitors, revealing a remarkable maximum capacitance of 312 F g-1 at a current density of 0.5 A g-1. An aqueous symmetric supercapacitor employing these high-surface-area electrodes exhibited an outstanding energy density of 18.9 Wh kg-1 at a power density of 250 W kg-1. Notably, the supercapacitor retained exceptional capacitance, maintaining 93% of its initial capacitance even after 5000 charge-discharge cycles

Men in nursing in Malaysia: breaking stereotypes and shaping the future of health care

More men are becoming nurses, breaking gender norms and reshaping health care in the country. Nursing has long been regarded as a profession for women, and the situation is still very much the case in Malaysia. But even though history has denoted this fact, recent years have shown that there is a remarkable shift in this trend, with more men entering the nursing profession, thus breaking gender norms and reshaping health care in the country

It’s Time For Long-Term Care Home To Make Mental Health A Priority

The 2024 World Mental Health Day theme, “It’s Time to Prioritize Mental Health in the Workplace,” highlights the need to focus on mental well-being in long-term care facilities, often a new ‘workplace’ for many elders. The challenge is to shift from prioritising physical care to recognising mental health as equally essential for overall well-being

Structural vaccinology, molecular simulation and immune simulation approaches to design multi-epitopes vaccine against John Cunningham virus

The JCV (John Cunningham Virus) is known to cause progressive multifocal leukoencephalopathy, a condition that results in the formation of tumors. Symptoms of this condition such as sensory defects, cognitive dysfunction, muscle weakness, homonosapobia, difficulties with coordination, and aphasia. To date, there is no specific and effective treatment to completely cure or prevent John Cunningham polyomavirus infections. Since the best way to control the disease is vaccination. In this study, the immunoinformatic tools were used to predict the high immunogenic and non-allergenic B cells, helper T cells (HTL), and cytotoxic T cells (CTL) epitopes from capsid, major capsid, and T antigen proteins of JC virus to design the highly efficient subunit vaccines. The specific immunogenic linkers were used to link together the predicted epitopes and subjected to 3D modeling by using the Robetta server. MD simulation was used to confirm that the newly constructed vaccines are stable and properly fold. Additionally, the molecular docking approach revealed that the vaccines have a strong binding affinity with human TLR-7. The codon adaptation index (CAI) and GC content values verified that the constructed vaccines would be highly expressed in E. coli pET28a (+) plasmid. The immune simulation analysis indicated that the human immune system would have a strong response to the vaccines, with a high titer of IgM and IgG antibodies being produced. In conclusion, this study will provide a pre-clinical concept to construct an effective, highly antigenic, non-allergenic, and thermostable vaccine to combat the infection of the John Cunningham virus