We aimed to investigate the effects that natural lipids, theobroma oil (TO) and beeswax (BW), might have on the physical properties of formulated nanoparticles and also the degree of expulsion of encapsulated amphotericin B (AmB) from the nanoparticles during storage. Lecithin and sodium cholate were used as emulsifiers whilst oleic acid (OA) was used to study the influence of the state of orderliness/disorderliness within the matrices of the nanoparticles on the degree of AmB expulsion during storage. BW was found to effect larger z-average diameter compared with TO. Lecithin was found to augment the stability of the nanoparticles imparted by BW and TO during storage. An encapsulation efficiency (%EE) of 59% was recorded when TO was the sole lipid as against 42% from BW. In combination however, the %EE dropped to 39%. When used as sole lipid, TO or BW formed nanoparticles with comparatively higher enthalpies, 21.1 and 23.3 J/g respectively, which subsequently caused significantly higher degree of AmB expulsion, 81 and 83% respectively, whilst only 11.8% was expelled from a binary TO/BW mixture. A tertiary TO/BW/OA mixture registered the lowest enthalpy at 8.07 J/g and expelled 12.6% of AmB but encapsulated only 22% of AmB. In conclusion, nanoparticles made from equal concentrations of TO and BW produced the most desirable properties and worthy of further investigations.
Pancytopenia can rarely complicate Grave's disease. It can be due to uncontrolled thyrotoxicosis or as a result of rare side effect of antithyroid medication. Pernicious anemia leading to Vitamin B12 deficiency is another rare associated cause. We report a case of a patient with Grave's disease and undiagnosed pernicious anemia whom was assumed to have antithyroid drug induced pancytopenia. Failure to recognize this rare association of pernicious anemia as a cause of pancytopenia had resulted in delay in treatment and neurological complication in our patient.
Since the inception of deep sequencing, isomiRs are consistently observed to be produced by most miRNA genes in a variety of cell types. IsomiRs appear as a variation in length from the canonical sequence annotated in miRBase, due to an addition or deletion of one or more nucleotides at the 5(') or 3(') ends or both. As the seed sequence is located at the 5(') end of the microRNA, the target mRNA will be theoretically different. Therefore, 5(')isomiRs might potentially target a new set mRNA compared to their canonical counterpart. This article gives an overview of investigations that explored the functional potential of isomiRs such as their ability to incorporate into Argonaute protein, the differential expression of isomiRs in various tissue types and cell lines, and the differences of mRNA targets between isomiR and its canonical microRNA. In addition, this article provides a brief introduction of RNA sponges as a potential way to inhibit isomiRs.
Cervical cancer is a common malignancy which poses a significant health burden among women, especially those living in the developing countries. Although human papillomavirus (HPV) infection has been unequivocally implicated in the etiopathogenesis of the cancer, it alone is not adequate to contribute to the malignant transformation of cervical cells. Most HPV infections regress spontaneously, and only a small proportion of women have persistent infections which eventually lead to malignancy. This suggests that interplays between HPV infection and other cofactors certainly exist during the process of cervical carcinogenesis, which synergistically contribute to the differential susceptibility of an individual to the malignancy. Undoubtedly, host genetic factors represent a major element involved in such a synergistic interaction, and accumulating evidence suggests that polymorphisms in apoptosis-related genes play an important role in the genetic susceptibility to cervical cancer. This review consolidates the recent literatures on the role of common polymorphisms in apoptosis-related genes in genetic susceptibility to cervical cancer.
Total lockdown caused deleterious mental health to many, resulting from a sudden change in daily routine, working and self-isolation at home, and job and income losses. Therefore, the current study aims to assess the social determinants of self-reported psychological distress in Malaysian adults during the COVID-19 pandemic. Snowball and purposive sampling approaches were adopted to enroll potential respondents. Respondents were required to self-report gender, age, ethnicity, educational attainment, marital status, number of dependents, and the presence of clinically diagnosed psychological disorders. Psychological distress during the pandemic was assessed using 21-item of the Depression Anxiety Stress Scales (DASS-21). The findings revealed that respondents with primary/secondary educational attainment were 1.962 times (95% CI: 1.018-3.781, p= 0.044) more likely to suffer from depression than those with tertiary educational attainment. Conversely, the Malaysian Indians had significantly lower odds for depression compared to Malaysian Malays (AOR = 0.538, 95% CI: 0.302-0.957, p= 0.035). Likewise, females were found to have significantly greater odds for anxiety (AOR = 2.369, 95% CI: 1.317-4.260, p= 0.004) and stress (AOR = 1.976, 95% CI: 1.007-3.879, p = 0.048) than males. Being single was at significantly higher odds for anxiety (AOR = 2.032, 95% CI: 1.133-3.646, p= 0.017) during the pandemic. This study highlights the urgency to address the escalated psychological distress in Malaysian adults during the pandemic.
This scoping review aimed to clarify and redefine the concepts of social and physical presence in the context of online livestreaming environments. Physical presence involves technical elements and nonhuman-to-human interaction, factors that inevitably influence social presence, which has human-to-human interactions at its core. Considering one type of presence to the exclusion of the other may not provide sufficiently informed decisions for user consumption. However, most previous studies have only studied either physical or social presence factors; few have systematically examined both to explain their influence. This review examined how the factors under these two presence influenced users' consumption decision-making process in TikTok live-stream retail purchases by synthesizing 60 studies conducted from 2019 to 2023 using Arksey and O'Malley's 5-step framework. Evidence of the specific attributes by which presence affects users' consumption decisions was elicited and reorganized. Using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) framework for scoping review and guided by the joanna briggs institute (JBI) methodological guidelines, the results reveal that out of the 60 studies, 36 were influenced by social presence and 24 by physical presence. When livestreaming online, social presence tends to include the user and anchor perspectives, which prompts users to make consumption decisions. However, online physical presence includes products, technology, and scenes as its main dimensions, and users make consumption decisions through perceptual control. This review clarifies new media livestreaming communication and the key factors influencing users' consumption decision-making systems. It also suggests that integrating online social and physical presence in future research will yield a better understanding of livestreaming purchase decisions.
In parallel to the uncontrolled use of antibiotics, the emergence of multidrug-resistant bacteria, like Acinetobacter baumannii, has posed a severe threat. A. baumannii predominates in the nosocomial setting due to its ability to persist in hospitals and survive antibiotic treatment, thereby eventually leading to an increasing prevalence and mortality due to its infection. With the increasing spectra of drug resistance and the incessant collapse of newly discovered antibiotics, new therapeutic countermeasures have been in high demand. Hence, recent research has shown favouritism towards the long-term solution of designing vaccines. Therefore, being a realistic alternative strategy to combat this pathogen, anti-A. Baumannii vaccines research has continued unearthing various antigens with variable results over the last decade. Again, other approaches, including pan-genomics, subtractive proteomics, and reverse vaccination strategies, have shown promise for identifying promiscuous core vaccine candidates that resulted in chimeric vaccine constructs. In addition, the integration of basic knowledge of the pathobiology of this drug-resistant bacteria has also facilitated the development of effective multiantigen vaccines. As opposed to the conventional trial-and-error approach, incorporating the in silico methods in recent studies, particularly network analysis, has manifested a great promise in unearthing novel vaccine candidates from the A. baumannii proteome. Some studies have used multiple A. baumannii data sources to build the co-functional networks and analyze them by k-shell decomposition. Additionally, Whole Genomic Protein Interactome (GPIN) analysis has utilized a rational approach for identifying essential proteins and presenting them as vaccines effective enough to combat the deadly pathogenic threats posed by A. baumannii. Others have identified multiple immune nodes using network-based centrality measurements for synergistic antigen combinations for different vaccination strategies. Protein-protein interactions have also been inferenced utilizing structural approaches, such as molecular docking and molecular dynamics simulation. Similar workflows and technologies were employed to unveil novel A. baumannii drug targets, with a similar trend in the increasing influx of in silico techniques. This review integrates the latest knowledge on the development of A. baumannii vaccines while highlighting the in silico methods as the future of such exploratory research. In parallel, we also briefly summarize recent advancements in A. baumannii drug target research.
Diagnosing and managing antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) remain a challenge for many clinicians, due to the complexity of the disease manifestations and its treatment. There has been a paradigm shift in ANCA vasculitis management, where treatment incorporates both emergency life- and organ-saving procedures and longer-term care to manage relapse and co-morbidity risk and the complications of organ damage. Here, we highlight 10 key tips for the management of ANCA-associated vasculitis based on current evidence and clinical experience. First, we advise making the diagnosis as early as possible, emphasizing the importance of using high-quality ANCA assays. Second, we recommend the use of glucocorticoids in combination with rituximab and/or cyclophosphamide as induction therapy. Third, plasma exchange should be considered in patients with severe renal impairment and diffuse alveolar haemorrhage. We advise the use of rapidly reducing glucocorticoid regimens and advocate consideration of avacopan early in the disease course. We recommend the use of rituximab as maintenance therapy and routine monitoring of kidney function, proteinuria, ANCA and immunoglobulin levels at baseline and during follow-up. The use of prophylactic antibiotics in susceptible patients and timely vaccination schedules is discussed. Rituximab is the preferred immune suppressive for treatment of relapse. Finally, we recommend switching treatment modalities in patients whose vasculitis is refractory to induction therapy and to consider plasma exchange in selected patients. These key tips aim to provide the necessary guidance to improve patient outcomes and reduce adverse events.
The dilemmas and uncertainties related to determining mental capacity and surrogate decision-making are universally recognised as one of the most important concepts in the field of clinical ethics. In Malaysia, healthcare practitioners often find both determining decision-making capacity of patients, and identifying surrogate decision makers for incapacitated patients confusing. This paper explores the concepts of decision-making capacity and surrogate decision-making, identifying key components and associated principles such as substituted judgement and best interests. It reviews current provisions and guidances available in Malaysia that are related to these issues, including the Power of Attorney Act 1949 (revised 1990), Mental Health Act 2001, and various guidelines. It then highlights the challenges encountered in the local clinical setting due to the lack of specific legislation and clear guidance. Finally, this paper provides recommendations for improvements to address these issues in order to safeguard both the clinical practice of healthcare professionals and the rights of patients. These recommendations include the establishment of a regulatory framework with four main domains: clear and objective criteria for mental capacity assessment, provisions for advance decision-making while patients still possess mental capacity, a ladder or hierarchy of surrogate decision-makers, and provisions for appropriate surrogate decision-making standards, as well as the need for advocacy and awareness education among both the general public and healthcare professionals.
In recent years, the demand for probiotic beverages has surged, with dairy products traditionally serving as the primary sources of probiotics. However, many consumers face health issues such as lactose intolerance, milk allergies, and high cholesterol, which prevent them from consuming dairy products. This has led to the exploration of nondairy alternatives, particularly fruit juices, as carriers for probiotics. Lactic acid bacteria (LAB) have been identified as beneficial probiotics that can be incorporated into these beverages. The inclusion of prebiotics, such as inulin and galacto-oligosaccharides (GOS), in fruit juices has shown promise in enhancing the growth and activity of LAB, thereby creating functional beverages that support digestive health. Despite numerous studies on fruit juice fermentation, there is limited data on the optimal pairing of probiotics and prebiotics to develop stable, nondairy functional drinks. This review underscores the potential of lactic acid fermentation and the integration of prebiotics and probiotics in fruit juices, highlighting the necessity for further research to optimize these combinations for enhanced health benefits and improved beverage stability.
Paragangliomas, a type of extra-adrenal tumour, albeit rare, are dangerous due to their high metastatic potential and risk of hypertensive crisis from massive catecholamine release. It typically presents with sympathetic overdrive symptoms such as diaphoresis, headache, and palpitation, accompanied by substantially high plasma metanephrines level and mass on contrasted computed tomography abdomen and pelvis, whilst some are found incidentally. In this report, we discuss a case of an extra-adrenal lesion located near susceptible major structures with extensive vascularisation, in a patient with near-death experience. Complete excision of the pulsatile mass with minimal bleeding and no complications, was made possible utilizing the da Vinci Robotic System. Robotic surgery, being a part of a multidisciplinary approach, leads to better patient outcomes and shorter hospitalisations. Moreover, it offers enhanced dexterity and improved depth perception compared to conventional methods. However, further studies are needed to validate its application in standard practice.
Platinum-based chemotherapy (PBC) is a widely used treatment for various solid tumors, including non-small cell lung cancer (NSCLC). However, its efficacy is often compromised by the emergence of drug resistance in patients. There is growing evidence that genetic variations may influence the susceptibility of NSCLC patients to develop resistance to PBC. Here, we provide a comprehensive overview of the mechanisms underlying platinum drug resistance and highlight the important role that genetic polymorphisms play in this process. This paper discussed the genetic variants that regulate DNA repair, cellular movement, drug transport, metabolic processing, and immune response, with a focus on their effects on response to PBC. The potential applications of these genetic polymorphisms as predictive indicators in clinical practice are explored, as are the challenges associated with their implementation.