Browse publications by year: 2024

  1. Yap XY, Khalid M, Raju G, Gew LT, Yow YY
    Int J Biol Macromol, 2024 Sep 07.
    PMID: 39256129 DOI: 10.1016/j.ijbiomac.2024.135205
    Rising concerns around plastic pollution from single-use plastic (SUPs), especially food packaging, have driven interest in sustainable alternatives. As such, algae biomass has gained attention for bioplastic production due to algae's rapid growth and abundant polysaccharides. This research focuses on extracting carrageenan from Kappaphycus alvarezii, extensively cultivated in Sabah, Malaysia, and utilizing it in combination with starch and glycerol to develop algae-based films. The physicochemical properties and degradation rate of these films were evaluated, revealing that the addition of carrageenan enhanced overall thermal stability meanwhile increasing water solubility, water content but reducing the degradation rate and swelling degree. This is primarily due to the crystalline structures of carrageenan, which provide a more rigid arrangement compared to the network of starch polymers. However, the incorporation of starch into the blends has enhanced the elongation and surface morphology, resulting in more balanced properties. Overall, these carrageenan films displayed impressive thermal, mechanical, and biodegradability characteristics, establishing their viability as substitutes for conventional plastics.
  2. Venugopal V, Ng DC
    BMJ Case Rep, 2024 Sep 10;17(9).
    PMID: 39256178 DOI: 10.1136/bcr-2024-261058
    The BCG vaccine is considered a safe and efficacious vaccine in the prevention of severe forms of tuberculosis. BCG osteomyelitis is a rare complication of the BCG vaccine that occurs in vaccinated young children. We report a case of BCG osteomyelitis in a male toddler, presenting with painful left wrist swelling without preceding fever or systemic symptoms. Radiographic evidence of osteomyelitis in the left wrist was observed. Initial treatment with conventional antibiotics for acute haematogenous osteomyelitis showed no improvement. The diagnosis of Mycobacterium bovis BCG osteomyelitis was confirmed via tissue samples for histopathological examination and mycobacterial cultures. The patient responded well to treatment with oral antituberculous therapy. This case highlights the importance of considering BCG osteomyelitis in the differential diagnosis of unexplained joint swelling in BCG-vaccinated young children.
    MeSH terms: Antitubercular Agents/therapeutic use; Diagnosis, Differential; Humans; Infant; Male; Vaccination/adverse effects
  3. Sardar F, Kamsani YS, Ramly F, Mohamed Noor Khan NA, Sardar R, Aminuddin AA
    Biol Trace Elem Res, 2024 Sep 10.
    PMID: 39256331 DOI: 10.1007/s12011-024-04364-5
    Preeclampsia (PE), caused by multiple factors, is one of the most serious complications of pregnancy. Cadmium (Cd) is a heavy metal environmental pollutant, reproductive toxicant, and endocrine disruptor, which can increase the risk of PE. Cd toxicity due to occupational, diet, and environmental factors has worsened the risk. Studies showed elevated Cd concentration in maternal blood and placenta of PE women. However, the implicit association between Cd associated PE is still not highlighted. We systematically reviewed Cd-associated PE and its effect on pregnancy and birth outcomes. Based on "Preferred reporting items for systematic reviews and meta-analyses (PRISMA)" guidelines, eighty-six studies were identified by PubMed, Web of Science (WOS), and Scopus databases. Publications were included until October 2023 and articles screened based on our inclusion criteria. Our study identified that the exposure of controlled and uncontrolled Cd induces PE, which negatively affects pregnancy and birth outcomes. Given the serious nature of this finding, Cd is a potential adverse agent that impacts pregnancy and future neonatal health. Further comprehensive studies covering the whole trimesters of pregnancy and neonatal developments are warranted. Data on the molecular mechanisms behind Cd-induced PE is also essential for potential preventive, diagnostic, or therapeutic targets.
  4. Njaka S, Hassan IIB, Nwedu AB, Bakar RSB, Cheng KY
    BMC Nurs, 2024 Sep 10;23(1):630.
    PMID: 39256707 DOI: 10.1186/s12912-024-02298-w
    BACKGROUND: Globally, there is increasingly high prevalence of mental disorders across all age groups and social classes with more being projected by 2030, but without commensurate resources for mental health care delivery especially in developing countries.

    PURPOSE: This study examined the impacts of clinical psychiatric posting on career choice in psychiatry among nursing students in Ebonyi state, Nigeria.

    METHODS: A prospective cohort research design was used and data were collected using attitude towards psychiatry (ATP), mental illness clinician attitude scale (MICA-4) and researcher developed questionnaires on career choice in pre and post clinical posting approach. This study was conducted between November, 2023 to May 2024. A sample size of 400 students (with data collected before posting and after posting) were involved in the study. Data were coded, cleaned and analyzed using SPSS version 26. McNemar Test was used to determine effects of clinical posting on career choices in psychiatry. Simple and multiple logistic regressions were used to analyze data on determinants of career choices in psychiatry. The hypotheses (Null and alternative hypotheses) were tested at p-value 

  5. Zakaria ER, Wan Ghazali WS, Sazali H, Shahril NS, Md Salleh S, Mohd Nawi SN
    BMC Rheumatol, 2024 Sep 10;8(1):41.
    PMID: 39256797 DOI: 10.1186/s41927-024-00413-7
    BACKGROUND: Acrocyanosis is characterised by persistent bluish discolouration of the extremities, resulting from reduced peripheral blood flow leading to increased oxygen extraction. The aetiology can be divided into primary and secondary causes. While primary acrocyanosis is generally painless and has a benign course, secondary causes may lead to complications. This case reported acrocyanosis secondary to cutaneous vasculitis which progressed to digital gangrene, which is a rare complication of cutaneous vasculitis.

    CASE PRESENTATION: A 68-year-old man presented with a four-day history of bluish discolouration involving bilateral toes associated with pain and started to become gangrenous. Investigations for critical limb ischemia did not show evidence of critical arterial stenosis. Further history revealed history of recent administration of intramuscular injections with diclofenac, a non-steroidal anti-inflammatory agent for renal colic pain a few days prior to the onset of the. Thorough skin search showed multiple purpuric rash of his thighs, buttocks and abdomen. Skin biopsy confirmed the diagnosis of cutaneous (lymphocytic) vasculitis, which was likely to be drug-induced. The acrocyanosis initially responded to methylprednisolone, however unfortunately it progressed further to digital gangrene which required bilateral transmetatarsal amputations.

    CONCLUSION: Knowledge on clinical features, aetiology and investigations of secondary acrocyanosis is crucial for early recognition and treatment of the underlying cause to prevent irreversible complications.

  6. Ahmad RM, Ali BR, Al-Jasmi F, Al Dhaheri N, Al Turki S, Kizhakkedath P, et al.
    Hum Genomics, 2024 Sep 11;18(1):99.
    PMID: 39256852 DOI: 10.1186/s40246-024-00667-9
    Single nucleotide variants (SNVs) can exert substantial and extremely variable impacts on various cellular functions, making accurate predictions of their consequences challenging, albeit crucial especially in clinical settings such as in oncology. Laboratory-based experimental methods for assessing these effects are time-consuming and often impractical, highlighting the importance of in-silico tools for variant impact prediction. However, the performance metrics of currently available tools on breast cancer missense variants from benchmarking databases have not been thoroughly investigated, creating a knowledge gap in the accurate prediction of pathogenicity. In this study, the benchmarking datasets ClinVar and HGMD were used to evaluate 21 Artificial Intelligence (AI)-derived in-silico tools. Missense variants in breast cancer genes were extracted from ClinVar and HGMD professional v2023.1. The HGMD dataset focused on pathogenic variants only, to ensure balance, benign variants for the same genes were included from the ClinVar database. Interestingly, our analysis of both datasets revealed variants across genes with varying penetrance levels like low and moderate in addition to high, reinforcing the value of disease-specific tools. The top-performing tools on ClinVar dataset identified were MutPred (Accuracy = 0.73), Meta-RNN (Accuracy = 0.72), ClinPred (Accuracy = 0.71), Meta-SVM, REVEL, and Fathmm-XF (Accuracy = 0.70). While on HGMD dataset they were ClinPred (Accuracy = 0.72), MetaRNN (Accuracy = 0.71), CADD (Accuracy = 0.69), Fathmm-MKL (Accuracy = 0.68), and Fathmm-XF (Accuracy = 0.67). These findings offer clinicians and researchers valuable insights for selecting, improving, and developing effective in-silico tools for breast cancer pathogenicity prediction. Bridging this knowledge gap contributes to advancing precision medicine and enhancing diagnostic and therapeutic approaches for breast cancer patients with potential implications for other conditions.
    MeSH terms: Artificial Intelligence*; Female; Humans; Software; Computational Biology/methods; Genetic Predisposition to Disease; Databases, Genetic*
  7. Teong YW, Mustapha KB, Ibitoye MO
    PMID: 39256915 DOI: 10.1080/10255842.2024.2399018
    Prior studies have revealed that the structural design of stents is critical to reducing some of the alarming post-operative complications associated with stent-related intervention. However, the technical search for stents that guarantee robustness against stent-induced post-intervention complications remains an open problem. Along this objective, this study investigates a re-entrant auxetic stent's structural response and performance optimizations. In pursuit of the goal, a nonlinear finite element analysis (FEA) is employed to uncover metrics characterizing the auxetic stent's mechanical behavior. Subsequently, the non-dominated sorting genetic algorithm (NSGA-II) is implemented to simultaneously minimize the stent's von Mises stress and the elastic radial recoil (ERR). Results from the FEA revealed a tight connection between the stent's response and the features of the base auxetic building block (the rib length, strut width, and the re-entrant angle). It is observed that the auxetic stent exhibits a much lower ERR. Besides, larger values of its rib length and re-entrant angle are noticed to favor smaller von Mises stress. The Pareto-optimal front from the NSGA-II-based optimization scheme revealed a sharp trade-off in the simultaneous minimization of the von Mises stress and the ERR. Moreover, an optimal combination of the auxetic unit cell's geometric parameters is found to yield a much lower maximum von Mises stress of ≈403 MPa and ERR of ≈0.4%.
  8. Abdul Halim N, Md Yassin M, Mohamad Ali ND, Miptah HN
    Am J Case Rep, 2024 Sep 11;25:e944399.
    PMID: 39256984 DOI: 10.12659/AJCR.944399
    BACKGROUND Eagle syndrome is an uncommon medical illness that can manifest as neck pain in primary care. It results from an abnormally unilateral or bilateral long styloid process that may compress and affect adjacent structures, which leads to the symptoms. Classical Eagle syndrome has been commonly reported, but this case highlights the uncommon involvement of autonomic nerve dysfunction. CASE REPORT This case report details a 43-year-old woman with chronic neck pain for 5 years who saw numerous medical professionals and underwent 8 physiotherapy sessions. Marginal improvement of her neck pain and recent development of imbalance and a floating sensation prompted escalation of radiological imaging that eventually led to the diagnosis of Eagle syndrome. She was subsequently subjected to tonsillectomy and styloidectomy to address the sources of her neck pain. CONCLUSIONS Neck pain is a common complaint in primary care, but Eagle syndrome is often overlooked due to its complex symptoms, which mimic other conditions resulting in missed diagnoses and prolonged diagnostic evaluations. To improve patient care and outcomes, primary care physicians should consider Eagle syndrome when evaluating neck pain. This involves taking a detailed clinical history, conducting a thorough physical examination, using appropriate imaging techniques, and knowing the treatment options. By considering this potential diagnosis, primary care physicians, other healthcare professionals, and physical therapists play an important role in referring these patients to an otorhinolaryngologist or a maxillofacial surgeon for a comprehensive evaluation and management.
    MeSH terms: Adult; Female; Humans; Primary Health Care
  9. Lim CC, Liew YT, Ghauth S, Narayanan P
    Turk Arch Otorhinolaryngol, 2024 Jul 03;62(1):33-37.
    PMID: 39257051 DOI: 10.4274/tao.2024.2023-12-15
    Endoscopic transoral excision of parapharyngeal space (PPS) tumors is often condemned for its many limitations. We revisit this approach and aim to introduce some updated perspectives following the advancement of endoscopic instrumentation, robotic transoral surgery, and radical tonsillectomy. We illustrate the techniques that were deployed for six patients with huge benign PPS tumors originating from the pre-styloid compartment at our center. Only patients who had a tumor size of five cm or larger were included in this study. We summarized our patients' outcomes, the important considerations, and the advantages and disadvantages of this approach. With accurate selection and surgical strategy, all our patients had good clinical outcomes. We demonstrated that even larger tumors can be safely removed endoscopically. Surely, this approach will gain traction, and better-designed studies should be conducted in the future to assess its credibility.
  10. Thevi T, Abas AL, Dua HS
    Indian J Ophthalmol, 2024 Sep 10.
    PMID: 39257085 DOI: 10.4103/IJO.IJO_300_24
    Management of nonhealing corneal ulcers is challenging as it can lead to complications such as melting, descemetocele, and perforation, which can be prevented by amniotic membrane graft (AMG). The absence of any review (English language) on AMG for corneal ulcers prompted us to conduct this review. We looked for clinical trials (randomized and controlled) on the effect of AMG combined with other treatments, through various search engines utilizing the terms amniotic membrane and corneal ulcer. All patients who received AMG and/or conventional medication were included. Risk of bias tools derived from Cochrane collaboration were used to ascertain the standard and quality of the trials. Visual acuity and epithelial healing time were the main outcome measures studied. Three trials were finally selected for analysis. AMG was noted to be associated with better uncorrected visual acuity and reduction in neovascularization. There was no difference in best corrected visual acuity, epithelial healing time, and corneal opacity. There is evidence that the use of AMG is associated with improved uncorrected visual acuity as well as reduction in neovascularization of the cornea among patients with corneal ulcers, but there was no improvement in epithelial healing time or corneal opacity. Further multicenter randomized controlled trials are needed to elicit the beneficial effects of the intervention and augment the validity of this review.
  11. Tomer S, Khati P, Suyal DC, Perveen K, Khan F, Barasarathi J
    Front Microbiol, 2024;15:1452553.
    PMID: 39257617 DOI: 10.3389/fmicb.2024.1452553
    The phosphate solubilizing properties of Lysinibacillus macroides ST-30, Pseudomonas pelleroniana N-26, and Bacillus cereus ST-6 were tested for the chickpea crop of the Tarai region of Uttarakhand. These microbially inoculated plants have shown significant (p > 0.05) improvement in the plant health and crop health parameters, viz., root length, shoot length, fresh weight, dry weight, nodule number, nodule fresh weight, nodule dry weight, chlorophyll content, and nitrate reductase. The highest shoot length (46.10 cm) and chlorophyll content (0.57 mg g-1 fresh weight) were observed in ST-30 at 75 DAS with 20 kg P2O5/ha. Similarly, for plant P content, an increase of 90.12% over control was recorded in the same treatment. Treatments consisting of Lysinibacillus macroides ST-30 along with 20 kg/ha P2O5 were found to be most suitable as phosphatic fertilizer. Conclusively, sustainable agriculture practices in the Tarai as well as the field region may be developed based on a strategy of exploring microbial inoculants from the pristine region of the Western Himalayas. The presence and abundance of bacterial inoculants were confirmed through qRT-PCT. We conclude that the effective plant growth-promoting bacterium Lysinibacillus macroides ST-30 broadens the spectrum of phosphate solubilizers available for field applications and might be used together with 20 Kg/ha P2O5.
  12. Rahmawati Z, Santoso L, Abdullah WNW, Hamid A, Jamari NLA, Sugiarso D, et al.
    RSC Adv, 2024 Sep 04;14(39):28827-28843.
    PMID: 39257661 DOI: 10.1039/d4ra04481a
    The huge demands for petrochemicals have led to a rapid increase in the production of these fossil-based derivatives. Biomass represents a promising feedstock for addressing the challenges related to petrochemicals in terms of the necessity to apply renewable sources and the need to decrease carbon emissions. Among the natural biomass products, most studies have attempted to upgrade natural oils owing to their promising advantages of worldwide availability, low-cost processing, and built-in functionality. This paper discusses the upgradation of natural oils to the most beneficial oleochemicals, including fatty acids, fatty alcohols, and fatty acid methyl esters. This review also covers the utility, physico-chemical properties, and the production processes for such materials. The interconnected reaction routes to produce oleochemicals and the affecting parameters (catalyst design, temperature, and pressure) are also elucidated. Furthermore, this article discusses the future perspective of oleochemicals based on their development in recent years.
  13. Wang LS, Aziz Z, Wang ES, Chik Z
    J Pharm Policy Pract, 2024;17(1):2395535.
    PMID: 39257836 DOI: 10.1080/20523211.2024.2395535
    BACKGROUND: Improper disposal of unused medicine can impact the environment causing significant healthcare and financial burdens. While the medicine take-back programme is an effective management strategy, its effectiveness differs across countries. This study aimed to systematically review the take-back programmes in various countries and to identify areas needing improvement for programme enhancement.

    METHODS: We conducted searches in Medline, EMBASE, CINAHL, Web of Science, Scopus, and Google Scholar, from database inception to June 2023.

    RESULTS: The review included 27 studies spanning 15 countries' medicine take-back programmes. While some programmes, mostly observed in the USA, were conducted at the local level with non-health-associated facilities, others were done at the national level within healthcare facilities. The cost of collected medicines ranged from US$7,416 to US$1,118,020, primarily involving medicines related to the nervous system, cardiovascular system, alimentary tract, and metabolism. Legislations pertaining to these programmes were available in the USA, most European countries, and Mexico, but unavailable in Spain, Austria, Australia, and New Zealand. However, despite this, the government or the industry in these countries managed the programmes.

    CONCLUSION: Well-structured take-back programmes featuring easily accessible collection points, regular collection schedules, clear programme ownership, with legislation defining financial responsibilities, showed positive outcomes.

  14. Aye LM, Tan MM, Schaefer A, Thurairajasingam S, Geldsetzer P, Soon LK, et al.
    Digit Health, 2024;10:20552076241278313.
    PMID: 39257871 DOI: 10.1177/20552076241278313
    BACKGROUND: Healthcare workers face burnout from high job demands and prolonged working conditions. While mental health services are available, barriers to access persist. Evidence suggests digital platforms can enhance accessibility. However, there is a lack of systematic reviews on the effectiveness of digital mental health interventions (DMHIs) for healthcare professionals. This review aims to synthesize evidence on DMHIs' effectiveness in reducing burnout, their acceptability by users, and implementation lessons learned.

    METHOD: This Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA)-guided review included 12 RCTs on DMHIs for healthcare professionals, published before 31 May 2024. The primary focus was on burnout, with secondary outcomes related to mental health and occupation. Quality appraisal used Cochrane risk of bias tools. A narrative synthesis explored DMHIs' effectiveness, acceptability, utilization, and implementation lessons.

    RESULTS: Significant improvements in mental health outcomes were observed in 10 out of 16 RCTs. Burnout and its constructs showed significant improvement in five RCTs. Studies that measured the acceptability of the interventions reported good acceptability. Factors such as attrition, intervention design and duration, cultural sensitivities, flexibility and ease of use, and support availability were identified as key implementation considerations.

    CONCLUSIONS: Web-based DMHIs positively impact burnout, mental health, and occupational outcomes among healthcare professionals, as shown in most RCTs. Future research should enhance DMHIs' effectiveness and acceptability by addressing identified factors. Increasing awareness of DMHIs' benefits will foster acceptance and positive attitudes. Lessons indicate that improving user engagement and effectiveness requires a multifaceted approach.

  15. Muhamad Nasir N, Taib H, Awang Nawi MA, Hassan A
    Cureus, 2024 Aug;16(8):e66605.
    PMID: 39258034 DOI: 10.7759/cureus.66605
    INTRODUCTION: Maintenance of dental implant with different hygiene methods or instruments may cause a surface alteration. It directly affects bacterial colonization and adhesion on titanium implant surfaces that result in peri-implant diseases. This study aimed to compare the Streptococcus sanguinis (S. sanguinis) adhesion on titanium implant abutments after instrumentation with a rubber cup with pumice and erbium, chromium-doped: yttrium, scandium, gallium, and garnet (Er, Cr: YSGG) laser using scanning electron microscope (SEM) observation and colony-forming unit (CFU) measurement.

    METHODS: Twenty-one MegaGen titanium implant abutments were randomly distributed into three groups. Seven abutments were respectively selected for the control/untreated (C) group, while the other two groups were treated with rubber cups with pumice (P) and Er, Cr: YSGG laser (L). All samples were cultured with S. sanguinis for bacterial colonization and adhesion. One sample for each group was selected for SEM observation, while the other samples were prepared for CFU calculation.

    RESULTS: For SEM results, at 2,000× magnification, machining marks were intact in the C group, roughened in the L group, and smoothened in the P group. At 5,000× and 10,000× magnifications, moderate colonies of S. sanguinis were revealed in C and L groups, while sparse bacterial colonies were detected in the P group. However, for CFU results, statistical analysis showed no significant value (p>0.05) comparing all three groups.

    CONCLUSION: P instrumentation revealed a lesser amount of S. sanguinis adhesion in SEM photographs, but no statistical significance of CFU results was noted for all three groups.

  16. Siti-Zubaidah MZ, Harafinova HS, Liba AN, Nordin ML, Hambali KA, Siti HN
    Vascul Pharmacol, 2024 Sep;156:107414.
    PMID: 39089528 DOI: 10.1016/j.vph.2024.107414
    Sepsis and atherosclerotic cardiovascular disease (ASCVD) are major health challenges involving complex processes like inflammation, renin-angiotensin system (RAS) dysregulation, and thrombosis. Despite distinct clinical symptoms, both conditions share mechanisms mediated by bradykinin. This review explores bradykinin's role in inflammation, RAS modulation, and thrombosis in sepsis and ASCVD. In sepsis, variable kininogen-bradykinin levels may correlate with disease severity and progression, though the effect of bradykinin receptor modulation on inflammation remains uncertain. RAS activation is present in both diseases, with sepsis showing variable or low levels of Ang II, ACE, and ACE2, while ASCVD consistently exhibits elevated levels. Bradykinin may act as a mediator for ACE2 and AT2 receptor effects in RAS regulation. It may influence clotting and fibrinolysis in sepsis-associated coagulopathy, but evidence for an antithrombotic effect in ASCVD is insufficient. Understanding bradykinin's role in these shared pathologies could guide therapeutic and monitoring strategies and inform future research.
    MeSH terms: Animals; Humans; Renin-Angiotensin System*; Thrombosis/blood; Thrombosis/metabolism; Thrombosis/physiopathology; Signal Transduction*; Receptors, Bradykinin/metabolism
  17. Tan KL, Haider S, Zois CE, Hu J, Turley H, Leek R, et al.
    Transl Oncol, 2024 Nov;49:102106.
    PMID: 39182365 DOI: 10.1016/j.tranon.2024.102106
    Current prognostic biomarkers fall short in stratifying Oestrogen receptor (ER)-negative breast cancer patients regarding tumour progression risk at diagnosis. The role of AIPL1 in activating its tumour suppressor client protein, NEDD8 Ultimate Buster-1 (NUB1) remains unknown in cancer. Our study demonstrated how downregulated AIPL1 results in the deactivated NUB1 protein under hypoxic conditions. We examined the AIPL1-NUB1 pathwayin vitro using cell lines i.e. MCF-7, MDA-MB-231, RCC4 etc. NUB1 expression was assessed using Oncomine, and cBioPortal was performed to assess NUB1's prognostic significance in human cancers. In the John Radcliffe Hospital cohort (n = 122), immunohistochemistry analysis revealed downregulated AIPL1 (Log2 fold change=-0.28; p < 0.001) and upregulated NUB1 transcripts (Log2 fold change=0.59; p < 0.001) compared to adjacent normal tissues. In severe chronic hypoxia, multimerised AIPL1 localisedin the cytoplasm while NUB1 protein migrated to the nucleus, where the absence of NUB1 nuclear localisation led to cell cycle arrest. Biopsies showed that patients with lower cytoplasmic NUB1 expression (n = 57) had poorer overall survival compared to those with higher cytoplasmic expression (n = 57), HR=1.78; 95 % CI=1.01-3.35, p = 0.048. Low NUB1 protein levels in both normoxic and hypoxic conditions were associated with cell cycle arrest and upregulation ofp21 and p27 in breast cancer cell lines, correlating significantly withpoorer survival outcomes in all breast cancer and ER-negative breast cancer patients.
  18. Hussain A, Ong EBB, Balaram P, Ismail A, Kien PK
    Virulence, 2024 Dec;15(1):2395831.
    PMID: 39185619 DOI: 10.1080/21505594.2024.2395831
    Salmonella enterica serovar Typhi (S. Typhi) causes typhoid fever, a systemic infection that affects millions of people worldwide. S. Typhi can invade and survive within host cells, such as intestinal epithelial cells and macrophages, by modulating their immune responses. However, the immunomodulatory capability of S. Typhi in relation to TolC-facilitated efflux pump function remains unclear. The role of TolC, an outer membrane protein that facilitates efflux pump function, in the invasion and immunomodulation of S. Typhi, was studied in human intestinal epithelial cells and macrophages. The tolC deletion mutant of S. Typhi was compared with the wild-type and its complemented strain in terms of their ability to invade epithelial cells, survive and induce cytotoxicity in macrophages, and elicit proinflammatory cytokine production in macrophages. The tolC mutant, which has a defective outer membrane, was impaired in invading epithelial cells compared to the wild-type strain, but the intracellular presence of the tolC mutant exhibited greater cytotoxicity and induced higher levels of proinflammatory cytokines (IL-1β and IL-8) in macrophages compared to the wild-type strain. These effects were reversed by complementing the tolC mutant with a functional tolC gene. Our results suggest that TolC plays a role in S. Typhi to efficiently invade epithelial cells and suppress host immune responses during infection. TolC may be a potential target for the development of novel therapeutics against typhoid fever.
    MeSH terms: Cell Line; Humans; Cytokines/immunology; Cytokines/metabolism; Interleukin-8/metabolism; Microbial Viability; Interleukin-1beta/immunology; Interleukin-1beta/metabolism; Immunomodulation
  19. Tan ZQ, Ooi EH, Chiew YS, Foo JJ, Ng YK, Ooi ET
    Comput Biol Med, 2024 Oct;181:109061.
    PMID: 39186904 DOI: 10.1016/j.compbiomed.2024.109061
    Sonothrombolysis is a technique that employs the ultrasound waves to break down the clot. Recent studies have demonstrated significant improvement in the treatment efficacy when combining two ultrasound waves of different frequencies. Nevertheless, the findings remain conflicted on the ideal frequency pairing that leads to an optimal treatment outcome. Existing experimental studies are constrained by the limited range of frequencies that can be investigated, while numerical studies are typically confined to spherical microbubble dynamics, thereby restricting the scope of the analysis. To overcome this, the present study investigated the microbubble dynamics caused by the different combinations of ultrasound frequencies. This was carried out using computational modelling as it enables the visualisation of the microbubble behaviour, which is difficult in experimental studies due to the opacity of blood. The results showed that the pairings of two ultrasound waves with low frequencies generally produced stronger cavitation and higher flow-induced shear stress on the clot surface. However, one should avoid the frequency pairings that are integer multipliers of each other, i.e., frequency ratio of 1/3, 1/2 and 2, as they led to resultant wave with low pressure amplitude that weakened the cavitation. At 0.5 + 0.85 MHz, the microbubble caused the highest shear stress of 60.5 kPa, due to its large translational distance towards the clot. Although the pressure threshold for inertial cavitation was reduced using dual-frequency ultrasound, the impact of the high-speed jet can only be realised when the microbubble travelled close to the clot. The results obtained from the present study provide groundwork for deeper understanding on the microbubble dynamics during dual-frequency sonothrombolysis, which is of paramount importance for its optimisations and the subsequent clinical translation.
    MeSH terms: Computer Simulation*; Humans; Models, Cardiovascular; Microbubbles*
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