Browse publications by year: 2024

  1. Leonhard SE, Papri N, Querol L, Rinaldi S, Shahrizaila N, Jacobs BC
    Nat Rev Dis Primers, 2024 Dec 19;10(1):97.
    PMID: 39702645 DOI: 10.1038/s41572-024-00580-4
    Guillain-Barré syndrome (GBS) is a rare immune-mediated polyradiculoneuropathy. Patients typically develop rapidly progressive weakness and sensory deficits that can result in complete paralysis requiring mechanical ventilation. GBS is usually a monophasic disease in which an aberrant immune response to an infection or other trigger damages the peripheral nerves. For example, in patients with preceding Campylobacter jejuni infection, molecular mimicry causes a cross-reactive antibody response to nerve gangliosides. Diagnosis is based on clinical features, supported by cerebrospinal fluid analysis and nerve conduction studies. Effective treatments include plasma exchange and intravenous immunoglobulins. However, ~20% of patients who received treatment are unable to walk after 6 months and ~5% die as a consequence of GBS. Important knowledge gaps in GBS include its pathogenesis, especially after viral infections. In addition, there is a lack of specific biomarkers to improve the diagnosis, monitor the disease activity, and predict the clinical course and outcome of GBS. Major challenges for the future include finding more effective and personalized treatments, which are affordable in low-income and middle-income countries, and preparation for outbreaks of infections as potential triggers for GBS.
    MeSH terms: Humans; Plasma Exchange/methods; Campylobacter jejuni/pathogenicity; Immunoglobulins, Intravenous/therapeutic use
  2. Kalam N, Balasubramaniam VRMT
    Influenza Other Respir Viruses, 2024 Dec;18(12):e70064.
    PMID: 39702696 DOI: 10.1111/irv.70064
    Enterovirus-D68 (EV-D68) was first identified in 1962 in pediatric patients with acute respiratory conditions in California, USA (US). From the 1970s to 2005, EV-D68 was underestimated due to limited data and serotyping methods. In 2014, the United States experienced outbreaks of acute flaccid myelitis (AFM) in children EV-D68 positive. WIN-like compounds (pleconaril, pocapavir, and vapendavir) bind to the virus capsid and have been tested against various enteroviruses (EVs) in clinical trials. However, these compounds encountered issues with resistance and adverse effects, which impeded their approval by the Food and Drug Administration (FDA). Presently, the medical field lacks FDA-approved antiviral treatments or vaccines for EV-D68. Ongoing research efforts are dedicated to identifying viable therapeutics to address EV-D68 infections. This review explores the current advancements in antiviral therapies and potential therapeutics to mitigate the significant impact of EV-D68 infection control.
    MeSH terms: Humans; Myelitis/drug therapy; Myelitis/epidemiology; Myelitis/therapy; Myelitis/virology; Neuromuscular Diseases; United States/epidemiology; Central Nervous System Viral Diseases
  3. Mohamed SM, Abou-Ghadir OMF, El-Mokhtar MA, Aboraia AS, Abdel-Moty SG, Abdel-Aal AM
    Chem Biol Drug Des, 2024 Dec;104(6):e70029.
    PMID: 39702898 DOI: 10.1111/cbdd.70029
    The immune system is essential for the defense against infections and is critically implicated in various disorders, including immunodeficiency, autoimmunity, inflammation and cancer. The current study includes a new design of palmitoylated derivatives of thioglycolic acids (PTGAs) capable of triggering innate immune responses. The new series were accessible through a three-step synthetic route, including N-palmitoylation, Claisen-Schmidt condensation and thia-Michael addition. Their structures were elucidated using different 1D and 2D NMR spectroscopic techniques and their purity was confirmed by elemental analysis. The most active PTGAs induced a 12-26-fold increase in the expression of TNF-α and IL-1β mRNA and triggered a marked release of NO in isolated macrophages. These levels were comparable to the responses elicited by heat-killed E. coli and S. aureus. The position of the palmitamide chain and aryl substitution had a significant effect on the TNF-α and IL-1β mRNA expression and NO release. Simulations of molecular dockings showed that the new PTGA derivatives occupy the same TLR2/TLR6 heterodimer active binding site of the microbial diacylated lipoproteins. The new immunomodulators may have a profound impact on various clinical disorders associated with dysfunctional innate immunity.
    MeSH terms: Animals; Escherichia coli/drug effects; Immunologic Factors/chemical synthesis; Immunologic Factors/pharmacology; Immunologic Factors/chemistry; Macrophages/drug effects; Macrophages/metabolism; Nitric Oxide/metabolism; Drug Design*; Toll-Like Receptor 2/metabolism; Mice; Lipoylation/drug effects; Molecular Docking Simulation
  4. Mohd Noor NA, Jun Quan N, Mazlan NAAA, Nurul AA, Ahmad Mohd Zain MR, Azlan M
    Immunol Invest, 2024 Dec 19.
    PMID: 39702926 DOI: 10.1080/08820139.2024.2443244
    BACKGROUND: Exosomes can be found in the synovial fluid of inflamed knee joints, which play a significant role in osteoarthritis (OA) progression. However, their role - in modulating the cellular environment within the body, particularly monocytes remain unexplored. This study aimed to evaluate the immunomodulatory effect of exosomes on monocytes.

    METHODS: Exosomes were isolated by ultracentrifugation and characterized using nanoparticle tracking analysis (NTA), scanning electron microscopy (SEM), and Western blot. The effect of exosomes in modulating monocyte phenotypes as well as cytokine secretion were further assessed in a co-culture condition using flow cytometry and ELISA accordingly.

    RESULTS: Exosomes were identified as spherical particles with a size distribution ranging from 30 nm to 150 nm. These nanoparticles intensely expressed exosome protein markers including CD9, CD63, CD81, and HSP70. The expression of HLA-DR, CD14, and CD11b on monocytes decreased in the presence of exosomes after 24 h of incubation, regardless of the dose. Exosomes significantly induced the release of anti-inflammatory cytokines IL-1Ra in a time- and dose-dependent manner, while TNF-α secretion remains unchanged regardless of the presence or absence of exosomes.

    CONCLUSION: This study highlights the immunoregulatory role of exosomes on monocytes, emphasizing the need for further studies into the underlying mechanism.

  5. Yang D, Zhang Z, Zhao L, Sui W, Li Y, Zhou Y, et al.
    Cell Biochem Funct, 2024 Dec;42(8):e70032.
    PMID: 39702946 DOI: 10.1002/cbf.70032
    Phospholipase A2 receptor 1 (PLA2R1) exists important role in membranous nephropathy. In this study, we evaluate a PLA2R1 in a middle-aged rat model of renal function repair to further investigate the molecular mechanisms of membranous nephropathy. We analyzed the PLA2R1 knockout (KO) model and PLA2R1 knock in (KI) model in rats, extending the time to 85 weeks of age. Urinary biochemical indicators were detected using a fully automated biochemical analyzer. The complement C3, IgG, and Nephrin were detected using the immunofluorescence method. Western blot was used to detect the expression levels of complement C3, IgA and PLA2R1 in middle-aged models. The KO model continues to display glomerular proteinuria, complement C3 aggregation, and IgA and IgG deposition. Comparing with the KO model, the deposition of complement C3 and IgA in the glomerulus of the KI chimeric model still exists and IgG expression weakened. Inserting humanized PLA2R1 into rats can continuously repair partial renal function and reduce proteinuria, which will help investigate the pathogenesis of membranous nephropathy and complement activation signaling pathways.
    MeSH terms: Animals; Disease Models, Animal*; Humans; Immunoglobulin A/metabolism; Immunoglobulin G; Kidney/metabolism; Kidney/pathology; Male; Membrane Proteins; Proteinuria/metabolism; Rats; Gene Knock-In Techniques
  6. Choon LK, Khiruddin AI
    PMID: 39703119 DOI: 10.1177/10806032241304734
    The Solanaceae plant family (Solanum), such as capsicum, eggplant, potato, and tomato, is made up of common plants consumed by humans. Despite having medicinal benefits, these plants can produce toxic alkaloid compounds. We report 2 cases of uncommon Solanum erianthum poisoning after consuming the berries as a meal. Both patients presented with slurring of speech, which is easily mistaken for a stroke. Symptoms developed 19 h after consuming the wild berries and resolved spontaneously 12 h after onset. Both patients recovered with no neurologic deficit. No antidote was given in either case. The Solanaceae plant family is a common group of plants consumed by humans and is considered one of the largest genera. The phytochemical profile showed that the leaves and berries contain toxic glycoalkaloid levels, which can cause gastrointestinal and neurologic symptoms in poisoning cases. Reports have shown that the toxic glycoalkaloids can inhibit the cholinesterase enzyme, thus producing cholinergic effects. Theoretically, atropine is the choice of antidote, but no case report of atropine use has been documented. Treatment of S erianthum poisoning remains supportive care. These cases highlight the rare occurrence of poisoning from S erianthum and emphasize the necessity for considering toxicologic causes in nonlocalizing neurologic symptoms.
  7. Geurts J, Singh-Povel C, Lee ST, Sekartini R, Poh BK, Rojroongwasinkul N, et al.
    Public Health Nutr, 2024 Dec 20;27(1):e261.
    PMID: 39703175 DOI: 10.1017/S1368980024001332
    OBJECTIVE: To describe the economic, lifestyle and nutritional impact of the COVID-19 pandemic on parents, guardians and children in Malaysia, Indonesia, Thailand and Vietnam.

    DESIGN: Data from the SEANUTS II cohort were used. Questionnaires, including a COVID-19 questionnaire, were used to study the impact of the pandemic on parents/guardians and their children with respect to work status, household expenditures and children's dietary intake and lifestyle behaviours.

    SETTING: Data were collected in Malaysia, Indonesia, Thailand and Vietnam between May 2019 and April 2021.

    PARTICIPANTS: In total, 9203 children, aged 0·5-12·9 years, including their parents/guardians.

    RESULTS: Children and their families were significantly affected by the pandemic. Although the impact of lockdown measures on children's food intake has been relatively mild in all countries, food security was negatively impacted, especially in Indonesia. Surprisingly, in Malaysia, lockdown resulted in overall healthier dietary patterns with more basic food groups and less discretionary foods. Consumption of milk/dairy products, however, decreased. In the other countries, intake of most food groups did not change much during lockdown for households based on self-reporting. Only in rural Thailand, some marginal decreases in food intakes during lockdown persisted after lockdown. Physical activity of children, monthly household income and job security of the parents/guardians were negatively affected in all countries due to the pandemic.

    CONCLUSION: The COVID-19 pandemic has significantly impacted societies in South-East Asia. To counteract negative effects, economic measures should be combined with strategies to promote physical activity and eating nutrient-adequate diets to increase resilience of the population.

    MeSH terms: Adult; Child; Child, Preschool; Diet/statistics & numerical data; Female; Humans; Indonesia/epidemiology; Infant; Life Style; Malaysia/epidemiology; Male; Parents/psychology; Surveys and Questionnaires; Thailand/epidemiology; Vietnam/epidemiology; Cohort Studies; Exercise; Pandemics
  8. Conway RB, Snell-Bergeon J, Honda-Kohmo K, Peddi AK, Isa SB, Sulong S, et al.
    J Endocr Soc, 2024 Nov 26;9(1):bvae210.
    PMID: 39703363 DOI: 10.1210/jendso/bvae210
    Globally, nearly 9 million people are living with type 1 diabetes (T1D). Although the incidence of T1D is not affected by socioeconomic status, the development of complications and limited access to modern therapy is overrepresented in vulnerable populations. Diabetes technology, specifically continuous glucose monitoring and automated insulin delivery systems, are considered the gold standard for management of T1D, yet access to these technologies varies widely across countries and regions, and varies widely even within high-income countries. This review focuses on disparities in diabetes technology use among adolescents and young adults with T1D, barriers to access and use, and summarizes common themes emerging across countries and regions. We conducted a survey among medical technology manufacturers and physicians in various countries across diverse geographical regions and performed extensive literature searches. Across all countries and regions, economic barriers stand out as the largest and most common barriers, either preventing market penetrance of technology into a country or limiting its access to the individual with diabetes due to high out of pocket costs. Other common barriers include structural or accessibility barriers, such as stringent eligibility requirements by insurance providers, regardless of whether the insurance was private or government-based, and provider/individual level barriers. Based on the evidence presented, we suggest the need for a joint effort involving governments, private health insurers, technology manufacturers, and healthcare providers to address the global disparities of diabetic technology utilization and ensure equitable access for all individuals living with T1D worldwide.
  9. Zhang X, Tang QQ, Cai YY
    Front Public Health, 2024;12:1445778.
    PMID: 39703487 DOI: 10.3389/fpubh.2024.1445778
    INTRODUCTION: The role of social media in providing fitness-related health information has been widely discussed; however, there is a notable lack of research on fitness-related health information behaviors among youth within the social media context. This study aims to address this gap by integrating Self-Determination Theory (SDT)-based internal factors and external factors (social media algorithms and source credibility).

    METHODS: A voluntary sample of 600 participants, aged 15 to 29, was recruited. Data were analyzed using Partial Least Squares-Structural Equation Modeling (PLS-SEM) to examine the relationships between variables.

    RESULTS: The analysis revealed that all three intrinsic needs-competence, autonomy, and relatedness-along with social media algorithms and source credibility, positively correlated with fitness-related health information use behaviors among youth. Additionally, social media algorithms moderated the relationship between the need for relatedness and fitness-related health information behavior.

    DISCUSSION: These findings provide new insights into developing health communication strategies on social media, particularly targeted toward the youth demographic, enhancing our understanding of effective health information dissemination in digital environments.

    MeSH terms: Adolescent; Adult; Algorithms; China; Female; Humans; Male; Physical Fitness; Surveys and Questionnaires; Personal Autonomy; Young Adult; Social Media*
  10. Xu L, Zhu Y, Wang Y, Zhang L, Li L, Looi LJ, et al.
    Front Plant Sci, 2024;15:1492036.
    PMID: 39703548 DOI: 10.3389/fpls.2024.1492036
    Climate change not only leads to high temperatures, droughts, floods, storms and declining soil quality, but it also affects the spread and mutation of pests and diseases, which directly influences plant growth and constitutes a new challenge to food security. Numerous hormones like auxin, ethylene and melatonin, regulate plant growth and development as well as their resistance to environmental stresses. To mitigate the impact of diverse biotic and abiotic stressors on crops, single or multiple phytohormones in combination have been applied. Melatonin is a multifunctional signaling molecule engaged in the development and stress response of plants. In the current review, we discuss the synthesis and action of melatonin, as well as its utilization for plant resistance to different stresses from the perspective of practical application. Simultaneously, we elucidate the regulatory effects and complex mechanisms of melatonin and other plant hormones on the growth of plants, explore the practical applications of melatonin in combination with other phytohormones in crops. This will aid in the planning of management strategies to protect plants from damage caused by environmental stress.
  11. Abdullah S, Ghazali KAB, Soh EZF, Sapuan J, Gill PS, Lim CH
    J Hand Surg Glob Online, 2024 Nov;6(6):814-817.
    PMID: 39703592 DOI: 10.1016/j.jhsg.2024.06.008
    PURPOSE: Fixation of metacarpal or phalanx bone fractures is usually performed under general anesthesia (GA) or regional anesthesia and with the use of a tourniquet to minimize bleeding. However, the use of tourniquet causes pain and discomfort after surgery. Wide-awake local anesthesia no tourniquet (WALANT) enables the surgery to be performed with the patient fully awake and without a tourniquet, which allows intraoperative assessment of function during surgery. This study aims to compare the perioperative parameters and clinical outcomes between GA versus WALANT in hand fracture fixations.

    METHODS: Forty-eight patients with hand fractures were recruited over a period of 15 months. Twenty-one patients had undergone fracture fixation under GA, whereas another 27 patients had the surgery under WALANT. Parameters including vital signs (heart rate and systolic blood pressure), surgery duration, estimated blood loss, visual analog scale, and quick disabilities of the arm, shoulder, and hand (QuickDASH) questionnaire were evaluated.

    RESULTS: Wide-awake local anesthesia no tourniquet group had significantly higher systolic blood pressure values and higher estimated blood less than GA group. Wide-awake local anesthesia no tourniquet group also documented shorter surgical time compared with GA group, but the difference was not significant. In terms of clinical outcomes, WALANT group recorded significantly lower visual analog scale score at 2 hours and 2 weeks postsurgery. However, WALANT has a comparable QuickDASH score with GA group except at 3 months postsurgery.

    CONCLUSIONS: Wide-awake local anesthesia no tourniquet surgery for hand fracture fixation provides a similar analgesic effect and comparable QuickDASH score except at 3 months postsurgery compared with GA.

    TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IIb.

  12. Wan-Chiew N, Baki MM, Lokanathan Y, Fauzi MB, Azman M
    Front Cell Dev Biol, 2024;12:1489901.
    PMID: 39703693 DOI: 10.3389/fcell.2024.1489901
    Approaches to regenerate vocal fold in glottic insufficiency remains to be a focus for exploration. This is attributed to the applications of cells or biological molecules alone result in fast degradation and inadequate for regeneration. Development of an injectable hydrogel for glottic insufficiency is challenging, as it needs to be non-cytotoxic, elastic yet possess good strength and easy to fabricate. This gap prompts us to study the feasibility of our genipin(gn)-crosslinked gelatin (G) hydrogel in encapsulating Wharton's Jelly Mesenchymal Stem Cells (WJMSCs) and basic fibroblast growth factor (bFGF) WJMSCs with the aim to provide regeneration in glottic insufficiency. WJMSCs was encapsulated into two optimised formulations with the density of 2,000,000 cells/mL. The encapsulated cells were tested for its morphology, cell viability, proliferation and migration. Then, the incorporation of basic fibroblast growth factor (bFGF) was done into a final formulation and was tested for the cellular response and in vitro inflammation. 6G 0.4gn demonstrated better cell viability after in vitro culturing for 7 day. After incorporation of bFGF into cell-laden 6G 0.4gn, encapsulated WJMSCs showed to have improved viability and migration. The inflammatory profile of the hydrogel was imperceptible and was regarded as minimal or no pro- and anti-inflammation. Altogether, we have first formulated 6G 0.4gn which is suitable to encapsulate WJMSCs and incorporation of bFGF. Current study fulfils the market need in vocal fold regeneration, by suggesting its rejuvenating potential in glottic insufficiency, yet this combined formulation should be studied further to justify its translation to clinical setting.
  13. Rajoo AR, Kannairan S, Habeebullah Khan HA, Md Idris MA, Tan GC, Chandra Sakaran KR, et al.
    Front Oncol, 2024;14:1462956.
    PMID: 39703846 DOI: 10.3389/fonc.2024.1462956
    Paragangliomas originating from blood vessels are exceptionally rare, presenting diagnostic challenges due to their histological resemblance to other vascular neoplasms. We present a case study of a 60-year-old woman with underlying hypertension and dyslipidemia with obesity, initially diagnosed with angiosarcoma based on imaging and histological characteristics viewed via CT-guided biopsy. Intraoperative exploration revealed a lobulated tumor located between the inferior vena cava (IVC) and aorta measuring 7 cm × 8 cm, during which the patient developed transient hemodynamic instabilities. Histopathological examination and immunohistochemical staining using neuroendocrine markers (chromogranin, synaptophysin, S-100 protein, and CD-56) later confirmed the tumor as a retroperitoneal paraganglioma. Retroperitoneal paraganglioma was initially misdiagnosed as angiosarcoma due to the overlapping imaging characteristics between the two tumors. This highlights the importance of raising suspicion on the possibility of retroperitoneal paraganglioma when imaging examination indicates angiosarcoma and to incorporate histopathological examination and immunohistochemistry in the diagnosis to avoid misdiagnosis.
  14. Ding J, Yeong C
    Front Oncol, 2024;14:1504139.
    PMID: 39703856 DOI: 10.3389/fonc.2024.1504139
    Small cell lung cancer (SCLC) remains one of the most aggressive and challenging malignancies to treat, with limited therapeutic options and poor outcomes. Recent advances in understanding SCLC biology have identified Delta-like ligand 3 (DLL3) as a promising target for novel therapies. This review explores the evolving landscape of DLL3-targeted therapies in SCLC, examining their mechanistic basis, preclinical promise, and clinical development. We discuss various therapeutic modalities, including antibody-drug conjugates (ADCs), bispecific T-cell engagers (BiTEs), chimeric antigen receptor T-cell (CAR-T) therapies, and emerging approaches such as near-infrared photoimmunotherapy (NIR-PIT) and radiopharmaceutical therapy (RPT). The review highlights the challenges encountered in translating these promising approaches into clinical practice, including the setbacks faced by early DLL3-targeted therapies like Rovalpituzumab Tesirine (Rova-T). We also explore potential strategies to overcome these obstacles, emphasizing the need for a more nuanced understanding of DLL3 biology and its role in SCLC pathogenesis. The integration of cutting-edge technologies and interdisciplinary collaboration is proposed as a path forward to optimize DLL3-targeted therapies and improve outcomes for SCLC patients. This comprehensive overview provides insights into the current state and future directions of DLL3-targeted therapies, underscoring their potential to revolutionize SCLC treatment paradigms.
  15. Engku Abd Rahman ENS, Irekeola AA, Yamin D, Elmi AH, Chan YY
    PeerJ, 2024;12:e18604.
    PMID: 39703916 DOI: 10.7717/peerj.18604
    Borderline oxacillin-resistant Staphylococcus aureus (BORSA) has been a persistent yet under-researched concern in the realm of antibiotic resistance, characterized by unique resistance mechanisms and potential for severe infections. This systematic review and meta-analysis consolidates data from 29 studies encompassing 18,781 samples, revealing a global BORSA prevalence of 6.6% (95% CI [4.0-10.7]). The highest prevalence was found in animals (46.3%), followed by food (8.9%), and humans (5.1%). Notably, significant regional disparities were observed, with Brazil exhibiting the highest prevalence at 70.0%, while The Netherlands reported just 0.5%. These findings underscore the multifaceted nature of BORSA epidemiology, influenced by local antibiotic usage practices and healthcare infrastructures. The analysis also reveals substantial heterogeneity (I2 = 96.802%), highlighting the need for improved reporting practices and tailored surveillance protocols that account for the specific contexts of each study. As antibiotic resistance continues to escalate, understanding BORSA's global footprint is crucial for informing targeted interventions and optimizing antibiotic stewardship programs. This study fills critical gaps in current knowledge of BORSA and highlights the need for coordinated efforts among researchers, healthcare providers, and policymakers to develop effective strategies for addressing the rising threat of antibiotic-resistant pathogens like BORSA, including further exploration of its genetic and phenotypic characteristics.
    MeSH terms: Animals; Humans; Staphylococcus aureus/drug effects; Global Health; Prevalence; Drug Resistance, Bacterial/drug effects
  16. Abid SK, Sulaiman N, Al-Wathinani AM, Goniewicz K
    J Glob Health, 2024 Dec 20;14:04290.
    PMID: 39703989 DOI: 10.7189/jogh.14.04290
    BACKGROUND: Flooding is a frequent and devastating hazard in Malaysia, exacerbated by the country's tropical climate and rapid urbanisation. Traditional flood management strategies, predominantly focused on engineering solutions, have proven inadequate in addressing evolving flood risks. Community-based flood mitigation (CBFM) has emerged as an alternative approach, leveraging local knowledge and public participation to enhance flood resilience. This study aims to evaluate the role of CBFM in Malaysia, focusing on the effectiveness of public involvement and policy implementation in flood risk management.

    METHODS: We conducted 20 in-depth interviews with stakeholders, including government officials, community members, and representatives of non-governmental organisations (NGOs), using a qualitative methodology. The data were analysed using thematic analysis to identify key themes surrounding public participation, policy challenges, and successful community-led flood mitigation initiatives.

    RESULTS: The findings highlight the critical role of public involvement in improving flood preparedness and resilience. Communities that actively participated in mitigation efforts, such as early warning systems and nature-based solutions, demonstrated enhanced resilience. However, significant challenges remain, including inadequate funding, outdated infrastructure, and bureaucratic delays. Public awareness and education on flood preparedness, especially in rural areas, were found to be insufficient, hindering the effectiveness of flood management strategies.

    CONCLUSIONS: The study concludes that while CBFM initiatives in Malaysia show promise, their success depends on stronger policy enforcement, increased public engagement, and sustained investments in both green and grey infrastructure. Greater collaboration between local communities, NGOs, and government agencies is essential for improving flood risk management and building long-term resilience, particularly in the face of increasing climate-driven disasters.

    MeSH terms: Consumer Participation*; Disaster Planning; Humans; Malaysia; Risk Management; Qualitative Research; Floods*
  17. Chan R, Mugisha CS, Chuenchob V, Moquin SA, Manjunatha UH, Jarrousse N, et al.
    SLAS Discov, 2024 Dec;29(8):100189.
    PMID: 39499968 DOI: 10.1016/j.slasd.2024.100189
    Over the past 25 years, the global community has faced challenges posed by three distinct outbreaks of coronaviruses including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The identification of a novel alphacoronavirus canine CoV (CCoV-HuPn2018) in human patients in Malaysia underscores the potential for crossover infections to humans. The threat of the ever-evolving nature of viral infections as well as the lingering health and socioeconomic effects of the recent SARS-CoV-2 pandemic emphasize the urgent need for advanced antiviral drug screening tools that can be quickly implemented to strengthen preparedness and preventive measures against future outbreaks. Here, we present the development and validation of a novel RNA-fluorescence in situ hybridization (FISH) imaging assay as a 384-well, high-throughput rapid response platform for antiviral drug discovery. RNA-FISH is a powerful tool to visualize specific mRNA in cultured cells using a high-content imaging platform. The flexibility of RNA-FISH probe sets allows for the rapid design of viral genome-specific probes, enabling in vitro assay development to test for inhibition of viral replication by either biologic or small molecule inhibitors. Screening of 170 antiviral compounds in concentration-response demonstrates a strong correlation between the RNA-FISH assay and an immunofluorescence assay (IFA) for both human coronaviruses HCoV-OC43 and HCoV-229E. Additionally, we successfully applied this methodology in the context of CCoV strain 1-71, proving rapid development and deployment, opening new avenues for the evaluation of antiviral drugs to potential future emerging threats.
    MeSH terms: Animals; Drug Evaluation, Preclinical/methods; Humans; RNA, Viral/genetics; Coronavirus/drug effects; Coronavirus/genetics
  18. Puspalingam K, Suppamutharwyam M
    Cureus, 2024 Nov;16(11):e73849.
    PMID: 39691137 DOI: 10.7759/cureus.73849
    Post-COVID-19 sequelae can include various complications, including musculoskeletal manifestations. Unvaccinated against COVID-19, a 21-year-old woman initially experienced severe COVID-19 and subsequently recovered. She later developed mild COVID-19, which was followed by severe myalgia and joint pain in her upper extremities. After a third COVID-19 infection, she experienced intense pain in multiple hand joints and lethargy. The blood tests were normal, and the ultrasound report revealed tenosynovitis of the wrist joint. Her pain improved with combined treatment approaches.  To our knowledge, this is the first case report of post-COVID-19 tenosynovitis. We have also highlighted the predisposing factors for the development of tenosynovitis, which may include being unvaccinated and lifestyle changes, such as a sedentary routine. This case also emphasizes the need for further research into the long-term effects of the condition on mobility and quality of life.
  19. Nasuruddin H, Che Yusoff MA, Che Ahmad A, Rosdi MH
    Cureus, 2024 Nov;16(11):e73848.
    PMID: 39691140 DOI: 10.7759/cureus.73848
    The increasing prevalence of proximal humerus fractures in the elderly population, particularly osteoporotic fractures, necessitates a biomechanical evaluation of Kirschner wire (K-wire) configurations used in percutaneous fixation. This study investigates the stability of different K-wire configurations and examines the effect of wire size and type (smooth vs. threaded). Using 27 synthetic humeri models, we compare three configurations as follows: four parallel ascending K-wires (box-type), two ascending and two descending K-wires, and a combination of both. Results show that adding descending K-wires significantly enhances stability, particularly against torsional forces. This study highlights the importance of wire type and configuration in stabilizing proximal humerus fractures. Multiplanar constructs with descending K-wires, especially threaded ones, offer better stability. These insights help improve surgical techniques for elderly and osteoporotic patients, but further research using cadaver models is needed for clinical validation.
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