Browse publications by year: 2024

  1. Ahmed U, Gew LT, Siddiqui R, Khan NA, Alharbi AM, Alhazmi A, et al.
    Acta Parasitol, 2024 Sep;69(3):1717-1723.
    PMID: 39153011 DOI: 10.1007/s11686-024-00891-2
    PURPOSE: The treatment of amoebic infections is often problematic, largely due to delayed diagnosis, amoebae transformation into resistant cyst form, and lack of availability of effective chemotherapeutic agents. Herein, we determined anti-Acanthamoeba castellanii properties of three metal oxide nanoparticles (TiO2, ZrO2, and Al2O3).

    METHODS: Amoebicidal assays were performed to determine whether metal oxide nanoparticles inhibit amoebae viability. Encystation assays were performed to test whether metal oxide nanoparticles inhibit cyst formation. By measuring lactate dehydrogenase release, cytotoxicity assays were performed to determine human cell damage. Hoechst 33342/PI staining was performed to determine programmed cell death (apoptosis) and necrosis in A. castellanii.

    RESULTS: TiO2-NPs significantly inhibited amoebae viability as observed through amoebicidal assays, as well as inhibited their phenotypic transformation as evident using encystation assays, and showed limited human cell damage as observed by measuring lactate dehydrogenase assays. Furthermore, TiO2-NPs altered parasite membranes and resulted in necrotic cell death as determined using double staining cell death assays with Hoechst33342/Propidium iodide (PI) observed through chromatin condensation. These findings suggest that TiO2-NPs offers a potential viable avenue in the rationale development of therapeutic interventions against Acanthamoeba infections.

    MeSH terms: Aluminum Oxide/pharmacology; Aluminum Oxide/chemistry; Amebiasis/drug therapy; Humans; Zirconium/pharmacology; Zirconium/chemistry
  2. Bakrim S, Elouafy Y, Touhtouh J, Aanniz T, El Kadri K, Khalid A, et al.
    Fitoterapia, 2024 Aug 15.
    PMID: 39153554 DOI: 10.1016/j.fitote.2024.106182
    Today, pharmaceutical drugs have been shown to have serious side effects, while the bioactive components of botanical plants are proven to be effective in the treatment of several diseases marked by enhanced oxidative stress and mild inflammation, often associated with minimal adverse events. Coumaroyltyramine, designated by various nomenclatures such as paprazine, N-p-trans-coumaroyltyramine, p-coumaroyltyramine and N-p-coumaroyltyramine, could be a promising bioactive ingredient to address health issues thanks to its powerful anti-inflammatory and antioxidant effects. This review represents the first in-depth analysis of coumaroyltyramine, an intriguing phenylpropanoid substance found in many species of plants. In fact, an in-depth examination of coumaroyltyramine's biological characteristics, chemical attributes, and synthesis process has been undertaken. All previous research relating to the discovery, extraction, biosynthesis, and characterization of the biologically and pharmacologically active properties of coumaroyltyramine has been reviewed and taken into consideration in this analysis. All articles published in a peer-reviewed English-language journal were examined between the initial compilations of the appropriate database until February 12, 2024. A variety of phytochemicals revealed that coumaroyltyramine is a neutral amide of hydroxycinnamic acid that tends to concentrate in plants as a reaction against infection caused by pathogens and is extracted from several medicinal herbs such as Cannabis sativa, Solanum melongena, Allium bakeri, Annona cherimola, Polygonatum zanlanscianense, and Lycopersicon esculentum. Thanks to its effectiveness in suppressing the effect of the enzyme α-glucosidase, coumaroltyramine has demonstrated antihyperglycemic activity and could have an impact on diabetes and metabolic disorders. It has considerable anti-inflammatory and antioxidant effects. These results were obtained through biological and pharmacological studies in silico, in vivo, and in vitro. In addition, coumaroyltyramine has demonstrated hypocholesterolemic and neuroprotective benefits, thereby diminishing heart and vascular disease incidence and helping to prevent neurological disorders. Other interesting properties of coumaroltyramine include anticancer, antibacterial, anti-urease, antifungal, antiviral, and antidysmenorrheal activities. Targeted pathways encompass activity at different molecular levels, notably through induction of endoplasmic reticulum stress-dependent apoptosis, arrest of the cell cycle, and inhibition of the growth of cancer cells, survival, and proliferation. Although the findings from in silico, in vivo, and in vitro experiments illustrate coumaroyltyramine's properties and modes of action, further research is needed to fully exploit its therapeutic potential. To improve our understanding of the compound's pharmacodynamic effects and pharmacokinetic routes, large-scale research should first be undertaken. To determine whether coumaroyltyramine is clinically safe and effective, further studies are required in the clinical and toxicological fields. This upcoming research will be crucial to achieving the overall potency of this substance as a natural drug and in terms of its potential synergies with other drugs.
  3. Sugumaran D, Yong ACH, Stanslas J
    Life Sci, 2024 Oct 15;355:122991.
    PMID: 39153596 DOI: 10.1016/j.lfs.2024.122991
    Psoriasis is a chronic inflammatory condition affecting approximately 2 % to 3 % of the global population. The pathogenesis of psoriasis is complex, involving immune dysregulation, hyperproliferation and angiogenesis. It is a multifactorial disease which is influenced by genetic and environmental factors. The development of various therapeutic agents, such as JAK inhibitors, small molecules, and biologics with potential anti-psoriatic properties was possible with the vast understanding of the pathogenesis of psoriasis. Various signalling pathways, including NF-κB, JAK-STAT, S1P, PDE-4, and A3AR that are involved in the pathogenesis of psoriasis as well as the preclinical models utilised in the research of psoriasis have been highlighted in this review. The review also focuses on technological advancements that have contributed to a better understanding of psoriasis. Then, the molecules targeting the respective signalling pathways that are still under clinical trials or recently approved as well as the latest breakthroughs in therapeutic and drug delivery approaches that can contribute to the improvement in the management of psoriasis are highlighted in this review. This review provides an extensive understanding of the current state of research in psoriasis, giving rise to opportunities for researchers to discover future therapeutic breakthroughs and personalised interventions. Efficient treatment options for individuals with psoriasis can be achieved by an extensive understanding of pathogenesis, therapeutic agents, and novel drug delivery strategies.
    MeSH terms: Animals; Humans; Drug Delivery Systems/methods
  4. Zhao Z, Gao Y, Sui W, Zhang Z, Feng L, Wang Z, et al.
    BMJ Open, 2024 Aug 17;14(8):e081485.
    PMID: 39153776 DOI: 10.1136/bmjopen-2023-081485
    OBJECTIVES: To seek a triple combination of biomarkers for early diagnosis of chronic kidney disease-mineral and bone metabolic disorder and to explore the diagnostic efficacy of β2-microglobulin, parathyroid hormone and blood urea nitrogen in chronic kidney disease-mineral and bone metabolic disorder.

    PARTICIPANTS: We collected medical records of 864 patients with chronic kidney disease (without direct contact with patients) and divided them into two groups based on the renal bone disease manifestations of all patients.

    PRIMARY AND SECONDARY OUTCOME MEASURES: There were 148 and 716 subjects in the Chronic kidney disease-mineral and bone metabolic disorder and the control groups, respectively. The aggregated data included basic information and various clinical laboratory indicators, such as blood lipid profile, antibody and electrolyte levels, along with renal function-related indicators.

    RESULTS: It was observed that most renal osteopathy occurs in the later stages of chronic kidney disease. In the comparison of two clinical laboratory indicators, 16 factors were selected for curve analysis and compared. We discovered that factors with high diagnostic values were β2-microglobulin, parathyroid hormone and blood urea nitrogen.

    CONCLUSIONS: The triple combination of β2-microglobulin+parathyroid hormone+blood urea nitrogen indicators can play the crucial role of a sensitive indicator for the early diagnosis of chronic kidney disease-mineral and bone metabolic disorder and in preventing or delaying the progress of chronic kidney disease-mineral and bone metabolic disorder.

    MeSH terms: Adult; Aged; Blood Urea Nitrogen*; China/epidemiology; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Early Diagnosis; Renal Insufficiency, Chronic/blood; Renal Insufficiency, Chronic/complications; Renal Insufficiency, Chronic/diagnosis
  5. Fisher JA, Bompart F, Montrasio L, Mwale S, Chew CK, Kurundkar SB, et al.
    Lancet, 2024 Aug 17;404(10453):651.
    PMID: 39153805 DOI: 10.1016/S0140-6736(24)01480-6
    MeSH terms: Humans; Global Health*; Healthy Volunteers*
  6. Restu WK, Aryana N, Septiyanti M, Triwulandari E, Sampora Y, Devy YA, et al.
    Chem Biodivers, 2024 Jun 26.
    PMID: 38927001 DOI: 10.1002/cbdv.202400861
    This research aims to create an emulsion formulation utilizing lignin as a carrier and citronella oil for its application as a herbicide. The formulation composition includes lignin solution 55-62 %v/v, Tween 80 25 %w/v, propylene glycol 10 %w/v, and citronella oil 3-10 %w/v. The preparation steps involve preparing the oil phase by mixing tween 80 surfactant, propylene glycol, and citronella oil; preparing the aqueous phase by mixing lignin into distilled water at pH 12 with stirring; mixing the oil phase and the water phase accompanied by stirring at 5000-10000 rpm for 1-5 minutes until a stable solution is formed as a natural herbicide. The application outcomes revealed that the formulation successfully eliminated specific weeds within two to three days at the maximum concentration of 10 %, leaving no detectable herbicide residue after 7 and 15 days of treatment. The result demonstrates how green technology has the capacity to replace herbicides derived from chemicals, especially in the agricultural sector.
  7. Chee NM, Sinnanaidu RP, Chan WK
    J Gastroenterol Hepatol, 2024 Dec;39(12):2545-2554.
    PMID: 39150005 DOI: 10.1111/jgh.16723
    BACKGROUND AND AIM: Multiple clinical trials have been conducted to study the potential benefits of vitamin E for the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD). Despite available evidence, vitamin E is not widely used. This study aimed to assess the effect of vitamin E on serum markers of liver inflammation, specifically serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and histology, including resolution of metabolic dysfunction-associated steatohepatitis (MASH), in adult patients with MASLD.

    METHODS: A systematic literature search on randomized controlled trials published in English was conducted using electronic databases. Standardized mean difference (SMD) and mean difference (MD) were used for continuous outcomes, while risk ratio (RR) was used for dichotomous outcomes, with corresponding 95% confidence interval (CI).

    RESULTS: A total of eight studies were included in the qualitative synthesis while seven studies were included in the meta-analysis. Vitamin E significantly reduced serum ALT and AST levels with SMD of -0.82 (95% CI, -1.13 to -0.51) and -0.68 (95% CI, -0.94 to -0.41), respectively. Vitamin E significantly reduced steatosis, lobular inflammation, and hepatocyte ballooning with a MD of -0.60 (95% CI, -0.83 to -0.37), -0.34 (95% CI, -0.53 to -0.16), -0.32 (95% CI, -0.53 to -0.12), and increased MASH resolution with a RR of 1.9 (95%CI, 1.20 to 3.02). However, vitamin E did not reduce fibrosis, with a MD of -0.23 (95% CI, -0.51 to 0.05).

    CONCLUSION: Vitamin E resulted in significant improvement in serum markers of liver inflammation and histology in patients with MASLD.

    MeSH terms: Adult; Female; Humans; Liver/pathology; Male; Metabolic Diseases/blood; Metabolic Diseases/etiology; Randomized Controlled Trials as Topic; Treatment Outcome
  8. Fish-Low CY, Than LTL, Ling KH, Sekawi Z
    J Proteome Res, 2024 Sep 06;23(9):4027-4042.
    PMID: 39150348 DOI: 10.1021/acs.jproteome.4c00376
    Leptospirosis, a notifiable endemic disease in Malaysia, has higher mortality rates than regional dengue fever. Diverse clinical symptoms and limited diagnostic methods complicate leptospirosis diagnosis. The demand for accurate biomarker-based diagnostics is increasing. This study investigated the plasma proteome of leptospirosis patients with leptospiraemia and seroconversion compared with dengue patients and healthy subjects using isobaric tags for relative and absolute quantitation (iTRAQ)-mass spectrometry (MS). The iTRAQ analysis identified a total of 450 proteins, which were refined to a list of 290 proteins through a series of exclusion criteria. Differential expression in the plasma proteome of leptospirosis patients compared to the control groups identified 11 proteins, which are apolipoprotein A-II (APOA2), C-reactive protein (CRP), fermitin family homolog 3 (FERMT3), leucine-rich alpha-2-glycoprotein 1 (LRG1), lipopolysaccharide-binding protein (LBP), myosin-9 (MYH9), platelet basic protein (PPBP), platelet factor 4 (PF4), profilin-1 (PFN1), serum amyloid A-1 protein (SAA1), and thrombospondin-1 (THBS1). Following a study on a verification cohort, a panel of eight plasma protein biomarkers was identified for potential leptospirosis diagnosis: CRP, LRG1, LBP, MYH9, PPBP, PF4, SAA1, and THBS1. In conclusion, a panel of eight protein biomarkers offers a promising approach for leptospirosis diagnosis, addressing the limitations of the "one disease, one biomarker" concept.
    MeSH terms: Acute-Phase Proteins/analysis; Adult; Serum Amyloid A Protein/analysis; C-Reactive Protein/analysis; Carrier Proteins/blood; Dengue/blood; Dengue/diagnosis; Female; Glycoproteins; Humans; Male; Membrane Glycoproteins/blood; Membrane Proteins/blood; Middle Aged; Platelet Factor 4/blood; Case-Control Studies; Thrombospondin 1/blood; Proteome/analysis; Proteomics/methods
  9. Dhivagar R, Suraparaju SK, Atamurotov F, Kannan KG, Opakhai S, Omara AAM
    Water Sci Technol, 2024 Jun;89(12):3325-3343.
    PMID: 39150427 DOI: 10.2166/wst.2024.189
    In this current investigation, the experimental performance of a solar still basin was significantly enhanced by incorporating snail shell biomaterials. The outcomes of the snail shell-augmented solar still basin (SSSS) are compared with those of a conventional solar still (CSS). The utilization of snail shells proved to facilitate the reduction of saline water and enhance its temperature, thereby improving the productivity of the SSSS. Cumulatively, the SSSS productivity was improved by 4.3% over CSS. Furthermore, the SSSS outperformed in energy and exergy efficiency of CSS by 4.5 and 3.5%, respectively. Economically, the cost per liter of distillate (CPL) for the CSS was 3.4% higher than SSSS. Moreover, the SSSS showed a shorter estimated payback period (PBP) of 141 days which was 6 days less than CSS. Considering the environmental impact, the observed CO2 emissions from the SSSS were approximately 14.6% higher than CSS over its 10-year lifespan. Notably, the SSSS exhibited a substantial increase in the estimated carbon credit earned (CCE) compared to the CSS. Ultimately, the research underscores the efficacy of incorporating snail shells into solar still basins as a commendable approach to organic waste management, offering economic benefits without compromising environmental considerations.
    MeSH terms: Animals; Biocompatible Materials/chemistry; Conservation of Natural Resources/methods; Snails*; Sunlight; Water Purification/methods; Animal Shells/chemistry
  10. Husna A, Miah MA, Zakaria L, Nor NMIM
    Curr Microbiol, 2024 Aug 16;81(10):308.
    PMID: 39150554 DOI: 10.1007/s00284-024-03823-5
    Rice is the main staple food crops for the Malaysian population. Rice is also susceptible to bakanae diseases caused by some Fusarium species and reducing yield, and quality of rice also profit. In this study, several rice fields were surveyed to collect Fusarium isolates associated with bakanae disease. The morphological features of Fusarium andiyazi isolates found on infected rice plants were identified in this investigation. For biological species identification, MAT-1 (Mating type idiomorphs) bearing isolates were crossed with MAT-2 isolates. Crossing was succeeded between cross of two different mating type bearing field isolates. Consequently, there is a possibility of exchange of genetic material within the F. andiyazi population in Malaysia. The identity of the isolates was further determined up to the species level by comparing DNA sequences and phylogenetic analysis of two genes. The phylogenetic analyses of the joined dataset of translation elongation factor 1-alpha (TEF1-α) and RNA polymerase subunit II (RPB2) revealed that all the isolates were F. andiyazi. In pathogenicity tests, F. andiyazi were found to be pathogenic on the susceptible rice cultivars MR211 and MR220. Inoculated rice seedling produced typical bakanae symptom like elongation, thin and yellow leaves. F. andiyazi was further confirmed as pathogenic species by Ultra High-Performance Liquid Chromatography (UPLC) detection of Gibberellic acid (GA3) and Fusaric acid. In this study, F. andiyazi strains have been identified as the responsible pathogen for causing rice bakanae disease in Malaysia and it is the first report of F. andiyazi, as a pathogenic species on rice in Malaysia.
    MeSH terms: Fungal Proteins/genetics; Malaysia; Phylogeny*
  11. Shanmugham S, Lee EL, Kumar S, Zuber M, Noreen N, Smales FC, et al.
    Int Urol Nephrol, 2024 Aug 16.
    PMID: 39150601 DOI: 10.1007/s11255-024-04184-5
    PURPOSE: The use of topical corticosteroids (TCSs) has become an efficient, less-invasive treatment for phimosis. Whether any significant difference in efficacy exists between TCSs based on their potency is unclear.

    METHODS: Electronic databases were searched up to March 2024 for randomised controlled trials (RCTs) comparing the use of any type or concentration of TCSs with placebo or no treatment in boys with any degree of physician diagnosed phimosis. A random-effects network meta-analysis (NMA) using a consistency model within a frequentist approach was employed. The primary outcome was partial or complete resolution of phimosis reported as a pooled risk ratio (RR) with 95% CI. Relative ranking was assessed with surface under the cumulative ranking curve (SUCRA) probabilities.

    RESULTS: Seventeen RCTs, containing 2057 participants were identified. NMA suggested that, compared with control, the high (RR 3.19 (95% CI 1.42 to 7.16), moderate (RR 2.68 (95% CI 1.87 to 3.83) and low (RR 3.05 (95% CI 1.63 to 5.71) potency TCSs statistically significantly increased complete or partial clinical resolution of phimosis. The SUCRA plot revealed that high potency (SUCRA = 0.76) was ranked first followed by low and moderate TCSs. When we assessed comparative efficacy among TCSs based on potency, none of the classes were superior to others. The certainty of the evidence for an effect of moderate potent TCSs was that of moderate GRADE quality.

    CONCLUSION: Moderate to low potency TCSs are of comparable therapeutic effect in the treatment of phimosis to that of highly potent formulations. More high-quality RCTs are warranted.

  12. Naqvi SAH, Farhan M, Ahmad M, Kiran R, Fatima N, Shahbaz M, et al.
    World J Microbiol Biotechnol, 2024 Aug 16;40(10):302.
    PMID: 39150639 DOI: 10.1007/s11274-024-04108-6
    The genus Phytophthora contains more than 100 plant pathogenic species that parasitize a wide range of plants, including economically important fruits, vegetables, cereals, and forest trees, causing significant losses. Global agriculture is seriously threatened by fungicide resistance in Phytophthora species, which makes it imperative to fully comprehend the mechanisms, frequency, and non-chemical management techniques related to resistance mutations. The mechanisms behind fungicide resistance, such as target-site mutations, efflux pump overexpression, overexpression of target genes and metabolic detoxification routes for fungicides routinely used against Phytophthora species, are thoroughly examined in this review. Additionally, it assesses the frequency of resistance mutations in various Phytophthora species and geographical areas, emphasizing the rise of strains that are resistant to multiple drugs. The effectiveness of non-chemical management techniques, including biological control, host resistance, integrated pest management plans, and cultural practices, in reducing fungicide resistance is also thoroughly evaluated. The study provides important insights for future research and the development of sustainable disease management strategies to counter fungicide resistance in Phytophthora species by synthesizing current information and identifying knowledge gaps.
    MeSH terms: Agriculture; Mutation
  13. Cheung DH, Samoh N, Jonas KJ, Lim SH, Kongjareon Y, Guadamuz TE
    Arch Sex Behav, 2024 Oct;53(9):3527-3536.
    PMID: 39150645 DOI: 10.1007/s10508-024-02868-8
    Sexualized substance use or "chemsex" may contribute to the HIV epidemic among men who have sex with men (MSM) in Thailand. Specific patterns of chemsex use may be associated with different HIV/STI transmission risks. We examined typologies and correlates of sexualized substance use among a sample of high-risk MSM (n = 532) who had attended a private sex party or circuit party in the past three years using latent class analysis. Multinomial regression was used to adjust for variables associated with the 3-class latent class model. We identified a 3-class model as the best fitting model, which included: (1) "negligible sexualized substance users" (36.7%), who had never engaged in chemsex in the past six months; (2) "sexualized substance users" (13.9%), who had a high level of sexualized alcohol use and a wide range of other substances before or during sex in the past six months; and (3) "exclusive chemsex users" (49.4%), who predominantly used crystal methamphetamine, amyl nitrite, and erectile dysfunctional drugs before or during sex in the past six months. Compared to negligible sexualized substance users, exclusive chemsex users were more likely to be HIV-positive, more likely to have six or more sexual partners in the past six months, less likely to have condom use at last anal intercourse, and more likely to have provided sex work. Relative to negligible sexualized substance users, sexualized substance users reported more frequent online sex-seeking behaviors. These subgroups of Thai MSM have unique substance use patterns and HIV-related risk profiles, underscoring the importance of targeted HIV prevention strategies.
    MeSH terms: Adult; Humans; Male; Risk-Taking*; Sexual Behavior/psychology; Sexual Behavior/statistics & numerical data; Sexual Partners/psychology; Thailand/epidemiology; Unsafe Sex/psychology; Unsafe Sex/statistics & numerical data; Young Adult
  14. Ao J, Xu Z, Li W, Zhao M, Xie Q, Ji S
    PLoS One, 2024;19(8):e0304104.
    PMID: 39150965 DOI: 10.1371/journal.pone.0304104
    As a significant trade item on the ancient Silk Road, the evolution of mug shapes represents a confluence of Eastern and Western economic history and cultural-artistic exchanges, also reflecting the flourishing export culture of Guangzhou. This paper analyzes the functional and social factors influencing the morphological changes of Lingnan mugs from 1616 to 1949 from the perspective of quantitative typological analysis. The overall design trend of these mugs transitioned from complex to simple, enhancing user comfort, while variations in mug scale reflect the diversity of consumer classes and regional drinking cultures. Among the 30 mugs analyzed, the average capacity was 356ml, with a range of 1588ml. Common shapes included cylindrical bodies and ear-shaped handles. Morphologically, the belly of the mugs transformed from arc-barrel bodies (emphasizing heat retention) to bulbous bodies, and eventually to cylindrical bodies (combining heat retention, practicality, and economy), with handles also showing signs of East-West integration. The analysis of the mug body' s inclination, with handle-side junction angles ranging from 34° to 53° and wall-side junction angles from 50° to 90°, indicates that these features are associated with stability in placement, aesthetic design, and practicality in liquid containment. These morphological evolutions reflect genuine responses to market demands and advancements in production technology, manifesting as products of market orientation and societal needs. By measuring changes in morphology, scale, volume, and external contour curves, this paper addresses how social factors shape material morphology in an academic context.
    MeSH terms: China; Humans; History, 18th Century; History, 19th Century; History, 20th Century
  15. Tan AF, Sakam SSB, Piera K, Rajahram GS, William T, Barber BE, et al.
    PLoS Negl Trop Dis, 2024 Aug;18(8):e0012424.
    PMID: 39150978 DOI: 10.1371/journal.pntd.0012424
    The risk of severe malaria from the zoonotic parasite Plasmodium knowlesi approximates that from P. falciparum. In severe falciparum malaria, neutrophil activation contributes to inflammatory pathogenesis, including acute lung injury (ALI). The role of neutrophil activation in the pathogenesis of severe knowlesi malaria has not been examined. We evaluated 213 patients with P. knowlesi mono-infection (138 non-severe, 75 severe) and 49 Plasmodium-negative controls from Malaysia. Markers of neutrophil activation (soluble neutrophil elastase [NE], citrullinated histone [CitH3] and circulating neutrophil extracellular traps [NETs]) were quantified in peripheral blood by microscopy and immunoassays. Findings were correlated with malaria severity, ALI clinical criteria, biomarkers of parasite biomass, haemolysis, and endothelial activation. Neutrophil activation increased with disease severity, with median levels higher in severe than non-severe malaria and controls for NE (380[IQR:210-930]ng/mL, 236[139-448]ng/mL, 218[134-307]ng/mL, respectively) and CitH3 (8.72[IQR:3.0-23.1]ng/mL, 4.29[1.46-9.49]ng/mL, 1.53[0.6-2.59]ng/mL, respectively)[all p<0.01]. NETs were higher in severe malaria compared to controls (126/μL[IQR:49-323] vs 51[20-75]/μL, p<0.001). In non-severe malaria, neutrophil activation fell significantly upon discharge from hospital (p<0.03). In severe disease, NETs, NE, and CitH3 were correlated with parasitaemia, cell-free haemoglobin and angiopoietin-2 (all Pearson's r>0.24, p<0.05). Plasma NE and angiopoietin-2 were higher in knowlesi patients with ALI than those without (p<0.008); neutrophilia was associated with an increased risk of ALI (aOR 3.27, p<0.01). In conclusion, neutrophil activation is increased in ALI and in proportion to disease severity in knowlesi malaria, is associated with endothelial activation, and may contribute to disease pathogenesis. Trials of adjunctive therapies to regulate neutrophil activation are warranted in severe knowlesi malaria.
    MeSH terms: Adolescent; Adult; Female; Histones/blood; Humans; Malaysia; Male; Middle Aged; Severity of Illness Index*; Biomarkers/blood; Plasmodium knowlesi*; Neutrophil Activation*; Leukocyte Elastase/blood; Young Adult
  16. Armijo-Olivo S, Barbosa-Silva J, de Castro-Carletti EM, de Oliveira-Souza AIS, Pelai EB, Mohamad N, et al.
    Am J Phys Med Rehabil, 2024 Sep 01;103(9):845-857.
    PMID: 38320245 DOI: 10.1097/PHM.0000000000002444
    This review presents a comprehensive summary and critical evaluation of intention-to-treat analysis, with a particular focus on its application to randomized controlled trials within the field of rehabilitation. Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a methodological review that encompassed electronic and manual search strategies to identify relevant studies. Our selection process involved two independent reviewers who initially screened titles and abstracts and subsequently performed full-text screening based on established eligibility criteria. In addition, we included studies from manual searches that were already cataloged within the first author's personal database. The findings are synthesized through a narrative approach, covering fundamental aspects of intention to treat, including its definition, common misconceptions, advantages, disadvantages, and key recommendations. Notably, the health literature offers a variety of definitions for intention to treat, which can lead to misinterpretations and inappropriate application when analyzing randomized controlled trial results, potentially resulting in misleading findings with significant implications for healthcare decision making. Authors should clearly report the specific intention-to-treat definition used in their analysis, provide details on participant dropouts, and explain upon their approach to managing missing data. Adherence to reporting guidelines, such as the Consolidated Standards of Reporting Trials for randomized controlled trials, is essential to standardize intention-to-treat information, ensuring the delivery of accurate and informative results for healthcare decision making.
    MeSH terms: Humans; Research Design; Randomized Controlled Trials as Topic*; Biomedical Research; Intention to Treat Analysis*
  17. Hollingworth M, Woodhouse LJ, Law ZK, Ali A, Krishnan K, Dineen RA, et al.
    Neurosurgery, 2024 Sep 01;95(3):605-616.
    PMID: 38785451 DOI: 10.1227/neu.0000000000002961
    BACKGROUND AND OBJECTIVES: An important proportion of patients with spontaneous intracerebral hemorrhage (ICH) undergo neurosurgical intervention to reduce mass effect from large hematomas and control the complications of bleeding, including hematoma expansion and hydrocephalus. The Tranexamic acid (TXA) for hyperacute primary IntraCerebral Hemorrhage (TICH-2) trial demonstrated that tranexamic acid (TXA) reduces the risk of hematoma expansion. We hypothesized that TXA would reduce the frequency of surgery (primary outcome) and improve functional outcome at 90 days in surgically treated patients in the TICH-2 data set.

    METHODS: Participants enrolled in TICH-2 were randomized to placebo or TXA. Participants randomized to either TXA or placebo were analyzed for whether they received neurosurgery within 7 days and their characteristics, outcomes, hematoma volumes (HVs) were compared. Characteristics and outcomes of participants who received surgery were also compared with those who did not.

    RESULTS: Neurosurgery was performed in 5.2% of participants (121/2325), including craniotomy (57%), hematoma drainage (33%), and external ventricular drainage (21%). The number of patients receiving surgery who received TXA vs placebo were similar at 4.9% (57/1153) and 5.5% (64/1163), respectively (odds ratio [OR] 0.893; 95% CI 0.619-1.289; P -value = .545). TXA did not improve outcome compared with placebo in either surgically treated participants (OR 0.79; 95% CI 0.30-2.09; P = .64) or those undergoing hematoma evacuation by drainage or craniotomy (OR 1.19 95% 0.51-2.78; P -value = .69). Postoperative HV was not reduced by TXA (mean difference -8.97 95% CI -23.77, 5.82; P -value = .45).

    CONCLUSION: TXA was not associated with less neurosurgical intervention, reduced HV, or improved outcomes after surgery.

    MeSH terms: Aged; Double-Blind Method; Female; Humans; Male; Middle Aged; Treatment Outcome
  18. Minaguchi K, Samejima M, Nambiar P, Kaneko Y, Ochiai E, Kakimoto Y, et al.
    Leg Med (Tokyo), 2024 Sep;70:102463.
    PMID: 38823287 DOI: 10.1016/j.legalmed.2024.102463
    Closely linked groups of markers on the X chromosome are very useful for testing complex kinship relationships involving X-STR transmission. The Argus X-12 kit, a unique commercially available kit, can obtain haplotypes of 4 linkage groups (LGs) consisting of 3 markers. Although many population data have been reported for forensic purposes, differences in discrimination ability exist between LG1 and LG2, 3, and 4 in East Asian populations, and the data of this kit would become more useful if the discrimination ability of the latter groups were increased. Therefore, for matches found using this kit for some linkage group data, then to increase the identification ability, we additionally introduced 13 X-STR loci and established a method allowing comparison using data from 25 loci. The 13X-STRs add two locus data to each of LG2, 3, and 4, and also add two closely linked group (CLG) data between LG2 and 3 and LG3 and 4 in one multiplex PCR. Assessment of this method for a Malay population for which data by Argus X-12 had already been reported showed that the frequencies of distinct haplotypes in LG2, 3, and 4 were increased by 33.0-42.6 %, and frequencies of unique haplotypes increased by 45.4-59.2 %. The respective haplotype diversity values of the additional 3-locus and 4-locus CLGs were 0.9838 and 0.9939, which helps to improve discriminatory power and to predict recombination locations on the X chromosome. Although we have been testing these loci with Japanese subjects, this system would also be useful for the Malay population.
    MeSH terms: Haplotypes; Humans; Genetic Linkage; Malaysia; DNA Fingerprinting/methods; Microsatellite Repeats*; Asian Continental Ancestry Group/genetics; Forensic Genetics/methods
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