Browse publications by year: 2024

  1. Zainal Adlishah ZA, Jamil A
    PMID: 39220237 DOI: 10.51866/oa.611
    INTRODUCTION: Skin barrier dysfunction is an important component of atopic dermatitis (AD) pathophysiology. Topical corticosteroids (TCSs) are the mainstay therapy, but steroid phobia is emerging due to potential side effects. We aimed to determine the short-term effect of clobetasone butyrate on patients with AD.

    METHODS: This investigator-blinded, randomised, moisturiser-controlled study evaluated patients with stable mild-to-moderate AD. Clobetasone butyrate ointment plus aqueous cream (Aq) or Aq alone was applied on randomised sites twice daily for 6 weeks. The itch score, modified Eczema Area and Severity Index (M-EASI) and epidermal biophysical parameters were assessed at baseline and 1 h, 3 h, 2 weeks and 6 weeks after application.

    RESULTS: Sixteen patients, among whom 14 (87.5%) were women and two (12.5%) were men, participated in the study. There were no significant differences in pH, transepidermal water loss (TEWL) and hydration between TCS + Aq and Aq from 1 h to 6 weeks. A non-significant trend of pH increment was observed with TCS + Aq from baseline to 6 weeks. TEWL and hydration improved at 6 weeks for both treatment arms. The difference in TEWL from baseline was significant with Aq (P=0.01). The M-EASI at 6 weeks was comparable between the two arms. TCS + Aq improved itch and erythema better than Aq (P=0.02). No cutaneous adverse effects were observed at both sites.

    CONCLUSION: Short-term application of clobetasone butyrate with Aq is safe with no significant changes in epidermal biophysical parameters while controlling the symptoms and signs of eczema faster than Aq alone.

  2. Ooi PS, Ismail H, Meganathan G, Nabila Saidi N, Dhamotharan Y, Chua HH
    PMID: 39220238 DOI: 10.51866/cr.581
    Pulmonary tuberculosis poses a diagnostic dilemma to clinicians especially in the absence of typical presentation. The hypersensitivity to tuberculosis infection in other parts of the body can lead to nondestructive, para-infectious arthritis. This is known as Poncet disease, one of the clinical syndromes of musculoskeletal tuberculosis. Herein, we report a case of smear-negative pulmonary tuberculosis presenting with atypical features. It started with multiple joint pain, followed by the presence of multiple tender nodular skin lesions over the bilateral shins and wrist. Subsequent investigations led to the diagnosis of smear-negative pulmonary tuberculosis. Joint pain and erythema nodosum disappeared soon after antituberculosis therapy, supporting the diagnosis of Poncet disease.
  3. Vijan K, Ali A, Mohamed Idrus NA, Lourdesamy P, Margammuthu S, Perumal S, et al.
    PMID: 39220239 DOI: 10.51866/oa.629
    INTRODUCTION: Metabolic-associated fatty liver disease (MAFLD) is the liver manifestation of metabolic syndrome, which is commonly seen in primary care settings. This study aimed to determine the knowledge and practice of primary care physicians regarding MAFLD in Seremban District, Negeri Sembilan.

    METHODS: This cross-sectional study was conducted among medical officers in 14 health clinics in Seremban District, using a validated, self-administered online questionnaire.

    RESULTS: A total of 240 medical officers from 14 health clinics in Seremban District, participated in this study. Most participants (85.4%) passed the knowledge test. Their practice was acceptable, but only a minority were familiar with non-invasive testing of liver fibrosis (e.g. APRI or FIB-4), medication and specific diet for the treatment of MAFLD.

    CONCLUSION: Most primary care physicians in Seremban District are knowledgeable in identifying risk factors and managing patients with MAFLD. However, there are still areas to improve in terms of management, particularly regarding the use of silymarin, vitamin E and pioglitazone.

  4. Chen YY, Ghazali SR, Said A
    PMID: 39220240 DOI: 10.51866/oa.557
    INTRODUCTION: Exploring the connections between traumatic experiences and subsequent health outcomes is vital for informing clinical practices and public health policies. The study aimed to investigate the relationship between lifetime trauma exposure and posttraumatic stress disorder (PTSD), depressive and cardiovascular disease (CVD) symptoms.

    METHODS: A total of 171 patients who received treatment in a local heart centre were included in this study. Several questionnaires such as the Life Event Checklist-5, Posttraumatic Stress Disorder Checklist for DSM-5 and Patient Health Questionnaire-9 were used to measure their traumatic experiences and PTSD and depressive symptoms, respectively. Physiological measures were also examined. Data were analysed using SPSS.

    RESULTS: The chi-square test showed significant differences in the percentage of reported PTSD symptoms among the patients with CVD (24.0%), patients with kidney disease (4.3%) and patients with other health problems (7.1%). The patients with CVD reported having a significantly higher percentage of PTSD and depressive symptoms than the patients with other medical conditions. The patients with CVD who reported having PTSD symptoms had significant systolic blood pressure (SBP) and heart rate changes compared to the patients who did not. The patients who reported PTSD symptoms had a significantly shorter sleep duration than their counterparts. The SBP and diastolic blood pressure differed significantly between the patients with and without PTSD symptoms.

    CONCLUSION: Earlier detection, prevention and intervention related to trauma exposure and PTSD symptoms are suggested to reduce the CVD risk.

  5. Junejo I, Saraih UN, Perez JAE, Ejaz S, Ejaz F, Hossain MB
    F1000Res, 2024;13:654.
    PMID: 39220384 DOI: 10.12688/f1000research.152351.1
    BACKGROUND: Sustainability in small and medium-sized enterprises (SMEs) which engage heavily in manufacturing provides them with an essential platform for implementing environmental strategy, which is aimed at reducing environmental damage and promoting environmental protection. This study aims to examine the impact of the reduction in resource use, the greening of processes and products on environmental strategy and the mediating role of green employee behaviour.

    METHODS: Primary data gathered with the help of questionnaires from employees of SMEs manufacturing in developing countries, Pakistan. The research gathered data from 211 participants by applying a pre-tested instrumental questionnaire and structural equation modelling (SEM) for data analysis.

    RESULTS: The results confirmed all direct effects, including a reduction in resource use, the greening of processes and products and green employee behaviour of environmental strategies in small and medium manufacturing firms. Also, confirmed partial mediation effect of green employee behavior between greening of processes and products and environmental strategy.

    CONCLUSION: The current study clearly showed the need for programs and infrastructures that support resource reduction and greening businesses in SMEs. Companies' implementation of green processes and technologies allows SMEs to take an environmentally responsible stand and become part of the movement toward sustainability. The research stresses the importance of green employee conduct as a mediator, the central point being the individual employee being engaged and aware of the subject and willing to participate in environmentally friendly practices. Therefore, small and medium enterprises should enlighten their staff to practice green behaviour, give them what they need and empower them to be change drivers that will trigger sustainability throughout the organisations.

    MeSH terms: Adult; Conservation of Natural Resources/methods; Developing Countries*; Female; Humans; Male; Middle Aged; Pakistan; Surveys and Questionnaires; Manufacturing Industry
  6. Parveez B, Jamal NA, Nazurah NI, Aabid A, Baig M
    ACS Omega, 2024 Aug 27;9(34):36690-36698.
    PMID: 39220517 DOI: 10.1021/acsomega.4c05354
    Porous aluminum (Al) is popular due to its lightweight properties and impact energy absorption. However, it often has a lower mechanical strength than solid Al. To improve the performance, diamond reinforcement was introduced into the matrix. Further, addressing the challenge of interfacial bonding between Al and diamond, coated diamond with varying contents of 5, 10, 15, and 20 wt % was added to the porous Al alloy matrix via the powder metallurgy technique. The porosities were formed by using poly(methyl methacrylate) (30 wt %) as a space holder. The densities of the resultant porous composites ranged from 2.20 to 2.37 g/cm3 and porosities ranged from 33 to 38% for 5-20 wt % diamond contents. Furthermore, the yield strength and plateau stress increased from 21.47 to 29.46 MPa and 14 to 20 MPa, respectively, up to 10 wt % diamond content but declined upon further addition. Similarly, the energy absorption capacity increased from 2.15 to 2.95 MJ/m3 up to 10 wt % diamond content and thereafter decreased. Thus, the addition of coated diamond and alloying elements in Al strengthened the porous Al composites, making it suitable for applications requiring good compressive strength and energy absorption capacity.
  7. Mohamed AA, Tan JK, Tan MM, Khoo CS, Wan Yahya WNN, Abd Rahman MSH, et al.
    Neuropsychiatr Dis Treat, 2024;20:1615-1628.
    PMID: 39220600 DOI: 10.2147/NDT.S473483
    PURPOSE: Stroke is the second leading cause of global deaths. Post-stroke seizures (PSS) can lead to lasting complications, such as prolonged hospitalizations, increased disability rates, and higher mortality. Our study investigates the associated factors that contribute to post-stroke seizures in patients at a local tertiary hospital.

    PATIENTS AND METHODS: We designed a case-control study where patients admitted with PSS were recruited with consent. Controls admitted for stroke without seizure were then included. Suitability based on exclusion criteria was ensured before recording their sociodemographic and clinical data. An EEG was performed and read by two certified neurologists before the data was analyzed.

    RESULTS: We recruited 180 participants, 90 cases and 90 matched controls. Gender (p=0.013), race (p=0.015), dyslipidemia (p<0.001), prior stroke (p<0.031), large artery atherosclerosis (p<0.001), small vessel occlusions (p<0.001), blood pressure on presentation (p<0.028) and thrombolysis administration (p<0.029) were significantly associated with the occurrence of PSS. An increase in odds of PSS was observed in the male gender (1.974), dyslipidemia (3.480), small vessel occlusions (4.578), and in participants with epileptiform changes on EEG (3.630). Conversely, lower odds of PSS were seen in participants with high blood pressure on presentation (0.505), large artery atherosclerosis (0.266), and those who underwent thrombolysis (0.319).

    CONCLUSION: This study emphasized that identifying post-stroke seizures may be aided by EEGs and recognizing at-risk groups, which include males of Chinese descent in Asia, dyslipidemia, small vessel occlusions, those with low to normal blood pressure on presentation, and epileptiform changes in EEGs.

  8. Velentzis LS, Egger S, Waller J, Jennett CJ, Brotherton JML, Smith MA, et al.
    Prev Med Rep, 2024 Sep;45:102849.
    PMID: 39220611 DOI: 10.1016/j.pmedr.2024.102849
    OBJECTIVE: The coronavirus pandemic impacted health-seeking behaviour and access to primary care in Australia. We investigated factors associated with intention-to-attend and attendance of cervical screening during the pandemic, mainly in Victoria, Australia.

    METHODS: We used questionnaire and attendance data (Aug 2020-Nov 2022) from Compass-PLUS, a sub-study of the Compass randomized-controlled trial of Human Papillomavirus-based vs cytology-based screening. Data was restricted to the HPV-screening arm for comparability to the national program. We investigated associations overall and for younger (25-39 years) and older (≥40 years) cohorts, between intention-to-attend/attendance, and socio-demographics, anxiety-related scores, and agreement with beliefs about screening during the pandemic (e.g. importance of screening, increased workload, working from home, risk of infection).

    RESULTS: Among 2,226 participants, positive intention to attend screening was more likely among those with a family history of cancer (p = 0.030) or living outside major cities (p = 0.024). Increased attendance was associated with increasing age (p 

  9. Cui S, Jiang J, Mu L
    Psychol Res Behav Manag, 2024;17:3067-3081.
    PMID: 39220632 DOI: 10.2147/PRBM.S467221
    BACKGROUND: With the advent of new media technology, WeChat, as China's largest social networking platform, has significantly impacted people's lives. Growing concerns exist about social media usage, particularly regarding mental health issues stemming from problematic smartphone use. However, limited research has explored the relationship between social media usage and mental health among older adults in China, particularly the mechanisms influencing this relationship. This study addresses this gap by investigating the relationship between excessive WeChat use and loneliness among older adults, examining the mediating roles of sensation seeking and fear of missing out (FoMO).

    METHODS: To clarify the intermediary role of sensation seeking and FoMO in the relationship between elderly loneliness and problematic phone use, this study employed the loneliness scale, brief sensation seeking scale, the scale of FoMO and WeChat overuse scale in a questionnaire survey on the Chinese elderly aged 55 to 89 (N=913). A chained mediation model was constructed, with descriptive statistics, Pearson correlation analysis, and mediation effect tests performed.

    RESULTS: The results indicate that the relationship between loneliness and excessive WeChat use among Chinese elderly is mediated by sensation seeking and FoMO.

    CONCLUSION: The findings reveal that loneliness, sensation seeking and FoMO and problematic mobile phone use (WeChat) are interconnected; (ii) sensation seeking and FoMO are the two important intermediary mechanisms between loneliness and problematic mobile phone use; and (iii) sensation seeking and FoMO can act as mediators in the relationship between loneliness and problematic mobile phone use among the elderly. In the difference test of demographic variables, it was found that women had more WeChat overuse behavior than men, and urban residents demonstrated significantly higher levels of overuse than their township residents. The study has revealed the psychological mechanism between loneliness and problematic mobile phone use among the elderly, which provides guiding suggestions for the prevention and intervention of such behaviors in the elderly.

  10. Rusli RA, Makmor Bakry M, Mohamed Shah N, Loo XL, Hung SKY
    Ther Clin Risk Manag, 2024;20:529-541.
    PMID: 39220771 DOI: 10.2147/TCRM.S467975
    AIM: Identifying a patient's risk for poor outcomes after starting antiseizure medication (ASM) therapy is crucial in managing epilepsy pharmacologically. To date, there is a lack of designated tools to assess such risks.

    PURPOSE: To develop and validate a risk assessment tool for the therapeutic outcomes of ASM therapy.

    PATIENTS AND METHODS: A cross-sectional study was carried out in a hospital-based specialist clinic from September 2022 to August 2023. Data was analyzed from patients' medical records and face-to-face assessments. The seizure control domain was determined from the patients' medical records while seizure severity (SS) and adverse effects (AE) of ASM were assessed using the Seizure Severity Questionnaire and the Liverpool Adverse Event Profile respectively. The developed tool was devised from prediction models using logistic and linear regressions. Concurrent validity and interrater reliability methods were employed for validity assessments.

    RESULTS: A total of 397 patients were included in the analysis. For seizure control, the identified predictors include ≥10 years' epilepsy duration (OR:1.87,95% CI:1.10-3.17), generalized onset (OR:7.42,95% CI:2.95-18.66), focal onset seizure (OR:8.24,95% CI:2.98-22.77), non-adherence (OR:3.55,95% CI:1.52-8.27) and having ≥3 ASM (OR:3.29,95% CI:1.32-8.24). Younger age at epilepsy onset (≤40) (OR:3.29,95% CI:1.32-8.24) and neurological deficit (OR:3.55,95% CI:1.52-8.27) were significant predictors for SS. For AE, the positive predictors were age >35 (OR:0.12,95% CI:0.03-0.20), <13 years epilepsy duration (OR:2.89,95% CI:0.50-5.29) and changes in ASM regimen (OR:2.93,95% CI: 0.24-5.62). The seizure control domain showed a good discriminatory ability with a c-index of 0.711. From the Bonferroni (ANOVA) analysis, only SS predicted scores generated a linear plot against the mean of the actual scores. The AE domain was omitted from the final tool because it did not meet the requirements for validity assessment.

    CONCLUSION: This newly developed tool (RAS-TO) is a promising tool that could help healthcare providers in determining optimal treatment strategies for adults with epilepsy.

  11. Anoraga SB, Shamsudin R, Hamzah MH, Sharif S, Saputro AD
    Heliyon, 2024 Aug 30;10(16):e35537.
    PMID: 39220910 DOI: 10.1016/j.heliyon.2024.e35537
    Cocoa is considered to be one of the most significant agricultural commodities globally, alongside Palm Oil and Rubber. Cocoa is the primary ingredient in the manufacturing of chocolate, a globally popular food product. Approximately 30 % of cocoa, specifically cocoa nibs, are used as the primary constituent in chocolate production., while the other portion is either discarded in landfills as compost or repurposed as animal feed. Cocoa by-products consist of cocoa pod husk (CPH), cocoa shell, and pulp, of which about 70 % of the fruit is composed of CPH. CPH is a renewable resource rich in dietary fiber, lignin, and bioactive antioxidants like polyphenols that are being underutilized. CPH has the potential to be used as a source of pectin, dietary fibre, antibacterial properties, encapsulation material, xylitol as a sugar substitute, a fragrance compound, and in skin care applications. Several methods can be used to manage CPH waste using green technology and then transformed into valuable commodities, including pectin sources. Innovations in extraction procedures for the production of functional compounds can be utilized to increase yields and enhance existing uses. This review focuses on the physicochemical of CPH, its potential use, waste management, and green technology of cocoa by-products, particularly CPH pectin, in order to provide information for its development.
  12. Lan H, Bailey R, Tan WH
    Heliyon, 2024 Aug 30;10(16):e35675.
    PMID: 39220952 DOI: 10.1016/j.heliyon.2024.e35675
    Rapid growth has been witnessed in digital technologies, resulting in significant productive changes in communication and information technology-oriented practices in different fields. Hybrid teaching or blended learning has gained progressively widespread acceptance in the educational process, and concerns about teachers' information and communication technology (ICT) competence or digital competence have become prevalent. This study adopts a systematic review to interpret and analyse the relevant research findings, aiming to systematically investigate the existing models and paradigms of ICT competence or digital capacities and to understand further how these models and paradigms are applied specifically within the context of Chinese universities. Based on inclusion and exclusion criteria, 12 out of 801 candidate studies were accessed from Web of Science, Scopus and the China National Knowledge Infrastructure (CNKI) databases. The findings indicate that the Technological Pedagogical Content Knowledge (TPACK) and the National Educational Technology Guides for Teachers in Higher Education (CETG) are frequently used to evaluate college educators' digital proficiency or ICT capability in China. Educators' demographic characteristics, self-efficacy, external factors such as institutional policies and the availability of infrastructure and training collectively influence how digital teaching is integrated within Chinese higher education institutions. By conducting a systematic review of research trends and the critical factors affecting the digital competence of faculty in Chinese universities, this study aims to equip policymakers and educators with a deeper understanding of how to prepare for educational shifts in the digital era and thereby ensure the sustainability of professional development.
  13. Abbas A, Anwar F, Ahmad N, Rehman AT, Mohammed OA, Abdel-Reheim MA, et al.
    Heliyon, 2024 Aug 30;10(16):e35282.
    PMID: 39220953 DOI: 10.1016/j.heliyon.2024.e35282
    This study reports the comparative evaluation of yield, physico-chemical composition and biological attributes (antioxidant activity, antimicrobial activity, biofilm inhibition and hemolytic activity) of peppermint (Mentha piperita L.) essential oil (EO) obtained by hydro-distillation (HD) and supercritical fluid (CO2) extraction (SCFE) methods. The yield (%) of EO obtained by HD (0.20 %) was significantly (p 
  14. Muzaffar FAS, Tan ST
    Health Sci Rep, 2024 Sep;7(9):e70042.
    PMID: 39221050 DOI: 10.1002/hsr2.70042
    BACKGROUND AND AIM: Literature suggests that individuals who have recovered from COVID-19 may experience post-COVID conditions, including sleep problems and alterations in smell or taste. Thus, this study aims to compare the sleep quality, diet quality, and weight change between COVID-19-recovered patients and healthy controls.

    METHODS: A matched case-control study involving young adults aged 18-30 years was conducted in the Klang Valley of Malaysia. The young adults were matched in a 1:1 ratio based on their sociodemographic characteristics, including gender, age, marital status, ethnicity, educational attainment, employment status, and monthly earned income. The Pittsburgh Sleep Quality Index was utilized to evaluate sleep quality, and the Diet Quality for Malaysia was used to determine the diet quality of all young adults. The young adults retrospectively recalled their prepandemic body weight in February 2020, while their current body weight in February 2023 was measured using a TANITA HD-314 digital weighing scale.

    RESULTS: Emerging findings suggest that sleep quality and weight change were comparable between COVID-19-recovered patients and healthy controls. However, healthy controls were reported to have a more diversified diet than COVID-19-recovered patients. Nevertheless, no significant main effects or interaction effects of sleep and diet quality on weight change were observed in COVID-19-recovered patients or healthy controls. In this study, young adults also reported suffering from sleep deprivation and deficiency due to the pandemic.

    CONCLUSION: Intervention programs that emphasize avoiding stimulants before bedtime for healthy controls, promoting the importance of having a diversified and balanced diet among the COVID-19-recovered patients, and achieving an ideal body weight for all young adults should be conducted after the COVID-19 pandemic.

  15. Adlim M, Surbakti MS, Omar AF, Rahmayani RFI, Hasmar AH, Ozmen I, et al.
    RSC Adv, 2024 Aug 29;14(38):27504-27513.
    PMID: 39221122 DOI: 10.1039/d4ra04901b
    A simple preparation of a paper strip test with a smartphone-based instrument for detecting dissolved mercury is still in development. This study aims to develop a smartphone-based colorimetric paper strip test using chitosan-stabilized silver nanoparticles for detecting dissolved mercury. The method demonstrated high sensitivity and selectivity for Hg2+ ions, with detection limits comparable to UV-vis spectrophotometry. Silver ions embedded in the chitosan matrix were reduced by either sodium NaBH4 or N2H4. Both chi-AgNP colloidal and chi-AgNP paper strips were tested for sensitivity of mercury(ii) solution detection with and without ion interference. The accuracy of colour change responding to the mercury concentration was recorded with several smartphones in a handmade cubical and a T-shape micro-studio. Only NaBH4 gives colloidal chi-AgNPs relatively dispersed, and the colloidal chi-AgNPs become aggregated when AgNP interacts with mercury(ii) ions. The colour change of chi-AgNP paper strips responding to the concentration of mercury(ii) and quantified using a smartphone is consistent when confirmed with UV-vis spectrophotometric determination with a comparable limit of detection (0.76 μM). The inferring ions do not significantly affect mercury(ii) analyses. Therefore, the paper strip integrated with the smartphone is effectively used for mercury(ii) detection in water as long as the mercury concentration is >1 μM. This finding might inspire advanced technology with a larger number of data references, and machine learning involvement to develop more compatible and simple mercury detection.
  16. Singh J, Ramely R, Wan Zain WZ, Zakaria AD, Md Hashim MN
    Cureus, 2024 Aug;16(8):e66010.
    PMID: 39221290 DOI: 10.7759/cureus.66010
    Brachial artery mycotic aneurysms are very rare and even more uncommon to present initially with bleeding or rupture. Initial presentation of ruptured brachial artery mycotic aneurysm in an active intravenous drug abuser is managed with brachial artery ligation with an option of revascularization later. Distal circulation is not commonly threatened as there is a presence of collaterals to perfuse the distal limb. In this case report, we present a case of limb-threatening brachial artery mycotic aneurysm rupture that needed emergency revascularization surgery.
  17. Wangdi L, Wai Wye NH, Meng Hsien Y, Naffi AA, Bastion MC
    Cureus, 2024 Aug;16(8):e65986.
    PMID: 39221292 DOI: 10.7759/cureus.65986
    BACKGROUND: Eye removal surgeries, also called anophthalmic surgeries, are usually performed for a painful blinded eye due to various underlying causes. In this case review, we intended to study the indications, the types of anophthalmic surgeries, and post-operative complications related to eye removal surgeries.

    METHOD:  Five years of retrospective case review of surgical eye removals was conducted from 1st June 2018 to 31st May 2023 at Hospital Canselor Tuanku Muhriz (HCTM), University of Kebangsaan Malaysia (UKM). Medical record files were used to analyse the age, gender, affected eye, types of surgeries, and indications of the eye removal surgery.

    RESULTS:  Fourteen eyes underwent anophthalmic surgeries inclusive of evisceration (78.57%, n = 11), enucleation (14.29%, n = 2), and exenteration (7.14%, n = 1). Among the evisceration group, 63.64% (n = 7) were due to endophthalmitis, 27.27% (n = 3) were due to ocular trauma, and 9.09% (n = 1) were done for a painful blind due to neovascular glaucoma. Two enucleation surgeries were performed for retinoblastoma and one exenteration for orbital metastatic malignancy.

    CONCLUSION:  The preferred choice of anophthalmic surgery was in favour of evisceration, especially when the underlying causes were due to benign conditions. The most common indications of anophthalmic surgeries were endophthalmitis, trauma, and malignancies. Enucleation and exenteration were performed mainly for the blinded eye due to the intraocular malignancies and malignancy with an extraocular spread. A fairly lesser number of anophthalmic surgeries over the five years could imply an improvement in the conservative management approach of a painful blinded eye.

  18. Anderson DC, Peterson MS, Lapp SA, Galinski MR
    J Proteomics, 2024 Jun 30;302:105197.
    PMID: 38759952 DOI: 10.1016/j.jprot.2024.105197
    The emerging malaria parasite Plasmodium knowlesi threatens the goal of worldwide malaria elimination due to its zoonotic spread in Southeast Asia. After brief ex-vivo culture we used 2D LC/MS/MS to examine the early and late ring stages of infected Macaca mulatta red blood cells harboring P. knowlesi. The M. mulatta clathrin heavy chain and T-cell and macrophage inhibitor ERMAP were overexpressed in the early ring stage; glutaredoxin 3 was overexpressed in the late ring stage; GO term differential enrichments included response to oxidative stress and the cortical cytoskeleton in the early ring stage. P. knowlesi clathrin heavy chain and 60S acidic ribosomal protein P2 were overexpressed in the late ring stage; GO term differential enrichments included vacuoles in the early ring stage, ribosomes and translation in the late ring stage, and Golgi- and COPI-coated vesicles, proteasomes, nucleosomes, vacuoles, ion-, peptide-, protein-, nucleocytoplasmic- and RNA-transport, antioxidant activity and glycolysis in both stages. SIGNIFICANCE: Due to its zoonotic spread, cases of the emerging human pathogen Plasmodium knowlesi in southeast Asia, and particularly in Malaysia, threaten regional and worldwide goals for malaria elimination. Infection by this parasite can be fatal to humans, and can be associated with significant morbidity. Due to zoonotic transmission from large macaque reservoirs that are untreatable by drugs, and outdoor biting mosquito vectors that negate use of preventive measures such as bed nets, its containment remains a challenge. Its biology remains incompletely understood. Thus we examine the expressed proteome of the early and late ex-vivo cultured ring stages, the first intraerythrocyte developmental stages after infection of host rhesus macaque erythrocytes. We used GO term enrichment strategies and differential protein expression to compare early and late ring stages. The early ring stage is characterized by the enrichment of P. knowlesi vacuoles, and overexpression of the M. mulatta clathrin heavy chain, important for clathrin-coated pits and vesicles, and clathrin-mediated endocytosis. The M. mulatta protein ERMAP was also overexpressed in the early ring stage, suggesting a potential role in early ring stage inhibition of T-cells and macrophages responding to P. knowlesi infection of reticulocytes. This could allow expansion of the host P. knowlesi cellular niche, allowing parasite adaptation to invasion of a wider age range of RBCs than the preferred young RBCs or reticulocytes, resulting in proliferation and increased pathogenesis in infected humans. Other GO terms differentially enriched in the early ring stage include the M. mulatta cortical cytoskeleton and response to oxidative stress. The late ring stage is characterized by overexpression of the P. knowlesi clathrin heavy chain. Combined with late ring stage GO term enrichment of Golgi-associated and coated vesicles, and enrichment of COPI-coated vesicles in both stages, this suggests the importance to P. knowlesi biology of clathrin-mediated endocytosis. P. knowlesi ribosomes and translation were also differentially enriched in the late ring stage. With expression of a variety of heat shock proteins, these results suggest production of folded parasite proteins is increasing by the late ring stage. M. mulatta endocytosis was differentially enriched in the late ring stage, as were clathrin-coated vesicles and endocytic vesicles. This suggests that M. mulatta clathrin-based endocytosis, perhaps in infected reticulocytes rather than mature RBC, may be an important process in the late ring stage. Additional ring stage biology from enriched GO terms includes M. mulatta proteasomes, protein folding and the chaperonin-containing T complex, actin and cortical actin cytoskeletons. P knowlesi biology also includes proteasomes, as well as nucleosomes, antioxidant activity, a variety of transport processes, glycolysis, vacuoles and protein folding. Mature RBCs have lost internal organelles, suggesting infection here may involve immature reticulocytes still retaining organelles. P. knowlesi parasite proteasomes and translational machinery may be ring stage drug targets for known selective inhibitors of these processes in other Plasmodium species. To our knowledge this is the first examination of more than one timepoint within the ring stage. Our results expand knowledge of both host and parasite proteins, pathways and organelles underlying P. knowlesi ring stage biology.
    MeSH terms: Animals; Host-Parasite Interactions; Humans; Macaca mulatta*; Malaria/metabolism; Malaria/parasitology; Malaria/transmission; Protozoan Proteins/metabolism
  19. Sathiyaseelar R, Kohli S
    Am J Med, 2024 Sep;137(9):e162-e163.
    PMID: 38795937 DOI: 10.1016/j.amjmed.2024.05.022
    MeSH terms: Humans
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