Browse publications by year: 2021

  1. Donnellan L, Simpson B, Dhillon VS, Costabile M, Fenech M, Deo P
    Mutagenesis, 2021 10 06;36(5):339-348.
    PMID: 34297102 DOI: 10.1093/mutage/geab028
    Type 2 diabetes is associated with elevated levels of DNA damage, in particular micronuclei (MNi) which are formed by acentric chromosome fragments caused by double-stranded DNA breaks (DSBs), or whole chromosomes which fail to segregate during mitosis. We investigated if methylglyoxal (MGO), a reactive dicarbonyl known to be elevated in type 2 diabetes is capable of increasing chromosomal instability and DNA damage as measured by the cytokinesis block micronucleus cytome (CBMNcyt) assay in B-lymphoblastoid WIL2-NS cells and primary peripheral blood lymphocytes (PBL). We also investigated the level of various dicarbonyl stress biomarkers, including extracellular and intracellular MGO, protein and MGO modifications of DNA. WIL2-NS cells exposed to either MGO or a glyoxalase 1 inhibitor showed increases in MNi and nuclear buds, which were associated with an increase in intracellular MGO. DNA damage in the form of MNi and nucleoplasmic bridges were observed in primary PBL exposed to 10 µM MGO, suggesting low concentrations of MGO may be genotoxic. Furthermore, we showed, using fluorescent in situ hybridisation, that the majority of MNi caused by MGO in WIL2-NS cells were caused by whole chromosome loss events, rather than DSBs. Our data suggest that MGO, a reactive metabolite elevated in type 2 diabetes and other pathologies, can affect genomic integrity by impairing chromosome segregation during mitosis.
  2. Darvishi B, Dinarvand R, Mohammadpour H, Kamarul T, Sharifi AM
    Mol Pharm, 2021 09 06;18(9):3302-3325.
    PMID: 34297586 DOI: 10.1021/acs.molpharmaceut.1c00248
    Microvascular complications are among the major outcomes of patients with type II diabetes mellitus, which are the consequences of impaired physiological functioning of small blood vessels and angiogenic responses in these patients. Overproduction and accumulation of methylglyoxal (MGO), a highly reactive dicarbonyl byproduct of glycolysis pathway, has been acclaimed as the main inducer of impaired angiogenic responses and microvascular dysfunction in diabetic patients with uncontrolled hyperglycemia. Hence, an effective approach to overcome diabetes-associated microvascular complications is to neutralize the deleterious activity of enhanced the concentration of MGO in the body. Owing to the glycation inhibitory activity of Aloe vera whole extract, and capability of l-carnosine, an endogenous dipeptide, in attenuating MGO's destructive activity, we examined whether application of a combination of l-carnosine and A. vera could be an effective way of synergistically weakening this reactive dicarbonyl's impaired angiogenic effects. Additionally, overcoming the poor cellular uptake and internalization of l-carnosine and A. vera, a nanophytosomal formulation of the physical mixture of two compounds was also established. Although l-carnosine and A. vera at whole studied combination ratios could synergistically enhance viability of human umbilical vein endothelial cells (HUVECs) treated with MGO, the 25:1 w/w ratio was the most effective one among the others (27 ± 0.5% compared to 12 ± 0.3 to 18 ± 0.4%; F (4, 15) = 183.9, P < 0.0001). Developing dual nanophytosomes of l-carnosine/A. vera (25:1) combination ratio, we demonstrated superiority of the nanophytosomal formulation in protecting HUVECs against MGO-induced toxicity following a 24-72 h incubation period (17.3, 15.8, and 12.4% respectively). Moreover, 500 μg/mL concentration of dual l-carnosine/A. vera nanophytosomes exhibited a superior free radical scavenging potency (63 ± 4 RFU vs 83 ± 5 RFU; F (5, 12) = 54.81, P < 0.0001) and nitric oxide synthesizing capacity (26.11 ± 0.19 vs 5.1 ± 0.33; F (5, 12) = 2537, P < 0.0001) compared to their physical combination counterpart. Similarly, 500 μg/mL dual l-carnosine/A. vera nanophytosome-treated HUVECs demonstrated a superior tube formation capacity (15 ± 3 vs 2 ± 0.3; F (5, 12) = 30.87, P < 0.001), wound scratch healing capability (4.92 ± 0.3 vs 3.07 ± 0.3 mm/h; F (5, 12) = 39.21, P < 0.0001), and transwell migration (586 ± 32 vs 394 ± 18; F (5, 12) = 231.8, P < 0.001) and invasion (172 ± 9 vs 115 ± 5; F (5, 12) = 581.1, P < 0.0001) activities compared to the physical combination treated ones. Further confirming the proangiogenic activity of the dual l-carnosine/A. vera nanophytosomes, a significant shift toward expression of proangiogenic genes including HIF-1α, VEGFA, bFGF, KDR, and Ang II was reported in treated HUVECs. Overall, dual l-carnosine/A. vera nanophytosomes could be a potential candidate for attenuating type II DM-associated microvascular complications with an impaired angiogenesis background.
    MeSH terms: Aloe/chemistry; Carnosine/pharmacology*; Carnosine/therapeutic use; Diabetic Angiopathies/drug therapy*; Diabetic Angiopathies/metabolism; Diabetic Angiopathies/pathology; Drug Synergism; Humans; Plant Extracts/pharmacology*; Plant Extracts/therapeutic use; Pyruvaldehyde/metabolism; Pyruvaldehyde/toxicity; Neovascularization, Physiologic/drug effects*; Nanoparticles/therapeutic use*; Microvessels/drug effects; Human Umbilical Vein Endothelial Cells
  3. Christwardana M, Yoshi LA, Setyonadi I, Maulana MR, Fudholi A
    Enzyme Microb Technol, 2021 Sep;149:109831.
    PMID: 34311895 DOI: 10.1016/j.enzmictec.2021.109831
    In this study, yeast microbial fuel cells (MFCs) were established as biosensors for in-situ monitoring of dissolved oxygen (DO) levels in environmental waters, with yeast and glucose substrates acting as biocatalyst and fuel, respectively. Diverse environmental factors, such as temperature, pH and conductivity, were considered. The sensor performance was first tested with distilled water with different DO levels ranging from 0 mg/L to 8 mg/L and an external resistance of 1000 Ω. The relationship between DO and current density was non-linear (exponential). This MFC capability was further explored under different environmental conditions (pH, temperature and conductivity), and the current density produced was within the range of 0.14-34.88 mA/m2, which increased with elevated DO concentration. The resulting regression was y = 1.3051e0.3548x, with a regression coefficient (R2) = 0.71, indicating that the MFC-based DO meter was susceptible to interference. When used in environmental water samples, DO measurements using MFC resulted in errors ranging from 6.25 % to 15.15 % when compared with commercial DO meters. The simple yeast-based MFC sensors demonstrate promising prospects for future monitoring in a variety of areas, including developing countries and remote locations.
    MeSH terms: Bioelectric Energy Sources*; Electrodes; Oxygen/analysis; Saccharomyces cerevisiae/genetics; Biosensing Techniques*; Biological Oxygen Demand Analysis
  4. Toh TH, Abdul-Aziz NA, Yahya MA, Goh KJ, Loh EC, Capelle DP, et al.
    Clin Neurophysiol, 2021 10;132(10):2722-2728.
    PMID: 34312065 DOI: 10.1016/j.clinph.2021.05.034
    OBJECTIVE: We aimed to develop a model to predict amyotrophic lateral sclerosis (ALS) disease progression based on clinical and neuromuscular ultrasound (NMUS) parameters.

    METHODS: ALS patients were prospectively recruited. Muscle fasciculation (≥2 over 30-seconds, examined in biceps brachii-brachialis (BB), brachioradialis, tibialis anterior and vastus medialis) and nerve cross-sectional area (CSA) (median, ulnar, tibial, fibular nerve) were evaluated through NMUS. Ultrasound parameters were correlated with clinical data, including revised ALS Functional Rating Scale (ALSFRS-R) progression at one year. A predictive model was constructed to differentiate fast progressors (ALSFRS-R decline ≥ 1/month) from non-fast progressors.

    RESULTS: 40 ALS patients were recruited. Three parameters emerged as strong predictors of fast progressors: (i) ALSFRS-R slope at time of NMUS (p = 0.041), (ii) BB fasciculation count (p = 0.027) and (iii) proximal to distal median nerve CSA ratio 

    MeSH terms: Aged; Amyotrophic Lateral Sclerosis/physiopathology; Fasciculation/physiopathology; Female; Follow-Up Studies; Humans; Male; Middle Aged; Models, Neurological*; Predictive Value of Tests; Prospective Studies; Ultrasonography, Interventional/methods*; Disease Progression*; Muscle, Skeletal/physiopathology
  5. Leo ZH, Mohammad Iskandar FF, Yeap TB, Bong CP
    BMJ Case Rep, 2021 Jul 26;14(7).
    PMID: 34312139 DOI: 10.1136/bcr-2021-243950
    Anaesthesia for patients with severe lung fibrosis post COVID-19 infection requires special consideration. This is due to its propensity to cause perioperative anaesthetic catastrophe and possibility of cross infection among healthcare workers if not properly managed. This interesting article elaborates in detail the anaesthetic and surgical challenges in a morbidly obese patient who had a severe COVID-19 infection presenting for an elective spine surgery.
    MeSH terms: Humans; Spine/surgery; Elective Surgical Procedures
  6. Saniasiaya J, Narayanan P
    BMJ Case Rep, 2021 Jul 26;14(7).
    PMID: 34312145 DOI: 10.1136/bcr-2021-245388
    MeSH terms: Ear, Middle; Humans; Nose; Hyphae*
  7. Lees S, Sariola S, Schmidt-Sane M, Enria L, Tan KA, Aedo A, et al.
    BMJ Glob Health, 2021 Jul;6(7).
    PMID: 34312181 DOI: 10.1136/bmjgh-2021-006741
    MeSH terms: Humans; Social Sciences
  8. Poli A, Abdul-Hamid S, Zaurito AE, Campagnoli F, Bevilacqua V, Sheth B, et al.
    Proc Natl Acad Sci U S A, 2021 08 03;118(31).
    PMID: 34312224 DOI: 10.1073/pnas.2010053118
    Regulatory T cells (Tregs) play fundamental roles in maintaining peripheral tolerance to prevent autoimmunity and limit legitimate immune responses, a feature hijacked in tumor microenvironments in which the recruitment of Tregs often extinguishes immune surveillance through suppression of T-effector cell signaling and tumor cell killing. The pharmacological tuning of Treg activity without impacting on T conventional (Tconv) cell activity would likely be beneficial in the treatment of various human pathologies. PIP4K2A, 2B, and 2C constitute a family of lipid kinases that phosphorylate PtdIns5P to PtdIns(4,5)P 2 They are involved in stress signaling, act as synthetic lethal targets in p53-null tumors, and in mice, the loss of PIP4K2C leads to late onset hyperinflammation. Accordingly, a human single nucleotide polymorphism (SNP) near the PIP4K2C gene is linked with susceptibility to autoimmune diseases. How PIP4Ks impact on human T cell signaling is not known. Using ex vivo human primary T cells, we found that PIP4K activity is required for Treg cell signaling and immunosuppressive activity. Genetic and pharmacological inhibition of PIP4K in Tregs reduces signaling through the PI3K, mTORC1/S6, and MAPK pathways, impairs cell proliferation, and increases activation-induced cell death while sparing Tconv. PIP4K and PI3K signaling regulate the expression of the Treg master transcriptional activator FOXP3 and the epigenetic signaling protein Ubiquitin-like containing PHD and RING finger domains 1 (UHRF1). Our studies suggest that the pharmacological inhibition of PIP4K can reprogram human Treg identity while leaving Tconv cell signaling and T-helper differentiation to largely intact potentially enhancing overall immunological activity.
    MeSH terms: Cell Survival; Cloning, Molecular; Humans; Immunosuppression; Quinazolines/pharmacology; Thiophenes/pharmacology; Signal Transduction; Gene Expression Regulation, Enzymologic/drug effects; Gene Expression Regulation, Enzymologic/immunology; Gene Expression Regulation, Enzymologic/physiology; Phosphotransferases (Alcohol Group Acceptor)/genetics; Phosphotransferases (Alcohol Group Acceptor)/metabolism*; Phosphatidylinositol 3-Kinases/genetics; Phosphatidylinositol 3-Kinases/metabolism*; CCAAT-Enhancer-Binding Proteins/genetics; CCAAT-Enhancer-Binding Proteins/metabolism*; Ubiquitin-Protein Ligases/genetics; Ubiquitin-Protein Ligases/metabolism*; Cell Proliferation; T-Lymphocytes, Regulatory/physiology*; Forkhead Transcription Factors/genetics; Forkhead Transcription Factors/metabolism*
  9. Yun J, Cho YH, Lee SM, Hwang J, Lee JS, Oh YM, et al.
    Sci Rep, 2021 07 26;11(1):15144.
    PMID: 34312450 DOI: 10.1038/s41598-021-94535-4
    Heterogeneous clinical manifestations and progression of chronic obstructive pulmonary disease (COPD) affect patient health risk assessment, stratification, and management. Pulmonary function tests are used to diagnose and classify the severity of COPD, but they cannot fully represent the type or range of pathophysiologic abnormalities of the disease. To evaluate whether deep radiomics from chest computed tomography (CT) images can predict mortality in patients with COPD, we designed a convolutional neural network (CNN) model for extracting representative features from CT images and then performed random survival forest to predict survival in COPD patients. We trained CNN-based binary classifier based on six-minute walk distance results (> 440 m or not) and extracted high-throughput image features (i.e., deep radiomics) directly from the last fully connected layer of it. The various sizes of fully connected layers and combinations of deep features were experimented using a discovery cohort with 344 patients from the Korean Obstructive Lung Disease cohort and an external validation cohort with 102 patients from Penang General Hospital in Malaysia. In the integrative analysis of discovery and external validation cohorts, with combining 256 deep features from the coronal slice of the vertebral body and two sagittal slices of the left/right lung, deep radiomics for survival prediction achieved concordance indices of 0.8008 (95% CI, 0.7642-0.8373) and 0.7156 (95% CI, 0.7024-0.7288), respectively. Deep radiomics from CT images could be used to predict mortality in COPD patients.
  10. Kwong QB, Wong YC, Lee PL, Sahaini MS, Kon YT, Kulaveerasingam H, et al.
    Sci Rep, 2021 07 26;11(1):15210.
    PMID: 34312480 DOI: 10.1038/s41598-021-94705-4
    Stomatal density is an important trait for breeding selection of drought tolerant oil palms; however, its measurement is extremely tedious. To accelerate this process, we developed an automated system. Leaf samples from 128 palms ranging from nursery (1 years old), juvenile (2-3 years old) and mature (> 10 years old) were collected to build an oil palm specific stomata detection model. Micrographs were split into tiles, then used to train a stomata object detection convolutional neural network model through transfer learning. The detection model was then tested on leaf samples acquired from three independent oil palm populations of young seedlings (A), juveniles (B) and productive adults (C). The detection accuracy, measured in precision and recall, was 98.00% and 99.50% for set A, 99.70% and 97.65% for set B, and 99.55% and 99.62% for set C, respectively. The detection model was cross-applied to another set of adult palms using stomata images taken with a different microscope and under different conditions (D), resulting in precision and recall accuracy of 99.72% and 96.88%, respectively. This indicates that the model built generalized well, in addition has high transferability. With the completion of this detection model, stomatal density measurement can be accelerated. This in turn will accelerate the breeding selection for drought tolerance.
  11. Jeyaraman M, Muthu S, Bapat A, Jain R, Sushmitha ES, Gulati A, et al.
    Heliyon, 2021 Jul;7(7):e07635.
    PMID: 34312598 DOI: 10.1016/j.heliyon.2021.e07635
    The contagiosity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has startled mankind and has brought our lives to a standstill. The treatment focused mainly on repurposed immunomodulatory and antiviral agents along with the availability of a few vaccines for prophylaxis to vanquish COVID-19. This seemingly mandates a deeper understanding of the disease pathogenesis. This necessitates a plausible extrapolation of cell-based therapy to COVID-19 and is regarded equivalently significant. Recently, correlative pieces of clinical evidence reported a robust decline in lymphocyte count in severe COVID-19 patients that suggest dysregulated immune responses as a key element contributing to the pathophysiological alterations. The large granular lymphocytes also known as natural killer (NK) cells play a heterogeneous role in biological functioning wherein their frontline action defends the body against a wide array of infections and tumors. They prominently play a critical role in viral clearance and executing immuno-modulatory activities. Accumulated clinical evidence demonstrate a decrease in the number of NK cells in circulation with or without phenotypical exhaustion. These plausibly contribute to the progression of pulmonary inflammation in COVID-19 pneumonia and result in acute lung injury. In this review, we have outlined the present understanding of the immunological response of NK cells in COVID-19 infection. We have also discussed the possible use of these powerful biological cells as a therapeutic agent in view of preventing immunological harms of SARS-CoV-2 and the current challenges in advocating NK cell therapy for the same.
  12. Si R, Aziz N, Raza A
    Environ Sci Pollut Res Int, 2021 Dec;28(45):64419-64430.
    PMID: 34312755 DOI: 10.1007/s11356-021-15474-1
    Climate change caused by different anthropogenic activities is a subject of attention globally. There is a concern on how to maintain a clean environment and at the same time achieve optimal use of land. To this end, this study examines the causal effects of land use including agricultural, forestry, and other land categories on greenhouse gas (GHG) emissions. The data for China is collected over the period 1990 to 2012 for the empirical examination. By employing vector error correction model (VECM), it is found that there is significant long-run causality among variables. However, in the short run expectedly, only land under agriculture has strong causality with the GHG emissions. The results in case of variance decomposition analysis highlight that land under agriculture and other use significantly causes the GHG emissions in the long run. Further, impulse responses of variables are also measured with the Cholesky one standard deviation. The results are robust and support the argument that different land uses cause GHG emissions in China. The study provides insights for policy makers to improve the activities occurring on agricultural and other land uses. Assessment of overall potential, including bio energy, needs to include analysis of trade-offs and feedbacks with land-use competition. Many positive linkages with sustainable development and with adaptation exist but are case and site specific as they depend on scale, scope, and pace of implementation.
    MeSH terms: Agriculture; Carbon Dioxide/analysis; China; Forestry; Greenhouse Effect
  13. Rehman S, Ranjha NM, Shoukat H, Madni A, Ahmad F, Raza MR, et al.
    AAPS PharmSciTech, 2021 Jul 26;22(6):209.
    PMID: 34312763 DOI: 10.1208/s12249-021-02082-y
    The aim of present research aims to fabricate a system of enteric coating of hydrogel beads with pH-sensitive polymer, which shows solubility at pH > 7, and explore their potential to target the colon for drug delivery. Hydrogel beads were fabricated through the extrusion-dripping technique followed by ion gelation crosslinking. Moreover, freeze-thaw cycle was implemented for crosslinking of polyvinyl alcohol (PVA)/Ca-alginate blend beads. The oil-in-oil solvent evaporation method was adopted for the Eudragit coating of hydrogel beads using different coat: core ratios (4:1 or 8:1). Coated and uncoated hydrogel beads were evaluated by in vitro physicochemical properties, swelling and drug release behaviours, and in vivo pharmacokinetics, swelling, and toxicity evaluation. Diclofenac sodium was loaded as an experimental drug. Drug entrapment efficiency for the PVA/Ca-alginate beads was calculated as 98%, and for Ca-alginate beads, it came out to a maximum of 74%. Drug release study at various pH suggested that, unlike uncoated hydrogel beads, the coated beads delay the release of diclofenac sodium in low pH of the gastric and intestinal environment, thus targeting the colon for the drug release. It was concluded that Eudragit S-100-coated hydrogel beads could serve as a more promising and reliable way to target the colon for drug delivery.Graphical abstract.
    MeSH terms: Alginates*; Colon; Hexuronic Acids; Hydrogen-Ion Concentration; Microspheres; Polymethacrylic Acids; Hydrogels*; Glucuronic Acid
  14. Sabarudin NS, Tan SW, Phang YF, Omar AR
    J Vet Sci, 2021 Jul;22(4):e42.
    PMID: 34313038 DOI: 10.4142/jvs.2021.22.e42
    BACKGROUND: Inclusion body hepatitis (IBH) is an economically important viral disease primarily affecting broiler and breeder chickens. All 12 serotypes of fowl adenovirus (FAdV) can cause IBH.

    OBJECTIVES: To characterize FAdV isolates based on phylogenetic analysis, and to study the pathogenicity of FAdV-8b in specific-pathogen-free (SPF) chickens following virus inoculation via oral and intramuscular (IM) routes.

    METHODS: Suspected organ samples were subjected to virus isolation and polymerase chain reaction (PCR) for FAdV detection. Hexon gene sequencing and phylogenetic analysis were performed on FAdV-positive samples for serotype identification. One FAdV-8b isolate, UPM/FAdV/420/2017, was selected for fiber gene characterization and pathogenicity study and was inoculated in SPF chickens via oral and IM routes.

    RESULTS: The hexon gene phylogenetic analysis revealed that all isolates belonged to FAdV-8b. The fiber gene-based phylogenetic analysis of isolate UPM/FAdV/420/2017 supported the grouping of that isolate into FAdV species E. Pathogenicity study revealed that, chickens infected with UPM/FAdV/420/2017 via the IM route had higher clinical score values, higher percent mortality, higher degree of the liver lesions, higher antibody response (p < 0.05), and higher virus shedding amounts (p < 0.05) than those infected via the oral route. The highest virus copy numbers were detected in liver and gizzard.

    CONCLUSIONS: FAdV-8b is the dominant FAdV serotype in Malaysia, and pathogenicity study of the FAdV-8b isolate UPM/FAdV/420/2017 indicated its ability to induce IBH in young SPF chickens when infected via oral or IM routes.

    MeSH terms: Adenoviridae Infections/epidemiology; Adenoviridae Infections/veterinary*; Adenoviridae Infections/virology; Aviadenovirus/classification*; Aviadenovirus/genetics; Amino Acid Sequence; Animals; Chickens*; Malaysia/epidemiology; Phylogeny; Poultry Diseases/epidemiology; Poultry Diseases/virology*; Serotyping; Specific Pathogen-Free Organisms; Viral Proteins/metabolism; Viral Proteins/chemistry
  15. Bhargava V, Jasuja S, Tang SC, Bhalla AK, Sagar G, Jha V, et al.
    Nephrology (Carlton), 2021 Nov;26(11):898-906.
    PMID: 34313370 DOI: 10.1111/nep.13949
    BACKGROUND: Peritoneal dialysis (PD) as a modality of kidney replacement therapy (KRT) is largely underutilized globally. We analyzed PD utilization, impact of economic status, projected growth and impact of state policy(s) on PD growth in South Asia and Southeast Asia (SA&SEA) region.

    METHODS: The National Nephrology Societies of the region responded to a questionnaire on KRT practices. The responses were based on the latest registry data, acceptable community-based studies and societal perceptions. The representative countries were divided into high income and higher-middle income (HI & HMI) and low income and lower-middle income (LI & LMI) groups.

    RESULTS: Data provided by 15 countries showed almost similar percentage of GDP as health expenditure (4%-7%). But there was a significant difference in per capita income (HI & HMI -US$ 28 129 vs. LI & LMI - US$ 1710.2) between the groups. Even after having no significant difference in monthly cost of haemodialysis (HD) and PD in LI & LMI countries, they have poorer PD utilization as compared to HI & HMI countries (3.4% vs. 10.1%); the reason being lack of formal training/incentives and time constraints for the nephrologist while lack of reimbursement and poor general awareness of modalities has been a snag for the patients. The region expects ≥10% PD growth in the near future. Hong Kong and Thailand with 'PD first' policy have the highest PD utilization.

    CONCLUSION: Important deterrents to PD underutilization were lack of PD centric policies, lackadaisical patient/physician's attitude, lack of structured patient awareness programs, formal training programs and affordability.

    MeSH terms: Asia/epidemiology; Attitude of Health Personnel; Health Expenditures/legislation & jurisprudence; Health Expenditures/trends*; Forecasting; Health Policy/economics; Health Policy/legislation & jurisprudence; Health Policy/trends*; Humans; Income; Kidney Diseases/economics; Kidney Diseases/epidemiology; Kidney Diseases/therapy*; Health Knowledge, Attitudes, Practice; Nephrology/economics; Nephrology/legislation & jurisprudence; Nephrology/trends*; Peritoneal Dialysis/economics; Peritoneal Dialysis/trends*; Practice Patterns, Physicians'/economics; Practice Patterns, Physicians'/legislation & jurisprudence; Practice Patterns, Physicians'/trends*; Policy Making; Health Care Surveys; Gross Domestic Product; Nephrologists/economics; Nephrologists/legislation & jurisprudence; Nephrologists/trends*
  16. Zarif F, Anasir MI, Koh JX, Chew MF, Poh CL
    Virus Res, 2021 Oct 02;303:198456.
    PMID: 34314773 DOI: 10.1016/j.virusres.2021.198456
    Enterovirus A71 (EV-A71) is one of the main causative agents of hand, foot and mouth disease (HFMD). SP40 peptide was previously identified to inhibit EV-A71 strains from genotypes A, B and C. However, the stability and antiviral activity of SP40 peptide in human serum are yet to be established. To address this, we evaluated the stability and anti-EV-A71 activity of SP40 peptide after incubation in 25 % human serum. Reverse-phase high-performance liquid chromatography (RP-HPLC) and liquid chromatography-mass spectrometry (LC/MS) were utilized to evaluate serum stability and cleavage patterns of SP40 peptide after incubation in human serum. Cell protection assay was used to evaluate the anti-EV-A71 activity of SP40 peptide after incubation in human serum and to identify the minimal active sequence of SP40 peptide that retained antiviral activity. The results showed that the SP40 peptide was stable in human serum with 56 % of the full-length SP40 peptide being detected after 48 h incubation in human serum. The SP40 peptide was mainly cleaved by exopeptidases and no endoprotease recognition sites were identified within the SP40 peptide. Cell protection assays revealed that the SP40 peptide retained substantial activity after 24 and 48 h incubation in human serum. Furthermore, the data revealed that three amino acids at the N-terminus and one amino acid at the C-terminus of the SP40 peptide were dispensable for its antiviral activity. Importantly, the four truncated peptides displayed better potency than the full-length SP40 peptide. Overall, this study provided insights into the stability and activity of SP40 peptide in human serum and will facilitate the development of SP40 peptide as an anti-EV-A71 agent.
  17. Eskin M, Baydar N, Harlak H, Hamdan M, Mechri A, Isayeva U, et al.
    J Affect Disord, 2021 11 01;294:366-374.
    PMID: 34315098 DOI: 10.1016/j.jad.2021.07.050
    BACKGROUND: Research on suicidality in low to middle-income countries is scarce. We addressed this issue by investigating suicidality in a cross-national college student samples from 11 predominantly low to middle-income majority Muslim countries.

    METHODS: The sample consisted of 7427 college students (56% female) who reported to be affiliated with Islam. Data on self-construal, social support, negative life-events, acceptability of suicide, suicidal ideation, and suicide attempts were collected with self-administered questionnaires.

    RESULTS: Acceptability of suicide and the experience of negative life-events were positively, and perceived social support was negatively associated with suicidal ideation. Interdependent self-construal was negatively related to the acceptability of suicide and positively associated with perceived social support, implying a negative indirect effect on suicidal ideation although its direct effect was positive. The number of negative life-events was the strongest positive predictor of ever attempting suicide. The interdependent self-construal moderated the association of negative life-events with suicide attempts.

    LIMITATIONS: Cross-sectional and self-report nature of the study were its major limitations. Participants may have suppressed their responses about suicide because of religious and legal reasons.

    CONCLUSION: Remarkable similarities across 11 country samples emerged in the linkages between cultural and interpersonal factors with suicidality. Our findings highlight the value of a nuanced approach to suicidality, that can recognize the differences in the processes associated with suicidal ideation and suicide attempts, as well as the need to consider the interplay of a broad range of personal, interpersonal, and cultural influences.

    MeSH terms: Cross-Sectional Studies; Female; Humans; Islam*; Male; Risk Factors; Students; Suicide, Attempted; Suicidal Ideation*
  18. Afiqah Hamzah N, Razak NAA, Sayuti Ab Karim M, Gholizadeh H
    Proc Inst Mech Eng H, 2021 Dec;235(12):1359-1374.
    PMID: 34304625 DOI: 10.1177/09544119211035200
    The development of the CAD/CAM (Computer-aided design and computer-aided manufacturing) system has globally changed the fabrication and delivery of prosthetics and orthotics. Furthermore, since the introduction of CAD/CAM in the 1980s, many successful CAD/CAM system are available in the market today. However, less than 20% of amputees have access to digital fabrication technology and large portion of the amputees are from the developing countries. This review designed to examine selected studies from 1980 to 2019 on CAD/CAM systems in the production of transtibial prosthetic sockets. A review was conducted based on articles gathered from Web of Science, Pubmed and Science Direct. From the findings, 92 articles found related to CAD/CAM-derived transtibial prosthetic socket (TPS). After a further screening of the articles, 20 studies were chosen and only one study was done in a developing country. The results showed an increase interest in CAD/CAM application in Transtibial prosthetic socket (TPS) production for both developed and developing countries, yet the technology has not fully utilised in the developing countries. Factors such as resources, accessibility, knowledge-gap and lack of experienced prosthetists remain the major causes of the lack of CAD/CAM system studies. Large-scale trials are required to employ digital fabrication in the developing regions, consequently advancing the production of high-quality CAD-CAM-derived TPS where most prosthetic and orthotics are needed.
    MeSH terms: Amputees*; Artificial Limbs*; Developing Countries; Humans; Prosthesis Design; Computer-Aided Design
  19. Laurson-Doube J, Rijke N, Helme A, Baneke P, Banwell B, Viswanathan S, et al.
    Mult Scler, 2021 Aug;27(9):1403-1410.
    PMID: 34304636 DOI: 10.1177/13524585211030207
    BACKGROUND: Off-label disease-modifying therapies (DMTs) for multiple sclerosis (MS) are used in at least 89 countries. There is a need for structured and transparent evidence-based guidelines to support clinical decision-making, pharmaceutical policies and reimbursement decisions for off-label DMTs.

    OBJECTIVES/RESULTS: The authors put forward general principles for the ethical use of off-label DMTs for treating MS and a process to assess existing evidence and develop recommendations for their use.

    CONCLUSION: The principles and process are endorsed by the World Federation of Neurology (WFN), American Academy of Neurology (AAN), European Academy of Neurology (EAN), Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS), European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), Middle-East North Africa Committee for Treatment and Research in Multiple Sclerosis (MENACTRIMS) and Pan-Asian Committee for Treatment and Research in Multiple Sclerosis (PACTRIMS), and we have regularly consulted with the Brain Health Unit, Mental Health and Substance Use Department at the World Health Organization (WHO).

  20. Suppiah S
    Med J Malaysia, 2021 07;76(4):451-453.
    PMID: 34305103
    Nuclear medicine (NM) has been established in Malaysia for almost 60 years. It is a specialty that utilizes radiopharmaceuticals for theranostics, by the assessment of bodily functions to diagnose certain diseases and conditions particularly in oncology, cardiology, and neurology as well as to provide therapeutic solutions in certain instances. The strengths of NM include the establishment of various nuclear medicine centres throughout the country, including in Sabah and Sarawak, particularly for general nuclear medicine, and the mushrooming of positron emission tomography computed tomography (PET/CT) centres along the states in the west coast of Malaysia, the institution of a formal national nuclear medicine physician training programme, and collaboration with international bodies to develop theranostic services. The challenges for NM ahead are namely regulatory and financial constraints for utilizing newer radiopharmaceuticals available in the international market, expansion of accredited training programmes to produce skilled healthcare workforce, optimization of resources at hand and multidisciplinary collaborations to reduce premature mortality of patients caused by noncommunicable diseases, particularly cancer.
    MeSH terms: Humans; Malaysia; Nuclear Medicine*; Physicians*; Radionuclide Imaging; Positron Emission Tomography Computed Tomography
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