Displaying publications 81 - 100 of 119 in total

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  1. Yau MQ, Wan AJ, Tiong ASH, Yiap YS, Loo JSE
    Chem Biol Drug Des, 2024 Jul;104(1):e14591.
    PMID: 39010276 DOI: 10.1111/cbdd.14591
    Computational target fishing plays an important role in target identification, particularly in drug discovery campaigns utilizing phenotypic screening. Numerous approaches exist to predict potential targets for a given ligand, but true targets may be inconsistently ranked. More advanced simulation methods may provide benefit in such cases by reranking these initial predictions. We evaluated the ability of binding pose metadynamics to improve the predicted rankings for three diverse ligands and their six true targets. Initial predictions using pharmacophore mapping showed no true targets ranked in the top 50 and two targets each ranked within the 50-100, 100-150, and 250-300 ranges respectively. Following binding pose metadynamics, ranking of true targets improved for four out of the six targets and included the highest ranked predictions overall, while rankings deteriorated for two targets. The revised rankings predicted two true targets ranked within the top 50, and one target each within the 50-100, 100-150, 150-200, and 200-250 ranges respectively. The findings of this study demonstrate that binding pose metadynamics may be of benefit in refining initial predictions from structure-based target fishing algorithms, thereby improving the efficiency of the target identification process in drug discovery efforts.
  2. Yang Y, Fedorov G, Shafranjuk SE, Klapwijk TM, Cooper BK, Lewis RM, et al.
    Nano Lett, 2015 Dec 09;15(12):7859-66.
    PMID: 26506109 DOI: 10.1021/acs.nanolett.5b02564
    Van Hove singularities (VHSs) are a hallmark of reduced dimensionality, leading to a divergent density of states in one and two dimensions and predictions of new electronic properties when the Fermi energy is close to these divergences. In carbon nanotubes, VHSs mark the onset of new subbands. They are elusive in standard electronic transport characterization measurements because they do not typically appear as notable features and therefore their effect on the nanotube conductance is largely unexplored. Here we report conductance measurements of carbon nanotubes where VHSs are clearly revealed by interference patterns of the electronic wave functions, showing both a sharp increase of quantum capacitance, and a sharp reduction of energy level spacing, consistent with an upsurge of density of states. At VHSs, we also measure an anomalous increase of conductance below a temperature of about 30 K. We argue that this transport feature is consistent with the formation of Cooper pairs in the nanotube.
  3. Tan CY, Thanawongnuwech R, Arshad SS, Hassan L, Lee CY, Low SE, et al.
    Trop Biomed, 2023 Sep 01;40(3):301-306.
    PMID: 37897162 DOI: 10.47665/tb.40.3.005
    Porcine circovirus type 4 (PCV4) is the newest member in the porcine circovirus family, first reported in 2020. To date, the presence of PCV4 has only been reported in China, South Korea and most recently in Thailand. Detection of PCV4 have been reported in various production stages of pigs from piglets, finishers to sows; associated with a myriad of clinical manifestations including porcine dermatitis and nephropathy syndrome (PDNS), postweaning multisystemic wasting syndrome (PMWS), respiratory, enteric and neurological diseases. While successful virus isolation and culture has yet to be reported, pathogenicity of PCV4 has been demonstrated through infectious clone studies. The objective of this study is to investigate the presence of PCV4 in Malaysian porcine population to update the epidemiology of porcine circoviruses in Malaysia. A total of 49 samples from commercial intensive pig farms, abattoir and wild boar population were subjected to conventional polymerase chain reaction assay to detect PCV4 capsid (cap) genome. Resulting cap nucleotide sequences were analyzed for maximum likelihood phylogeny relationship. Results revealed that PCV4 is present in Peninsular Malaysia at a molecular prevalence of 4.08% (2 / 49 samples). Both PCV4 positive samples originated from clinically healthy finishers. Malaysian PCV4 strains were classified as genotype PCV4b, and were found to be phylogenetically distinct from the China, South Korea and Thailand strains. With this latest update of the novel PCV4 in Malaysia, it is clear that more attention needs to be given to the investigation of novel porcine circoviruses (PCV) and management of PCV diseases.
  4. Akram W, Hussein MS, Ahmad S, Mamat MN, Ismail NE
    Saudi Pharm J, 2015 Oct;23(5):499-503.
    PMID: 26594115 DOI: 10.1016/j.jsps.2015.01.011
    There is no instrument which collectively assesses the knowledge, attitude and perceived practice of asthma among community pharmacists. Therefore, this study aimed to validate the instrument which measured the knowledge, attitude and perceived practice of asthma among community pharmacists by producing empirical evidence of validity and reliability of the items using Rasch model (Bond & Fox software®) for dichotomous and polytomous data. This baseline study recruited 33 community pharmacists from Penang, Malaysia. The results showed that all PTMEA Corr were in positive values, where an item was able to distinguish between the ability of respondents. Based on the MNSQ infit and outfit range (0.60-1.40), out of 55 items, 2 items from the instrument were suggested to be removed. The findings indicated that the instrument fitted with Rasch measurement model and showed the acceptable reliability values of 0.88 and 0.83 and 0.79 for knowledge, attitude and perceived practice respectively.
  5. Lam SE, Bradley DA, Mat Nawi SN, Khandaker MU, Abdul Sani SF
    Appl Radiat Isot, 2023 Sep;199:110920.
    PMID: 37419002 DOI: 10.1016/j.apradiso.2023.110920
    The present study continues research into the utilisation of carbonaceous media for medical radiation dosimetry, focusing on the effects of surface area-to-volume ratio and carbon content on structural interaction alterations and dosimetric properties in sheet- and bead-type graphitic materials (with the respective carbon content of ∼98 wt% and ∼90 wt%). Using 60Co gamma-rays and doses from 0.5 Gy to 20 Gy, the study has been made of the response of commercially available graphite in the form of 0.1 mm, 0.2 mm, 0.3 mm and 0.5 mm thick sheets, also of activated carbon beads. Confocal Raman and photoluminescence spectroscopy have been employed, examining radiation-induced structural interaction alterations. Dose-dependent variation in the Raman intensity ratio ID/IG relates to the varying dominance of defect generation and dose-driven defect annealing. Of the various thickness graphite sheets, the 0.1 mm thick medium possesses the greatest surface area-to-volume ratio. Perhaps unsurprisingly, it also exhibits the greatest thermoluminescence (TL) yield compared to that of the other carbonaceous sheet foils used herein. Moreover, the second greatest mass-normalised TL yield has been observed to be that of the porous beads, reflected in the greater defect density (ID/IG > 2) when compared to the other media, due in part to their inherent feature of large internal surface area. Considering the challenge posed in matching skin thickness with skin dose, the near tissue equivalent graphite sheets show particular promise as a skin dosimeter, sensitive as a function of depth.
  6. Tsan SEH, Viknaswaran NL, Cheong CC, Cheah S, Ng KT, Mong SXY, et al.
    Anaesthesia, 2023 Sep;78(9):1153-1161.
    PMID: 37314744 DOI: 10.1111/anae.16058
    Tranexamic acid is an antifibrinolytic drug that is widely used during surgery, but there are concerns about its thromboembolic effects. We aimed to investigate the effect of prophylactic intravenous tranexamic acid on thromboembolic outcomes in patients undergoing non-cardiac surgery. The MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials were searched. Randomised controlled trials comparing intravenous tranexamic acid with placebo or no treatment in patients undergoing non-cardiac surgery were included. The primary outcome was a composite of peri-operative cardiovascular thromboembolic events, defined as any deep vein thrombosis, pulmonary embolism, myocardial ischaemia/infarction or cerebral ischaemia/infarction. A total of 191 randomised controlled trials (40,621 patients) were included in the review. The primary outcome occurred in 4.5% of patients receiving intravenous tranexamic acid compared with 4.9% of patients in the control group. Our analysis showed that there was no difference between groups for composite cardiovascular thromboembolic events (risk ratio 1.02, 95%CI 0.94-1.11, p = 0.65, I2 0%, n = 37,512). This finding remained robust when sensitivity analysis was performed with continuity correction and in studies with a low risk of bias. However, in trial sequential analysis, our meta-analysis only achieved 64.6% of the required information size. There was no association between intravenous tranexamic acid and seizure rate or mortality rate within 30 days. Intravenous tranexamic acid was associated with a reduced blood transfusion rate compared with control (9.9% vs. 19.4%, risk ratio 0.46, 95%CI 0.41-0.51, p 
  7. Burden AD, Okubo Y, Zheng M, Thaçi D, van de Kerkhof P, Hu N, et al.
    Exp Dermatol, 2023 Aug;32(8):1279-1283.
    PMID: 37140190 DOI: 10.1111/exd.14824
    Effisayil 1 was a multicentre, randomized, double-blind, placebo-controlled study of the anti-interleukin (IL)-36 receptor monoclonal antibody, spesolimab, in patients presenting with a generalized pustular psoriasis (GPP) flare. Previously published data from this study revealed that within 1 week, rapid pustular and skin clearance were observed in patients receiving spesolimab versus placebo. In this pre-specified subgroup analysis, the efficacy of spesolimab was evaluated according to patient demographic and clinical characteristics at baseline in patients receiving spesolimab (n = 35) or placebo (n = 18) on Day 1. Efficacy was by assessed by achievement of primary endpoint (Generalized Pustular Psoriasis Physician Global Assessment [GPPGA] pustulation subscore of 0 at Week 1) and key secondary endpoint (GPPGA total score of 0 or 1 at Week 1). Safety was assessed at Week 1. Spesolimab was found to be efficacious and had a consistent and favourable safety profile in patients presenting with a GPP flare, regardless of patient demographics and clinical characteristics at baseline.
  8. Shalihin MSE, Suhaimi NAN, Hamzah HA, Abidin S, Aidid ME, Musa R
    Med J Malaysia, 2023 Nov;78(6):830-844.
    PMID: 38031228
    INTRODUCTION: Mounting evidence has shown the significant correlation between periodontitis and the development of other comorbidities, such as cardiovascular disease due to periodontopathogenic bacterial migration and colonisation. As the main etiologic agent of periodontitis, the role of Porphyromonas gingivalis (P. gingivalis) has been widely explored as the main culprit and its early detection is crucial to control the exacerbation of diseases. This review aims to identify and summarise all clinical diseases that potentially developed due to the presence of P. gingivalis and discover all its detection methods that have been developed.

    MATERIALS AND METHODS: Full-text articles of case report, case control, cohort and cross-sectional studies that were published from 1st January 2012 until 30th June 2022, were searched using PubMed, CINAHL and Scopus. Periodontal related diseases were excluded in this review due to its wellknown associated disease with P. gingivalis. A comparison studies of detection methods were also excluded in this review.

    RESULTS: Out of 612 articles that were screened, only 106 met the eligibility criteria to be selected for further review. Risk of bias was performed using FEAT principles and reviewers' discussion. A total of 21 final articles that were reviewed showed significant correlation with P. gingivalis and were classified into several clinical domains. Twelve out of 13 detection methods showed high sensitivity and specificity with short duration analysis.

    CONCLUSION: Due to asymptomatic periodontal disease and the high prevalence of P. gingivalis-associated clinical diseases, this review suggests the need for oral public health awareness and early screening for the bacterium detection especially among elderly groups to maintain their quality of life.

  9. Suwendar S, Jantan I, Fakih TM, Priani SE, Mulyanti D, Patricia VM, et al.
    J Biomol Struct Dyn, 2025 Feb;43(3):1539-1551.
    PMID: 38084758 DOI: 10.1080/07391102.2023.2292294
    This research is part of the research umbrella regarding the use of watery rose apple leaf [Eugenia aqueum (Burm. F) Alston] in the health sector. Infectious diseases of worms, are still a health problem with a high burden based on the incidence and mortality rates in Southeast Asian countries. Therefore, we tried to create a 3D structure of vital receptors of worms including Nicotinic Cholinergic Receptor (NCR), Acetylcholinesterase Enzymes (AE), and Phosphorylase Enzymes (PE) using homology modeling method through the SWISS-MODEL webserver, then conducted a molecular dynamics simulations using active metabolite of watery rose apple leaf i.e. 2',4'‑dihydroxy‑6'‑methoxy‑3',5'‑dimethylchalcone which was then compared with Piperazine Citrate and Pyrantel Pamoate which are anthelmintic drugs on the market. Based on the results of the study, the structure of the three receptors with high resolution was successfully obtained which was characterized by a good Ramachandran value, which was above 90%. Then the ligand structure was successfully modeled in a three-dimensional model and optimized geometrically using GaussView 5.0.8 and Gaussian09 software. In further, Root Mean Square Deviation (RMSD) and Root Mean Square Fluctuation (RMSF) analysis of molecular dynamics simulations ligand against the three receptors, compound 2',4'‑dihydroxy‑6'‑methoxy‑3',5'‑dimethylchalcone showed better stability than Piperazine Citrate and Pyrantel Pamoate at 50 ns simulation, although from the calculation of binding free energy Molecular Mechanics Poisson-Boltzmann Surface Area (MM/PBSA) is not better than the two comparisons. It can be concluded that the compound 2',4'‑dihydroxy‑6'‑methoxy‑3',5'‑dimethylchalcone from watery rose apple leaf showed potential as anthelmintic candidates.Communicated by Ramaswamy H. Sarma.
  10. Ismail MS, Hasinah AB, Syaiful MN, Murshidah HB, Thong TJ, Zairi Z, et al.
    Clin Ter, 2012;163(2):115-22.
    PMID: 22555825
    In an effort to improve pre-hospital care, the authors assessed the availability and utility of ambulance devices. The study aimed to identify commonly used devices for managing emergency cases in Klang Valley of Malaysia.
  11. Chang CC, Ng CC, Too CL, Choon SE, Lee CK, Chung WH, et al.
    Pharmacogenomics J, 2017 03;17(2):170-173.
    PMID: 26927288 DOI: 10.1038/tpj.2016.10
    Phenytoin (PHT) is a common cause of severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS). Although HLA-B*15:02 is associated with PHT-induced SJS/TEN (PHT-SJS/TEN) in Han Chinese and Thais, the genetic basis for susceptibility to PHT-induced SCARs (PHT-SCAR) in other populations remains unclear. We performed a case-control association study by genotyping the human leukocyte antigen (HLA)-B alleles of 16 Malay PHT-SCAR patients (13 SJS/TEN and 3 DRESS), 32 PHT-tolerant controls and 300 healthy ethnicity-matched controls. A novel genetic biomarker, HLA-B*15:13, showed significant association with PHT-SJS/TEN (53.8%, 7/13 cases) (odds ratio (OR) 11.28, P=0.003) and PHT-DRESS (100%, 3/3 cases) (OR 59.00, P=0.003) when compared with PHT-tolerant controls (9.4%, 3/32 controls). We also confirmed HLA-B*15:02 association with PHT-SJS/TEN (61.5%, 8/13 cases vs 21.9%, 7/32 controls; OR 5.71, P=0.016) when compared with PHT-tolerant controls. These alleles may serve as markers to predict PHT-SCAR in Malays.
  12. Abdullah N, Abdul Murad NA, Attia J, Oldmeadow C, Mohd Haniff EA, Syafruddin SE, et al.
    Diabet Med, 2015 Oct;32(10):1377-84.
    PMID: 25711284 DOI: 10.1111/dme.12735
    AIMS: To characterize the association with Type 2 diabetes of known Type 2 diabetes risk variants in people in Malaysia of Malay, Chinese and Indian ancestry who participated in the Malaysian Cohort project.
    METHODS: We genotyped 1604 people of Malay ancestry (722 cases, 882 controls), 1654 of Chinese ancestry (819 cases, 835 controls) and 1728 of Indian ancestry (851 cases, 877 controls). First, 62 candidate single-nucleotide polymorphisms previously associated with Type 2 diabetes were assessed for association via logistic regression within ancestral groups and then across ancestral groups using a meta-analysis. Second, estimated odds ratios were assessed for excess directional concordance with previously studied populations. Third, a genetic risk score aggregating allele dosage across the candidate single-nucleotide polymorphisms was tested for association within and across ancestral groups.
    RESULTS: After Bonferroni correction, seven individual single-nucleotide polymorphisms were associated with Type 2 diabetes in the combined Malaysian sample. We observed a highly significant excess in concordance of effect directions between Malaysian and previously studied populations. The genetic risk score was strongly associated with Type 2 diabetes in all Malaysian groups, explaining from 1.0 to 1.7% of total Type 2 diabetes risk variance.
    CONCLUSION: This study suggests there is substantial overlap of the genetic risk alleles underlying Type 2 diabetes in Malaysian and other populations.
    Study name: The Malaysian Cohort (TMC) project
  13. Fouad EA, Toaleb NI, Hassan SE, El Shanawany EE, Keshta HG, Abdel-Rahman EH, et al.
    Trop Biomed, 2021 Jun 01;38(2):102-110.
    PMID: 34172697 DOI: 10.47665/tb.38.2.041
    The use of natural products for disease control is a promising approach to solving the problem of drug resistance. The aim of the research reported here was to evaluate the fasciolicidal and anti-Clostridium novyi type B activities of propolis administered orally to sheep infected with Fasciola gigantica and C. novyi type B. Sheep infected with both pathogens were divided into two groups: an infected treated group and an infected non-treated group. The treatment was oral administration of 50 mg propolis extract/kg daily for 15 days. The body weight of the sheep, fecal egg counts of F. gigantica, serum levels of F. gigantica IgG, concentrations of cytokines (IL-2, IL-10, and IL-17), and bacterial counts of C. novyi were evaluated. Following treatment, the sheep had increased body weight and a significant decrease in the egg count, which was reduced by 54.54% at 15 days post treatment. The level of anti- Fasciola IgG increased, whereas levels of IL-2, IL-10, and IL-17 decreased in propolistreated sheep. Treatment of sheep with propolis produced a significant reduction in fecal count of C. novyi, from 8 × 109 to 3 × 103 colony units per gram at 15 days post treatment. This research highlights the therapeutic potential of Egyptian propolis extract as a treatment against F. gigantica and C. novyi type B infections, and investigated its mode of action through its effect on some cellular and humoral responses in sheep with both infections.
  14. Nielsen SSE, Siupka P, Georgian A, Preston JE, Tóth AE, Yusof SR, et al.
    J Vis Exp, 2017 09 24.
    PMID: 28994773 DOI: 10.3791/56277
    The aim of this protocol presents an optimized procedure for the purification and cultivation of pBECs and to establish in vitro blood-brain barrier (BBB) models based on pBECs in mono-culture (MC), MC with astrocyte-conditioned medium (ACM), and non-contact co-culture (NCC) with astrocytes of porcine or rat origin. pBECs were isolated and cultured from fragments of capillaries from the brain cortices of domestic pigs 5-6 months old. These fragments were purified by careful removal of meninges, isolation and homogenization of grey matter, filtration, enzymatic digestion, and centrifugation. To further eliminate contaminating cells, the capillary fragments were cultured with puromycin-containing medium. When 60-95% confluent, pBECs growing from the capillary fragments were passaged to permeable membrane filter inserts and established in the models. To increase barrier tightness and BBB characteristic phenotype of pBECs, the cells were treated with the following differentiation factors: membrane permeant 8-CPT-cAMP (here abbreviated cAMP), hydrocortisone, and a phosphodiesterase inhibitor, RO-20-1724 (RO). The procedure was carried out over a period of 9-11 days, and when establishing the NCC model, the astrocytes were cultured 2-8 weeks in advance. Adherence to the described procedures in the protocol has allowed the establishment of endothelial layers with highly restricted paracellular permeability, with the NCC model showing an average transendothelial electrical resistance (TEER) of 1249 ± 80 Ω cm2, and paracellular permeability (Papp) for Lucifer Yellow of 0.90 10-6 ± 0.13 10-6 cm sec-1 (mean ± SEM, n=55). Further evaluation of this pBEC phenotype showed good expression of the tight junctional proteins claudin 5, ZO-1, occludin and adherens junction protein p120 catenin. The model presented can be used for a range of studies of the BBB in health and disease and, with the highly restrictive paracellular permeability, this model is suitable for studies of transport and intracellular trafficking.
  15. Khandaker MU, Nawi SNM, Lam SE, Sani SFA, Islam MA, Islam MA, et al.
    Appl Radiat Isot, 2023 Jun;196:110771.
    PMID: 36933313 DOI: 10.1016/j.apradiso.2023.110771
    Thermoluminescence (TL) materials have a broad variety of uses in various fields, such as clinical research, individual dosimetry, and environmental dosimetry, amongst others. However, the use of individual neutron dosimetry has been developing more aggressively lately. In this regard, present study establishes a relationship between the neutron dosage and the optical property changes of graphite-rich materials caused by high doses of neutron radiation. This has been done with the intention of developing a novel, graphite-based radiation dosimeter. Herein, the TL yield of commercially graphite-rich materials (i.e. graphite sheet, 2B and HB grade pencils) irradiated by neutron radiation with doses ranging from 250 Gy to 1500 Gy has been investigated. The samples were bombarded with thermal neutrons as well as a negligible amount of gamma rays, from the nuclear reactor TRIGA-II installed at the Bangladesh Atomic Energy Commission. The shape of the glow curves was observed to be independent of the given dosage, with the predominant TL dosimetric peak maintained within the region of 163 °C-168 °C for each sample. By studying the glow curves of the irradiated samples, some of the most well theoretical models and techniques were used to compute the kinetic parameters such as the order of kinetics (b), activation energy (E) or trap depth, frequency factor (s) or escape probability, and trap lifetime (τ). All of the samples were found to have a good linear response over the whole dosage range, with 2B grade of polymer pencil lead graphite (PPLGs) demonstrating a higher level of sensitivity than both HB grade and graphite sheet (GS) samples. Additionally, the level of sensitivity shown by each of them is highest at the lowest dosage that was given, and it decreases as the dose increases. Importantly, the phenomenon of dose-dependent structural modifications and internal annealing of defects has been observed by assessing the area of deconvoluted micro-Raman spectra of graphite-rich materials in high-frequency areas. This trend is consistent with the cyclical pattern reported in the intensity ratio of defect and graphite modes in previously investigated carbon-rich media. Such recurrent occurrences suggest the idea of employing Raman microspectroscopy as a radiation damage study tool for carbonaceous materials. The excellent responses of the key TL properties of the 2B grade pencil demonstrate its usefulness as a passive radiation dosimeter. As a consequence, the findings suggest that graphite-rich materials have the potential to be useful as a low-cost passive radiation dosimeter, with applications in radiotherapy and manufacturing.
  16. Mohammad Aidid E, Shalihin MSE, Md Nor A, Hamzah HA, Ab Hamid NF, Saipol Bahri NAN, et al.
    Med J Malaysia, 2023 May;78(3):404-410.
    PMID: 37271851
    INTRODUCTION: World Health Organization (2019) has declared colorectal cancer (CRC) as the second most common cancer in females and third in males, where the incidence seems to rise year by year. One of the very few potential pathogens specifically associated with malignant colonic diseases is Streptococcus gallolyticus (Sg). Sg is a part of the intestinal flora which formerly known as biotype I of Streptococcus bovis, belongs to Group D streptococci. Owing to only a few researches done in determining evidence to support Sg as a determinant of CRC, a systematic review is constructed.

    MATERIALS AND METHODS: Full-text articles on case-control and cohort studies published from 1st January 2010 to 1st October 2020 were searched using Google Scholar, PubMed and JSTOR. People of all age groups and Sg bacteraemia or colonisation were the type of participant and exposure used for the search strategy, respectively. Data collection was done by three reviewers and checked by two reviewers for discrepancies. All the papers were critically appraised using the STROBE statement. Qualitative synthesis was done by descriptive comparison, distribution of Sg according to stage comparison, method used for Sg detection comparison and risk of bias comparison.

    RESULT: Seven out of 11 articles that fulfil the eligibility criteria were selected. Four papers have low overall risk of bias due to low confounding or selection bias. Sg is found to be a risk factor for CRC from three papers studied, whereas the other four papers did not include the strength of association. Only two papers studied the association between the distribution of Sg and stages of CRC, where the results were contradictory from each other, making it to be inconclusive. The most common method used for Sg detection is a culturing technique, followed by molecular and biochemical techniques.

    CONCLUSION: There is insufficient evidence to prove the association between Sg bacteraemia as the risk factor for CRC as well as the association between the Sg distribution and stages of CRC. Culturing technique is the most common method used for the detection of bacteria, but it requires subsequent investigations to confirm the presence of Sg. Thus, it is recommended that more studies need to be done using strong statistical analysis to control for most of the confounders with comprehensive explanation and use of more methods in the detection of Sg.

  17. Choon SE, De La Cruz C, Wolf P, Jha RK, Fischer KI, Goncalves-Bradley DC, et al.
    J Eur Acad Dermatol Venereol, 2024 Feb;38(2):265-280.
    PMID: 37750484 DOI: 10.1111/jdv.19530
    Generalized pustular psoriasis (GPP) is a rare, chronic, neutrophilic inflammatory skin disease characterized by episodes of widespread eruption of sterile, macroscopic pustules that can be accompanied by systemic inflammation and symptoms. A systematic literature review and narrative synthesis were conducted to determine the impact of GPP on patients' health-related quality of life (HRQoL) and patient-reported severity of symptoms and to compare its impact to patients with plaque psoriasis (plaque PsO). Searches were undertaken in Embase, MEDLINE and the Cochrane Library from 1 January 2002 to 15 September 2022. Screening was carried out by two reviewers independently. Outcome measures included generic (e.g. EQ-5D, SF-36) and dermatology-specific (e.g. DLQI) clinical outcome assessments, and other relevant patient-reported outcome measures (PROMs) (e.g. severity of pain measured by a numerical rating scale). Overall, 20 studies were found to be eligible for inclusion, of which seven also had data for plaque PsO. The DLQI was the most frequently reported outcome measure (16 out of 20 studies). When reported, mean DLQI (SD) scores varied from 5.7 (1.2) to 15.8 (9.6) across the studies, indicating a moderate to very large effect on HRQoL; the wide range of scores and large SDs were explained by the small population sizes (n ≤ 12 for all studies except two). Similar ranges and large SDs were also observed for other measures within individual studies. However, in general, people with GPP reported a greater impact of their skin condition on HRQoL, when compared to people with plaque PsO (i.e. higher DLQI scores) and higher severity for itch, pain and fatigue. This systematic review highlighted the need for studies with a larger population size, a better understanding of the impact of cutaneous and extracutaneous symptoms and comorbidities on HRQoL during and between GPP flares, and outcome measures specifically tailored to the unique symptoms and the natural course/history of GPP.
  18. Ashley SE, Tan HT, Peters R, Allen KJ, Vuillermin P, Dharmage SC, et al.
    Clin Exp Allergy, 2017 Aug;47(8):1032-1037.
    PMID: 28544327 DOI: 10.1111/cea.12942
    BACKGROUND: Food allergies pose a considerable world-wide public health burden with incidence as high as one in ten in 12-month-old infants. Few food allergy genetic risk variants have yet been identified. The Th2 immune gene IL13 is a highly plausible genetic candidate as it is central to the initiation of IgE class switching in B cells.

    OBJECTIVE: Here, we sought to investigate whether genetic polymorphisms at IL13 are associated with the development of challenge-proven IgE-mediated food allergy.

    METHOD: We genotyped nine IL13 "tag" single nucleotide polymorphisms (tag SNPs) in 367 challenge-proven food allergic cases, 199 food-sensitized tolerant cases and 156 non-food allergic controls from the HealthNuts study. 12-month-old infants were phenotyped using open oral food challenges. SNPs were tested using Cochran-Mantel-Haenszel test adjusted for ancestry strata. A replication study was conducted in an independent, co-located sample of four paediatric cohorts consisting of 203 food allergic cases and 330 non-food allergic controls. Replication sample phenotypes were defined by clinical history of reactivity, 95% PPV or challenge, and IL13 genotyping was performed.

    RESULTS: IL13 rs1295686 was associated with challenge-proven food allergy in the discovery sample (P=.003; OR=1.75; CI=1.20-2.53). This association was also detected in the replication sample (P=.03, OR=1.37, CI=1.03-1.82) and further supported by a meta-analysis (P=.0006, OR=1.50). However, we cannot rule out an association with food sensitization. Carriage of the rs1295686 variant A allele was also associated with elevated total plasma IgE.

    CONCLUSIONS AND CLINICAL RELAVANCE: We show for the first time, in two independent cohorts, that IL13 polymorphism rs1295686 (in complete linkage disequilibrium with functional variant rs20541) is associated with challenge-proven food allergy.

  19. Duff-Farrier CRA, Mbanzibwa DR, Nanyiti S, Bunawan H, Pablo-Rodriguez JL, Tomlinson KR, et al.
    Mol Biotechnol, 2019 Feb;61(2):93-101.
    PMID: 30484144 DOI: 10.1007/s12033-018-0139-7
    Cassava brown streak disease (CBSD) has major impacts on yield and quality of the tuberous roots of cassava in Eastern and Central Arica. At least two Potyviridae species cause the disease: Cassava brown streak virus (CBSV) and Ugandan cassava brown streak virus (UCBSV). Cloned viral genome sequences known as infectious clones (ICs) have been important in the study of other viruses, both as a means of standardising infectious material and characterising viral gene function. IC construction is often technically challenging for Potyviridae due to sequence instability in E. coli. Here, we evaluate three methods for the construction of infectious clones for CBSD. Whilst a simple IC for in vitro transcription was made for UCBSV isolate 'Kikombe', such an approach failed to deliver full-length clones for CBSV isolates 'Nampula' or 'Tanza', necessitating more complex approaches for their construction. The ICs successfully generated symptomatic infection in the model host N. benthamiana and in the natural host cassava. This shows that whilst generating ICs for CBSV is still a technical challenge, a structured approach, evaluating both in vitro and in planta transcription systems should successfully deliver ICs, allowing further study into the symptomology and virulence factors in this important disease complex.
  20. Abdullah N, Abdul Murad NA, Mohd Haniff EA, Syafruddin SE, Attia J, Oldmeadow C, et al.
    Public Health, 2017 Aug;149:31-38.
    PMID: 28528225 DOI: 10.1016/j.puhe.2017.04.003
    OBJECTIVE: Malaysia has a high and rising prevalence of type 2 diabetes (T2D). While environmental (non-genetic) risk factors for the disease are well established, the role of genetic variations and gene-environment interactions remain understudied in this population. This study aimed to estimate the relative contributions of environmental and genetic risk factors to T2D in Malaysia and also to assess evidence for gene-environment interactions that may explain additional risk variation.
    STUDY DESIGN: This was a case-control study including 1604 Malays, 1654 Chinese and 1728 Indians from the Malaysian Cohort Project.
    METHODS: The proportion of T2D risk variance explained by known genetic and environmental factors was assessed by fitting multivariable logistic regression models and evaluating McFadden's pseudo R(2) and the area under the receiver-operating characteristic curve (AUC). Models with and without the genetic risk score (GRS) were compared using the log likelihood ratio Chi-squared test and AUCs. Multiplicative interaction between genetic and environmental risk factors was assessed via logistic regression within and across ancestral groups. Interactions were assessed for the GRS and its 62 constituent variants.
    RESULTS: The models including environmental risk factors only had pseudo R(2) values of 16.5-28.3% and AUC of 0.75-0.83. Incorporating a genetic score aggregating 62 T2D-associated risk variants significantly increased the model fit (likelihood ratio P-value of 2.50 × 10(-4)-4.83 × 10(-12)) and increased the pseudo R(2) by about 1-2% and AUC by 1-3%. None of the gene-environment interactions reached significance after multiple testing adjustment, either for the GRS or individual variants. For individual variants, 33 out of 310 tested associations showed nominal statistical significance with 0.001 
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