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  1. Aisyah HA, Paridah MT, Sapuan SM, Ilyas RA, Khalina A, Nurazzi NM, et al.
    Polymers (Basel), 2021 Feb 02;13(3).
    PMID: 33540731 DOI: 10.3390/polym13030471
    Over the last decade, the progressive application of natural fibres in polymer composites has had a major effect in alleviating environmental impacts. Recently, there is a growing interest in the development of green materials in a woven form by utilising natural fibres from lignocellulosic materials for many applications such as structural, non-structural composites, household utilities, automobile parts, aerospace components, flooring, and ballistic materials. Woven materials are one of the most promising materials for substituting or hybridising with synthetic polymeric materials in the production of natural fibre polymer composites (NFPCs). These woven materials are flexible, able to be tailored to the specific needs and have better mechanical properties due to their weaving structures. Seeing that the potential advantages of woven materials in the fabrication of NFPC, this paper presents a detailed review of studies related to woven materials. A variety of factors that influence the properties of the resultant woven NFRC such as yarn characteristics, fabric properties as well as manufacturing parameters were discussed. Past and current research efforts on the development of woven NFPCs from various polymer matrices including polypropylene, polylactic acid, epoxy and polyester and the properties of the resultant composites were also compiled. Last but not least, the applications, challenges, and prospects in the field also were highlighted.
  2. Deris ZZ, Leow VM, Wan Hassan WM, Nik Lah NA, Lee SY, Siti Hawa H, et al.
    Trop Biomed, 2009 Dec;26(3):320-5.
    PMID: 20237446
    Vibrio cholerae infection is mainly caused acute diarrhoea disease. Bacteraemia due to non-O1 V. cholerae is rare and mainly reported in liver cirrhotic patients. We report one case of non-O1 V. cholerae bacteraemia in splenectomised thalassaemic patient who presented with septic shock secondary to abdominal sepsis. She had undergone emergency laporatomy and was managed in the intensive care unit for nine days. She was treated with meropenem and doxycyline and discharged well after fourteen days of admission. The V. cholerae was identified by API 20NE, serotype and polymerase chain reaction showed as non-O1, non-O139 strain. Besides known cholera-like toxin and El Tor hemolysin, with increasing reported cases of V. cholerae bacteraemia, there is possibility of other virulence factors that allow this organism to invade the bloodstream.
  3. Cheah PY, Liong ML, Yuen KH, Lee S, Yang JR, Teh CL, et al.
    World J Urol, 2006 Feb;24(1):79-87.
    PMID: 16465553 DOI: 10.1007/s00345-005-0037-z
    The objective of the study is to determine the short- and long-term utility of the Chinese, Malay and English versions of the National Institutes of Health--Chronic Prostatitis Symptom Index (NIH-CPSI) in our ethnically diverse population. The NIH-CPSI was translated into Chinese and Malay, and then verified by back translation into English. Subjects included 100 new chronic prostatitis/chronic pelvic pain (CP/CPPS) patients, 71 new benign prostatic hyperplasia patients and 97 healthy individuals. Reliability was evaluated with test-retest reproducibility (TR) by calculating intraclass correlation coefficients (ICC). Internal consistency was evaluated by calculating Cronbach's alpha (alpha). Validity assessments included discriminant and construct validity. (Presented in the order of Chinese, Malay then English). ICC values for short-term (1 week) TR were 0.90, 0.80 and 0.89, while ICC values for long-term (14 weeks) TR were 0.54, 0.61 and 0.61. Cronbach's alpha values were 0.63, 0.62 and 0.57. The NIH-CPSI total score discriminated CP/CPPS patients (P<0.001) from the control groups with receiver operating curve values of 0.95, 0.98 and 0.94, respectively. Construct validity, reflected by the correlation coefficient values between the International Prostate Symptom Score and the NIH-CPSI of CP/CPPS patients were 0.72, 0.49 and 0.63 (all P<0.05). The Chinese, Malay and English versions of the NIH-CPSI each proved effective in our population. Short-term TR and discriminant validity were excellent for all three versions. However, long-term TR was only moderate, which might reflect variation in patients' perceptions of symptoms over time.
  4. Park JJ, Lee SE, Cho HJ, Choi JO, Yoo BS, Kang SM, et al.
    Int J Heart Fail, 2022 Oct;4(4):193-204.
    PMID: 36381016 DOI: 10.36628/ijhf.2022.0015
    Background and Objectives: Differences in drug prescriptions exist between clinical trials and real-world practice. We evaluated the real-world treatment patterns of sacubitril/valsartan in Korean patients with heart failure (HF).

    Methods: In this retrospective, multicenter cohort study, 600 patients with HF with reduced left-ventricular ejection fraction (LVEF <40%) with ≥1 sacubitril/valsartan prescription were identified by reviewing patient-level medical records at six academic tertiary hospitals in Korea between February 2017 and April 2019.

    Results: At baseline, 59.2%, 28.3%, 4.8%, and 7.7% of the patients received low (50 mg bid), moderate (100 mg bid), target (200 mg bid), and unconventional dose of sacubitril/valsartan, respectively. Patients with low and moderate doses experienced either 'no-titration' (39.8%) or 'stable up-titration' (41.5%). At 12 months, 31.7%, 28.5%, 24.8%, and 15% received low, moderate, target doses, and unconventional dose, respectively. On follow-up, 31 (5.2%) patients discontinued sacubitril/valsartan. The time-averaged N-terminal pro-B-type natriuretic peptide (NT-proBNP) level decreased from 879.6 to 406 pg/mL (ratio, 0.5; 95% confidence interval, 0.4-0.5). The mean LVEF increased by 10.4±12.2% from 27.2±5.8 to 36.3±11.1%, whereas LV end-diastolic volume index decreased by 18.7±26.1 mL/m2 from 114.5±37.7 mL/m2 to 98.9±42.3 mL/m2 at baseline and follow-up, respectively.

    Conclusions: In real-world practice, 95% patients started with low and moderate doses of sacubitril/valsartan. Many patients experienced dose up-titration during follow-up; 30% reached the target dose. Cardiac reverse remodelling was reflected by a profound NT-proBNP level and LV size reduction, and LVEF increment. This study confirms the gap in treatment patterns between clinical trials and real-world practice.

  5. Blebil AQ, Dujaili JA, Mohammed AH, Thiruchelvam K, Lee S, Elkalmi R, et al.
    Adv Med Educ Pract, 2022;13:95-102.
    PMID: 35082550 DOI: 10.2147/AMEP.S344872
    Introduction: There is a predicted growth of up to 17% in an older adult of Malaysian above 60 years of age by 2040. This will increase the workload of almost every healthcare provider to ensure optimal geriatric care.

    Purpose: This study aimed to assess pharmacy students' knowledge and attitudes towards geriatric pharmacy education and older patients to determine their preparation in delivering appropriate medical care to the geriatric population.

    Methods: Self-administered questionnaires were distributed among pharmacy students in different Malaysian universities. The survey included several sections to assess multiple aspects such as sociodemographic information, assessment of knowledge using a validated 28-item Geriatric Knowledge Assessment Scale (GKAS), and attitudes towards geriatrics education.

    Results: The response rate was around 70% of the respondents. The mean (± standard deviation) age of the cohort was 22.28 (±1.12) years. Despite around 78% of pharmacy students claiming that their knowledge of geriatric care is adequate, their GKAS score showed that only around 20% have high geriatric knowledge. Around 80% of them showed a positive attitude on the importance of taking courses focused on geriatric care and demonstrated interest to further knowledge and training in geriatric care. However, more than half of the students were uncertain of their answers towards their attitudes regarding older patients.

    Conclusion: Given the growing role of pharmacists in the ageing population, this study highlights the importance of geriatric care education among potential pharmacists. Therefore, we urge the need to improve/develop geriatrics education and training into the pharmacy curriculum to ensure sufficient preparation for actual practice after graduation.

  6. Nair T, Choo CSC, Abdullah NS, Lee S, Teo LLE, Chen Y, et al.
    Eur J Anaesthesiol, 2021 Aug 01;38(8):880-887.
    PMID: 33186309 DOI: 10.1097/EJA.0000000000001385
    BACKGROUND: Hospital admissions and surgical operations commonly trigger anxiety in young children. Despite employing numerous support measures in our hospital, such as a pre-operative play room, the encouragement of parental companionship during induction of anaesthesia and distraction therapy, allaying the anxiety of our young surgical patients remains a challenge.

    OBJECTIVES: To evaluate the effectiveness of a Home-Initiated-Programme-to-Prepare-for-Operation (HIPPO) on emotional manifestation and anxiety in children undergoing surgery.

    DESIGN, SETTING AND PATIENTS: One hundred and thirty children were randomly assigned to either control or intervention group between February 2018 and April 2019 in a tertiary paediatric hospital in Singapore.

    INTERVENTION: In addition to our standard pre-operative workflow, the intervention group received an additional home preparation kit consisting of an animated video on preoperative preparation and age-specific preoperative preparation activity sheets.

    MAIN OUTCOME MEASURES: The primary outcome was the Children's Emotional Manifestation Scale score to evaluate behaviour and emotion in the children before and during induction of anaesthesia. Secondary outcomes evaluated anxiety levels in parents and children, the child's behaviour and degree of co-operation using the State-Trait Anxiety Inventory scores, State-Trait Anxiety Inventory Children scores, the Induction Compliance Checklist scores, the Visual Analogue Scale scores for anxiety and the feedback questionnaire.

    RESULTS: The difference between the Children's Emotional Manifestation Scale score in control and intervention groups was not statistically significant. A promising difference was however observed in one of the secondary outcomes where the state-State-Trait Anxiety Inventory Children scores of 7 to 10-year olds in the intervention group almost reached significance; P = 0.067.

    CONCLUSION: Despite being a child-friendly, easily accessible and affordable tool for patient education, HIPPO did not reduce anxiety experienced by children in the pre-operative waiting area or during induction of anaesthesia.

    TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT04271553.

  7. Aisyah HA, Paridah MT, Khalina A, Sapuan SM, Wahab MS, Berkalp OB, et al.
    Polymers (Basel), 2018 Nov 28;10(12).
    PMID: 30961245 DOI: 10.3390/polym10121320
    The effects of different fabric materials namely weave designs (plain and satin) and fabric counts (5 × 5 and 6 × 6) on the properties of laminated woven kenaf/carbon fibre reinforced epoxy hybrid composites were evaluated. The hybrid composites were fabricated from two types of fabric, i.e., woven kenaf that was made from a yarn of 500tex and carbon fibre, by using vacuum infusion technique and epoxy resin as matrix. The panels were tested for tensile, flexural, and impact strengths. The results have revealed that plain fabric is more suitable than satin fabric for obtaining high tensile and impact strengths. Using a fabric count of 5 × 5 has generated composites that are significantly higher in flexural modulus as compared to 6 × 6 which may be attributed to their structure and design. The scanned electron micrographs of the fractured surfaces of the composites demonstrated that plain woven fabric composites had better adhesion properties than satin woven fabric composites, as indicated by the presence of notably lower amount of fibre pull out.
  8. Hor SY, Lee SC, Wong CI, Lim YW, Lim RC, Wang LZ, et al.
    Pharmacogenomics J, 2008 Apr;8(2):139-46.
    PMID: 17876342
    Previously studied candidate genes have failed to account for inter-individual variability of docetaxel and doxorubicin disposition and effects. We genotyped the transcriptional regulators of CYP3A and ABCB1 in 101 breast cancer patients from 3 Asian ethnic groups, that is, Chinese, Malays and Indians, in correlation with the pharmacokinetics and pharmacodynamics of docetaxel and doxorubicin. While there was no ethnic difference in docetaxel and doxorubicin pharmacokinetics, ethnic difference in docetaxel- (ANOVA, P=0.001) and doxorubicin-induced (ANOVA, P=0.003) leukocyte suppression was observed, with Chinese and Indians experiencing greater degree of docetaxel-induced myelosuppression than Malays (Bonferroni, P=0.002, P=0.042), and Chinese experiencing greater degree of doxorubicin-induced myelosuppression than Malays and Indians (post hoc Bonferroni, P=0.024 and 0.025). Genotyping revealed both PXR and CAR to be well conserved; only a PXR 5'-untranslated region polymorphism (-24381A>C) and a silent CAR variant (Pro180Pro) were found at allele frequencies of 26 and 53%, respectively. Two non-synonymous variants were identified in HNF4alpha (Met49Val and Thr130Ile) at allele frequencies of 55 and 1%, respectively, with the Met49Val variant associated with slower neutrophil recovery in docetaxel-treated patients (ANOVA, P=0.046). Interactions were observed between HNF4alpha Met49Val and CAR Pro180Pro, with patients who were wild type for both variants experiencing least docetaxel-induced neutropenia (ANOVA, P=0.030). No other significant genotypic associations with pharmacokinetics or pharmacodynamics of either drug were found. The PXR-24381A>C variants were significantly more common in Indians compared to Chinese or Malays (32/18/21%, P=0.035) Inter-individual and inter-ethnic variations of docetaxel and doxorubicin pharmacokinetics or pharmacodynamics exist, but genotypic variability of the transcriptional regulators PAR, CAR and HNF4alpha cannot account for this variability.
  9. Tan SY, Chen TP, Lee SH, Tan PS, Chua CT, Teo SM, et al.
    Transplant Proc, 2000 Nov;32(7):1811-2.
    PMID: 11119947
  10. Thirthagiri E, Lee SY, Kang P, Lee DS, Toh GT, Selamat S, et al.
    Breast Cancer Res, 2008;10(4):R59.
    PMID: 18627636 DOI: 10.1186/bcr2118
    The cost of genetic testing and the limited knowledge about the BRCA1 and BRCA2 genes in different ethnic groups has limited its availability in medium- and low-resource countries, including Malaysia. In addition, the applicability of many risk-assessment tools, such as the Manchester Scoring System and BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm) which were developed based on mutation rates observed primarily in Caucasian populations using data from multiplex families, and in populations where the rate of breast cancer is higher, has not been widely tested in Asia or in Asians living elsewhere. Here, we report the results of genetic testing for mutations in the BRCA1 or BRCA2 genes in a series of families with breast cancer in the multi-ethnic population (Malay, Chinese and Indian) of Malaysia.
  11. Choon JWY, Wu DBC, Chong HY, Lo WTL, Chong CSY, Chung WS, et al.
    J Med Econ, 2019 Mar;22(3):273-279.
    PMID: 30561238 DOI: 10.1080/13696998.2018.1560749
    BACKGROUND: Very few data are available to demonstrate the economic benefit of early paliperidone palmitate once-monthly long-acting injectable (PP1M) treatment in patients with schizophrenia or schizoaffective disorder.

    METHODS AND MATERIALS: This study has retrospectively compared the healthcare utilization and associated costs of pre- and post-PPIM treatment in 413 patients with schizophrenia or schizoaffective disorder recruited from three major public hospitals providing psychiatric services in Hong Kong. Patients were categorized into early treatment (≤3 years since diagnosis) and chronic (>3 years) groups, and also whether they were receiving polypharmacy (POP).

    RESULTS: It was found that patients who were started on early therapy with no POP had the most favourable outcomes. Overall results of the entire cohort, including both early and late treatments, indicate that there was a slight increase in annual in-patient days (IP) per patient and outpatient visit (OP) by 3.18 and 1.87, respectively, and a decrease in emergency room visit (ER) of 0.9 (p 

  12. Wong CK, Hor JY, Loo YP, Heng HS, Lee S, Perianen PP, et al.
    J Neuroimmunol, 2021 07 15;356:577584.
    PMID: 33933821 DOI: 10.1016/j.jneuroim.2021.577584
    NMDAR encephalitis may be more common among non-Caucasians. A population-based study was conducted to estimate its incidence in Sabah, Malaysia, where the population consists predominantly of Austronesians (84%), and with a Chinese minority. Registries of NMDAR encephalitis at neurology referral centers were reviewed for case ascertainment. The annual incidence was 2.29/million (Austronesians: 2.56/million, Chinese: 1.31/million). Among pediatric population, the incidence was: Austronesians: 3.63/million, Chinese: 2.59/million. Our study demonstrated a higher incidence of NMDAR encephalitis among Austronesians than the predominantly Caucasian populations in Europe (0.5-0.9/million; pediatric: 0.7-1.5/million). Racial and genetic factors may contribute to risks of developing NMDAR encephalitis.
  13. Cho YH, Seo JB, Lee SM, Kim N, Yun J, Hwang JE, et al.
    Eur Radiol, 2021 Oct;31(10):7316-7324.
    PMID: 33847809 DOI: 10.1007/s00330-021-07747-7
    OBJECTIVES: To apply radiomics analysis for overall survival prediction in chronic obstructive pulmonary disease (COPD), and evaluate the performance of the radiomics signature (RS).

    METHODS: This study included 344 patients from the Korean Obstructive Lung Disease (KOLD) cohort. External validation was performed on a cohort of 112 patients. In total, 525 chest CT-based radiomics features were semi-automatically extracted. The five most useful features for survival prediction were selected by least absolute shrinkage and selection operation (LASSO) Cox regression analysis and used to generate a RS. The ability of the RS for classifying COPD patients into high or low mortality risk groups was evaluated with the Kaplan-Meier survival analysis and Cox proportional hazards regression analysis.

    RESULTS: The five features remaining after the LASSO analysis were %LAA-950, AWT_Pi10_6th, AWT_Pi10_heterogeneity, %WA_heterogeneity, and VA18mm. The RS demonstrated a C-index of 0.774 in the discovery group and 0.805 in the validation group. Patients with a RS greater than 1.053 were classified into the high-risk group and demonstrated worse overall survival than those in the low-risk group in both the discovery (log-rank test, < 0.001; hazard ratio [HR], 5.265) and validation groups (log-rank test, < 0.001; HR, 5.223). For both groups, RS was significantly associated with overall survival after adjustments for patient age and body mass index.

    CONCLUSIONS: A radiomics approach for survival prediction and risk stratification in COPD patients is feasible, and the constructed radiomics model demonstrated acceptable performance. The RS derived from chest CT data of COPD patients was able to effectively identify those at increased risk of mortality.

    KEY POINTS: • A total of 525 chest CT-based radiomics features were extracted and the five radiomics features of %LAA-950, AWT_Pi10_6th, AWT_Pi10_heterogeneity, %WA_heterogeneity, and VA18mm were selected to generate a radiomics model. • A radiomics model for predicting survival of COPD patients demonstrated reliable performance with a C-index of 0.774 in the discovery group and 0.805 in the validation group. • Radiomics approach was able to effectively identify COPD patients with an increased risk of mortality, and patients assigned to the high-risk group demonstrated worse overall survival in both the discovery and validation groups.

  14. Pushparajah V, Fatima A, Chong CH, Gambule TZ, Chan CJ, Ng ST, et al.
    Sci Rep, 2016 07 27;6:30010.
    PMID: 27460640 DOI: 10.1038/srep30010
    Lignosus rhinocerotis (Tiger milk mushroom) is an important folk medicine for indigenous peoples in Southeast Asia. We previously reported its de novo assembled 34.3 Mb genome encoding a repertoire of proteins including a putative bioactive fungal immunomodulatory protein. Here we report the cDNA of this new member (FIP-Lrh) with a homology range of 54-64% to FIPs from other mushroom species, the closest is with FIP-glu (LZ-8) (64%) from Ganoderma lucidum. The FIP-Lrh of 112 amino acids (12.59 kDa) has a relatively hydrophobic N-terminal. Its predicted 3-dimensional model has identical folding patterns to FIP-fve and contains a partially conserved and more positively charged carbohydrates binding pocket. Docking predictions of FIP-Lrh on 14 glycans commonly found on cellular surfaces showed the best binding energy of -3.98 kcal/mol to N-acetylgalactosamine and N-acetylglucosamine. Overexpression of a 14.9 kDa soluble 6xHisFIP-Lrh was achieved in pET-28a(+)/BL21 and the purified recombinant protein was sequence verified by LC-MS/MS (QTOF) analysis. The ability to haemagglutinate both mouse and human blood at concentration ≥0.34 μM, further demonstrated its lectin nature. In addition, the cytotoxic effect of 6xHisFIP-Lrh on MCF-7, HeLa and A549 cancer cell lines was detected at IC50 of 0.34 μM, 0.58 μM and 0.60 μM, respectively.
  15. Tien Bui D, Shirzadi A, Shahabi H, Chapi K, Omidavr E, Pham BT, et al.
    Sensors (Basel), 2019 May 29;19(11).
    PMID: 31146336 DOI: 10.3390/s19112444
    In this study, we introduced a novel hybrid artificial intelligence approach of rotation forest (RF) as a Meta/ensemble classifier based on alternating decision tree (ADTree) as a base classifier called RF-ADTree in order to spatially predict gully erosion at Klocheh watershed of Kurdistan province, Iran. A total of 915 gully erosion locations along with 22 gully conditioning factors were used to construct a database. Some soft computing benchmark models (SCBM) including the ADTree, the Support Vector Machine by two kernel functions such as Polynomial and Radial Base Function (SVM-Polynomial and SVM-RBF), the Logistic Regression (LR), and the Naïve Bayes Multinomial Updatable (NBMU) models were used for comparison of the designed model. Results indicated that 19 conditioning factors were effective among which distance to river, geomorphology, land use, hydrological group, lithology and slope angle were the most remarkable factors for gully modeling process. Additionally, results of modeling concluded the RF-ADTree ensemble model could significantly improve (area under the curve (AUC) = 0.906) the prediction accuracy of the ADTree model (AUC = 0.882). The new proposed model had also the highest performance (AUC = 0.913) in comparison to the SVM-Polynomial model (AUC = 0.879), the SVM-RBF model (AUC = 0.867), the LR model (AUC = 0.75), the ADTree model (AUC = 0.861) and the NBMU model (AUC = 0.811).
  16. Lewis HIJ, Jin X, Guo B, Lee S, Jung H, Kodati SH, et al.
    Sci Rep, 2023 Jun 19;13(1):9936.
    PMID: 37336988 DOI: 10.1038/s41598-023-36744-7
    Al0.85Ga0.15As0.56Sb0.44 has recently attracted significant research interest as a material for 1550 nm low-noise short-wave infrared (SWIR) avalanche photodiodes (APDs) due to the very wide ratio between its electron and hole ionization coefficients. This work reports new experimental excess noise data for thick Al0.85Ga0.15As0.56Sb0.44 PIN and NIP structures, measuring low noise at significantly higher multiplication values than previously reported (F = 2.2 at M = 38). These results disagree with the classical McIntyre excess noise theory, which overestimates the expected noise based on the ionization coefficients reported for this alloy. Even the addition of 'dead space' effects cannot account for these discrepancies. The only way to explain the low excess noise observed is to conclude that the spatial probability distributions for impact ionization of electrons and holes in this material follows a Weibull-Fréchet distribution function even at relatively low electric-fields. Knowledge of the ionization coefficients alone is no longer sufficient to predict the excess noise properties of this material system and consequently the electric-field dependent electron and hole ionization probability distributions are extracted for this alloy.
  17. Nyanti LE, Lee SSY, Shanmugam V, Muien MZBA, Othman AA, Chia YL, et al.
    Int J Tuberc Lung Dis, 2023 Oct 01;27(10):724-728.
    PMID: 37749834 DOI: 10.5588/ijtld.23.0079
    Melioidosis is a potentially life-threatening infection caused by the Gram-negative bacillus Burkholderia pseudomallei. Mediastinal melioidosis has a range of clinical presentations, making it difficult to diagnose: we therefore reviewed the evidence on the clinical characteristics, radiological features and invasive diagnostic modalities or interventions. An electronic search was conducted on three databases (PubMed, SCOPUS, Google Scholar) from November to December 2022. The initial search yielded 120 results, of which 34 studies met the inclusion criteria, but only 31 full-texts were retrievable. Among these, 4 were cohort studies, 26 case reports or series and 1 a conference abstract. The four main themes covered were mediastinal melioidosis as a diagnostic dilemma, unexpected complications, invasive interventions or an accompanying thoracic feature. Radiological manifestations included matting, necrosis and abscess-like collection. Severe presentations of mediastinal melioidosis included superior vena cava obstruction, sinus tract formation and pericardial tamponade. Transbronchial needle aspiration was the most common invasive diagnostic modality. Further research is needed to understand the relationship between the thoracic features of melioidosis on patient prognosis, its relationship to melioidosis transmission and potential preventive measures.
  18. Lee S, Sbihi H, MacIsaac JL, Balshaw R, Ambalavanan A, Subbarao P, et al.
    Environ Health Perspect, 2024 Apr;132(4):47004.
    PMID: 38573328 DOI: 10.1289/EHP13034
    BACKGROUND: Evidence suggests that prenatal air pollution exposure alters DNA methylation (DNAm), which could go on to affect long-term health. It remains unclear whether DNAm alterations present at birth persist through early life. Identifying persistent DNAm changes would provide greater insight into the molecular mechanisms contributing to the association of prenatal air pollution exposure with atopic diseases.

    OBJECTIVES: This study investigated DNAm differences associated with prenatal nitrogen dioxide (NO2) exposure (a surrogate measure of traffic-related air pollution) at birth and 1 y of age and examined their role in atopic disease. We focused on regions showing persistent DNAm differences from birth to 1 y of age and regions uniquely associated with postnatal NO2 exposure.

    METHODS: Microarrays measured DNAm at birth and at 1 y of age for an atopy-enriched subset of Canadian Health Infant Longitudinal Development (CHILD) study participants. Individual and regional DNAm differences associated with prenatal NO2 (n=128) were identified, and their persistence at age 1 y were investigated using linear mixed effects models (n=124). Postnatal-specific DNAm differences (n=125) were isolated, and their association with NO2 in the first year of life was examined. Causal mediation investigated whether DNAm differences mediated associations between NO2 and age 1 y atopy or wheeze. Analyses were repeated using biological sex-stratified data.

    RESULTS: At birth (n=128), 18 regions of DNAm were associated with NO2, with several annotated to HOX genes. Some of these regions were specifically identified in males (n=73), but not females (n=55). The effect of prenatal NO2 across CpGs within altered regions persisted at 1 y of age. No significant mediation effects were identified. Sex-stratified analyses identified postnatal-specific DNAm alterations.

    DISCUSSION: Regional cord blood DNAm differences associated with prenatal NO2 persisted through at least the first year of life in CHILD participants. Some differences may represent sex-specific alterations, but replication in larger cohorts is needed. The early postnatal period remained a sensitive window to DNAm perturbations. https://doi.org/10.1289/EHP13034.

  19. Kim JK, Choi E, Hong YH, Kim H, Jang YJ, Lee JS, et al.
    J Ethnopharmacol, 2021 May 10;271:113887.
    PMID: 33539951 DOI: 10.1016/j.jep.2021.113887
    ETHNOPHARMACOLOGICAL RELEVANCE: Melicope accedens (Blume) Thomas G. Hartley is a plant included in the family Rutaceae and genus Melicope. It is a native plant from Vietnam that has been used for ethnopharmacology. In Indonesia and Malaysia, the leaves of M. accedens are applied externally to decrease fever.

    AIM OF THE STUDY: The molecular mechanisms of the anti-inflammatory properties of M. accedens are not yet understood. Therefore, we examined those mechanisms using a methanol extract of M. accedens (Ma-ME) and determined the target molecule in macrophages.

    MATERIALS AND METHODS: We evaluated the anti-inflammatory effects of Ma-ME in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and in an HCl/EtOH-triggered gastritis model in mice. To investigate the anti-inflammatory activity, we performed a nitric oxide (NO) production assay and ELISA assay for prostaglandin E2 (PGE2). RT-PCR, luciferase gene reporter assays, western blotting analyses, and a cellular thermal shift assay (CETSA) were conducted to identify the mechanism and target molecule of Ma-ME. The phytochemical composition of Ma-ME was analyzed by HPLC and LC-MS/MS.

    RESULTS: Ma-ME suppressed the production of NO and PGE2 and the mRNA expression of proinflammatory genes (iNOS, IL-1β, and COX-2) in LPS-stimulated RAW264.7 cells without cytotoxicity. Ma-ME inhibited NF-κB activation by suppressing signaling molecules such as IκBα, Akt, Src, and Syk. Moreover, the CETSA assay revealed that Ma-ME binds to Syk, the most upstream molecule in the NF-κB signal pathway. Oral administration of Ma-ME not only alleviated inflammatory lesions, but also reduced the gene expression of IL-1β and p-Syk in mice with HCl/EtOH-induced gastritis. HPLC and LC-MS/MS analyses confirmed that Ma-ME contains various anti-inflammatory flavonoids, including quercetin, daidzein, and nevadensin.

    CONCLUSIONS: Ma-ME exhibited anti-inflammatory activities in vitro and in vivo by targeting Syk in the NF-κB signaling pathway. Therefore, we propose that Ma-ME could be used to treat inflammatory diseases such as gastritis.

  20. Park YH, Senkus-Konefka E, Im SA, Pentheroudakis G, Saji S, Gupta S, et al.
    Ann Oncol, 2020 04;31(4):451-469.
    PMID: 32081575 DOI: 10.1016/j.annonc.2020.01.008
    In view of the planned new edition of the most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of primary breast cancer published in 2015, it was decided at the ESMO Asia Meeting in November 2018, by both the ESMO and the Korean Society of Medical Oncology (KSMO), to convene a special face-to-face guidelines meeting in 2019 in Seoul. The aim was to adapt the latest ESMO 2019 guidelines to take into account the ethnic and geographical differences associated with the treatment of early breast cancer in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with early breast cancer representing the oncology societies of Korea (KSMO), China (CSCO), India (ISMPO) Japan (JSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence, and was independent of both the current treatment practices, and the drug availability and reimbursement situations, in the individual participating Asian countries.
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