Browse publications by year: 2019

  1. Khan F, Sarker MMR, Ming LC, Mohamed IN, Zhao C, Sheikh BY, et al.
    Front Pharmacol, 2019;10:1223.
    PMID: 31736747 DOI: 10.3389/fphar.2019.01223
    Gymnema sylvestre is a plant included in Apocynaceae family and is located in many regions of Asia, Africa and Australia. This plant is widely used as a traditional therapy for different purposes. Even now it is being used as a dietary supplement due to its numerous therapeutic uses. It is known to have blood glucose lowering potential and, thus, is widely used in traditional and Ayurvedic systems of medicine. It renders glucose lowering activity due to the presence of phytochemicals, such as gurmarin, gymnemic acid as well as gymnemasaponins. Gymnema sylvestre is also known to have anti-oxidant, antibiotic, anti-inflammatory, antiviral, gastro and hepatoprotective, anticancer and lipid-lowering activities. This review discusses in details on different pharmacological and clinical potentials of Gymnema sylvestre and its chemical constituents associated with its therapeutic potentials.
  2. Zin CS, Taufek NH, Ahmad MM
    Front Pharmacol, 2019;10:1286.
    PMID: 31736760 DOI: 10.3389/fphar.2019.01286
    Limited data are available on the adherence to opioid therapy and the influence of different patient groups on adherence. This study examined the patterns of adherence in opioid naïve and opioid existing patients with varying age and gender. This retrospective cohort study was conducted using the prescription databases in tertiary hospital settings in Malaysia from 2010 to 2016. Adult patients aged ≥18 years, receiving at least two opioid prescriptions, were included and stratified into the opioid naïve and existing patient groups. Adherence to opioid therapy was measured using the proportion of days covered (PDC), which was derived by dividing the total number of days covered with any opioids by the number of days in the follow-up period. Generalized linear modeling was used to assess factors associated with PDC. A total of 10,569 patients with 36,650 prescription episodes were included in the study. Of these, 91.7% (n = 9,696) were opioid naïve patients and 8.3% (n = 873) were opioid existing patients. The median PDC was 35.5% (interquartile range (IQR) 10.3-78.7%) and 26.8% (IQR 8.8-69.5%) for opioid naïve and opioid existing patients, respectively. A higher opioid daily dose (coefficient 0.010, confidence interval (CI) 0.009, 0.012 p < 0.0001) and increasing age (coefficient 0.002, CI 0.001, 0.003 p < 0.0001) were associated with higher levels of PDC, while lower PDC values were associated with male subjects (coefficient -0.0041, CI -0.072, -0.010 p = 0.009) and existing opioid patients (coefficient -0.134, CI -0.191, -0.077 p < 0.0001). The suboptimal adherence to opioid medications was commonly observed among patients with non-cancer pain, and the opioid existing patients were less adherent compared to opioid naïve patients. Increasing age and a higher daily opioid dose were factors associated with higher levels of adherence, while male and opioid existing patients were potential determinants for lower levels of adherence to opioid medications.
    MeSH terms: Adult; Analgesics, Opioid; Follow-Up Studies; Humans; Malaysia; Male; Neoplasms; Pain; Retrospective Studies; Confidence Intervals; Linear Models; Databases, Factual; Prescriptions; Tertiary Care Centers
  3. Lee NLY, Huang D, Quek ZBR, Lee JN, Wainwright BJ
    Front Microbiol, 2019;10:2456.
    PMID: 31736902 DOI: 10.3389/fmicb.2019.02456
    Marine fungi on the whole remain understudied, especially in the highly diverse Southeast Asian region. We investigated the fungal communities associated with the mangrove tree Avicennia alba throughout Singapore and Peninsular Malaysia. At each sampling location, we examined ten individual trees, collecting leaves, fruits, pneumatophores, and an adjacent sediment sample from each plant. Amplicon sequencing of the fungal internal transcribed spacer 1 and subsequent analyses reveal significant differences in fungal communities collected from different locations and host structures. Mantel tests and multiple regression on distance matrices show a significant pattern of distance decay with samples collected close to one another having more similar fungal communities than those farther away. Submergence appears to drive part of the variation as host structures that are never submerged (leaves and fruits) have more similar fungal communities relative to those that are covered by water during high tide (pneumatophores and sediment). We suggest that fungi of terrestrial origins dominate structures that are not inundated by tidal regimes, while marine fungi dominate mangrove parts and sediments that are submerged by the incoming tide. Given the critical functions fungi play in all plants, and the important role they can have in determining the success of restoration schemes, we advocate that fungal community composition should be a key consideration in any mangrove restoration or rehabilitation project.
    MeSH terms: Drive; Fruit; Fungi; Malaysia; Plants; Singapore; Trees; Water; Plant Leaves; Avicennia
  4. Yang Y, Mi J, Liang J, Liao X, Ma B, Zou Y, et al.
    Front Microbiol, 2019;10:2506.
    PMID: 31736928 DOI: 10.3389/fmicb.2019.02506
    Despite our continuous improvement in understanding the evolution of antibiotic resistance, the changes in the carbon metabolism during the evolution of antibiotic resistance remains unclear. To investigate the evolution of antibiotic resistance and the changes in carbon metabolism under antibiotic pressure, Escherichia coli K-12 was evolved for 38 passages under a concentration gradient of doxycycline (DOX). The 0th-passage sensitive strain W0, the 20th-passage moderately resistant strain M20, and the 38th-passage highly resistant strain E38 were selected for the determination of biofilm formation, colony area, and carbon metabolism levels, as well as genome and transcriptome sequencing. The MIC of DOX with E. coli significantly increased from 4 to 96 μg/ml, and the IC50 increased from 2.18 ± 0.08 to 64.79 ± 0.75 μg/ml after 38 passages of domestication. Compared with the sensitive strain W0, the biofilm formation amount of the resistant strains M20 and E38 was significantly increased (p < 0.05). Single-nucleotide polymorphisms (SNPs) were distributed in antibiotic resistance-related genes such as ribosome targets, cell membranes, and multiple efflux pumps. In addition, there were no mutated genes related to carbon metabolism. However, the genes involved in the biosynthesis of secondary metabolites and carbon metabolism pathway were downregulated, showing a significant decrease in the metabolic intensity of 23 carbon sources (p < 0.05). The results presented here show that there may be a correlation between the evolution of E. coli DOX resistance and the decrease of carbon metabolism, and the mechanism was worthy of further research, providing a theoretical basis for the prevention and control of microbial resistance.
    MeSH terms: Anti-Bacterial Agents; Biochemical Phenomena; Carbon; Cell Membrane; Doxycycline; Drug Resistance, Microbial; Escherichia coli; Mutation; Nucleotides; Ribosomes; Biofilms; Inhibitory Concentration 50; Polymorphism, Single Nucleotide; Escherichia coli K12; Transcriptome; Domestication
  5. Loo GH, Lim LY, Zainuddin ZM, Fam XI
    Ann Med Surg (Lond), 2019 Dec;48:73-76.
    PMID: 31737262 DOI: 10.1016/j.amsu.2019.10.024
    Introduction: Giant condyloma acuminata (GCA), also known as Bushke-Lowenstein tumour, is a rare disease which affects 0.1% of the population. Although histopathologically benign, it tends to be locally destructive. The common sites of involvement include the penis and the anorectum. Due to the rarity of the disease, there is a lack of controlled studies on the optimal management of this entity. Thus, we report a case of anogenital GCA in a 40-year-old HIV-positive man.

    Case presentation: A 40-year-old man presented with progressive anogenital warts associated with foul-smelling discharge and fever. He has been diagnosed with HIV and was on HAART on presentation. A warty excrescence had infiltrated the entire external genitalia, gluteals and sacral region. Serial excision was performed along with a defunctioning colostomy. The patient recovered well, and the final histopathological showed features of GCA.

    Discussion: With HIV, the HPV infection goes unchecked may develop into GCA. Malignant transformation to squamous cell carcinoma may occur in more than half of the cases. A complex interaction between HIV and HPV may lead to a higher risk of recurrence even after resection. The diagnosis is usually clinical. Imaging modalities may be used in identifying the extent and depth of invasion.

    Conclusion: The optimal management of anogenital giant condyloma acuminata remains to be determined. Staged surgical excision should be conducted to achieve an optimum outcome. Radical reconstructive surgery should be reserved for patients with recurrence, malignant transformation or sphincter involvement.

    MeSH terms: Adult; Carcinoma, Squamous Cell; Colostomy; Condylomata Acuminata; Genitalia; Humans; Male; Neoplasm Recurrence, Local; Patient Discharge; Penis; Sacrococcygeal Region; Warts; HIV Infections; Reconstructive Surgical Procedures; Antiretroviral Therapy, Highly Active; Papillomavirus Infections; Rare Diseases; Buschke-Lowenstein Tumor
  6. Erejuwa OO, Gan SH, Romani AMP, Kamal MA, Nammi S
    Int J Hypertens, 2019 10 13;2019:2907675.
    PMID: 31737360 DOI: 10.1155/2019/2907675
    [This corrects the article DOI: 10.1155/2019/6709817.].
    MeSH terms: Humans
  7. Tong CV, Rajoo S
    Case Rep Endocrinol, 2019;2019:2986312.
    PMID: 31737375 DOI: 10.1155/2019/2986312
    Approach to patients who manifest with features of Cushing's syndrome often begin with exclusion of exposure to excessive exogenous source of glucocorticoids (GC). Most guidelines advocate no further assessment if excessive exogenous GC use is present. We present a case of a 66-year-old lady who was noted to have typical features of Cushing's syndrome. As she gave a very clear history of ingesting exogenous GC for a year, no further work up was undertaken. Despite cessation of GC for a year, she continued to have thin skin and easy bruising. Upon admission for hypertensive emergency, her clinician took note of her changes and investigated her for endogenous Cushing's syndrome. Her cortisol post overnight dexamethasone suppression test was 707 nmol/l. Post low dose dexamethasone suppression test yielded a cortisol of 1133.2 nmol/l. 24 hours urine cortisol was 432.2 nmol/l. Plasma ACTH was 1.1 pmol/l, indicating an ACTH independent Cushing's syndrome. We proceeded with Computed tomography scan (CT scan) of adrenals which revealed a right adrenal adenoma measuring 4.4 × 3.4 × 4.0 cm. Right retroperiteneoscopic adrenalectomy was done. Histopathology examination was consistent with adrenal cortical adenoma with foci of myelolipoma. Post adrenalectomy she developed hypocortisolism secondary to contralateral adrenal suppression which lasted up to the present date. Her cutaneous and musculoskeletal manifestations improved substantially. Co-occurrence of endogenous and exogenous Cushing's syndromes is uncommon but should be considered in patients whose Cushingnoid features do not resolve after cessation of exogenous GC.
    MeSH terms: Addison Disease; Adenoma; Adrenal Gland Neoplasms; Adrenal Glands; Adrenalectomy; Adrenocorticotropic Hormone; Cushing Syndrome; Dexamethasone; Endocrine System Diseases; Female; Glucocorticoids; Humans; Hydrocortisone; Tomography; Tomography, X-Ray Computed; Myelolipoma; Adrenocortical Adenoma
  8. Xing Z, Yu F, Du J, Walker JS, Paulson CB, Mani NS, et al.
    J Med Internet Res, 2019 11 18;21(11):e14672.
    PMID: 31738171 DOI: 10.2196/14672
    BACKGROUND: Conversational interfaces (CIs) in different modalities have been developed for health purposes, such as health behavioral intervention, patient self-management, and clinical decision support. Despite growing research evidence supporting CIs' potential, CI-related research is still in its infancy. There is a lack of systematic investigation that goes beyond publication review and presents the state of the art from perspectives of funding agencies, academia, and industry by incorporating CI-related public funding and patent activities.

    OBJECTIVE: This study aimed to use data systematically extracted from multiple sources (ie, grant, publication, and patent databases) to investigate the development, research, and fund application of health-related CIs and associated stakeholders (ie, countries, organizations, and collaborators).

    METHODS: A multifaceted search query was executed to retrieve records from 9 databases. Bibliometric analysis, social network analysis, and term co-occurrence analysis were conducted on the screened records.

    RESULTS: This review included 42 funded projects, 428 research publications, and 162 patents. The total dollar amount of grants awarded was US $30,297,932, of which US $13,513,473 was awarded by US funding agencies and US $16,784,459 was funded by the Europe Commission. The top 3 funding agencies in the United States were the National Science Foundation, National Institutes of Health, and Agency for Healthcare Research and Quality. Boston Medical Center was awarded the largest combined grant size (US $2,246,437) for 4 projects. The authors of the publications were from 58 countries and 566 organizations; the top 3 most productive organizations were Northeastern University (United States), Universiti Teknologi MARA (Malaysia), and the French National Center for Scientific Research (CNRS; France). US researchers produced 114 publications. Although 82.0% (464/566) of the organizations engaged in interorganizational collaboration, 2 organizational research-collaboration clusters were observed with Northeastern University and CNRS as the central nodes. About 112 organizations from the United States and China filed 87.7% patents. IBM filed most patents (N=17). Only 5 patents were co-owned by different organizations, and there was no across-country collaboration on patenting activity. The terms patient, child, elderly, and robot were frequently discussed in the 3 record types. The terms related to mental and chronic issues were discussed mainly in grants and publications. The terms regarding multimodal interactions were widely mentioned as users' communication modes with CIs in the identified records.

    CONCLUSIONS: Our findings provided an overview of the countries, organizations, and topic terms in funded projects, as well as the authorship, collaboration, content, and related information of research publications and patents. There is a lack of broad cross-sector partnerships among grant agencies, academia, and industry, particularly in the United States. Our results suggest a need to improve collaboration among public and private sectors and health care organizations in research and patent activities.

    MeSH terms: Humans; Publications/standards*; Publishing/standards*; Bibliometrics*; Biomedical Research
  9. Cheong HC, Yap PSX, Chong CW, Cheok YY, Lee CYQ, Tan GMY, et al.
    PLoS One, 2019;14(11):e0224658.
    PMID: 31738795 DOI: 10.1371/journal.pone.0224658
    The cervical microbiota constitutes an important protective barrier against the invasion of pathogenic microorganisms. A disruption of microbiota within the cervical milieu has been suggested to be a driving factor of sexually transmitted infections. These include Chlamydia trachomatis which frequently causes serious reproductive sequelae such as infertility in women. In this study, we profiled the cervical microbial composition of a population of 70 reproductive-age Malaysian women; among which 40 (57.1%) were diagnosed with genital C. trachomatis infection, and 30 (42.8%) without C. trachomatis infection. Our findings showed a distinct compositional difference between the cervical microbiota of C. trachomatis-infected subjects and subjects without C. trachomatis infection. Specifically, significant elevations of mostly strict and facultative anaerobes such as Streptococcus, Megasphaera, Prevotella, and Veillonella in the cervical microbiota of C. trachomatis-positive women were detected. The results from the current study highlights an interaction of C. trachomatis with the environmental microbiome in the endocervical region.
    MeSH terms: Academic Medical Centers; Adult; Bacteria, Anaerobic/immunology; Bacteria, Anaerobic/isolation & purification; Cervix Uteri/microbiology*; Chlamydia Infections/complications; Chlamydia Infections/immunology; Chlamydia Infections/microbiology*; Chlamydia trachomatis/isolation & purification*; Chlamydia trachomatis/pathogenicity; DNA, Bacterial/genetics; DNA, Bacterial/isolation & purification; Female; Humans; Infertility/immunology; Infertility/microbiology*; Malaysia; Outpatient Clinics, Hospital; RNA, Ribosomal, 16S/genetics; Cohort Studies; Host-Pathogen Interactions/immunology; Young Adult; Metagenomics; Microbiota/genetics; Microbiota/immunology*
  10. Wong JHD, Anem LEA, Tan S, Tan SK, Ng KH
    Phys Med, 2019 Dec;68:47-51.
    PMID: 31739145 DOI: 10.1016/j.ejmp.2019.11.007
    OBJECTIVE: This study measured the radiation exposure of the eye lens of medical personnel performing fluoroscopy and interventional procedures at the Sarawak General Hospital in Kuching, Sarawak, Malaysia. This study was the first in Malaysia to utilise in vivo radiation measurement relatively near the eye lens.

    METHODS: 41 medical personnel performing 79 procedures were monitored for their eye lens exposure using the NanoDot™ optically-stimulated luminescence dosimeters (OSLD) taped to the outer canthus of their eyes. The air-kerma area product (KAP), fluoroscopy time (FT) and number of procedure runs were also recorded.

    RESULTS: KAP, FT and number of runs were strongly correlated. However, only weak to moderate correlations were observed between these parameters with the measured eye lens doses. The average median equivalent eye lens dose was 0.052 mSv (ranging from 0.0155 to 0.672 mSv). The eye lens doses of primary operators were found to be significantly higher than their assistants due to the closer proximity to the patient and X-ray tube. The left eye lens of the operators received the highest amount of radiation due to their habitual positioning towards the radiation source.

    CONCLUSION: KAP and FT were not useful in predicting the equivalent eye lens dose exposure in interventional radiological procedures. Direct in vivo measurements were needed to provide a better estimate of the eye lens doses received by medical personnel during these procedures. This study highlights the importance of using direct measurement, such as OSLDs, instead of just indirect factors to monitor dose in the eye lens in radiological procedures.

    MeSH terms: Fluoroscopy/adverse effects; Health Personnel*; Hospitals*; Humans; Lens, Crystalline/radiation effects*; Malaysia; Radiation Dosage*; Radiology, Interventional*; Occupational Exposure/adverse effects; Occupational Exposure/analysis*
  11. Liou AT, Liao CC, Chou SF, Chang YS, Chang CS, Shih C
    J Biomed Sci, 2019 Nov 11;26(1):93.
    PMID: 31711481 DOI: 10.1186/s12929-019-0585-y
    BACKGROUND: Enterovirus 71 (EV71 or EV-A71) was first identified in California about half a century ago. In recent years, outbreaks of EV-A71 were prevalent worldwide, including Taiwan, Malaysia, Singapore, Japan, and China. Between 2008 and 2011, China alone reported 1894 deaths associated with EV-A71 infection. In mild cases, EV-A71 can cause herpangina and hand-foot-and-mouth disease (HFMD). However, in severe cases, it could cause neurological disorders, including meningitis and encephalitis. Cardiopulmonary failure is common among hospitalized children with EV-A71 infection. No effective FDA-approved therapeutics against EV-A71 are clinically available.

    METHODS: We report the establishment of an immunocompetent wild type strain 129 (wt-129) mouse model, which can be cross-species infected with human EV-A71 clinical isolates via an intraperitoneal route.

    RESULTS: One intriguing disease phenotype of this new model is the development of characteristic "White-Jade" patches in the muscle, which lost sporadically the normal pink color of uninfected muscle. Viral VP1 protein and massive leukocyte infiltration were detected in muscles with or without white-jades. We demonstrated further that hypoxia is a general phenomenon associated with white-jades in both immunocompetent and immunodeficient mouse models. Therefore, hypoxia appears to be a feature intrinsic to EV-A71 infection, irrespective of its host's immunogenetic background. To date, no effective treatment for EV-A71 is available. Here, using this new wt-129 mouse model, we showed that timely treatment with compound R837 (a TLR7 immune modulator) via oral or intraperitoneal routes, rescued the hypoxia, limb paralysis, and death at a high therapeutic efficacy.

    CONCLUSIONS: In this new immunocompetent mouse 129 model, we observed an unexpected white-jade phenotype and its associated hypoxia. The successful treatment with TLR7 immune modulators via an oral route, provide us a new research direction for EV-A71 basic science and translational research. It remains an open issue whether R837 or its related compounds, will be a promising drug candidate in clinical trials in EV-A71 endemic or epidemic areas in the future.

    MeSH terms: Animals; California; Child; Child, Hospitalized; China; Encephalitis; Enterovirus; Foot-and-Mouth Disease; Hand, Foot and Mouth Disease; Herpangina; Humans; Immunogenetics; Japan; Leukocytes; Malaysia; Meningitis; Phenotype; Singapore; Taiwan; Enterovirus A, Human; Mice; Translational Medical Research; Mice, 129 Strain; Epidemics
  12. Bartlett AW, Lumbiganon P, Jamal Mohamed TA, Lapphra K, Muktiarti D, Du QT, et al.
    J Acquir Immune Defic Syndr, 2019 12 15;82(5):431-438.
    PMID: 31714422 DOI: 10.1097/QAI.0000000000002184
    BACKGROUND: Perinatally HIV-infected adolescents (PHIVA) are an expanding population vulnerable to loss to follow-up (LTFU). Understanding the epidemiology and factors for LTFU is complicated by varying LTFU definitions.

    SETTING: Asian regional cohort incorporating 16 pediatric HIV services across 6 countries.

    METHODS: Data from PHIVA (aged 10-19 years) who received combination antiretroviral therapy 2007-2016 were used to analyze LTFU through (1) an International epidemiology Databases to Evaluate AIDS (IeDEA) method that determined LTFU as >90 days late for an estimated next scheduled appointment without returning to care and (2) the absence of patient-level data for >365 days before the last data transfer from clinic sites. Descriptive analyses and competing-risk survival and regression analyses were used to evaluate LTFU epidemiology and associated factors when analyzed using each method.

    RESULTS: Of 3509 included PHIVA, 275 (7.8%) met IeDEA and 149 (4.3%) met 365-day absence LTFU criteria. Cumulative incidence of LTFU was 19.9% and 11.8% using IeDEA and 365-day absence criteria, respectively. Risk factors for LTFU across both criteria included the following: age at combination antiretroviral therapy initiation <5 years compared with age ≥5 years, rural clinic settings compared with urban clinic settings, and high viral loads compared with undetectable viral loads. Age 10-14 years compared with age 15-19 years was another risk factor identified using 365-day absence criteria but not IeDEA LTFU criteria.

    CONCLUSIONS: Between 12% and 20% of PHIVA were determined LTFU with treatment fatigue and rural treatment settings consistent risk factors. Better tracking of adolescents is required to provide a definitive understanding of LTFU and optimize evidence-based models of care.

    MeSH terms: Adolescent; Age Factors; Asia; Child; Female; Humans; Male; Pregnancy; Pregnancy Complications, Infectious/drug therapy; Risk Factors; HIV Infections/drug therapy*; HIV Infections/transmission*; Infectious Disease Transmission, Vertical*; Rural Health Services/statistics & numerical data; Urban Health Services/statistics & numerical data; Viral Load; Parturition; Anti-Retroviral Agents/therapeutic use*; Young Adult; Lost to Follow-Up*
  13. Pang KL, Chin KY
    Int J Mol Sci, 2019 Oct 25;20(21).
    PMID: 31731474 DOI: 10.3390/ijms20215318
    Selenium is a trace element essential to humans and forms complexes with proteins, which exert physiological functions in the body. In vitro studies suggested that selenium possesses anticancer effects and may be effective against osteosarcoma. This review aims to summarise current evidence on the anticancer activity of inorganic and organic selenium on osteosarcoma. Cellular studies revealed that inorganic and organic selenium shows cytotoxicity, anti-proliferative and pro-apoptotic effects on various osteosarcoma cell lines. These actions may be mediated by oxidative stress induced by selenium compounds, leading to the activation of p53, proapoptotic proteins and caspases. Inorganic selenium is selective towards cancer cells, but can cause non-selective cell death at a high dose. This condition challenges the controlled release of selenium from biomaterials. Selenium treatment in animals inoculated with osteosarcoma reduced the tumour size, but did not eliminate the incidence of osteosarcoma. Only one study investigated the relationship between selenium and osteosarcoma in humans, but the results were inconclusive. In summary, although selenium may exert anticancer properties on osteosarcoma in experimental model systems, its effects in humans require further investigation.
    MeSH terms: Animals; Antineoplastic Agents/therapeutic use*; Bone Neoplasms/drug therapy*; Bone Neoplasms/metabolism; Bone Neoplasms/pathology; Humans; Neoplasms, Experimental/drug therapy*; Neoplasms, Experimental/metabolism; Neoplasms, Experimental/pathology; Osteosarcoma/drug therapy*; Osteosarcoma/metabolism; Osteosarcoma/pathology; Selenium/therapeutic use*; Tumor Suppressor Protein p53/metabolism; Oxidative Stress/drug effects; Cell Line, Tumor
  14. Tan BL, Norhaizan ME
    Nutrients, 2019 Oct 25;11(11).
    PMID: 31731503 DOI: 10.3390/nu11112579
    Cognitive dysfunction is linked to chronic low-grade inflammatory stress that contributes to cell-mediated immunity in creating an oxidative environment. Food is a vitally important energy source; it affects brain function and provides direct energy. Several studies have indicated that high-fat consumption causes overproduction of circulating free fatty acids and systemic inflammation. Immune cells, free fatty acids, and circulating cytokines reach the hypothalamus and initiate local inflammation through processes such as microglial proliferation. Therefore, the role of high-fat diet (HFD) in promoting oxidative stress and neurodegeneration is worthy of further discussion. Of particular interest in this article, we highlight the associations and molecular mechanisms of HFD in the modulation of inflammation and cognitive deficits. Taken together, a better understanding of the role of oxidative stress in cognitive impairment following HFD consumption would provide a useful approach for the prevention of cognitive dysfunction.
    MeSH terms: Cognition/drug effects*; Dietary Fats/pharmacology*; Humans; Inflammation*; Oxidative Stress/drug effects*; Cell Proliferation/drug effects; Diet, High-Fat/adverse effects*; Mild Cognitive Impairment/etiology
  15. Chan CY, Subramaniam S, Chin KY, Ima-Nirwana S, Muhammad N, Fairus A, et al.
    Int J Environ Res Public Health, 2019 Oct 25;16(21).
    PMID: 31731507 DOI: 10.3390/ijerph16214115
    Osteoporosis is a skeletal disorder commonly found among the elderly, in which the bones become weak, brittle, and more susceptible to fracture. Adequate knowledge and positive attitude towards the disease and osteoprotective activities may prevent osteoporosis, but comprehensive studies to verify this hypothesis are limited in Malaysia. This study aims to bridge the research gap by determining the levels of knowledge, beliefs, and practices regarding osteoporosis and their associations with bone mineral density (BMD) among men and women ≥ 40 years in Klang Valley, Malaysia. In this cross-sectional study, 786 Malaysians (382 men, 404 women) completed a questionnaire on knowledge, beliefs, and osteoprotective practices, and underwent BMD scan using a dual-energy X-ray absorptiometry device. The current study found moderate levels of knowledge and beliefs regarding osteoporosis but poor osteoprotective practices. Osteoporosis knowledge, beliefs, and practices were significantly different based on subjects' demographic characteristics (p < 0.05). Osteoporosis knowledge and beliefs were correlated significantly with osteoprotective practices (p < 0.05). Bone health status of the subjects was associated positively with calcium supplement intake, and negatively with exercise barriers and smoking status of the subjects (p < 0.05). However, no significant correlation was noted between osteoporosis knowledge and bone health (p > 0.05). Conclusively, despite some correlations between individual components, the detachment between bone health knowledge and beliefs, and osteoprotective practices among Malaysians is apparent. Integrating all three components into a comprehensive osteoporosis prevention program is warranted.
    MeSH terms: Adult; Calcium, Dietary; Cross-Sectional Studies; Female; Humans; Health Knowledge, Attitudes, Practice*; Malaysia; Male; Middle Aged; Osteoporosis*; Surveys and Questionnaires; Absorptiometry, Photon; Bone Density*; Fractures, Bone
  16. Tan YY, Tan K
    Clin Med (Lond), 2019 Nov;19(6):511-513.
    PMID: 31732595 DOI: 10.7861/clinmed.2019-0247
    Hypertensive encephalopathy (HE) is a subset of posterior reversible encephalopathy syndrome. It typically involves the posterior supratentorial structures, but variations do occur. However, isolated brainstem involvement in HE is rare, with a few cases reported in the literature. Herein, we report a case of acute hypertensive brainstem encephalopathy in which the patient had mild symptoms with very high blood pressure and normal neurological examination. The computed tomography of the brain showed diffuse hypodensity at brainstem. The patient's symptoms improved drastically after hypertension had been controlled. Marked clinical-radiologic dissociation in this particular case was highly suggestive of hypertensive brainstem encephalopathy. Prompt recognition of the condition and aggressive treatment of hypertension in such patients is crucial to relieve oedema and to prevent life-threatening progression. Nevertheless, there is still a lack of awareness among physicians and radiologists regarding this rare clinical entity.
    MeSH terms: Antihypertensive Agents/therapeutic use; Humans; Hypertension/diagnosis; Hypertension/drug therapy; Male; Middle Aged; Tomography, X-Ray Computed; Posterior Leukoencephalopathy Syndrome*
  17. Tong CV
    Clin Med (Lond), 2019 Nov;19(6):536.
    PMID: 31732607 DOI: 10.7861/clinmed.Let-19-6-1b
    MeSH terms: Diabetes Mellitus, Type 1*; Humans; Diabetic Ketoacidosis*
  18. Ting CY, Liew SM, Price A, Gan GG, Bee-Lan Ong D, Tan SY, et al.
    Crit Rev Oncol Hematol, 2019 Dec;144:102818.
    PMID: 31733445 DOI: 10.1016/j.critrevonc.2019.102818
    The clinical significance of aberrantly expressed microRNAs in predicting treatment response to chemotherapy in diffuse large B-cell lymphoma patients (DLBCL) remains uncertain. Feasibility of microRNA testing to predict treatment outcome was evaluated. Twenty-two types of aberrantly expressed microRNAs were associated with poor treatment response; pooled hazard ratio (HR) was 2.14 [95%CI:1.78-2.57, P 
    MeSH terms: Humans; Neoplasm Recurrence, Local; Prognosis; Biomarkers, Tumor; Gene Expression Regulation, Neoplastic; Proportional Hazards Models; Lymphoma, Large B-Cell, Diffuse*; MicroRNAs*
  19. Watts N, Amann M, Arnell N, Ayeb-Karlsson S, Belesova K, Boykoff M, et al.
    Lancet, 2019 Nov 16;394(10211):1836-1878.
    PMID: 31733928 DOI: 10.1016/S0140-6736(19)32596-6
    The Lancet Countdown is an international, multidisciplinary collaboration, dedicated to monitoring the evolving health profile of climate change, and providing an independent assessment of the delivery of commitments made by governments worldwide under the Paris Agreement. The 2019 report presents an annual update of 41 indicators across five key domains: climate change impacts, exposures, and vulnerability; adaptation, planning, and resilience for health; mitigation actions and health co-benefits; economics and finance; and public and political engagement. The report represents the findings and consensus of 35 leading academic institutions and UN agencies from every continent. Each year, the methods and data that underpin the Lancet Countdown’s indicators are further developed and improved, with updates described at each stage of this report. The collaboration draws on the world-class expertise of climate scientists; ecologists; mathematicians; engineers; energy, food, and transport experts; economists; social and political scientists; public health professionals; and doctors, to generate the quality and diversity of data required. The science of climate change describes a range of possible futures, which are largely dependent on the degree of action or inaction in the face of a warming world. The policies implemented will have far-reaching effects in determining these eventualities, with the indicators tracked here monitoring both the present-day effects of climate change, as well as the worldwide response. Understanding these decisions as a choice between one of two pathways—one that continues with the business as usual response and one that redirects to a future that remains “well below 2°C”—helps to bring the importance of recognising the effects of climate change and the necessary response to the forefront. Evidence provided by the Intergovernmental Panel on Climate Change, the International Energy Agency, and the US National Aeronautics and Space Administration clarifies the degree and magnitude of climate change experienced today and contextualises these two pathways.

    THE IMPACTS OF CLIMATE CHANGE ON HUMAN HEALTH: The world has observed a 1°C temperature rise above pre-industrial levels, with feedback cycles and polar amplification resulting in a rise as high as 3°C in north western Canada., Eight of the ten hottest years on record have occurred in the past decade. Such rapid change is primarily driven by the combustion of fossil fuels, consumed at a rate of 171 000 kg of coal, 116 000 000 L of gas, and 186 000 L of oil per s.– Progress in mitigating this threat is intermittent at best, with carbon dioxide emissions continuing to rise in 2018. Importantly, many of the indicators contained in this report suggest the world is following this “business as usual” pathway. The carbon intensity of the energy system has remained unchanged since 1990 (indicator 3.1.1), and from 2016 to 2018, total primary energy supply from coal increased by 1·7%, reversing a previously recorded downward trend (indicator 3.1.2). Correspondingly, the health-care sector is responsible for about 4·6% of global emissions, a value which is steadily rising across most major economies (indicator 3.6). Global fossil fuel consumption subsidies increased by 50% over the past 3 years, reaching a peak of almost US$430 billion in 2018 (indicator 4.4.1). A child born today will experience a world that is more than four degrees warmer than the pre-industrial average, with climate change impacting human health from infancy and adolescence to adulthood and old age. Across the world, children are among the worst affected by climate change. Downward trends in global yield potential for all major crops tracked since 1960 threaten food production and food security, with infants often the worst affected by the potentially permanent effects of undernutrition (indicator 1.5.1). Children are among the most susceptible to diarrhoeal disease and experience the most severe effects of dengue fever. Trends in climate suitability for disease transmission are particularly concerning, with nine of the ten most suitable years for the transmission of dengue fever on record occurring since 2000 (indicator 1.4.1). Similarly, since an early 1980s baseline, the number of days suitable for Vibrio (a pathogen responsible for part of the burden of diarrhoeal disease) has doubled, and global suitability for coastal Vibrio cholerae has increased by 9·9% indicator 1.4.1). Through adolescence and beyond, air pollution—principally driven by fossil fuels, and exacerbated by climate change—damages the heart, lungs, and every other vital organ. These effects accumulate over time, and into adulthood, with global deaths attributable to ambient fine particulate matter (PM2·5) remaining at 2·9 million in 2016 (indicator 3.3.2) and total global air pollution deaths reaching 7 million. Later in life, families and livelihoods are put at risk from increases in the frequency and severity of extreme weather conditions, with women among the most vulnerable across a range of social and cultural contexts. Globally, 77% of countries experienced an increase in daily population exposure to wildfires from 2001–14 to 2015–18 (indicator 1.2.1). India and China sustained the largest increases, with an increase of over 21 million exposures in India and 17 million exposures in China over this time period. In low-income countries, almost all economic losses from extreme weather events are uninsured, placing a particularly high burden on individuals and households (indicator 4.1). Temperature rise and heatwaves are increasingly limiting the labour capacity of various populations. In 2018, 133·6 billion potential work hours were lost globally, 45 billion more than the 2000 baseline, and southern areas of the USA lost 15–20% of potential daylight work hours during the hottest month of 2018 (indicator 1.1.4). Populations aged 65 years and older are particularly vulnerable to the health effects of climate change, and especially to extremes of heat. From 1990 to 2018, populations in every region have become more vulnerable to heat and heatwaves, with Europe and the Eastern Mediterranean remaining the most vulnerable (indicator 1.1.1). In 2018, these vulnerable populations experienced 220 million heatwave exposures globally, breaking the previous record of 209 million set in 2015 (indicator 1.1.3). Already faced with the challenge of an ageing population, Japan had 32 million heatwave exposures affecting people aged 65 years and older in 2018, the equivalent of almost every person in this age group experiencing a heatwave. Finally, although difficult to quantify, the downstream risks of climate change, such as migration, poverty exacerbation, violent conflict, and mental illness, affect people of all ages and all nationalities. A business as usual trajectory will result in a fundamentally altered world, with the indicators described providing a glimpse of the implications of this pathway. The life of every child born today will be profoundly affected by climate change. Without accelerated intervention, this new era will come to define the health of people at every stage of their lives.

    RESPONDING TO CLIMATE CHANGE FOR HEALTH: The Paris Agreement has set a target of “holding the increase in the global average temperature to well below 2°C above pre-industrial levels and pursuing efforts to limit the temperature increase to 1·5°C.” In a world that matches this ambition, a child born today would see the phase-out of all coal in the UK and Canada by their sixth and 11th birthday; they would see France ban the sale of petrol and diesel cars by their 21st birthday; and they would be 31 years old by the time the world reaches net-zero in 2050, with the UK’s recent commitment to reach this goal one of many to come. The changes seen in this alternate pathway could result in cleaner air, safer cities, and more nutritious food, coupled with renewed investment in health systems and vital infrastructure. This second path—which limits the global average temperature rise to “well below 2°C”—is possible, and would transform the health of a child born today for the better, right the way through their life. Considering the evidence available in the 2019 indicators, such a transition could be beginning to unfold. Despite a small increase in coal use in 2018, in key countries such as China, it continued to decrease as a share of electricity generation (indicator 3.1.2). Correspondingly, renewables accounted for 45% of global growth in power generation capacity that year, and low-carbon electricity reached a high of 32% of global electricity in 2016 (indicator 3.1.3). Global per capita use of electric vehicles increased by 20·6% between 2015 and 2016, and now represents 1·8% of China’s total transportation fuel use (indicator 3.4). Improvements in air pollution seen in Europe from 2015 to 2016, could result in a reduction of Years of Life Lost (YLL) worth €5·2 billion annually, if this reduction remained constant across a lifetime (indicator 4.2). In several cases, the economic savings from a healthier and more productive workforce, with fewer health-care expenses, will cover the initial investment costs of these interventions. Similarly, cities and health systems are becoming more resilient to the effects of climate change; about 50% of countries and 69% of cities surveyed reported efforts to conduct national health adaptation plans or climate change risk assessments (indicators 2.1.1, 2.1.2, and 2.1.3). These plans are now being implemented, with the number of countries providing climate services to the health sector increasing from 55 in 2018 to 70 in 2019 (indicator 2.2) and 109 countries reporting medium to high implementation of a national health emergency framework (indicator 2.3.1). Growing demand is coupled with a steady increase in health adaptation spending, which represents 5% (£13 billion) of total adaptation funding in 2018 and has increased by 11·8% over the past 12 months (indicator 2.4). This increase is in part funded by growing revenues from carbon pricing mechanisms, with a 30% increase to US$43 billion in funds raised between 2017 and 2018 (indicator 4.4.3). However, current progress is inadequate, and despite the beginnings of the transition described, the indicators published in the Lancet Countdown’s 2019 report are suggestive of a world struggling to cope with warming that is occurring faster than governments are able, or willing to respond. Opportunities are being missed, with the Green Climate Fund yet to receive projects specifically focused on improving climate-related public health, despite the fact that in other forums, leaders of small island developing states are recognising the links between health and climate change (indicator 5.3). In response, the generation that will be most affected by climate change has led a wave of school strikes across the world. Bold new approaches to policy making, research, and business are needed in order to change course. An unprecedented challenge demands an unprecedented response, and it will take the work of the 7·5 billion people currently alive to ensure that the health of a child born today is not defined by a changing climate.

    MeSH terms: Child Health*; Communicable Diseases/epidemiology; Conservation of Natural Resources; Delivery of Health Care/methods; Food Supply/statistics & numerical data; Health Policy; Humans; International Cooperation; Weather; Global Health*; Malnutrition/epidemiology; Extreme Heat/adverse effects; Climate Change*
  20. Tan YH, Lim PE, Beardall J, Poong SW, Phang SM
    Aquat Toxicol, 2019 Dec;217:105349.
    PMID: 31734626 DOI: 10.1016/j.aquatox.2019.105349
    Ocean acidification, due to increased levels of anthropogenic carbon dioxide, is known to affect the physiology and growth of marine phytoplankton, especially in polar regions. However, the effect of acidification or carbonation on cellular metabolism in polar marine phytoplankton still remains an open question. There is some evidence that small chlorophytes may benefit more than other taxa of phytoplankton. To understand further how green polar picoplankton could acclimate to high oceanic CO2, studies were conducted on an Antarctic Chlorella sp. Chlorella sp. maintained its growth rate (∼0.180 d-1), photosynthetic quantum yield (Fv/Fm = ∼0.69) and chlorophyll a (0.145 fg cell-1) and carotenoid (0.06 fg cell-1) contents under high CO2, while maximum rates of electron transport decreased and non-photochemical quenching increased under elevated CO2. GCMS-based metabolomic analysis reveal that this polar Chlorella strain modulated the levels of metabolites associated with energy, amino acid, fatty acid and carbohydrate production, which could favour its survival in an increasingly acidified ocean.
    MeSH terms: Acclimatization/drug effects; Amino Acids/biosynthesis; Antarctic Regions; Carbon Dioxide/analysis; Carbon Dioxide/toxicity; Chlorella/drug effects; Chlorella/metabolism*; Electron Transport/drug effects; Fatty Acids/biosynthesis; Hydrogen-Ion Concentration; Oceans and Seas; Photosynthesis/drug effects; Seawater/chemistry*; Water Pollutants, Chemical/analysis; Water Pollutants, Chemical/toxicity; Metabolomics; Metabolome/drug effects*; Microalgae/drug effects; Microalgae/metabolism*
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