Browse publications by year: 2020

  1. Vallavan V, Krishnasamy G, Zin NM, Abdul Latif M
    Molecules, 2020 Dec 11;25(24).
    PMID: 33322256 DOI: 10.3390/molecules25245848
    Fungi are a rich source of secondary metabolites with several pharmacological activities such as antifungal, antioxidant, antibacterial and anticancer to name a few. Due to the large number of diverse structured chemical compounds they produce, fungi from the phyla Ascomycota, Basidiomycota and Muccoromycota have been intensively studied for isolation of bioactive compounds. Basidiomycetes-derived secondary metabolites are known as a promising source of antibacterial compounds with activity against Gram-positive bacteria. The continued emergence of antimicrobial resistance (AMR) poses a major challenge to patient health as it leads to higher morbidity and mortality, higher hospital-stay duration and substantial economic burden in global healthcare sector. One of the key culprits for AMR crisis is Staphylococcus aureus causing community-acquired infections as the pathogen develops resistance towards multiple antibiotics. The recent emergence of community strains of S. aureus harbouring methicillin-resistant (MRSA), vancomycin-intermediate (VISA) and vancomycin-resistant (VRSA) genes associated with increased virulence is challenging. Despite the few significant developments in antibiotic research, successful MRSA therapeutic options are still needed to reduce the use of scanty and expensive second-line treatments. This paper provides an overview of findings from various studies on antibacterial secondary metabolites from basidiomycetes, with a special focus on antistaphylococcal activity.
    MeSH terms: Animals; Anti-Bacterial Agents/pharmacology; Ascomycota/metabolism; Basidiomycota/metabolism*; Biological Products; Chemistry, Pharmaceutical/methods; Humans; Microbial Sensitivity Tests; Staphylococcal Infections/drug therapy*; Staphylococcal Infections/microbiology; Staphylococcus aureus/drug effects*; Vancomycin; Community-Acquired Infections/microbiology; Drug Resistance, Bacterial*; Methicillin-Resistant Staphylococcus aureus
  2. Radzali SA, Markom M, Saleh NM
    Molecules, 2020 Dec 11;25(24).
    PMID: 33322389 DOI: 10.3390/molecules25245859
    A preliminary study was conducted to study the effects of different types and concentrations of co-solvents based on yield, composition and antioxidants capacity of extract prior to optimization studies of supercritical fluid extraction (SFE) of Labisia pumila (locally referred to as 'kacip fatimah'). The following co-solvents were studied prior to the optimization of supercritical carbon dioxide (SC-CO2) technique: ethanol, water, methanol, as well as aqueous solutions of ethanol-water and methanol-water (50% and 70% v/v). By using the selected co-solvents, identification of phenolic acids (gallic acid, methyl gallate and caffeic acid) was determined by using High-Performance Liquid Chromatography (HPLC). Then, the antioxidant capacity was evaluated by using three different assays: total phenolic content (TPC), ferric reducing/antioxidant power (FRAP) and free radical-scavenging capacity of 2,2-diphenyl-1-picrylhydrazyl (DPPH). SC-CO2 with 70% ethanol-water co-solvent was superior in terms of a higher combination of phenolic compounds extracted and antioxidants capacity. Overall, SC-CO2 with co-solvent 70% ethanol-water technique was efficient in extracting phenolic compounds from L. pumila, and thus the usage of this solvent system should be considered for further optimization studies.
    MeSH terms: Ethanol/chemistry; Antioxidants/chemistry*; Biphenyl Compounds; Chromatography, High Pressure Liquid; Materials Testing; Microscopy, Electron, Scanning; Phenols/chemistry*; Picrates; Plant Extracts; Solvents/chemistry*; Water; Free Radical Scavengers; Plant Leaves; Inhibitory Concentration 50; Chromatography, Supercritical Fluid/methods*; Primulaceae/metabolism*; Hydroxybenzoates/chemistry
  3. Phang WK, Hamid MHA, Jelip J, Mudin RN, Chuang TW, Lau YL, et al.
    PMID: 33322414 DOI: 10.3390/ijerph17249271
    The life-threatening zoonotic malaria cases caused by Plasmodium knowlesi in Malaysia has recently been reported to be the highest among all malaria cases; however, previous studies have mainly focused on the transmission of P. knowlesi in Malaysian Borneo (East Malaysia). This study aimed to describe the transmission patterns of P. knowlesi infection in Peninsular Malaysia (West Malaysia). The spatial distribution of P. knowlesi was mapped across Peninsular Malaysia using Geographic Information System techniques. Local indicators of spatial associations were used to evaluate spatial patterns of P. knowlesi incidence. Seasonal autoregressive integrated moving average models were utilized to analyze the monthly incidence of knowlesi malaria in the hotspot region from 2012 to 2017 and to forecast subsequent incidence in 2018. Spatial analysis revealed that hotspots were clustered in the central-northern region of Peninsular Malaysia. Time series analysis revealed the strong seasonality of transmission from January to March. This study provides fundamental information on the spatial distribution and temporal dynamic of P. knowlesi in Peninsular Malaysia from 2011 to 2018. Current control policy should consider different strategies to prevent the transmission of both human and zoonotic malaria, particularly in the hotspot region, to ensure a successful elimination of malaria in the future.
    MeSH terms: Adolescent; Adult; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Malaysia/epidemiology; Male; Middle Aged; Plasmodium knowlesi*; Young Adult; Spatio-Temporal Analysis
  4. Abdul Halim SI, Chan CH, Kressler J
    Polymers (Basel), 2020 Dec 11;12(12).
    PMID: 33322501 DOI: 10.3390/polym12122963
    The studies of phase behavior, dielectric relaxation, and other properties of poly(ethylene oxide) (PEO)/poly(methyl acrylate) (PMA) blends with the addition of lithium perchlorate (LiClO4) were done for different blend compositions. Samples were prepared by a solution casting technique. The binary PEO/PMA blends exhibit a single and compositional-dependent glass transition temperature (Tg), which is also true for ternary mixtures of PEO/PMA/LiClO4 when PEO was in excess with low content of salt. These may indicate miscibility of the constituents for the molten systems and amorphous domains of the systems at room temperature from the macroscopic point of view. Subsequently, the morphology of PEO/PMA blends with or without salt are correlated to the phase behavior of the systems. Phase morphology and molecular interaction of polymer chains by salt ions of the systems may rule the dielectric or electric relaxation at room temperature, which was estimated using electrochemical impedance spectroscopy (EIS). The frequency-dependent impedance spectra are of interest for the elucidation of polarization and relaxation of the charged entities for the systems. Relaxation can be noted only when a sufficient amount of salt is added into the systems.
    MeSH terms: Acrylates; Ethylene Oxide; Ions; Perchlorates; Polyethylene Glycols; Polymers; Temperature; Electric Impedance; Lithium Compounds; Transition Temperature; Dielectric Spectroscopy
  5. Toopkanloo SP, Tan TB, Abas F, Azam M, Nehdi IA, Tan CP
    Molecules, 2020 Dec 11;25(24).
    PMID: 33322600 DOI: 10.3390/molecules25245873
    In order to improve the membrane lipophilicity and the affinity towards the environment of lipid bilayers, squalene (SQ) could be conjugated to phospholipids in the formation of liposomes. The effect of membrane composition and concentrations on the degradation of liposomes prepared via the extrusion method was investigated. Liposomes were prepared using a mixture of SQ, cholesterol (CH) and Tween80 (TW80). Based on the optimal conditions, liposome batches were prepared in the absence and presence of SQ. Their physicochemical and stability behavior were evaluated as a function of liposome constituent. From the optimization study, the liposomal formulation containing 5% (w/w) mixed soy lecithin (ML), 0.5% (w/w) SQ, 0.3% (w/w) CH and 0.75% (w/w) TW80 had optimal physicochemical properties and displayed a unilamellar structure. Liposome prepared using the optimal formulation had a low particle size (158.31 ± 2.96 nm) and acceptable %increase in the particle size (15.09% ± 3.76%) and %trolox equivalent antioxidant capacity (%TEAC) loss (35.69% ± 0.72%) against UV light treatment (280-320 nm) for 6 h. The interesting outcome of this research was the association of naturally occurring substance SQ for size reduction without the extra input of energy or mechanical procedures, and improvement of vesicle stability and antioxidant activity of ML-based liposome. This study also demonstrated that the presence of SQ in the membrane might increase the acyl chain dynamics and decrease the viscosity of the dispersion, thereby limiting long-term stability of the liposome.
    MeSH terms: Antioxidants/chemistry; Chemistry, Pharmaceutical; Cholesterol/chemistry; Drug Stability; Light; Lipid Bilayers; Liposomes/chemistry*; Particle Size; Phospholipids/chemistry; Soybeans/metabolism*; Squalene/chemistry*; Ultraviolet Rays; Viscosity; X-Ray Diffraction; Spectroscopy, Fourier Transform Infrared; Microscopy, Electron, Transmission; Lecithins/chemistry*
  6. Srivastava KC, Shrivastava D, Nagarajappa AK, Khan ZA, Alzoubi IA, Mousa MA, et al.
    PMID: 33322604 DOI: 10.3390/ijerph17249293
    The detection of pulp stone in a patient suffering from undiagnosed systemic diseases can be an early diagnostic indicator. Thus, the aim of the study was to assess the prevalence of pulp stones in the Saudi Arabian population with cardiovascular diseases and diabetes mellitus. In a retrospective study, we included cone-beam computed tomography (CBCT) scans of 73 patients with cardiovascular disease and 76 patients with diabetes mellitus as group I and II, respectively. Group III comprised of CBCT scan of 80 healthy controls. From a total of 229 scans, 4807 teeth were screened for pulp stones throughout the arches. A chi-square test was used for comparing the prevalence of pulp stones among the groups. Univariable and multivariable analysis was done to evaluate the independent risk indicators for pulp stones. The tooth-wise prevalence of pulp stones in group I, II, and III was found to be 16.65%, 9.01%, and 3.86%, respectively. Patient-wise (p < 0.01) and tooth-wise (p < 0.01) prevalence was recorded significantly highest in the cardiovascular group followed by the diabetic group. The control group had the least prevalence. Significantly (p < 0.01) higher number of pulp stones were found in cardiovascular patients with age > 50 years compared to other groups. Similarly, a significantly increased number of pulp stones were seen in the 1st molar (p < 0.05) and the maxillary jaw (p < 0.05) of patients with cardiovascular diseases. Subjects with cardiovascular disease and diabetes were found to have 2.94 times (p < 0.001; CI 1.54-3.10) and 1.81 times (p < 0.01; CI 0.48-2.06) higher risk of having pulp stones in comparison to healthy subjects. The first molar has 2.20 times (p < 0.001; CI 0.84-2.45) increased the risk of having pulp stones compared to other tooth types. Systemic disease such as cardiovascular disease and diabetes mellitus poses a higher risk for the development of pulp stones. Among the systemic disease group, patients in the cardiovascular group showed a higher risk for pulp stones and also reported the maximum number of pulp stones compared to the diabetic and healthy subjects.
    MeSH terms: Adult; Dental Pulp Calcification/epidemiology*; Female; Humans; Male; Middle Aged; Retrospective Studies; Saudi Arabia/epidemiology; Prevalence; Case-Control Studies; Spiral Cone-Beam Computed Tomography*; Young Adult
  7. Higashi SL, Rozi N, Hanifah SA, Ikeda M
    Int J Mol Sci, 2020 Dec 12;21(24).
    PMID: 33322664 DOI: 10.3390/ijms21249458
    Supramolecular architectures that are built artificially from biomolecules, such as nucleic acids or peptides, with structural hierarchical orders ranging from the molecular to nano-scales have attracted increased attention in molecular science research fields. The engineering of nanostructures with such biomolecule-based supramolecular architectures could offer an opportunity for the development of biocompatible supramolecular (nano)materials. In this review, we highlighted a variety of supramolecular architectures that were assembled from both nucleic acids and peptides through the non-covalent interactions between them or the covalently conjugated molecular hybrids between them.
    MeSH terms: Nucleic Acids/ultrastructure; Nucleic Acids/chemistry*; Peptides/chemistry*; Protein Structure, Secondary; Protein Structure, Tertiary; Peptide Nucleic Acids/ultrastructure; Peptide Nucleic Acids/chemistry*; Nanotechnology/methods*; Microscopy, Electron, Transmission; Nanostructures/ultrastructure; Nanostructures/chemistry*; Hydrophobic and Hydrophilic Interactions
  8. Rosli NHM, Yahya HM, Ibrahim FW, Shahar S, Ismail IS, Azam AA, et al.
    Nutrients, 2020 Dec 12;12(12).
    PMID: 33322743 DOI: 10.3390/nu12123812
    Functional foods such as pomegranate, dates and honey were shown by various previous studies to individually have a neuroprotective effect, especially in neurodegenerative disease such as Alzheimer's disease (AD). In this novel and original study, an 1H NMR spectroscopy tool was used to identify the metabolic neuroprotective mechanism of commercially mixed functional foods (MFF) consisting of pomegranate, dates and honey, in rats injected with amyloid-beta 1-42 (Aβ-42). Forty-five male albino Wistar rats were randomly divided into five groups: NC (0.9% normal saline treatment + phosphate buffer solution (PBS) solution injection), Abeta (0.9% normal saline treatment + 0.2 µg/µL Aβ-42 injection), MFF (4 mL/kg MFF treatment + PBS solution injection), Abeta-MFF (4 mL/kg MFF treatment + 0.2 µg/µL Aβ-42 injection) and Abeta-NAC (150 mg/kg N-acetylcysteine + 0.2 µg/µL Aβ-42 injection). Based on the results, the MFF and NAC treatment improved the spatial memory and learning using Y-maze. In the metabolic analysis, a total of 12 metabolites were identified, for which levels changed significantly among the treatment groups. Systematic metabolic pathway analysis found that the MFF and NAC treatments provided a neuroprotective effect in Aβ-42 injected rats by improving the acid amino and energy metabolisms. Overall, this finding showed that MFF might serve as a potential neuroprotective functional food for the prevention of AD.
    MeSH terms: Animals; Disease Models, Animal; Honey*; Male; Magnetic Resonance Spectroscopy/methods; Amyloid beta-Peptides/administration & dosage*; Rats, Wistar; Neurodegenerative Diseases/blood*; Neurodegenerative Diseases/diet therapy*; Neurodegenerative Diseases/prevention & control; Rats; Metabolomics/methods; Functional Food*; Phoeniceae/metabolism*
  9. Nipun TS, Khatib A, Ibrahim Z, Ahmed QU, Redzwan IE, Saiman MZ, et al.
    Molecules, 2020 Dec 12;25(24).
    PMID: 33322801 DOI: 10.3390/molecules25245885
    Psychotria malayana Jack has traditionally been used to treat diabetes. Despite its potential, the scientific proof in relation to this plant is still lacking. Thus, the present study aimed to investigate the α-glucosidase inhibitors in P.malayana leaf extracts using a metabolomics approach and to elucidate the ligand-protein interactions through in silico techniques. The plant leaves were extracted with methanol and water at five various ratios (100, 75, 50, 25 and 0% v/v; water-methanol). Each extract was tested for α-glucosidase inhibition, followed by analysis using liquid chromatography tandem to mass spectrometry. The data were further subjected to multivariate data analysis by means of an orthogonal partial least square in order to correlate the chemical profile and the bioactivity. The loading plots revealed that the m/z signals correspond to the activity of α-glucosidase inhibitors, which led to the identification of three putative bioactive compounds, namely 5'-hydroxymethyl-1'-(1, 2, 3, 9-tetrahydro-pyrrolo (2, 1-b) quinazolin-1-yl)-heptan-1'-one (1), α-terpinyl-β-glucoside (2), and machaeridiol-A (3). Molecular docking of the identified inhibitors was performed using Auto Dock Vina software against the crystal structure of Saccharomyces cerevisiae isomaltase (Protein Data Bank code: 3A4A). Four hydrogen bonds were detected in the docked complex, involving several residues, namely ASP352, ARG213, ARG442, GLU277, GLN279, HIE280, and GLU411. Compound 1, 2, and 3 showed binding affinity values of -8.3, -7.6, and -10.0 kcal/mol, respectively, which indicate the good binding ability of the compounds towards the enzyme when compared to that of quercetin, a known α-glucosidase inhibitor. The three identified compounds that showed potential binding affinity towards the enzymatic protein in molecular docking interactions could be the bioactive compounds associated with the traditional use of this plant.
    MeSH terms: alpha-Glucosidases/metabolism*; Computer Simulation; Plant Extracts/isolation & purification; Plant Extracts/pharmacology*; Plant Extracts/chemistry; Molecular Structure; Multivariate Analysis; Plant Leaves/chemistry; Psychotria/chemistry*; Metabolomics; Molecular Docking Simulation; Glycoside Hydrolase Inhibitors/isolation & purification*; Glycoside Hydrolase Inhibitors/pharmacology; Glycoside Hydrolase Inhibitors/chemistry
  10. Kurniawan SB, Abdullah SRS, Imron MF, Said NSM, Ismail N', Hasan HA, et al.
    Int J Environ Res Public Health, 2020 Dec 12;17(24).
    PMID: 33322826 DOI: 10.3390/ijerph17249312
    The utilization of metal-based conventional coagulants/flocculants to remove suspended solids from drinking water and wastewater is currently leading to new concerns. Alarming issues related to the prolonged effects on human health and further pollution to aquatic environments from the generated nonbiodegradable sludge are becoming trending topics. The utilization of biocoagulants/bioflocculants does not produce chemical residue in the effluent and creates nonharmful, biodegradable sludge. The conventional coagulation-flocculation processes in drinking water and wastewater treatment, including the health and environmental issues related to the utilization of metal-based coagulants/flocculants during the processes, are discussed in this paper. As a counterpoint, the development of biocoagulants/bioflocculants for drinking water and wastewater treatment is intensively reviewed. The characterization, origin, potential sources, and application of this green technology are critically reviewed. This review paper also provides a thorough discussion on the challenges and opportunities regarding the further utilization and application of biocoagulants/bioflocculants in water and wastewater treatment, including the importance of the selection of raw materials, the simplification of extraction processes, the application to different water and wastewater characteristics, the scaling up of this technology to a real industrial scale, and also the potential for sludge recovery by utilizing biocoagulants/bioflocculants in water/wastewater treatment.
    MeSH terms: Animals; Bacillaceae; Bacillus; Chlorella*; Chromobacterium; Flocculation; Humans; Sewage; Waste Disposal, Fluid; Water Purification*; Paenibacillus; Drinking Water*; Waste Water
  11. Zeng H, Wu M, Wang HQ, Zheng JC, Kang J
    Materials (Basel), 2020 Dec 12;13(24).
    PMID: 33322841 DOI: 10.3390/ma13245686
    The magnetic and electronic properties of boron-doped SrTiO3 have been studied by first-principles calculations. We found that the magnetic ground states of B-doped SrTiO3 strongly depended on the dopant-dopant separation distance. As the dopant-dopant distance varied, the magnetic ground states of B-doped SrTiO3 can have nonmagnetic, ferromagnetic or antiferromagnetic alignment. The structure with the smallest dopant-dopant separation exhibited the lowest total energy among all configurations considered and was characterized by dimer pairs due to strong attraction. Ferromagnetic coupling was observed to be stronger when the two adjacent B atoms aligned linearly along the B-Ti-B axis, which could be associated with their local bonding structures. Therefore, the symmetry of the local structure made an important contribution to the generation of a magnetic moment. Our study also demonstrated that the O-Ti-O unit was easier than the Ti-B-Ti unit to deform. The electronic properties of boron-doped SrTiO3 tended to show semiconducting or insulating features when the dopant-dopant distance was less than 5 Å, which changed to metallic properties when the dopant-dopant distance was beyond 5 Å. Our calculated results indicated that it is possible to manipulate the magnetism and band gap via different dopant-dopant separations.
    MeSH terms: Boron; Electronics; Family Characteristics; Oxides; Strontium; Titanium; Physical Phenomena; Magnetic Phenomena
  12. Ekeuku SO, Thong BKS, Quraisiah A, Annuar F, Hanafiah A, Nur Azlina MF, et al.
    Drug Des Devel Ther, 2020;14:5359-5366.
    PMID: 33324037 DOI: 10.2147/DDDT.S287239
    Purpose: Triple therapy is the standard therapy to eradicate Helicobacter pylori (H.pylori) infection. Chronic use of proton pump inhibitors (PPIs), a component of triple therapy, is associated with osteoporosis. However, the skeletal effects of short-term triple therapy containing PPI remain elusive. This study aims to determine the skeletal effect of short-term triple therapy in a rat model of gastric ulcer induced by H. pylori.

    Methods: Three-month-old male Sprague Dawley rats were assigned to normal control, H. pylori-inoculated group (negative control) and H. pylori-inoculated group receiving triple therapy consisting of omeprazole [2.035 mg/kg body weight (b.w)], amoxicillin (102.80 mg/kg b.w) and clarithromycin (51.37 mg/kg b.w) (n=6/group). H. pylori infection developed for four weeks after inoculation, followed by two-week triple therapy. At the end of the treatment period, femoral bones of the rats were harvested for analysis. Bone mineral density and content of the femurs were determined using dual-energy X-ray absorptiometry, while bone strength was measured with a universal mechanical tester.

    Results: Bone mineral content was significantly lower in the negative control group compared to the triple therapy group (p=0.014). Triple therapy decreased strain (vs negative control, p=0.002) and displacement of the femur (vs normal control, p=0.004; vs untreated control, p=0.005). No significant difference was observed in other parameters among the study groups (p>0.05).

    Conclusion: Short-term triple therapy increases bone mineral content but decreases bone strength of rats. Skeletal prophylaxis should be considered for patients on short-term triple therapy containing PPI.

    MeSH terms: Animals; Anti-Ulcer Agents/pharmacology*; Anti-Bacterial Agents/pharmacology*; Bone and Bones/drug effects*; Bone and Bones/pathology; Drug Therapy, Combination; Male; Helicobacter pylori/drug effects*; Helicobacter Infections/drug therapy*; Rats, Sprague-Dawley; Rats
  13. Mohd Zaffarin AS, Ng SF, Ng MH, Hassan H, Alias E
    Int J Nanomedicine, 2020;15:9961-9974.
    PMID: 33324057 DOI: 10.2147/IJN.S276355
    Vitamin E belongs to the family of lipid-soluble vitamins and can be divided into two groups, tocopherols and tocotrienols, with four isomers (alpha, beta, gamma and delta). Although vitamin E is widely known as a potent antioxidant, studies have also revealed that vitamin E possesses anti-inflammatory properties. These crucial properties of vitamin E are beneficial in various aspects of health, especially in neuroprotection and cardiovascular, skin and bone health. However, the poor bioavailability of vitamin E, especially tocotrienols, remains a great limitation for clinical applications. Recently, nanoformulations that include nanovesicles, solid-lipid nanoparticles, nanostructured lipid carriers, nanoemulsions, and polymeric nanoparticles have shown promising outcomes in improving the efficacy and bioavailability of vitamin E. This review focuses on the pharmacological properties and pharmacokinetics of vitamin E and current advances in vitamin E nanoformulations for future clinical applications. The limitations and future recommendations are also discussed in this review.
    MeSH terms: Biological Availability; Drug Compounding; Humans; Vitamin E/pharmacokinetics*; Vitamin E/pharmacology*; Vitamin E/chemistry; Nanostructures/chemistry*
  14. Elnaem MH, Mansour NO, Nahas AF, Baraka MA, Elkalmi R, Cheema E
    Int J Gen Med, 2020;13:1395-1409.
    PMID: 33324086 DOI: 10.2147/IJGM.S285191
    Background: This study aims to discuss, summarize and compare the renal outcomes associated with non-insulin antidiabetic (AD) pharmacotherapy prescribed for patients with type 2 diabetes mellitus (T2DM).

    Methods: A systematic search using predefined search terms in three scholarly databases, ScienceDirect, Google Scholar, and PubMed, was conducted. Original research articles published in the English language between 2012 and 2020 that reported renal outcomes associated with the use of non-insulin AD pharmacotherapy were eligible for inclusion. Review articles, meta-analysis studies, and conference proceedings were excluded. A study-specific data extraction form was designed to extract the author's name, country, publication year, study design, study population, objectives, key findings, and conclusions. A narrative review of the key findings that focused on renal outcomes and renal safety issues was conducted.

    Results: Of the 18,872 results identified through the initial search, a total of 32 articles were included in this review. Of these, 18 of the included articles reported the renal outcomes of newer antidiabetic medications, eg, SGLT2 inhibitors and GLP-1 agonists. Eight studies focussed on the well-established antidiabetic medications, eg, metformin and sulphonylureas. The review reported three main types of the clinical impact of the prescribed AD on the renal outcomes: "renoprotective effects", "no additional risk" and "associated with a decline in renal parameters". Seventeen studies reported the renoprotective effects of AD, including SGLT2i studies (n=8), GLP1 studies (n=6), and DPP4i studies (n=3). The reported renoprotective effects included slowing down the GFR decline, improving albuminuria, and reducing renal adverse events. The "no additional risk" impact was reported in eight studies, including DPP4i studies (n=3), two SGLT2i studies (n=2), metformin studies (n=2), and one study involving pioglitazone. Furthermore, seven studies highlighted the "associated with a decline in renal parameters" effect. Of these, three involved SGLT2i, two with metformin, and one for each DPP4i and sulphonylurea.

    Conclusion: More than half of the studies included in this review supported the renoprotective effects associated with the use of AD medications, particularly GLP-1A, SGLT2i, and some of the DPP4i. Further studies involving patients with various stages of chronic kidney disease (CKD) are required to compare AD medications' renal effects, particularly the newer agents.

    MeSH terms: Albuminuria; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Language; Metformin; Peptide Fragments; Plant Extracts; Sulfonylurea Compounds; PubMed; Renal Insufficiency, Chronic; Glucagon-Like Peptide 1
  15. Cheema E, McGuinness K, Hadi MA, Paudyal V, Elnaem MH, Alhifany AA, et al.
    J Pain Res, 2020;13:3281-3294.
    PMID: 33324089 DOI: 10.2147/JPR.S280462
    PURPOSE: Fentanyl poisoning has been widely reported, yet there is a lack of systematic evaluation of the nature and toxicology of associated deaths in the published literature. This article aims to systematically review the nature, causes, routes of administration and toxicology of fentanyl-associated deaths using case studies and case series in peer-reviewed published literature.

    METHODS: Four electronic databases including Embase, Medline (via Ovid), Scopus and Google Scholar were searched from inception until October 2019 to identify the studies reporting fentanyl related deaths. Two independent reviewers screened and selected the titles and then evaluated the full texts. Only case studies and case series were included. A structured data extraction tool was used to extract data on the number of deaths, routes of administration, concomitant drug use and toxicological data. The Joanna Briggs Institute quality assessment tool was used to evaluate the quality of included studies. Data were synthesized narratively.

    RESULTS: Of 1251 articles identified during initial search, 8 case reports and 9 case series met the inclusion criteria. A total of 1969 deaths were reported in the included studies. Deaths were concentrated in the north American region (n = 1946) and the Nordic region (n = 22). Reported causes of death included fentanyl overdose (n = 321, 56.4%), mixed drug toxicity (n = 196, 34.5%), natural (n = 28, 4.9%), other drug toxicity (n = 10, 1.8%), fentanyl and ethanol intoxication (n = 8, 1.4%), incidental (n = 5, <1%) and aspiration (n = 1). Most common routes of use were intravenous (70.5%) and transdermal routes (23.0%). Deaths came swiftly via the intravenous route. Mean level of blood fentanyl amongst all reported deaths was 0.024 µg/mL.

    CONCLUSION: Literature related to fentanyl-associated deaths predominantly come from North America. Deaths are comparatively lower or not reported in peer-reviewed publications from the rest of the world. Abuse through intravenous administration, mixed drug toxicities and self-treatment of breakthrough pain are mainly responsible for majority of the reported deaths.

  16. Mujib Kamal S, Babini MH, Krejcar O, Namazi H
    Front Physiol, 2020;11:602027.
    PMID: 33324242 DOI: 10.3389/fphys.2020.602027
    Walking is an everyday activity in our daily life. Because walking affects heart rate variability, in this research, for the first time, we analyzed the coupling among the alterations of the complexity of walking paths and heart rate. We benefited from the fractal theory and sample entropy to evaluate the influence of the complexity of paths on the complexity of heart rate variability (HRV) during walking. We calculated the fractal exponent and sample entropy of the R-R time series for nine participants who walked on four paths with various complexities. The findings showed a strong coupling among the alterations of fractal dimension (an indicator of complexity) of HRV and the walking paths. Besides, the result of the analysis of sample entropy also verified the obtained results from the fractal analysis. In further studies, we can analyze the coupling among the alterations of the complexities of other physiological signals and walking paths.
    MeSH terms: Activities of Daily Living; Algorithms; Heart Rate; Humans; Walking; Fractals; Entropy
  17. Singh D, Brown PN, Cinosi E, Corazza O, Henningfield JE, Garcia-Romeu A, et al.
    Front Psychiatry, 2020;11:574483.
    PMID: 33324252 DOI: 10.3389/fpsyt.2020.574483
    Kratom (Mitragyna speciosa Korth., Rubiaceae) is native to and has traditional use in Southeast Asia. The number of kratom users outside of Southeast Asia has increased significantly in recent decades with use spreading to the Unites States (US) and Europe. Because of its reputed opioid-like psychoactive effects at higher doses, kratom has been regulated in several countries and is subject to an import ban by the US Food and Drug Administration. Nonetheless, in the US it is estimated that 10-15 million people consume kratom primarily for the self-treatment of pain, psychiatric disorders, to mitigate withdrawal from or dependence on opioids, and to self-treat opioid use disorder or other substance use disorders (SUDs). Due to the global COVID-19 pandemic, a shortage in the supply of kratom products may place unexpected burdens on kratom users, potentially influencing some who use kratom for SUD self-treatment to regress to harmful drug use, hence increasing the likelihood of adverse outcomes, including overdose. Inadequate treatment, treatment barriers, and increases in the sales of adulterated kratom products on the internet or in convenience stores could exacerbate circumstances further. Although there are currently no verified indications of kratom scarcity, researchers and clinicians should be aware of and remain vigilant to this unanticipated possibility.
    MeSH terms: Analgesics, Opioid; Asia, Southeastern; Commerce; Europe; Humans; Opioid-Related Disorders; Pain; United States; United States Food and Drug Administration; Rubiaceae; Internet; Mitragyna; Pandemics; Drug Overdose
  18. Dieterich AV, Müller AM, Akksilp K, K C S, Dabak SV, Rouyard T
    BMJ Open Sport Exerc Med, 2020;6(1):e000909.
    PMID: 33324487 DOI: 10.1136/bmjsem-2020-000909
    BACKGROUND AND OBJECTIVE: Increasing rates of urbanisation have been accompanied by higher levels of sedentary behaviour (SB) and reduced physical activity (PA) worldwide. While physical inactivity has long been identified as a major risk factor for morbidity and mortality, increased concerns about the detrimental associations between SB and health has led to the development of many interventions aimed at reducing SB and/or promoting PA. Due to the prominence of sedentary time spent at work, the workplace has been identified as a key setting to implement such interventions. Building an evidence base of effective strategies to reduce SB and/or promote PA at work is needed to help reduce the health risks faced by many employees.

    METHODS AND ANALYSIS: We aim to conduct a review of reviews (RoR) to identify, evaluate and synthesise all systematic reviews (SRs) of workplace interventions aimed at reducing SB and/or promoting PA among adults. Systematic searches for relevant SRs will be conducted in six databases: Cochrane Systematic Review Database, Cumulative Index to Nursing & Allied Health Literature through EBSCOhost, EMBASE, PubMed including MEDLINE, Scopus and Web of Science. Selection for final inclusion and data extraction will be performed by two independent reviewers. SRs will be included if they assessed interventions aimed at reducing SB or promoting PA in the workplace, and if they report on changes in the respective behavioural outcomes in the occupational domain.

    DISCUSSION: This RoR will be valuable to policy-makers and employers who are looking for strategies to promote health at work. This will also allow potential research gaps to be identified, so that the design of future studies can be better informed.

    TRIAL REGISTERATION: This study has been registered with the PROSPERO International Prospective Register of Systematic Reviews (registration number CRD42020171774).

  19. Zahidi I, Wilson G, Brown K, Hou FKK
    J Health Pollut, 2020 Dec;10(28):201207.
    PMID: 33324504 DOI: 10.5696/2156-9614-10.28.201207
    Background: Rivers are susceptible to pollution and water pollution is a growing problem in low- and middle-income countries (LMIC) with rapid development and minimal environmental protections. There are universal pollutant threshold values, but they are not directly linked to river activities such as sand mining and aquaculture. Water quality modelling can support assessments of river pollution and provide information on this important environmental issue.

    Objectives: The objective of the present study was to demonstrate water quality modelling methodology in reviewing existing policies for Malaysian river catchments based on an example case study.

    Methods: The MIKE 11 software developed by the Danish Hydraulic Institute was used to model the main pollutant point sources within the study area - sand mining and aquaculture. Water quality data were obtained for six river stations from 2000 to 2015. All sand mining and aquaculture locations and approximate production capacities were quantified by ground survey. Modelling of the sand washing effluents was undertaken with the advection-dispersion module due to the nature of the fine sediment. Modelling of the fates of aquaculture deposits required both advection-dispersion and Danish Hydraulic Institute ECO Lab modules to simulate the detailed interactions between water quality determinants.

    Results: According to the Malaysian standard, biochemical oxygen command (BOD) and ammonium (NH4) parameters fell under Class IV at most of the river reaches, while the dissolved oxygen (DO) parameter varied between Classes II to IV. Total suspended solids (TSS) fell within Classes IV to V along the mid river reaches of the catchment.

    Discussion: Comparison between corresponding constituents and locations showed that the water quality model reproduced the long-term duration exceedance for the main body of the curves. However, the water quality model underestimated the infrequent high concentration observations. A standard effluent disposal was proposed for the development of legislation and regulations by authorities in the district that could be replicated for other similar catchments.

    Conclusions: Modelling pollutants enables observation of trends over the years and the percentage of time a certain class is exceeded for each individual pollutant. The catchment did not meet Class II requirements and may not be able to reach Class I without extensive improvements in the quality and reducing the quantity of both point and non-point effluent sources within the catchment.

    Competing Interests: The authors declare no competing financial interests.

    MeSH terms: Data Accuracy; Conservation of Natural Resources; Denmark; Developing Countries; Environmental Pollutants; Mining; Oxygen; Surveys and Questionnaires; Water; Water Pollution; Aquaculture; Rivers; Water Quality; Ammonium Compounds
  20. Akhtar A, Khan AH, Zainal H, Ahmad Hassali MA, Ali I, Ming LC
    Front Public Health, 2020;8:601961.
    PMID: 33324603 DOI: 10.3389/fpubh.2020.601961
    Background: Unnecessary antimicrobial use is an emerging problem throughout the world. To design future interventions to ensure rational antimicrobial use and decrease the risk of antimicrobial resistance, physician's knowledge and prescribing practices of antimicrobials should be assessed. Therefore, the main objective of this study is to investigate the physician's knowledge along with their prescribing patterns of antimicrobials in their health care system. Methods: The present qualitative study was conducted in a tertiary care public hospital located at Penang island, situated in Northwest of Malaysia. A total of 12 semi-structured, face to face interviews were conducted with purposive sampling technique. Physicians recruited had different specialties. All interviews were audio recorded, then transcribed into English language and analyze by thematic content analysis. Results: Four major themes were identified: (1) prescribing patterns of physicians regarding antimicrobials; (2) physician's knowledge about antimicrobials; (3) antimicrobial resistance; (4) satisfaction with management of infections. Physicians believed in regular educational activities and updates about the latest antimicrobial guidelines may change the prescribing behavior of physicians to optimize the use of antimicrobials. This may lead to decrease in burden of antimicrobial resistance in their health care system. Physicians emphasized that stricter rules and regular monitoring of antimicrobial use should be implemented to overcome the main challenges of antimicrobial resistance. Conclusion: Different factors were identified to assist optimized use of antimicrobials and decrease the risk of antimicrobial resistance. The present study helps to design targeted future interventions to ensure rational antimicrobial use and decrease the impact of antimicrobial resistance in Malaysia.
    MeSH terms: Anti-Bacterial Agents/therapeutic use; Humans; Malaysia/epidemiology; Practice Patterns, Physicians'; Physicians*
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