Browse publications by year: 2021

  1. Alfatama M, Lim LY, Wong TW
    Carbohydr Polym, 2021 Dec 01;273:118487.
    PMID: 34560934 DOI: 10.1016/j.carbpol.2021.118487
    This study designed chitosan species-coated calcium alginate beads through concurrent core-coat formation. Chitosan oleate was synthesized by carbodiimide chemistry and characterized by 1H NMR and FTIR techniques. Chitosan or chitosan oleate was coated onto the forming alginate or alginate/tripolyphosphate core using vibratory nozzle extrusion-microencapsulation approach, followed by calcium crosslinking. Chlorpheniramine maleate served as a model water-soluble drug. The molecular characteristics, size, shape, morphology, swelling, erosion, water uptake, drug content and drug release profiles of beads were evaluated. Discrete spherical coated beads were obtained through minimizing successive bead adhesion through an interplay of nozzle vibrational frequency and polymeric solution flow rate. The tripolyphosphate ions in the core possessed higher diffusional kinetics than alginate and were better able to attract chitosan species onto bead surfaces to facilitate alginate-chitosan coacervation. Amphiphilic chitosan oleate formed smaller aggregates than chitosan. It interacted with greater ease with core alginate and tripolyphosphate. The gain in alginate/tripolyphosphate interaction with chitosan oleate at the core-coat interface enhanced bead robustness against swelling and water uptake with drug release consequently dependent on the loss of alginate-drug interaction.
  2. Yusefi M, Lee-Kiun MS, Shameli K, Teow SY, Ali RR, Siew KK, et al.
    Carbohydr Polym, 2021 Dec 01;273:118523.
    PMID: 34560940 DOI: 10.1016/j.carbpol.2021.118523
    Magnetic polymer nanocomposites are inherently multifunctional and harbor assorted physiochemical actions for applications thereof as novel drug nanocarriers. Herein, Fe3O4-nanoparticles were supported on rice straw cellulose for 5-fluorouracil carrier abbreviated as MC/5-FU for potential colorectal cancer treatments. Several analyses indicated the multifunctional properties of MC/5-FU bionanocomposites. Transmission and scanning electron microscopy study demonstrated that Fe3O4 nanofillers covered the cellulose matrix. The drug release from MC/5-FU was evaluated under various pH and temperature conditions, showing the maximum release at pH 7.4 and 44.2 °C. In in vitro anticancer assay, MC/5-FU exhibited enhanced selectivity and anticancer actions against 2D monolayer and 3D tumour spheroid models colorectal cancer cells. The anticancer effects of MC/5-FU with magnetic targeting and heat induction were also examined. This easily synthesized MC/5-FU indicated the potential in application as a low-cost drug formulation for colorectal cancer treatments.
  3. Latifi M, Ahmad A, Hassan NH, Ben Youcef H, Kaddami H
    Carbohydr Polym, 2021 Dec 01;273:118542.
    PMID: 34560954 DOI: 10.1016/j.carbpol.2021.118542
    Carboxymethyl chitin (CMChit) has the potential to be used as a solid polymer electrolyte (SPE) based on its ionic conductivity value of the order of 10-6 S·cm-1 in self-standing membranes. In controlled humidity of 65RH%, carboxymethyl chitin based membrane blended with 1-Butyl-3-methylimidazolium acetate (BMIM[Ac]) ionic liquid (IL) (40 wt%) showed a threshold value of ionic conductivity in the order of 10-4 S·cm-1 and electrochemical stability was up to 2.93 V. The effects of the relative humidity and ionic liquid weight fraction on the ionic conductivity and structural changes were investigated in detail. Furthermore, the X-ray diffraction (XRD) diffractogram indicated a clear reduction of crystallinity of the CMChit. The Field-emission scanning electron microscopy (FESEM) observation of the cross-sections confirmed the homogeneity of the prepared blend. This electrolyte was tested in symmetric cells based on Zn//SPE//Zn and showed good reversibility and potential for application in proton-conducting batteries.
  4. Madkhali AM, Abdulhaq AA, Atroosh WM, Ghzwani AH, Zain KA, Ghailan KY, et al.
    Parasitol Res, 2021 Nov;120(11):3771-3781.
    PMID: 34561749 DOI: 10.1007/s00436-021-07323-4
    This study investigated the polymorphism in the P. falciparum chloroquine resistance transporter (pfcrt) gene 11 years after chloroquine (CQ) cessation in Jazan region, southwestern Saudi Arabia. Two hundred and thirty-five P. falciparum isolates were amplified to detect mutations in the pfcrt gene. The pfcrt 76 T molecular marker for CQ resistance was detected in 66.4% (156/235) of the isolates, while the K76 CQ-sensitive wild type was detected in 33.6%. The pfcrt 74I and pfcrt 75E point mutations were each found to be present in 56.2% of isolates, while only four isolates (1.7%) were found to carry the pfcrt 72S mutation. Moreover, four pfcrt haplotypes were identified as follows: the CVIET triple-allele (56.2%), SVMET double-allele (1.7%) and CVMNT single-allele (8.5%) mutant haplotypes and the CVMNK wild haplotype (33.6%). The analysis also revealed significant associations between the prevalence of mutant pfcrt alleles and haplotypes and the age group, governorate and nationality of the patients as well as the parasitaemia level (p 
    MeSH terms: Animals; Chloroquine/pharmacology; Chloroquine/therapeutic use; Drug Resistance/genetics; Humans; Mutation; Parasites*; Plasmodium falciparum/genetics; Saudi Arabia; Protozoan Proteins/genetics
  5. Huang F, Srisuka W, Aupalee K, Streit A, Fukuda M, Pitasawat B, et al.
    Acta Trop, 2021 Dec;224:106140.
    PMID: 34562429 DOI: 10.1016/j.actatropica.2021.106140
    Black flies (Diptera: Simuliidae) are known as vectors of disease agents in humans and livestock, with some species being vectors of Onchocerca volvulus, the filarial nematode that is the causative agent of human onchocerciasis. Nematode infections in adult female black flies have been reported from some areas in northern and western Thailand, but not from other regions of Thailand. In this study, wild-caught adult female black flies from the central region of Thailand were examined for infections with nematodes. Collections of adult females were carried out at Khlong Lan district, Kamphaeng Phet province, central Thailand. A molecular approach, based on the mitochondrial (cox1, 12S rRNA) and nuclear (18S rRNA) genes, was used to identify the species of nematodes recovered from the specimens collected. A total of 911 wild-caught adult black flies were collected. Simulium nigrogilvum was the most abundant species (n = 708), followed by S. doipuiense complex (n = 179), S. chamlongi (n = 11), S. umphangense (n = 10), S. chumpornense (n = 1), S. multistriatum species-group (n = 1), and S. maewongense (n = 1). Nematode infections were detected in nine specimens of S. nigrogilvum, of which two were positive for filarial worms (one worm each, infection rate 0.28%) and seven were positive for non-filarial nematodes (11 worms in total, infection rate 0.99%). The two filarial nematodes (third-stage larvae) were identified molecularly as Onchocerca species type I, while the 11 non-filarial nematodes were classified into ascaridoid (n = 2), tylenchid (n = 6) and mermithid (n = 3) nematodes. The results of this study demonstrated that adult female S. nigrogilvum were parasitized with diverse nematodes (filarial and non-filarial). Detection of the infective larvae of Onchocerca sp. type I in S. nigrogilvum confirms that occurrence of zoonotic onchocerciasis is highly possible in Thailand. Additional in-depth investigation of the morphology, life cycle and host-parasite relationship of nematodes that parasitized this black fly host is still needed.
    MeSH terms: Animals; Bites and Stings*; Female; Humans; Onchocerca/genetics; Simuliidae*; Thailand
  6. Moshikur RM, Ali MK, Wakabayashi R, Moniruzzaman M, Goto M
    Int J Pharm, 2021 Oct 25;608:121129.
    PMID: 34562557 DOI: 10.1016/j.ijpharm.2021.121129
    Oral delivery of the sparingly soluble drug methotrexate (MTX) is challenging owing to its poor bioavailability and low solubility. To address this challenge, the present study reports the conversion of MTX into a series of five ionic liquids (ILs) comprising a cationic component-i.e., cholinium (Cho), tetramethylammonium (TMA), tetrabutylphosphonium (TBP), or an amino acid ester-and an anionic component-i.e., MTX. The biocompatibility, pharmacokinetics, tissue distribution, and antitumor efficacy of each MTX-based IL were investigated to determine its usefulness as a pharmaceutical. Oral administration to mice revealed that proline ethyl ester MTX (IL[ProEt][MTX]) had 4.6-fold higher oral bioavailability than MTX sodium, followed by aspartic diethyl ester MTX, IL[TBP][MTX], IL[Cho][MTX], and IL[TMA][MTX]. The peak plasma concentration, elimination half-life, area under the plasma concentration, mean absorption time, and body clearance of IL[ProEt][MTX] were significantly (p 
    MeSH terms: Animals; Antineoplastic Agents*; Methotrexate; Solubility; Tissue Distribution; Mice; Ionic Liquids*
  7. Zeimaran E, Pourshahrestani S, Fathi A, Razak NABA, Kadri NA, Sheikhi A, et al.
    Acta Biomater, 2021 12;136:1-36.
    PMID: 34562661 DOI: 10.1016/j.actbio.2021.09.034
    Successful tissue regeneration requires a scaffold with tailorable biodegradability, tissue-like mechanical properties, structural similarity to extracellular matrix (ECM), relevant bioactivity, and cytocompatibility. In recent years, injectable hydrogels have spurred increasing attention in translational medicine as a result of their tunable physicochemical properties in response to the surrounding environment. Furthermore, they have the potential to be implanted via minimally invasive procedures while enabling deep penetration, which is considered a feasible alternative to traditional open surgical procedures. However, polymeric hydrogels may lack sufficient stability and bioactivity in physiological environments. Composite hydrogels containing bioactive glass (BG) particulates, synergistically combining the advantages of their constituents, have emerged as multifunctional biomaterials with tailored mechanical properties and biological functionalities. This review paper highlights the recent advances in injectable composite hydrogel systems based on biodegradable polymers and BGs. The influence of BG particle geometry, composition, and concentration on gel formation, rheological and mechanical behavior as well as hydration and biodegradation of injectable hydrogels have been discussed. The applications of these composite hydrogels in tissue engineering are additionally described, with particular attention to bone and skin. Finally, the prospects and current challenges in the development of desirable injectable bioactive hydrogels for tissue regeneration are discussed to outline a roadmap for future research. STATEMENT OF SIGNIFICANCE: Developing a biomaterial that can be readily available for surgery, implantable via minimally invasive procedures, and be able to effectively stimulate tissue regeneration is one of the grand challenges in modern biomedicine. This review summarizes the state-of-the-art of injectable bioactive glass-polymer composite hydrogels to address several challenges in bone and soft tissue repair. The current limitations and the latest evolutions of these composite biomaterials are critically examined, and the roles of design parameters, such as composition, concentration, and size of the bioactive phase, and polymer-glass interactions on the rheological, mechanical, biological, and overall functional performance of hydrogels are detailed. Existing results and new horizons are discussed to provide a state-of-the-art review that may be useful for both experienced and early-stage researchers in the biomaterials community.
  8. Hashemi Moosavi M, Mousavi Khaneghah A, Javanmardi F, Hadidi M, Hadian Z, Jafarzadeh S, et al.
    Ultrason Sonochem, 2021 Nov;79:105755.
    PMID: 34562735 DOI: 10.1016/j.ultsonch.2021.105755
    Innovative technologies for the pasteurization of food products have increased due to the global demand for higher-quality food products. In this regard, the current article aimed to provide an overview regarding the latest research on US application in the decontamination of fungi in food products and highlight the parameters influencing the effectiveness of this method. Therefore, the related article with inactivation of fungi and mycotoxins by ultrasound among last four years (2018-2021) by using terms such as 'mycotoxin,' 'inactivation,' 'ultrasound,' 'decontamination' among some international databases such as PubMed, Web of Science, Embase and Google Scholar" was retrieved. Ultrasound (US) is considered a non-thermal decontamination method for food products. In US, the release of energy due to the acoustic phenomenon destroys microorganisms. This technology is advantageous as it is inexpensive, eco-friendly, and does not negatively affect food products' food structure and organoleptic properties. The influence of the US on food structure and organoleptic properties dramatically depends on the intensity and energy density applied In addition, it can preserve higher levels of ascorbic acid, lycopene, and chlorophyll in sonicated food products. The treatment conditions, including frequency, intensity, duration, temperature, and processing pressure, influence the effectiveness of decontamination. However, US displays synergistic or antagonistic effects on bacteria, yeasts, molds, and mycotoxins when combined with other types of decontamination methods such as chemical and thermal approaches. Thus, further research is needed to clarify these effects. Overall, the application of US methods in the food industry for decreasing the microbial content of food products during processing has been applied. However, the use of US with other techniques needs to be studied further.
    MeSH terms: Ultrasonic Waves*; Bacteria; Decontamination*; Food Contamination*; Fungi
  9. Martin CJ, Kron T, Vassileva J, Wood TJ, Joyce C, Ung NM, et al.
    Phys Med, 2021 Oct;90:53-65.
    PMID: 34562809 DOI: 10.1016/j.ejmp.2021.09.004
    Improvements in delivery of radiation dose to target tissues in radiotherapy have increased the need for better image quality and led to a higher frequency of imaging patients. Imaging for treatment planning extends to function and motion assessment and devices are incorporated into medical linear accelerators (linacs) so that regions of tissue can be imaged at time of treatment delivery to ensure dose distributions are delivered as accurately as possible. A survey of imaging in 97 radiotherapy centres in nine countries on six continents has been undertaken with an on-line questionnaire administered through the International Commission on Radiological Protection mentorship programme to provide a snapshot of imaging practices. Responses show that all centres use CT for planning treatments and many utilise additional information from magnetic resonance imaging and positron emission tomography scans. Most centres have kV cone beam CT attached to at least some linacs and use this for the majority of treatment fractions. The imaging options available declined with the human development index (HDI) of the country, and the frequency of imaging during treatment depended more on country than treatment site with countries having lower HDIs imaging less frequently. The country with the lowest HDI had few kV imaging facilities and relied on MV planar imaging intermittently during treatment. Imaging protocols supplied by vendors are used in most centres and under half adapt exposure conditions to individual patients. Recording of patient doses, a knowledge of which is important in optimisation of imaging protocols, was limited primarily to European countries.
    MeSH terms: Humans; Particle Accelerators; Surveys and Questionnaires; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Radiation Oncology*; Phantoms, Imaging; Cone-Beam Computed Tomography; Radiotherapy, Image-Guided*
  10. Paterson RRM
    J Environ Manage, 2021 Dec 15;300:113785.
    PMID: 34562818 DOI: 10.1016/j.jenvman.2021.113785
    Palms are iconic plants. Oil palms are very important economically and originate in Africa where they can act as a model for palms in general. The effect of future climate on the growth of oil palm will be very detrimental. Latitudinal migration of tropical crops to climate refuges may be impossible, and longitudinal migration has only been confirmed for oil palm, of all the tropical crops. The previous method to determine the longitudinal trend for oil palm used the longitudes of various countries in Africa and plotted these against the percentage suitable climate for growing oil palms in each country. An increasing longitudinal trend was observed from west to east. However, the longitudes of the countries were randomly distributed which may have introduced bias and the procedure was time consuming. The present report presents an optimised and systematic procedure that divided the regions, as presented on a map derived from a CLIMEX model, into ten equal sectors and the percentage suitable climates for growing oil palm were determined for each sector. This approach was quicker, systematic and straight forward and will be useful for management of oil palm plantations under climate change. The method confirmed and validated the trends reported in the original method although the suitability values were often lower and there was less spread of values around the trend. The values for the CSIRO MK3.0 and MIROC H models demonstrated considerable similarities to each other, contributing to validation of the method. The procedure of dividing maps equally into sectors derived from models, could be used for other crops, regions, or systems more generally, where the alternative may be a more superficial visual examination of the maps. Methods are required to mitigate the effects of climate change and stakeholders need to contribute more actively to the current climate debate with tangible actions.
    MeSH terms: Africa; Forecasting; Crops, Agricultural; Arecaceae*; Climate Change
  11. Awang MS, Bustami Y, Hamzah HH, Zambry NS, Najib MA, Khalid MF, et al.
    Biosensors (Basel), 2021 Sep 18;11(9).
    PMID: 34562936 DOI: 10.3390/bios11090346
    Large-scale food-borne outbreaks caused by Salmonella are rarely seen nowadays, thanks to the advanced nature of the medical system. However, small, localised outbreaks in certain regions still exist and could possess a huge threat to the public health if eradication measure is not initiated. This review discusses the progress of Salmonella detection approaches covering their basic principles, characteristics, applications, and performances. Conventional Salmonella detection is usually performed using a culture-based method, which is time-consuming, labour intensive, and unsuitable for on-site testing and high-throughput analysis. To date, there are many detection methods with a unique detection system available for Salmonella detection utilising immunological-based techniques, molecular-based techniques, mass spectrometry, spectroscopy, optical phenotyping, and biosensor methods. The electrochemical biosensor has growing interest in Salmonella detection mainly due to its excellent sensitivity, rapidity, and portability. The use of a highly specific bioreceptor, such as aptamers, and the application of nanomaterials are contributing factors to these excellent characteristics. Furthermore, insight on the types of biorecognition elements, the principles of electrochemical transduction elements, and the miniaturisation potential of electrochemical biosensors are discussed.
    MeSH terms: Food Microbiology*; Salmonella*; Biosensing Techniques; Nanostructures; Aptamers, Nucleotide; Electrochemical Techniques*; Limit of Detection
  12. Zhang Q, Yang R, Lim PE, Chin Y, Zhou S, Gao Y, et al.
    Nutr Cancer, 2021 Sep 23.
    PMID: 34555987 DOI: 10.1080/01635581.2021.1981403
    5-fluorouracil (5-FU)-induced intestinal mucositis (IM) often makes chemotherapy patients suffer from physical and psychological suffering. Kappaphycus alvarezii (KA) is known for its potent multiple biological activities from decades. In the current study, we explored the effect of sun-dried and air-dried Kappaphycus alvarezii as a whole food supplement on 5-FU-induced IM. Diets supplemented with sun-dried Kappaphycus alvarezii (SKA, 3%), air-dried Kappaphycus alvarezii (AKA, 3%), and 5-aminosalicylic acid (0.005%) for consecutive14 days. While intraperitoneal injection of 5-FU (50 mg/kg) induced IM for last three consecutive days, and IM was assessed by the disease activity index (DAI) and inflammatory cytokine levels. Pretreatment of KA could alleviate phenotypic index, inhibit the increase of DAI, and reverse villus/crypt ratio. On the 14th day, AKA significantly increased the weight growth rate of the mice. The intervention of SKA significantly reduced the level of TNF-α and IL-1β (P 
  13. Abd Wahab M, Safaai S, Mohd Saiboon I
    Int J Emerg Med, 2021 Sep 23;14(1):59.
    PMID: 34556031 DOI: 10.1186/s12245-021-00384-3
    BACKGROUND: A binary triage system based on infectivity and facilitated by departmental restructuring was developed to manage suspected COVID-19 patients with an aim to provide effective prevention and control of infection among health care workers (HCWs) in the emergency department. This study analyses the effectiveness of the new triage system and structural reorganization in response to the COVID-19 pandemic.

    METHODS: A cross-sectional observational study was conducted in the Emergency and Trauma Department, Hospital Kuala Lumpur (ETDHKL). The implementation of a binary triage system separates patients with risk of COVID-19 who present with fever and respiratory symptoms from other patients. Data on exposed HCWs to COVID-19 patients were captured pre-restructuring and post-restructuring of the emergency department and analysed using descriptive statistics.

    RESULTS: A total of 846 HCWs were involved in this study. Pre-restructuring reported 542 HCWs exposed to COVID-19 patients while post-restructuring reported 122. Using the four categorical exposure risks for HCWs which are no identifiable risk, low risk, medium risk, and high risk, the number of HCWs exposed during pre-restructuring were 15(1.8%), 504 (59.6%), 15 (1.8%), and 8 (0.9%), respectively, while post-restructuring the numbers were 122 (14.4%), 8 (0.9%), 109 (12.9%), and 5 (0.1%), respectively. There was a 77.5% reduction in the number of exposed HCWs after our implementation of the new system (542 vs 122).

    CONCLUSION: A binary triage system based on severity and infectivity and supported with structural reorganization can be effective in reducing HCWs COVID-19 exposure.

  14. Ahmad A, Zulaily N, Shahril MR, Wafa SW, Mohd Amin R, Piernas C, et al.
    BMC Pediatr, 2021 09 23;21(1):418.
    PMID: 34556071 DOI: 10.1186/s12887-021-02899-3
    BACKGROUND: Childhood obesity has been associated with increased odds of adult obesity and co-morbidities in later life. Finding the key determinants may help in designing the most appropriate and effective interventions to prevent obesity. This study aimed to identify the determinants of obesity among school adolescents in a sub-urban state of Malaysia.

    METHODS: This cross-sectional study involved 1,404 school adolescents aged 12 years (46% boys and 54% girls). Socio-demographic, dietary and physical activity data were collected using questionnaires whilst body weight and height were measured and body mass index was classified based on WHO BMI-for-age Z-scores cut-off.

    RESULTS: A multivariable linear regression model showed that BMI z-score was positively associated with parents' BMI (P<0.001), birth weight (P=0.003), and serving size of milk and dairy products (P=0.036) whilst inversely associated with household size (P=0.022). Overall, 13.1% of the variances in BMI Z-scores were explained by parents' BMI, birth weight, servings of milk and dairy products and household size.

    CONCLUSION: This study found important determinants of body weight status among adolescents mainly associated with family and home environmental factor. This evidence could help to form the effective and tailored strategies at the earliest stage to prevent obesity in this population.

    MeSH terms: Adolescent; Child; Cross-Sectional Studies; Female; Humans; Male; Schools; Exercise; Body Mass Index
  15. Poornima P, Krithikadatta J, Ponraj RR, Velmurugan N, Kishen A
    BMC Oral Health, 2021 09 23;21(1):465.
    PMID: 34556107 DOI: 10.1186/s12903-021-01805-8
    BACKGROUND: Orthodontic treatment poses an increased risk of plaque accumulation and demineralisation of enamel leading to white spot lesion around the brackets. This parallel arm trial aims to assess the degree of bacterial plaque formation adjacent to orthodontic brackets, following the application of a chitosan-based varnish or chlorhexidene-fluoride varnish.

    METHODS: A total of 200 teeth from 20 patients undergoing fixed orthodontic therapy were assessed and biofilm formation around the brackets were recorded using the Bonded Bracket Index (Plaque index) at baseline and weekly for 6 weeks. The bacterial count and plaque pH at corresponding weekly intervals were also recorded. Following bracket bonding, the patients were cluster randomised to receive chitosan-based varnish-CHS (UNO Gel Bioschell, Germiphene corp., Brantford, Canada) or chlorhexidine-fluoride varnish-CFV (Cervitec F, Ivoclar Vivadent, Schaan, Liechtenstein) every week on the representative teeth respectively. BBI proportions were compared between groups at all time intervals using Chi square test. Mean plaque bacterial count and plaque pH were compared using Mann Whitney U test and Tukey's HSD test respectively.

    RESULTS: Baseline characteristics were similar between the groups: Mean age was CHS = 23 and CFV = 21; male to female ratio was CHS = 5/5, CFV = 7/3. At the end of 6 weeks, chitosan-based varnish performed equal to chlorhexidine-fluoride varnish (P > 0.05) with 98% and 95% of teeth with acceptable scores respectively. The plaque bacterial count significantly reduced at 6 weeks for both varnish compared to the baseline; The value for CHS was 0.43 ± 0.4 × 104 and CFV was 0.77 ± 0.64 × 104 CFU (P 

    MeSH terms: Cariostatic Agents; Chlorhexidine; Female; Fluorides; Fluorides, Topical; Humans; Male; Biofilms; Chitosan*
  16. Hanoon MS, Ahmed AN, Zaini N, Razzaq A, Kumar P, Sherif M, et al.
    Sci Rep, 2021 09 23;11(1):18935.
    PMID: 34556676 DOI: 10.1038/s41598-021-96872-w
    Accurately predicting meteorological parameters such as air temperature and humidity plays a crucial role in air quality management. This study proposes different machine learning algorithms: Gradient Boosting Tree (G.B.T.), Random forest (R.F.), Linear regression (LR) and different artificial neural network (ANN) architectures (multi-layered perceptron, radial basis function) for prediction of such as air temperature (T) and relative humidity (Rh). Daily data over 24 years for Kula Terengganu station were obtained from the Malaysia Meteorological Department. Results showed that MLP-NN performs well among the others in predicting daily T and Rh with R of 0.7132 and 0.633, respectively. However, in monthly prediction T also MLP-NN model provided closer standards deviation to actual value and can be used to predict monthly T with R 0.8462. Whereas in prediction monthly Rh, the RBF-NN model's efficiency was higher than other models with R of 0.7113. To validate the performance of the trained both artificial neural network (ANN) architectures MLP-NN and RBF-NN, both were applied to an unseen data set from observation data in the region. The results indicated that on either architecture of ANN, there is good potential to predict daily and monthly T and Rh values with an acceptable range of accuracy.
  17. Aguilar-Toalá JE, Arioli S, Behare P, Belzer C, Berni Canani R, Chatel JM, et al.
    Nat Rev Gastroenterol Hepatol, 2021 11;18(11):825-826.
    PMID: 34556825 DOI: 10.1038/s41575-021-00521-6
  18. Dutta S, Gorain B, Choudhury H, Roychoudhury S, Sengupta P
    PMID: 34558053 DOI: 10.1007/s11356-021-16581-9
    Untainted environment promotes health, but the last few decades experienced steep upsurge in environmental contaminants posing detrimental physiological impact. The responsible factors mainly include the exponential growth of human population, havoc rise in industrialization, poorly planned urbanization, and slapdash environment management. Environmental degradation can increase the likelihood of human exposure to heavy metals, resulting in health consequences such as reproductive problems. As a result, research into metal-induced causes of reproductive impairment at the genetic, epigenetic, and biochemical levels must be strengthened further. These metals impact upon the female reproduction at all strata of its regulation and functions, be it development, maturation, or endocrine functions, and are linked to an increase in the causes of infertility in women. Chronic exposures to the heavy metals may lead to breast cancer, endometriosis, endometrial cancer, menstrual disorders, and spontaneous abortions, as well as pre-term deliveries, stillbirths. For example, endometriosis, endometrial cancer, and spontaneous abortions are all caused by the metalloestrogen cadmium (Cd); lead (Pb) levels over a certain threshold can cause spontaneous abortion and have a teratogenic impact; toxic amounts of mercury (Hg) have an influence on the menstrual cycle, which can lead to infertility. Impact of environmental exposure to heavy metals on female fertility is therefore a well-known fact. Thus, the underlying mechanisms must be explained and periodically updated, given the growing evidence on the influence of increasing environmental heavy metal load on female fertility. The purpose of this review is to give a concise overview of how heavy metal affects female reproductive health.
  19. Kirubakaran R, Hennig S, Maslen B, Day RO, Carland JE, Stocker SL
    Br J Clin Pharmacol, 2021 Sep 23.
    PMID: 34558092 DOI: 10.1111/bcp.15091
    BACKGROUND AND AIM: Identification of the most appropriate population pharmacokinetic model-based Bayesian estimation is required prior to its implementation in routine clinical practice to inform tacrolimus dosing decisions. This study aimed to determine the predictive performances of relevant population pharmacokinetic models of tacrolimus developed from various solid organ transplant recipient populations in adult heart transplant recipients, stratified based on concomitant azole antifungal use. Concomitant azole antifungal therapy alters tacrolimus pharmacokinetics substantially necessitating dose adjustments.

    METHODS: Population pharmacokinetic models of tacrolimus were selected (n=17) for evaluation from a recent systematic review. The models were transcribed and implemented in NONMEM version 7.4.3. Data from 85 heart transplant recipients (2387 tacrolimus concentrations) administered the oral immediate-release formulation of tacrolimus (Prograf®) were obtained up to 391 days post-transplant. The performance of each model was evaluated using (1) prediction-based assessment (bias and imprecision) of the individual predicted tacrolimus concentration of the fourth dosing occasion (MAXEVAL=0, FOCE-I) from 1-3 prior dosing occasions and (2) simulation-based assessment (prediction-corrected visual predictive check, pcVPC). Both assessments were stratified based on concomitant azole antifungal use.

    RESULTS: Regardless of the number of prior dosing occasions (1-3) and concomitant azole antifungal use, all models demonstrated unacceptable individual predicted tacrolimus concentration of the fourth dosing occasion (n=152). The pcVPC graphics indicated these models inadequately predicted observed tacrolimus concentrations.

    CONCLUSIONS: All models evaluated were unable to adequately describe tacrolimus pharmacokinetics in adult heart transplant recipients included in this study. Further work is required to describe tacrolimus pharmacokinetics for our heart transplant recipient cohort.

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