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Fulltext Decoding Antioxidant and Antibacterial Potentials of Malaysian Green Seaweeds: Caulerpa racemosa and Caulerpa lentillifera

Yap WF, Tay V, Tan SH, Yow YY, Chew J

Antibiotics (Basel), 2019 Sep 17;8(3).
PMID: 31533237 DOI: 10.3390/antibiotics8030152

Seaweeds are gaining a considerable amount of attention for their antioxidant and antibacterial properties. Caulerpa racemosa and Caulerpa lentillifera, also known as 'sea grapes', are green seaweeds commonly found in different parts of the world, but the antioxidant and antibacterial potentials of Malaysian C. racemosa and C. lentillifera have not been thoroughly explored. In this study, crude extracts of the seaweeds were prepared using chloroform, methanol, and water. Total phenolic content (TPC) and total flavonoid content (TFC) were measured, followed by in vitro antioxidant activity determination using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. Antibacterial activities of these extracts were tested against Methicillin-resistant Staphylococcus aureus (MRSA) and neuropathogenic Escherichia coli K1. Liquid chromatography-mass spectrometry (LCMS) analysis was then used to determine the possible compounds present in the extract with the most potent antioxidant and antibacterial activity. Results showed that C. racemosa chloroform extract had the highest TPC (13.41 ± 0.86 mg GAE/g), antioxidant effect (EC50 at 0.65 ± 0.03 mg/mL), and the strongest antibacterial effect (97.7 ± 0.30%) against MRSA. LCMS analysis proposed that the chloroform extracts of C. racemosa are mainly polyunsaturated and monounsaturated fatty acids, terpenes, and alkaloids. In conclusion, C. racemosa can be a great source of novel antioxidant and antibacterial agents, but isolation and purification of the bioactive compounds are needed to study their mechanism of action.
Fulltext Electrochemical Biosensor for Nitrite Based on Polyacrylic-Graphene Composite Film with Covalently Immobilized Hemoglobin

Raja Jamaluddin RZA, Yook Heng L, Tan LL, Chong KF

Sensors (Basel), 2018 Apr 26;18(5).
PMID: 29701688 DOI: 10.3390/s18051343

A new biosensor for the analysis of nitrite in food was developed based on hemoglobin (Hb) covalently immobilized on the succinimide functionalized poly(n-butyl acrylate)-graphene [poly(nBA)-rGO] composite film deposited on a carbon-paste screen-printed electrode (SPE). The immobilized Hb on the poly(nBA)-rGO conducting matrix exhibited electrocatalytic ability for the reduction of nitrite with significant enhancement in the reduction peak at −0.6 V versus Ag/AgCl reference electrode. Thus, direct determination of nitrite can be achieved by monitoring the cathodic peak current signal of the proposed polyacrylic-graphene hybrid film-based voltammetric nitrite biosensor. The nitrite biosensor exhibited a reproducible dynamic linear response range from 0.05⁻5 mg L−1 nitrite and a detection limit of 0.03 mg L−1. No significant interference was observed by potential interfering ions such as Ca2+, Na⁺, K⁺, NH₄⁺, Mg2+, and NO₃− ions. Analysis of nitrite in both raw and processed edible bird’s nest (EBN) samples demonstrated recovery of close to 100%. The covalent immobilization of Hb on poly(nBA)-rGO composite film has improved the performance of the electrochemical nitrite biosensor in terms of broader detection range, lower detection limit, and prolonged biosensor stability.
The inhibitory effects of mitragynine on P-glycoprotein in vitro

Rusli N, Amanah A, Kaur G, Adenan MI, Sulaiman SF, Wahab HA, et al.

Naunyn Schmiedebergs Arch Pharmacol, 2019 04;392(4):481-496.
PMID: 30604191 DOI: 10.1007/s00210-018-01605-y

Mitragynine is a major component isolated from Mitragyna speciosa Korth or kratom, a medicinal plant known for its opiate-like and euphoric properties. Multiple toxicity and fatal cases involving mitragynine or kratom have been reported but the underlying causes remain unclear. P-glycoprotein (P-gp) is a multidrug transporter which modulates the pharmacokinetics of xenobiotics and plays a key role in mediating drug-drug interactions. This study investigated the effects of mitragynine on P-gp transport activity, mRNA, and protein expression in Caco-2 cells using molecular docking, bidirectional assay, RT-qPCR, Western blot analysis, and immunocytochemistry techniques, respectively. Molecular docking simulation revealed that mitragynine interacts with important residues at the nucleotide binding domain (NBD) site of the P-gp structure but not with the residues from the substrate binding site. This was consistent with subsequent experimental work as mitragynine exhibited low permeability across the cell monolayer but inhibited digoxin transport at 10 μM, similar to quinidine. The reduction of P-gp activity in vitro was further contributed by the downregulation of mRNA and protein expression of P-gp. In summary, mitragynine is likely a P-gp inhibitor in vitro but not a substrate. Hence, concurrent administration of mitragynine-containing kratom products with psychoactive drugs which are P-gp substrates may lead to clinically significant toxicity. Further clinical study to prove this point is needed.
Fulltext Potential Antimicrobial Applications of Chitosan Nanoparticles (ChNP)

Rozman NAS, Tong WY, Leong CR, Tan WN, Hasanolbasori MA, Abdullah SZ

J Microbiol Biotechnol, 2019 Jul 28;29(7):1009-1013.
PMID: 31288302 DOI: 10.4014/jmb.1904.04065

Polymeric nanoparticles are widely used for drug delivery due to their biodegradability property. Among the wide array of polymers, chitosan has received growing interest among researchers. It was widely used as a vehicle in polymeric nanoparticles for drug targeting. This review explored the current research on the antimicrobial activity of chitosan nanoparticles (ChNP) and the impact on the clinical applications. The antimicrobial activities of ChNP were widely reported against bacteria, fungi, yeasts and algae, in both in vivo and in vitro studies. For pharmaceutical applications, ChNP were used as antimicrobial coating for promoting wound healing, preventing infections and combating the rise of infectious disease. Besides, ChNP also exhibited significant inhibitory on foodborne microorganisms, particularly on fruits and vegetables. It is noteworthy that ChNP can be also applied to deliver antimicrobial drugs, which further enhance the efficiency and stability of the antimicrobial agent. The present review addresses the potential antimicrobial applications of ChNP from these few aspects.
Fulltext Infectious hematopoietic necrosis virus: advances in diagnosis and vaccine development

Yong CY, Ong HK, Tang HC, Yeap SK, Omar AR, Ho KL, et al.

PeerJ, 2019;7:e7151.
PMID: 31341728 DOI: 10.7717/peerj.7151

The aquaculture of salmonid fishes is a multi-billion dollar industry with production over 3 million tons annually. However, infectious hematopoietic necrosis virus (IHNV), which infects and kills salmon and trout, significantly reduces the revenue of the salmon farming industry. Currently, there is no effective treatment for IHNV infected fishes; therefore, early detection and depopulation of the infected fishes remain the most common practices to contain the spread of IHNV. Apart from hygiene practices in aquaculture and isolation of infected fishes, loss of fishes due to IHNV infection can also be significantly reduced through vaccination programs. In the current review, some of the diagnostic methods for IHNV, spanning from clinical diagnosis to cell culture, serological and molecular methods are discussed in detail. In addition, some of the most significant candidate vaccines for IHNV are also extensively discussed, particularly the DNA vaccines.
Purified ingredient-based high-fat diet is superior to chow-based equivalent in the induction of metabolic syndrome

Cheng HS, Phang SCW, Ton SH, Abdul Kadir K, Tan JBL

J Food Biochem, 2019 02;43(2):e12717.
PMID: 31353646 DOI: 10.1111/jfbc.12717

The present study aimed to outline the physiological and metabolic disparity between chow- and purified ingredient-based high-fat diets and their efficacy in the induction of metabolic syndrome (MetS). Male, 3-week-old Sprague Dawley rats were randomly assigned to chow-based control diet, chow-based high-fat diet, purified control diet, and purified high-fat diet for 12 weeks. Physical and biochemical changes were documented. Chow-based diets, irrespective of the lipid content, resulted in significantly lower weight gain and organ weight compared to purified ingredient-based diets. Circulating insulin, total proteins, albumin, and certain lipid components like the triglycerides, total cholesterol, and high-density lipoprotein-cholesterol were also lower in the chow-based diet groups. Both chow- and purified high-fat diets induced central obesity, hypertension, and hyperglycaemia, but the latter was associated with earlier onset of the metabolic aberrations and additionally, dyslipidaemia. In conclusion, purified high-fat diet is a better diet for MetS induction in rats. PRACTICAL APPLICATIONS: Modeling metabolic syndrome is commonly accomplished with the use of chow- or purified ingredient diets enriched with carbohydrates and/or lipids, but the differences and associated drawbacks are unclear. This study highlights that chow- or modified chow-based diets have a tendency to introduce unwanted metabolic changes which are inconsistent with the progression of metabolic syndrome. Thus, the use of these diets in metabolic disease study should be avoided. On the other hand, purified high-fat diet which can effectively induce the features of metabolic syndrome is highly recommended.
Immune responses against enterovirus A71 infection: Implications for vaccine success

Aw-Yong KL, NikNadia NMN, Tan CW, Sam IC, Chan YF

Rev Med Virol, 2019 09;29(5):e2073.
PMID: 31369184 DOI: 10.1002/rmv.2073

Enterovirus A71 (EV-A71) from the Picornaviridae family is an important emerging pathogen causing hand, foot, and mouth disease (HFMD) outbreaks worldwide. EV-A71 also caused fatal neurological complications in young children especially in Asia. On the basis of seroepidemiological studies from many Asian countries, EV-A71 infection is very common. Children of very young age are particularly vulnerable. Large-scale epidemics that occur every 3 to 4 years are associated with accumulation of an immunologically naive younger population. Capsid proteins especially VP1 with the presence of major B- and T-cell epitopes are the most antigenic proteins. The nonstructural proteins mainly contribute to T-cell epitopes that induce cross-reactive immune responses against other enteroviruses. Dominant epitopes and their neutralization magnitudes differ in mice, rabbits, and humans. Neutralizing antibody is sufficient for immune protection, but poorer cellular immunity may lead to severe neurological complications and deaths. Some chemokines/cytokines are consistently found in severely ill patients, for example, IL-6, IL-10, IL-17A, MCP-1, IL-8, MIG, IP-10, IFN-γ, and G-CSF. An increase in white cell counts is a risk factor for severe HFMD. Recent clinical trials on EV-A71 inactivated vaccine showed >90% efficacy and a robust neutralization response that was protective, indicating neutralizing antibody correlates for protection. No protection against other enteroviruses was observed. A comprehensive understanding of the immune responses to EV-A71 infection will benefit the development of diagnostic tools, potential therapeutics, and subunit vaccine candidates. Future development of a multivalent enterovirus vaccine will require knowledge of correlates of protection, understanding of cross-protection and memory T-cell responses among enteroviruses.
Fulltext Hyperglycemia-Associated Hemichorea-Hemiballismus with Predominant Ipsilateral Putaminal Abnormality on Neuroimaging

Fong SL, Tan AH, Lau KF, Ramli N, Lim SY

J Mov Disord, 2019 Sep;12(3):187-189.
PMID: 31390855 DOI: 10.14802/jmd.19014
A new machine learning technique for an accurate diagnosis of coronary artery disease

Abdar M, Książek W, Acharya UR, Tan RS, Makarenkov V, Pławiak P

Comput Methods Programs Biomed, 2019 Oct;179:104992.
PMID: 31443858 DOI: 10.1016/j.cmpb.2019.104992

BACKGROUND AND OBJECTIVE: Coronary artery disease (CAD) is one of the commonest diseases around the world. An early and accurate diagnosis of CAD allows a timely administration of appropriate treatment and helps to reduce the mortality. Herein, we describe an innovative machine learning methodology that enables an accurate detection of CAD and apply it to data collected from Iranian patients.
METHODS: We first tested ten traditional machine learning algorithms, and then the three-best performing algorithms (three types of SVM) were used in the rest of the study. To improve the performance of these algorithms, a data preprocessing with normalization was carried out. Moreover, a genetic algorithm and particle swarm optimization, coupled with stratified 10-fold cross-validation, were used twice: for optimization of classifier parameters and for parallel selection of features.
RESULTS: The presented approach enhanced the performance of all traditional machine learning algorithms used in this study. We also introduced a new optimization technique called N2Genetic optimizer (a new genetic training). Our experiments demonstrated that N2Genetic-nuSVM provided the accuracy of 93.08% and F1-score of 91.51% when predicting CAD outcomes among the patients included in a well-known Z-Alizadeh Sani dataset. These results are competitive and comparable to the best results in the field.
CONCLUSIONS: We showed that machine-learning techniques optimized by the proposed approach, can lead to highly accurate models intended for both clinical and research use.
Fulltext Gravid oviposition sticky trap and dengue non-structural 1 antigen test for early surveillance of dengue in multi-storey dwellings: study protocol of a cluster randomized controlled trial

Liew JWK, Selvarajoo S, Tan W, Ahmad Zaki R, Vythilingam I

Infect Dis Poverty, 2019 Sep 03;8(1):71.
PMID: 31477185 DOI: 10.1186/s40249-019-0584-y

BACKGROUND: Dengue is a global disease, transmitted by the Aedes vectors. In 2018, there were 80 615 dengue cases with 147 deaths in Malaysia. Currently, the nationwide surveillance programs are dependent on Aedes larval surveys and notifications of lab-confirmed human infections. The existing, reactive programs appear to lack sensitivity and proactivity. More efficient dengue vector surveillance/control methods are needed.
METHODS: A parallel, cluster, randomized controlled, interventional trial is being conducted for 18 months in Damansara Damai, Selangor, Malaysia, to determine the efficacy of using gravid oviposition sticky (GOS) trap and dengue non-structural 1 (NS1) antigen test for early surveillance of dengue among Aedes mosquitoes to reduce dengue outbreaks. Eight residential apartments were randomly assigned into intervention and control arms. GOS traps are set at the apartments to collect Aedes weekly, following which dengue NS1 antigen is detected in these mosquitoes. When a dengue-positive mosquito is detected, the community will be advised to execute vector search-and-destroy and protective measures. The primary outcome concerns the the percentage change in the (i) number of dengue cases and (ii) durations of dengue outbreaks. Whereas other outcome measures include the change in density threshold of Aedes and changes in dengue-related knowledge, attitude and practice among cluster inhabitants.
DISCUSSION: This is a proactive and early dengue surveillance in the mosquito vector that does not rely on notification of dengue cases. Surveillance using the GOS traps should be able to efficiently provide sufficient coverage for multistorey dwellings where population per unit area is likely to be higher. Furthermore, trapping dengue-infected mosquitoes using the GOS trap, helps to halt the dengue transmission carried by the mosquito. It is envisaged that the results of this randomized controlled trial will provide a new proactive, cheap and targeted surveillance tool for the prevention and control of dengue outbreaks.
TRIAL REGISTRATION: This is a parallel-cluster, randomized controlled, interventional trial, registered at ClinicalTrials.gov (ID: NCT03799237), on 8th January 2019 (retrospectively registered).
Fulltext First Reported Case of Neuroleptospirosis Complicated With Anton's Syndrome

Saeed N, Khoo CS, Remli R, Law ZK, Periyasamy P, Osman SS, et al.

Front Neurol, 2018;9:966.
PMID: 30564184 DOI: 10.3389/fneur.2018.00966

Leptospirosis is a spirochetal zoonotic disease with a wide clinical spectrum, often underdiagnosed especially when presented as an acute neurological manifestation. We report a case of a 24-year-old man with serologically positive leptospirosis, who presented with altered sensorium, seizures and subsequently developed cortical blindness. His brain MRI revealed bilateral occipital and later parietal lobe cerebritis.
Contributing factors to outpatient pharmacy near miss errors: a Malaysian prospective multi-center study

Rajah R, Hanif AA, Tan SSA, Lim PP, Karim SA, Othman E, et al.

Int J Clin Pharm, 2019 Feb;41(1):237-243.
PMID: 30506127 DOI: 10.1007/s11096-018-0762-1

Background Detecting errors before medication dispensed or 'near misses' is a crucial step to combat the incidence of dispensing error. Despite this, no published evidence available in Malaysia relating to these issues. Objective To determine the incidence of medication labeling and filling errors, frequency of each type of the errors and frequency of the contributing factors at the final stage before dispensing. Setting Six Penang public funded hospitals outpatient pharmacies. Methods A prospective multicentre study, over 8 week's period. Pharmacists identified and recorded the details of either medication labeling and/or filling error at the final stage of counter-checking before dispensing. Besides, the contributing factors for each error were determined and recorded in data collection form. Descriptive analysis was used to explain the study data. Main outcome measure The incidence of near misses. Results A total of 187 errors (near misses) detected, with 59.4% (n = 111) were medication filling errors and 40.6% (n = 76) were labeling errors. Wrong drug (n = 44, 39.6%) was identified as the highest type of filling errors while incorrect dose (n = 34, 44.7%) was identified as the highest type of labeling errors. Distracted and interrupted work environment was reported to lead the highest labeling and filling errors, followed by lack of knowledge and skills for filling errors and high workload for labeling errors. Conclusion The occurrence of near misses related to medication filling and labelling errors is substantial at outpatient pharmacy in Penang public funded hospitals. Further research is warranted to evaluate the intervention strategies needed to reduce the near misses.
Fulltext Inhibitors targeting CDK4/6, PARP and PI3K in breast cancer: a review

Nur Husna SM, Tan HT, Mohamud R, Dyhl-Polk A, Wong KK

Ther Adv Med Oncol, 2018;10:1758835918808509.
PMID: 30542378 DOI: 10.1177/1758835918808509

Breast cancer is the global leading cause of cancer-related death in women and it represents a major health burden worldwide. One of the promising breast cancer therapeutic avenues is through small molecule inhibitors (SMIs) which have undergone rapid progress with successful clinical trials. Recently, three emerging and vital groups of proteins are targeted by SMIs for breast cancer treatment, namely cyclin-dependent kinase 4 and 6 (CDK4/6), poly (adenosine diphosphate-ribose) polymerase (PARP) and phosphoinositide 3-kinase (PI3K). Several of these inhibitors have been approved for the treatment of breast cancer patients or progressed into late-stage clinical trials. Thus, modeling from these successful clinical trials, as well as their limitations, is pivotal for future development and trials of other inhibitors or therapeutic regimens targeting breast cancer patients. In this review, we discuss eight recently approved or novel SMIs against CDK4/6 (palbociclib, ribociclib and abemaciclib), PARP (olaparib, veliparib and talazoparib), and PI3K (buparlisib and alpelisib). The mechanisms of action, series of clinical trials and limitations are described for each inhibitor.
Orientation and verbal fluency in the English Longitudinal Study of Ageing: modifiable risk factors for falls?

Smith TO, Neal SR, Peryer G, Sheehan KJ, Tan MP, Myint PK

Int Psychogeriatr, 2019 10;31(10):1491-1498.
PMID: 30522546 DOI: 10.1017/S1041610218002065

OBJECTIVES: To determine the relationship between falls and deficits in specific cognitive domains in older adults.
DESIGN: An analysis of the English Longitudinal Study of Ageing (ELSA) cohort.
SETTING: United Kingdom community-based.
PARTICIPANTS: 5197 community-dwelling older adults recruited to a prospective longitudinal cohort study.
MEASUREMENTS: Data on the occurrence of falls and number of falls, which occurred during a 12-month follow-up period, were assessed against the specific cognitive domains of memory, numeracy skills, and executive function. Binomial logistic regression was performed to evaluate the association between each cognitive domain and the dichotomous outcome of falls in the preceding 12 months using unadjusted and adjusted models.
RESULTS: Of the 5197 participants included in the analysis, 1308 (25%) reported a fall in the preceding 12 months. There was no significant association between the occurrence of a fall and specific forms of cognitive dysfunction after adjusting for self-reported hearing, self-reported eyesight, and functional performance. After adjustment, only orientation (odds ratio [OR]: 0.80; 95% confidence intervals [CI]: 0.65-0.98, p = 0.03) and verbal fluency (adjusted OR: 0.98; 95% CI: 0.96-1.00; p = 0.05) remained significant for predicting recurrent falls.
CONCLUSIONS: The cognitive phenotype rather than cognitive impairment per se may predict future falls in those presenting with more than one fall.
Fulltext Preparation, optimization and swelling study of carboxymethyl sago starch (CMSS)-acid hydrogel

Tuan Mohamood NFA, Zainuddin N, Ahmad Ayob M, Tan SW

Chem Cent J, 2018 Dec 06;12(1):133.
PMID: 30523481 DOI: 10.1186/s13065-018-0500-8

In this study, sago starch was modified in order to enhance its physicochemical properties. Carboxymethylation was used to introduce a carboxymethyl group into a starch compound. The carboxymethyl sago starch (CMSS) was used to prepare smart hydrogel by adding acetic acid into the CMSS powder as the crosslinking agent. The degree of substitution of the CMSS obtained was 0.6410. The optimization was based on the gel content and degree of swelling of the hydrogel. In this research, four parameters were studied in order to optimize the formation of CMSS-acid hydrogel. The parameters were; CMSS concentration, acetic acid concentration, reaction time and reaction temperature. From the data analyzed, 76.69% of optimum gel content was obtained with 33.77 g/g of degree of swelling. Other than that, the swelling properties of CMSS-acid hydrogel in different media such as salt solution, different pH of phosphate buffer saline solution as well as acidic and alkaline solution were also investigated. The results showed that the CMSS-acid hydrogel swelled in both alkaline and salt solution, while in acidic or low pH solution, it tended to shrink and deswell. The production of the hydrogel as a smart material offers a lot of auspicious benefits in the future especially related to swelling behaviour and properties of the hydrogel in different types of media.
Fulltext Development of a NS2B/NS3 protease inhibition assay using AlphaScreen® beads for screening of anti-dengue activities

Abduraman MA, Hariono M, Yusof R, Rahman NA, Wahab HA, Tan ML

Heliyon, 2018 Dec;4(12):e01023.
PMID: 30560214 DOI: 10.1016/j.heliyon.2018.e01023

Background: Dengue infection is an endemic infectious disease and it can lead to dengue fever, dengue hemorrhagic fever, and/or dengue shock syndromes. Dengue NS2B/NS3 protease complex is essential for viral replication and is a primary target for anti-dengue drug development. In this study, a NS2B/NS3 protease inhibition assay was developed using AlphaScreen® beads and was used to screen compounds for their protease inhibition activities.
Methods: The assay system utilized a known NS2B/NS3 peptide substrate, a recombinant of NS2B/NS3 protease with proprietary StrepTactin® donor and nickel chelate acceptor beads in 384-well format.
Results: The optimized assay to screen for NS2B/NS3 protease inhibitors was demonstrated to be potentially useful with reasonable z' factor, coefficient variance and signal to background ratio. However, screening of synthesized thioguanine derivatives using the optimized AlphaScreen® assay revealed weak NS2B/NS3 inhibition activities.
Conclusion: The AlphaScreen® assay to screen for NS2B/NS3 protease inhibitors is potentially applicable for high throughput screening.
Fulltext An Influenza A Vaccine Based on the Extracellular Domain of Matrix 2 Protein Protects BALB/C Mice Against H1N1 and H3N2

Ong HK, Yong CY, Tan WS, Yeap SK, Omar AR, Razak MA, et al.

Vaccines (Basel), 2019 08 19;7(3).
PMID: 31430965 DOI: 10.3390/vaccines7030091

Current seasonal influenza A virus (IAV) vaccines are strain-specific and require annual reconstitution to accommodate the viral mutations. Mismatches between the vaccines and circulating strains often lead to high morbidity. Hence, development of a universal influenza A vaccine targeting all IAV strains is urgently needed. In the present study, the protective efficacy and immune responses induced by the extracellular domain of Matrix 2 protein (M2e) displayed on the virus-like particles of Macrobrachium rosenbergii nodavirus (NvC-M2ex3) were investigated in BALB/c mice. NvC-M2ex3 was demonstrated to be highly immunogenic even in the absence of adjuvants. Higher anti-M2e antibody titers corresponded well with increased survival, reduced immunopathology, and morbidity of the infected BALB/c mice. The mice immunized with NvC-M2ex3 exhibited lower H1N1 and H3N2 virus replication in the respiratory tract and the vaccine activated the production of different antiviral cytokines when they were challenged with H1N1 and H3N2. Collectively, these results suggest that NvC-M2ex3 could be a potential universal influenza A vaccine.
Zinc(II) salphen complex-based fluorescence optical sensor for biogenic amine detection

Sahudin MA, Su'ait MS, Tan LL, Lee YH, Abd Karim NH

Anal Bioanal Chem, 2019 Sep;411(24):6449-6461.
PMID: 31392436 DOI: 10.1007/s00216-019-02025-4

Biogenic amines have attracted interest among researchers because of their importance as biomarkers in determining the quality of food freshness in the food industry. A rapid and simple technique that is able to detect biogenic amines is needed. In this work, a new optical sensing material for one of the biogenic amines, histamine, based on a new zinc(II) salphen complex was developed. The binding of zinc(II) complexes without an electron-withdrawing group (complex 1) and with electron-withdrawing groups (F, complex 2; Cl, complex 3) to histamine resulted in enhancement of fluorescence. All complexes exhibited high affinity for histamine [binding constant of (7.14 ± 0.80) × 104, (3.33 ± 0.03) × 105, and (2.35 ± 0.14) × 105 M-1, respectively]. Complex 2 was chosen as the sensing material for further development of an optical sensor for biogenic amines in the following step since it displayed enhanced optical properties in comparison with complexes 1 and 3. The optical sensor for biogenic amines used silica microparticles as the immobilisation support and histamine as the analyte. The optical sensor had a limit of detection for histamine of 4.4 × 10-12 M, with a linear working range between 1.0 × 10-11 and 1.0 × 10-6 M (R2 = 0.9844). The sensor showed good reproducibility, with a low relative standard deviation (5.5 %). In addition, the sensor exhibited good selectivity towards histamine and cadaverine over other amines, such as 1,2-phenylenediamine, triethylamine, and trimethylamine. Recovery and real sample studies suggested that complex 2 could be a promising biogenic amine optical sensing material that can be applied in the food industry, especially in controlling the safety of food for it to remain fresh and healthy for consumption.
Fulltext Antibiotic prophylaxis in ragged placental membranes: a prospective, multicentre, randomized trial

Voon HY, Pow JY, Tan LN, Suharjono HN, Teo WS

BMC Pregnancy Childbirth, 2019 Jul 11;19(1):240.
PMID: 31296180 DOI: 10.1186/s12884-019-2373-9

BACKGROUND: Ragged placental membranes is a distinct entity from retained placenta and not uncommonly reported in midwifery texts. Although the incidence of postpartum endometritis is merely 1-5% after vaginal births, it remains the most common source of puerperal sepsis, contributing up to 15% of maternal mortality in low income countries. Geographically-remote centres in Malaysia prophylactically administer antibiotics for women with ragged placental membranes after vaginal birth, extrapolating evidence from retained placenta. We sought to clarify the rationale in continuing such practices.
METHODS: This was an open-label, prospective, multicentre, randomized trial. Three hospitals where the current protocol was to administer prophylactic amoxycillin-clavulanic acid served as the sites of recruitment. Women who delivered vaginally beyond 24+ 0 weeks of gestation with ragged membranes were invited to participate in the trial and randomized into prophylaxis or expectant management with medical advice by blocks of 10, at a 1:1 ratio. A medication adherence diary was provided and patients followed up at 2 weeks and 6 weeks postpartum.
RESULTS: A total of 6569 women gave birth vaginally in three centres during the trial period, of which 10.9% had ragged membranes. The incidence of endometritis was not significantly raised in women with or without prophylaxis (0.90% vs 0.29%; p = 0.60). All cases of endometritis presented within the first 2 weeks and preventive use of antibiotics did not ameliorate the severity of endometritis since rates of ICU admission, surgical evacuation and transfusion were comparable.
CONCLUSION: Preventive use of antibiotics after vaginal delivery in women with ragged placental membranes did not result in a reduction of endometritis. Educating women on the signs and symptoms of endometritis would suffice. Based on the reported incidence of ragged membranes, a change in practice would result in 1500 less prescriptions of antibiotics per annum in these three centres.
TRIAL REGISTRATION: NCT03459599 (Retrospectively registered on 9 March 2018).
Francisella spp. detected in Dermacentor ticks in Malaysian forest reserve areas

Koh FX, Nurhidayah MN, Tan PE, Kho KL, Tay ST

Vet Parasitol Reg Stud Reports, 2019 08;17:100315.
PMID: 31303231 DOI: 10.1016/j.vprsr.2019.100315

Limited information is available on tropical ticks and tick-borne bacteria affecting the health of humans and animals in the Southeast Asia region. Francisella tularensis is a tick-borne bacterium which causes a potentially life-threatening disease known as tularemia. This study was conducted to determine the occurrence of Francisella spp. in questing ticks collected from Malaysian forest reserve areas. A total of 106 ticks (mainly Dermacentor and Haemaphysalis spp.) were examined for Francisella DNA using a Polymerase chain reaction (PCR) assay targeting the bacterial 16S rDNA. Francisella DNA was detected from 12 Dermacentor ticks. Sequence analysis of the amplified 16S rDNA sequences (1035 bp) show >99% identity with that of Francisella endosymbiont reported in a tick from Thailand. A dendrogram constructed based on the bacterial 16S rDNA shows that the Francisella spp. were distantly related to the pathogenic strains of F. tularensis. Three Francisella-positive ticks were identified as Dermacentor atrosignatus, based on sequence analysis of the tick mitochondrial 16S rRNA gene. Further screening of cattle and sheep ticks (Haemaphysalis bispinosa and Rhipicephalus microplus) and animal samples (cattle, sheep, and goats) did not yield any positive findings. Our findings provide the first molecular data on the occurrence of a Francisella strain with unknown pathogenicity in Dermacentor questing ticks in Malaysia.

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