Browse publications by year: 2018

Attenuated Total Reflection Fourier Transform Infrared (ATR FT-IR) Spectroscopy as an Analytical Method to Investigate the Secondary Structure of a Model Protein Embedded in Solid Lipid Matrices

Zeeshan F, Tabbassum M, Jorgensen L, Medlicott NJ

Appl Spectrosc, 2018 Feb;72(2):268-279.
PMID: 29022355 DOI: 10.1177/0003702817739908

Protein drugs may encounter conformational perturbations during the formulation processing of lipid-based solid dosage forms. In aqueous protein solutions, attenuated total reflection Fourier transform infrared (ATR FT-IR) spectroscopy can investigate these conformational changes following the subtraction of spectral interference of solvent with protein amide I bands. However, in solid dosage forms, the possible spectral contribution of lipid carriers to protein amide I band may be an obstacle to determine conformational alterations. The objective of this study was to develop an ATR FT-IR spectroscopic method for the analysis of protein secondary structure embedded in solid lipid matrices. Bovine serum albumin (BSA) was chosen as a model protein, while Precirol AT05 (glycerol palmitostearate, melting point 58 ℃) was employed as the model lipid matrix. Bovine serum albumin was incorporated into lipid using physical mixing, melting and mixing, or wet granulation mixing methods. Attenuated total reflection FT-IR spectroscopy and size exclusion chromatography (SEC) were performed for the analysis of BSA secondary structure and its dissolution in aqueous media, respectively. The results showed significant interference of Precirol ATO5 with BSA amide I band which was subtracted up to 90% w/w lipid content to analyze BSA secondary structure. In addition, ATR FT-IR spectroscopy also detected thermally denatured BSA solid alone and in the presence of lipid matrix indicating its suitability for the detection of denatured protein solids in lipid matrices. Despite being in the solid state, conformational changes occurred to BSA upon incorporation into solid lipid matrices. However, the extent of these conformational alterations was found to be dependent on the mixing method employed as indicated by area overlap calculations. For instance, the melting and mixing method imparted negligible effect on BSA secondary structure, whereas the wet granulation mixing method promoted more changes. Size exclusion chromatography analysis depicted the complete dissolution of BSA in the aqueous media employed in the wet granulation method. In conclusion, an ATR FT-IR spectroscopic method was successfully developed to investigate BSA secondary structure in solid lipid matrices following the subtraction of lipid spectral interference. The ATR FT-IR spectroscopy could further be applied to investigate the secondary structure perturbations of therapeutic proteins during their formulation development.

MeSH terms: Diglycerides/chemistry*; Models, Chemical; Proteins/analysis*; Proteins/chemistry*; Serum Albumin, Bovine/analysis; Serum Albumin, Bovine/chemistry; Protein Structure, Secondary/physiology*; Spectroscopy, Fourier Transform Infrared/methods*
Developmental Approach for Behavior Learning Using Primitive Motion Skills

Dawood F, Loo CK

Int J Neural Syst, 2018 May;28(4):1750038.
PMID: 29022403 DOI: 10.1142/S0129065717500381

Imitation learning through self-exploration is essential in developing sensorimotor skills. Most developmental theories emphasize that social interactions, especially understanding of observed actions, could be first achieved through imitation, yet the discussion on the origin of primitive imitative abilities is often neglected, referring instead to the possibility of its innateness. This paper presents a developmental model of imitation learning based on the hypothesis that humanoid robot acquires imitative abilities as induced by sensorimotor associative learning through self-exploration. In designing such learning system, several key issues will be addressed: automatic segmentation of the observed actions into motion primitives using raw images acquired from the camera without requiring any kinematic model; incremental learning of spatio-temporal motion sequences to dynamically generates a topological structure in a self-stabilizing manner; organization of the learned data for easy and efficient retrieval using a dynamic associative memory; and utilizing segmented motion primitives to generate complex behavior by the combining these motion primitives. In our experiment, the self-posture is acquired through observing the image of its own body posture while performing the action in front of a mirror through body babbling. The complete architecture was evaluated by simulation and real robot experiments performed on DARwIn-OP humanoid robot.

MeSH terms: Artificial Intelligence*; Biomechanical Phenomena; Computer Simulation; Exploratory Behavior; Humans; Imitative Behavior*; Learning*; Markov Chains; Models, Biological; Motor Skills*; Pattern Recognition, Automated; Posture; Robotics/methods*; Visual Perception
Critical Parameters for Particle-Based Pulmonary Delivery of Chemotherapeutics

Dabbagh A, Abu Kasim NH, Yeong CH, Wong TW, Abdul Rahman N

J Aerosol Med Pulm Drug Deliv, 2018 06;31(3):139-154.
PMID: 29022837 DOI: 10.1089/jamp.2017.1382

Targeted delivery of chemotherapeutics through the respiratory system is a potential approach to improve drug accumulation in the lung tumor, while decreasing their negative side effects. However, elimination by the pulmonary clearance mechanisms, including the mucociliary transport system, and ingestion by the alveolar macrophages, rapid absorption into the blood, enzymatic degradation, and low control over the deposition rate and location remain the main complications for achieving an effective pulmonary drug delivery. Therefore, particle-based delivery systems have emerged to minimize pulmonary clearance mechanisms, enhance drug therapeutic efficacy, and control the release behavior. A successful implementation of a particle-based delivery system requires understanding the influential parameters in terms of drug carrier, inhalation technology, and health status of the patient's respiratory system. This review aims at investigating the parameters that significantly drive the clinical outcomes of various particle-based pulmonary delivery systems. This should aid clinicians in appropriate selection of a delivery system according to their clinical setting. It will also guide researchers in addressing the remaining challenges that need to be overcome to enhance the efficiency of current pulmonary delivery systems for aerosols.

MeSH terms: Aerosols; Drug Carriers; Humans; Lung/metabolism*; Lung Neoplasms/drug therapy; Particle Size; Drug Delivery Systems*; Dry Powder Inhalers
Fulltext Local context influences memory for emotional stimuli but not electrophysiological markers of emotion-dependent attention

Barnacle GE, Tsivilis D, Schaefer A, Talmi D

Psychophysiology, 2018 04;55(4).
PMID: 29023754 DOI: 10.1111/psyp.13014

Emotional enhancement of free recall can be context dependent. It is readily observed when emotional and neutral scenes are encoded and recalled together in a "mixed" list, but diminishes when these scenes are encoded separately in "pure" lists. We examined the hypothesis that this effect is due to differences in allocation of attention to neutral stimuli according to whether they are presented in mixed or pure lists, especially when encoding is intentional. Using picture stimuli that were controlled for semantic relatedness, our results contradicted this hypothesis. The amplitude of well-known electrophysiological markers of emotion-related attention-the early posterior negativity (EPN), the late positive potential (LPP), and the slow wave (SW)-was higher for emotional stimuli. Crucially, the emotional modulation of these ERPs was insensitive to list context, observed equally in pure and mixed lists. Although list context did not modulate neural markers of emotion-related attention, list context did modulate the effect of emotion on free recall. The apparent decoupling of the emotional effects on attention and memory, challenges existing hypotheses accounting for the emotional enhancement of memory. We close by discussing whether findings are more compatible with an alternative hypothesis, where the magnitude of emotional memory enhancement is, at least in part, a consequence of retrieval dynamics.

MeSH terms: Adolescent; Adult; Attention/physiology*; Brain/physiology*; Electroencephalography; Emotions/physiology*; Evoked Potentials/physiology*; Female; Humans; Male; Young Adult; Memory, Episodic*
A new system for classifying tooth, root and canal anomalies

Ahmed HMA, Dummer PMH

Int Endod J, 2018 Apr;51(4):389-404.
PMID: 29023779 DOI: 10.1111/iej.12867

Understanding the normal anatomical features as well as the more unusual developmental anomalies of teeth, roots and root canals is essential for successful root canal treatment. In addition to various types of root canal configuration and accessory canal morphology, a wide range of developmental tooth, root and canal anomalies exists, including C-shaped canals, dens invaginatus, taurodontism, root fusion, dilacerations and palato-gingival grooves. There is a direct association between developmental anomalies and pulp and periradicular diseases that usually require a multidisciplinary treatment approach to achieve a successful outcome. A number of classifications have categorized tooth, root and canal anomalies; however, several important details are often missed making the classifications less than ideal and potentially confusing. Recently, a new coding system for classifying root, root canal and accessory canal morphology has been introduced. The purpose of this article is to introduce a new system for classifying tooth, root and canal anomalies for use in research, clinical practice and training, which can serve as complementary codes to the recently described system for classifying root, as well as main and accessory canal morphology.

MeSH terms: Dens in Dente/classification; Dental Pulp/abnormalities; Dental Pulp Cavity/abnormalities*; Humans; Periapical Diseases; Root Canal Therapy; Tooth/anatomy & histology*; Tooth Root/abnormalities*; Clinical Coding
Asian Organization for Crohn's and Colitis and Asian Pacific Association of Gastroenterology consensus on tuberculosis infection in patients with inflammatory bowel disease receiving anti-tumor necrosis factor treatment. Part 1: Risk assessment

Park DI, Hisamatsu T, Chen M, Ng SC, Ooi CJ, Wei SC, et al.

J Gastroenterol Hepatol, 2018 Jan;33(1):20-29.
PMID: 29023903 DOI: 10.1111/jgh.14019

Because anti-tumor necrosis factor (anti-TNF) therapy has become increasingly popular in many Asian countries, the risk of developing active tuberculosis (TB) among anti-TNF users may raise serious health problems in this region. Thus, the Asian Organization for Crohn's and Colitis and the Asian Pacific Association of Gastroenterology have developed a set of consensus statements about risk assessment, detection, and prevention of latent TB infection and management of active TB infection in patients with inflammatory bowel disease (IBD) receiving anti-TNF treatment. Twenty-three consensus statements were initially drafted and then discussed by the committee members. The quality of evidence and the strength of recommendations were assessed by using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Web-based consensus voting was performed by 211 IBD specialists from nine Asian countries concerning each statement. A consensus statement was accepted if at least 75% of the participants agreed. Part 1 of the statements comprised two parts: (i) risk of TB infection during anti-TNF therapy and (ii) screening for TB infection prior to commencing anti-TNF therapy. These consensus statements will help clinicians optimize patient outcomes by reducing the morbidity and mortality related to TB infections in patients with IBD receiving anti-TNF treatment.

MeSH terms: Adalimumab/adverse effects; Adalimumab/therapeutic use*; Infliximab/adverse effects; Infliximab/therapeutic use*; Antibodies, Monoclonal/adverse effects; Antibodies, Monoclonal/therapeutic use*; Asia; Drug Therapy, Combination; Gastroenterology/organization & administration*; Humans; Immunosuppressive Agents/therapeutic use; Tuberculosis/diagnosis; Tuberculosis/etiology*; Tuberculosis/prevention & control; Tumor Necrosis Factor-alpha/immunology; Tumor Necrosis Factor-alpha/physiology; Inflammatory Bowel Diseases/complications; Inflammatory Bowel Diseases/drug therapy*; Risk Assessment*; Consensus*
Fulltext Asian Organization for Crohn's and Colitis and Asia Pacific Association of Gastroenterology consensus on tuberculosis infection in patients with inflammatory bowel disease receiving anti-tumor necrosis factor treatment. Part 2: management

Park DI, Hisamatsu T, Chen M, Ng SC, Ooi CJ, Wei SC, et al.

Intest Res, 2018 Jan;16(1):17-25.
PMID: 29422794 DOI: 10.5217/ir.2018.16.1.17

Because anti-tumor necrosis factor (anti-TNF) therapy has become increasingly popular in many Asian countries, the risk of developing active tuberculosis (TB) among anti-TNF users may raise serious health problems in this region. Thus, the Asian Organization for Crohn's and Colitis and the Asia Pacific Association of Gastroenterology have developed a set of consensus statements about risk assessment, detection and prevention of latent TB infection, and management of active TB infection in patients with inflammatory bowel disease (IBD) receiving anti-TNF treatment. Twenty-three consensus statements were initially drafted and then discussed by the committee members. The quality of evidence and the strength of recommendations were assessed by using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Web-based consensus voting was performed by 211 IBD specialists from 9 Asian countries concerning each statement. A consensus statement was accepted if at least 75% of the participants agreed. Part 2 of the statements comprised 3 parts: management of latent TB in preparation for anti-TNF therapy, monitoring during anti-TNF therapy, and management of an active TB infection after anti-TNF therapy. These consensus statements will help clinicians optimize patient outcomes by reducing the morbidity and mortality related to TB infections in patients with IBD receiving anti-TNF treatment.

MeSH terms: Asia; Colitis; Crohn Disease; Gastroenterology; Humans; Politics; Specialization; Tuberculosis; Tumor Necrosis Factor-alpha; Inflammatory Bowel Diseases; Risk Assessment; Internet; Committee Membership; Consensus; Latent Tuberculosis
Perception of Special Needs Dentistry education and practice amongst Australian dental auxiliary students

Borromeo GL, Ahmad MS, Buckley S, Bozanic M, Cao A, Al-Dabbagh M, et al.

Eur J Dent Educ, 2018 Aug;22(3):e321-e326.
PMID: 29024268 DOI: 10.1111/eje.12296

INTRODUCTION: The role of dental auxiliaries in collaborative care of patients with special needs is compelling. This study was undertaken to investigate the perceptions of Special Needs Dentistry (SND) education and practice amongst students enrolled in Australian programmes in dental auxiliary, namely dental hygiene, dental therapy and oral health therapy (DH/DT/OHT).
MATERIALS AND METHODS: All Australian institutions offering DH/DT/OHT programmes (n = 14) were invited to participate in a self-administered questionnaire survey, conducted online, involving students across all academic years. Twelve institutions agreed to participate, but only five institutions were included in the final analysis, with a student response rate of 31.1%. Answers to open-ended questions were coded and grouped for measurement of frequencies. Quantitative data were analysed via chi-squared and Fisher's exact tests (significance taken as P
Synthesis of carbon-based quantum dots from starch extracts: Optical investigations

Al-Douri Y, Badi N, Voon CH

Luminescence, 2018 Mar;33(2):260-266.
PMID: 29024360 DOI: 10.1002/bio.3408

Carbon-based quantum dots (C-QDs) were synthesized through microwave-assisted carbonization of an aqueous starch suspension mediated by sulphuric and phosphoric acids. The as-prepared C-QDs showed blue, green and yellow luminescence without the addition of any surface-passivating agent. The C-QDs were further analyzed by UV-vis spectroscopy to measure the optical response of the organic compound. The energy gaps revealed narrow sizing of C-QDs in the semiconductor range. The optical refractive index and dielectric constant were investigated. The C-QDs size distribution was characterized. The results suggested an easy route to the large scale production of C-QDs materials.

MeSH terms: Carbon/chemistry*; Particle Size; Spectrum Analysis; Starch/chemistry*; Quantum Dots/chemistry*; Luminescence
Fulltext WHO guide on the economic evaluation of influenza vaccination

Newall AT, Chaiyakunapruk N, Lambach P, Hutubessy RCW

Influenza Other Respir Viruses, 2018 Mar;12(2):211-219.
PMID: 29024434 DOI: 10.1111/irv.12510

Influenza is responsible for substantial morbidity and mortality across the globe, with a large share of the total disease burden occurring in low- and middle-income countries (LMICs). There have been relatively few economic evaluations assessing the value of seasonal influenza vaccination in LMICs. The purpose of this guide is to outline the key theoretical concepts and best practice in methodologies and to provide guidance on the economic evaluation of influenza vaccination in LMICs. It outlines many of the influenza vaccine-specific challenges and should help to provide a framework for future evaluations in the area to build upon.

MeSH terms: Cost-Benefit Analysis*; Developing Countries; Humans; Influenza, Human/economics*; Influenza, Human/prevention & control*; Influenza Vaccines/administration & dosage*; Influenza Vaccines/economics*; Vaccination/economics*; World Health Organization
The effects of combined probiotic ingestion and circuit training on muscular strength and power and cytokine responses in young males

Ibrahim NS, Muhamad AS, Ooi FK, Meor-Osman J, Chen CK

Appl Physiol Nutr Metab, 2018 Feb;43(2):180-186.
PMID: 29024599 DOI: 10.1139/apnm-2017-0464

To our knowledge, the efficacy of combined probiotic supplementation with circuit training has not been evaluated. Thus, we investigated the effects of probiotic supplementation combined with circuit training on isokinetic muscular strength and power and cytokine responses in young males. Forty-eight healthy sedentary young males were recruited and randomised into 4 separate groups: sedentary placebo control, probiotics (P), circuit training with placebo (CT), and circuit training with probiotics (CTP). Participants in the CT and CTP groups performed circuit training 3 times/week with 2 circuits of exercises from weeks 1-8 followed by 3 circuits of exercises from weeks 9-12. Participants in the P and CTP groups consumed multi-strain probiotics containing 3 × 1010 colony-forming units of Lactobacillus acidophilus, L. lactis, L. casei, Bifidobacterium longum, B. bifidum and B. infantis twice daily for 12 weeks. Measurements of body height and weight, blood pressure, resting heart rate, blood samples, and isokinetic muscular strength and power were carried out at pre- and post-tests. Isokinetic knee strength and power in CT and CTP groups were significantly higher (P < 0.05) at post-test. In addition, interleukin (IL)-10 concentration was significantly increased (P < 0.0001) at post-test in P and CT but a trend toward significant increase in CTP (P = 0.09). Nevertheless, there was no significant difference in IL-6. This study suggests that 12 weeks of circuit training alone and the combination of circuit training and probiotic consumption improved muscular performance while circuit training alone and probiotics alone increased IL-10 concentration.

MeSH terms: Adult; Humans; Male; Patient Compliance; Cytokines/blood*; Muscle, Skeletal/physiology*; Probiotics/administration & dosage*; Muscle Strength*; Young Adult; Sedentary Lifestyle; Sports Nutritional Physiological Phenomena; Circuit-Based Exercise*
Incorporation of surface plasmon resonance with novel valinomycin doped chitosan-graphene oxide thin film for sensing potassium ion

Zainudin AA, Fen YW, Yusof NA, Al-Rekabi SH, Mahdi MA, Omar NAS

Spectrochim Acta A Mol Biomol Spectrosc, 2018 Feb 15;191:111-115.
PMID: 29024848 DOI: 10.1016/j.saa.2017.10.013

In this study, the combination of novel valinomycin doped chitosan-graphene oxide (C-GO-V) thin film and surface plasmon resonance (SPR) system for potassium ion (K+) detection has been developed. The novel C-GO-V thin film was deposited on the gold surface using spin coating technique. The system was used to monitor SPR signal for K+ in solution with and without C-GO-V thin film. The K+ can be detected by measuring the SPR signal when C-GO-V thin film is exposed to K+ in solution. The sensor produces a linear response for K+ ion up to 100ppm with sensitivity and detection limit of 0.00948°ppm-1 and 0.001ppm, respectively. These results indicate that the C-GO-V film is high potential as a sensor element for K+ that has been proved by the SPR measurement.

MeSH terms: Excipients; Gold; Graphite; Ions; Organic Chemicals; Oxides; Potassium; Valinomycin; Surface Plasmon Resonance; Chitosan; Limit of Detection
The relationship between schizotypal facets and conspiracist beliefs via cognitive processes

Barron D, Furnham A, Weis L, Morgan KD, Towell T, Swami V

Psychiatry Res, 2018 01;259:15-20.
PMID: 29024855 DOI: 10.1016/j.psychres.2017.10.001

This study sought to replicate previous work showing relationships between components of schizotypy and conspiracist beliefs, and extend it by examining the mediating role of cognitive processes. An international online sample of 411 women and men (mean age = 35.41 years) completed measures of the schizotypal facets of Odd Beliefs or Magical Thinking and Ideas of Reference, conspiracist beliefs, and cognitive processes related to need for cognition, analytic thinking, and cognitive insight. Path analysis confirmed the associations between both schizotypal facets and conspiracist beliefs in the present sample. Confirmatory evidence was found for the association between analytic thinking and conspiracist beliefs, and results also suggested an association between cognitive insight and conspiracist beliefs. Cognitive insight also mediated the link between Odd Beliefs or Magical Thinking and Ideas of Reference with conspiracist beliefs. However, analytic thinking provided a mediating link to conspiracy ideation for Odd Beliefs or Magical Thinking and not Ideas of Reference. Finally, there was an association between Odd Beliefs or Magical Thinking and need for cognition, but this path did not extend to conspiracist beliefs. These results suggest possible mediating roles for analytic thinking and self-certainty between schizotypy and conspiracist beliefs.

MeSH terms: Adult; Cognition*; Culture*; Female; Humans; Magic*; Male; Schizotypal Personality Disorder/psychology*; Thinking*
Antenatal scoring system in predicting the success of planned vaginal birth following one previous caesarean section

Kalok A, Zabil SA, Jamil MA, Lim PS, Shafiee MN, Kampan N, et al.

J Obstet Gynaecol, 2018 Apr;38(3):339-343.
PMID: 29017359 DOI: 10.1080/01443615.2017.1355896

This was a prospective observational study to determine the predictive factors for a successful vaginal birth after caesarean section (VBAC) and to develop a relevant antenatal scoring system. Patients with one previous caesarean section were included in this study. All data including maternal demographics, obstetric history, pregnancy progress and outcomes were collected and analysed. A total of 142 out of the 186 women (76.3%) had successful VBAC. History of previous vaginal delivery and non-recurrent indications for previous caesarean section were the significant predictive factors for a successful VBAC. Five variables for our scoring tool were selected. By using a proposed mean score of 4 out of 7, the scoring system had a sensitivity of 81.0%, specificity of 52.3% and a positive predictive value of 84.6%. VBAC antenatal scoring system was potentially a useful predictive tool in antenatal counselling. Impact statement What is already known on this subject: Planned vaginal birth after caesarean section (VBAC) is an important strategy to limit the overall caesarean section rate, which is related to maternal morbidities. However, trial of vaginal delivery does involve potential complications including scar dehiscence, postpartum haemorrhage and emergency hysterectomy. What the results of this study add: Clinical predictors of a successful VBAC include non-recurrent indications for the previous caesarean section, previous vaginal delivery, spontaneous onset of labour and birthweight less than 4kg. There were multiple screening tools developed to predict the likelihood of successful VBAC. These scoring systems involved various variables such as age, ethnicity, Bishop's score and previous caesarean indication. We had prospectively developed an antenatal scoring system based on five variables. Our result showed that patient with a score of four and above will have around 85% chance of successful VBAC. What the implications are of these findings for clinical practice and/or further research: We have also found that, estimated foetal weight based on ultrasound scan is a potential predictor for successful VBAC. This simple scoring method will be useful in-patient counselling regarding mode of delivery after one previous caesarean section. A multicentre study involving large cohort of patients is ideal to validate our scoring system.

MeSH terms: Adult; Cesarean Section/statistics & numerical data; Female; Humans; Pregnancy; Pregnancy Outcome/epidemiology*; Prenatal Care/methods*; Prospective Studies; Risk Factors; Trial of Labor; Vaginal Birth after Cesarean/statistics & numerical data*; Fetal Weight; Delivery, Obstetric/statistics & numerical data; Continental Population Groups
Rampant polyphyly in the Arracacia clade (Apiaceae) and an assessment of the phylogenetic utility of 20 noncoding plastid loci

Danderson CA, Downie SR, Hermann M

Mol Phylogenet Evol, 2018 01;118:286-305.
PMID: 29017853 DOI: 10.1016/j.ympev.2017.10.006

The Arracacia clade (Apiaceae, Apioideae) is a heterogeneous assemblage of 12 genera, comprising 111 known species distributed in high montane temperate and sub-alpine habitats of meso- and South America. Previous studies have indicated that the genera Arracacia, Coulterophytum, and Prionosciadium are polyphyletic, but for the most part relationships among the members of the clade are largely unknown. Initially, cladistic analyses of nrDNA ITS sequences were carried out on 212 accessions (122 taxa), representing 92 species of the Arracacia clade and outgroups from the closely-related páramo genera Cotopaxia, Niphogeton, and Perissocoeleum and members of the Perennial Endemic North American clade and its allies. Using the ITS results to inform sampling of a small subset of taxa, a pilot study examining the phylogenetic utility of 20 noncoding chloroplast loci was subsequently performed to identify those regions most useful at resolving relationships. A cost-benefit analysis determined that five loci (trnQ-5'rps16, trnD-trnT, rpl32-trnL, psbD-trnT, ndhA intron) would maximize resolution and branch support in the clade. Cladistic analyses of four of these loci (trnQ-5'rps16, trnD-trnT, rpl32-trnL, ndhA intron) and the ITS region, separately and combined, revealed that Arracacia, Coaxana, Coulterophytum, Prionosciadium, and Rhodosciadium are each polyphyletic and that Donnellsmithia and Myrrhidendron are each monophyletic. Although most relationships in the Arracacia clade and among the closely-related genera Cotopaxia, Niphogeton, and Perissocoeleum are poorly resolved and supported, ten groups are recognized for future revisionary studies. Polyploidy and rapid species radiation have likely confounded generic circumscriptions and interpretation of relationships.

MeSH terms: Base Sequence; Bayes Theorem; Cell Nucleus/genetics; Introns; Phylogeny; Sequence Alignment; Sequence Analysis, DNA; Plastids/genetics; DNA, Chloroplast/isolation & purification; DNA, Chloroplast/metabolism; DNA, Chloroplast/chemistry; Apiaceae/classification*; Apiaceae/genetics; Genetic Loci
Functional properties and utilization of Artocarpus heterophyllus Lam seed starch from new species in China

Zhang Y, Hu M, Zhu K, Wu G, Tan L

Int J Biol Macromol, 2018 Feb;107(Pt B):1395-1405.
PMID: 29017887 DOI: 10.1016/j.ijbiomac.2017.10.001

Jackfruit is now receiving extensive attention as a new source of starch. However, jackfruit seeds are discarded as waste, although they are rich in starch. The functional properties of the starches were investigated from new Chinese jackfruit species. All the starches have a high amylose (26.56-38.34%) with a potential to become functional foods rich in resistant starch. The jackfruit starches varied from trigonal and tetragonal, round to semi-oval/bell shapes and showed significant variations in particle sizes (5.53-14.46μm). These variations led to significant differences in their functional properties, and significant correlations were found in their pasting, thermal, crystal and texture parameters. Hierarchical cluster analysis sorted the samples into three groups of 1) Malaysia 8 (M8) and ZhenZhu (ZZ); 2) Malaysia 2, Malaysia 3 and Malaysia 4, (M2, M3, M4); and 3) Xiangyinsuo 11, Xiangyinsuo 4, Xiangyinsuo 3 and Xiangyinsuo 2 (X11, X4, X3, X2). The first group could be used as food thickening or gelling agents. The second group could be applied in glutinous foods. The third group make them suitable for fillings in confectionery or weaning foods.

MeSH terms: Calibration; Calorimetry, Differential Scanning; China; Crystallization; Seeds/chemistry*; Solubility; Starch/metabolism*; Starch/ultrastructure; Starch/chemistry; Temperature; X-Ray Diffraction; Cluster Analysis; Porosity; Artocarpus/chemistry*
Fulltext Phase III HEAT Study Adding Lyso-Thermosensitive Liposomal Doxorubicin to Radiofrequency Ablation in Patients with Unresectable Hepatocellular Carcinoma Lesions

Tak WY, Lin SM, Wang Y, Zheng J, Vecchione A, Park SY, et al.

Clin Cancer Res, 2018 01 01;24(1):73-83.
PMID: 29018051 DOI: 10.1158/1078-0432.CCR-16-2433

Purpose: Lyso-thermosensitive liposomal doxorubicin (LTLD) consists of doxorubicin contained within a heat-sensitive liposome. When heated to ≥40°C, LTLD locally releases a high concentration of doxorubicin. We aimed to determine whether adding LTLD improves the efficacy of radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) lesions with a maximum diameter (dmax) of 3 to 7 cm.Experimental Design: The HEAT Study was a randomized, double-blind, dummy-controlled trial of RFA ± LTLD. The 701 enrolled patients had to have ≤4 unresectable HCC lesions, at least one of which had a dmax of 3 to 7 cm. The primary endpoint was progression-free survival (PFS) and a key secondary endpoint was overall survival (OS). Post hoc subset analyses investigated whether RFA duration was associated with efficacy.Results: The primary endpoint was not met; in intention-to-treat analysis, the PFS HR of RFA + LTLD versus RFA alone was 0.96 [95% confidence interval (CI), 0.79-1.18; P = 0.71], and the OS HR ratio was 0.95 (95% CI, 0.76-1.20; P = 0.67). Among 285 patients with a solitary HCC lesion who received ≥45 minutes RFA dwell time, the OS HR was 0.63 (95% CI, 0.41-0.96; P < 0.05) in favor of combination therapy. RFA + LTLD had reversible myelosuppression similar to free doxorubicin.Conclusions: Adding LTLD to RFA was safe but did not increase PFS or OS in the overall study population. However, consistent with LTLD's heat-based mechanism of action, subgroup analysis suggested that RFA + LTLD efficacy is improved when RFA dwell time for a solitary lesion ≥45 minutes. Clin Cancer Res; 24(1); 73-83. ©2017 AACR.

MeSH terms: Adolescent; Adult; Antibiotics, Antineoplastic/administration & dosage; Antibiotics, Antineoplastic/adverse effects; Antibiotics, Antineoplastic/therapeutic use*; Combined Modality Therapy; Doxorubicin/administration & dosage; Doxorubicin/adverse effects; Doxorubicin/analogs & derivatives*; Doxorubicin/therapeutic use; Female; Carcinoma, Hepatocellular/mortality; Carcinoma, Hepatocellular/pathology*; Carcinoma, Hepatocellular/therapy*; Humans; Liver Neoplasms/mortality; Liver Neoplasms/pathology*; Liver Neoplasms/therapy*; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Polyethylene Glycols/administration & dosage; Polyethylene Glycols/adverse effects; Polyethylene Glycols/therapeutic use; Treatment Outcome; Kaplan-Meier Estimate; Young Adult
Environmental triggers in IBD: a review of progress and evidence

Ananthakrishnan AN, Bernstein CN, Iliopoulos D, Macpherson A, Neurath MF, Ali RAR, et al.

Nat Rev Gastroenterol Hepatol, 2018 Jan;15(1):39-49.
PMID: 29018271 DOI: 10.1038/nrgastro.2017.136

A number of environmental factors have been associated with the development of IBD. Alteration of the gut microbiota, or dysbiosis, is closely linked to initiation or progression of IBD, but whether dysbiosis is a primary or secondary event is unclear. Nevertheless, early-life events such as birth, breastfeeding and exposure to antibiotics, as well as later childhood events, are considered potential risk factors for IBD. Air pollution, a consequence of the progressive contamination of the environment by countless compounds, is another factor associated with IBD, as particulate matter or other components can alter the host's mucosal defences and trigger immune responses. Hypoxia associated with high altitude is also a factor under investigation as a potential new trigger of IBD flares. A key issue is how to translate environmental factors into mechanisms of IBD, and systems biology is increasingly recognized as a strategic tool to unravel the molecular alterations leading to IBD. Environmental factors add a substantial level of complexity to the understanding of IBD pathogenesis but also promote the fundamental notion that complex diseases such as IBD require complex therapies that go well beyond the current single-agent treatment approach. This Review describes the current conceptualization, evidence, progress and direction surrounding the association of environmental factors with IBD.

MeSH terms: Environment*; Humans; Risk Factors; Socioeconomic Factors; Inflammatory Bowel Diseases/diagnosis; Inflammatory Bowel Diseases/etiology*; Inflammatory Bowel Diseases/therapy
Artemether-Lumefantrine Versus Chloroquine for the Treatment of Uncomplicated Plasmodium knowlesi Malaria: An Open-Label Randomized Controlled Trial CAN KNOW

Grigg MJ, William T, Barber BE, Rajahram GS, Menon J, Schimann E, et al.

Clin Infect Dis, 2018 Jan 06;66(2):229-236.
PMID: 29020373 DOI: 10.1093/cid/cix779

BACKGROUND: Plasmodium knowlesi is reported increasingly across Southeast Asia and is the most common cause of malaria in Malaysia. No randomized trials have assessed the comparative efficacy of artemether-lumefantrine (AL) for knowlesi malaria.
METHODS: A randomized controlled trial was conducted in 3 district hospitals in Sabah, Malaysia to compare the efficacy of AL against chloroquine (CQ) for uncomplicated knowlesi malaria. Participants were included if they weighed >10 kg, had a parasitemia count <20000/μL, and had a negative rapid diagnostic test result for Plasmodium falciparum histidine-rich protein 2. Diagnosis was confirmed by means of polymerase chain reaction. Patients were block randomized to AL (total target dose, 12 mg/kg for artemether and 60 mg/kg for lumefantrine) or CQ (25 mg/kg). The primary outcome was parasite clearance at 24 hours in a modified intention-to-treat analysis.
RESULTS: From November 2014 to January 2016, a total of 123 patients (including 18 children) were enrolled. At 24 hours after treatment 76% of patients administered AL (95% confidence interval [CI], 63%-86%; 44 of 58) were aparasitemic, compared with 60% administered CQ (47%-72%; 39 of 65; risk ratio, 1.3 [95% CI, 1.0-1.6]; P = .06). Overall parasite clearance was shorter after AL than after CQ (median, 18 vs 24 hours, respectively; P = .02), with all patients aparasitemic by 48 hours. By day 42 there were no treatment failures. The risk of anemia during follow-up was similar between arms. Patients treated with AL would require lower bed occupancy than those treated with CQ (2414 vs 2800 days per 1000 patients; incidence rate ratio, 0.86 [95% CI, .82-.91]; P < .001). There were no serious adverse events.
CONCLUSIONS: AL is highly efficacious for treating uncomplicated knowlesi malaria; its excellent tolerability and rapid therapeutic response allow earlier hospital discharge, and support its use as a first-line artemisinin-combination treatment policy for all Plasmodium species in Malaysia.
CLINICAL TRIALS REGISTRATION: NCT02001012.

MeSH terms: Adolescent; Adult; Aged; Antimalarials/administration & dosage*; Antimalarials/adverse effects; Child; Child, Preschool; Chloroquine/administration & dosage*; Chloroquine/adverse effects; Female; Humans; Malaria/drug therapy*; Malaria/parasitology; Malaysia; Male; Middle Aged; Plasmodium knowlesi/isolation & purification*; Treatment Outcome; Young Adult; Drug-Related Side Effects and Adverse Reactions/epidemiology; Drug-Related Side Effects and Adverse Reactions/pathology
A sequential treatment of intermediate tropical landfill leachate using a sequencing batch reactor (SBR) and coagulation

Yong ZJ, Bashir MJK, Ng CA, Sethupathi S, Lim JW

J Environ Manage, 2018 Jan 01;205:244-252.
PMID: 28987987 DOI: 10.1016/j.jenvman.2017.09.068

The increase in landfill leachate generation is due to the increase of municipal solid waste (MSW) as global development continues. Landfill leachate has constantly been the most challenging issue in MSW management as it contains high amount of organic and inorganic compounds that might cause pollution to water resources. Biologically treated landfill leachate often fails to fulfill the regulatory discharge standards. Thus, to prevent environmental pollution, many landfill leachate treatment plants involve multiple stages treatment process. The Papan Landfill in Perak, Malaysia currently has no proper leachate treatment system. In the current study, sequential treatment via sequencing batch reactor (SBR) followed by coagulation was used to treat chemical oxygen demand (COD), ammoniacal nitrogen (NH3-N), total suspended solids (TSS), and colour from raw landfill leachate. SBR optimum aeration rate, L/min, optimal pH and dosage (g/L) of Alum for coagulation as a post-treatment were determined. The two-step sequential treatment by SBR followed by coagulation (Alum) achieved a removal efficiency of 84.89%, 94.25%, 91.82% and 85.81% for COD, NH3-N, TSS and colour, respectively. Moreover, the two-stage treatment process achieved 95.0% 95.0%, 95.3%, 100.0%, 87.2%, 62.9%, 50.0%, 41.3%, 41.2, 34.8, and 22.9 removals of Cadmium, Lead, Copper, Selenium, Barium, Iron, Silver, Nickel, Zinc, Arsenic, and Manganese, respectively.

MeSH terms: Iron; Malaysia; Nitrogen; Refuse Disposal*; Water Pollutants, Chemical*; Bioreactors*; Biological Oxygen Demand Analysis

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