Displaying publications 1 - 20 of 28 in total

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  1. A cross-country comparative overview of the asbestos situation in ten Asian countries
    Takahashi K, Karjalainen A
    Int J Occup Environ Health, 2003 Jul-Sep;9(3):244-8.
    PMID: 12967160
    Information about asbestos issues at the national level was compiled for ten Asian countries (China, Indonesia, Japan, Korea, Malaysia, Philippines, Singapore, Taiwan, Thailand, and Vietnam) regarding 1) bans and consumption levels; 2) occupational exposure limits (OELs) and medical follow-up schemes; and 3) statistics and compensation status of asbestosis and mesothelioma victims. Only Singapore and recently Japan have adopted a total ban an asbestos. China, a major producer of chrysotile, showed an increasing consumption trend, which was typical of the less industrialized countries. Considerable differences between countries existed in OELs (0.1 to 5.0 fibers/mL) and medical follow-up of exposed workers. National statistics for asbestosis and mesothelioma were available for only the industrialized countries, where reported cases as well as compensated cases were relatively few. There is need to improve the quality and quantity of information, but the available information attests to unfavorable conditions in the less industrialized countries. Hence the experience of industrialized countries regarding asbestos and its use should be utilized to the fullest to improve the situation worldwide.
  2. Current HIV type 1 molecular epidemiology profile and identification of unique recombinant forms in Jakarta, Indonesia
    Sahbandar IN, Takahashi K, Djoerban Z, Firmansyah I, Naganawa S, Motomura K, et al.
    AIDS Res Hum Retroviruses, 2009 Jul;25(7):637-46.
    PMID: 19621986 DOI: 10.1089/aid.2008.0266
    HIV infection is a major problem in Indonesia. The number of people living with HIV has been increasing from year to year, especially among injecting drug users (IDUs). Since there were only limited data about molecular epidemiology profiles of HIV/AIDS in Indonesia, a cross-sectional study involving 208 HIV-1-seropositive individuals was conducted in 2007 in Jakarta. The majority of participants were 16-30 years of age (64.9%) and 74.5% were male. The most frequent risk factor was injecting drug use (IDU) (45.7%) followed by heterosexual transmission (34.1%). Phylogenetic analysis of gag (p17 and p6) and env C2V3 regions showed 200 (96.2%) of 208 DNA samples were CRF01_AE and only 3 (1.4%) were subtype B. Five samples (2.4%) indicated discordant subtypes between the three aforementioned regions: three of them showed unique CRF01_AE/B recombination patterns in 2.3-kbp nucleotide sequences (from p17 to part of RT), including one sample showing similarity to CRF33_01B, reported previously in Malaysia. This study shows the current predominant subtype is CRF01_AE in every risk group, with a decreasing number of pure subtype B, and the first identification of CRF01_AE/B recombinant forms among HIV-1-seropositive Indonesians.
  3. Fulltext The indonesian variants of CRF33_01B: Near-full length sequence analysis
    SahBandar IN, Takahashi K, Motomura K, Djoerban Z, Firmansyah I, Kitamura K, et al.
    AIDS Res Hum Retroviruses, 2011 Jan;27(1):97-102.
    PMID: 20958201 DOI: 10.1089/aid.2010.0163
    Cocirculation of subtype B and CRF01_AE in Southeast Asia has led to the establishment of new recombinant forms. In our previous study, we found five samples suspected of being recombinants between subtype B and CRF01_AE, and here, we analyzed near full-length sequences of two samples and compared them to known CRFs_01B, subtype B, and CRF01_AE. Five overlapped segments were amplified with nested PCR from PBMC DNA, sequenced, and analyzed for genome mosaicism. The two Indonesian samples, 07IDJKT189 and 07IDJKT194, showed genome-mosaic patterns similar to CRF33_01B references from Malaysia, with one short segment in the 3' end of the p31 integrase-coding region, which was rather more similar to subtype B than CRF01_AE, consisting of unclassified sequences. These results suggest gene-specific continuous diversification and spread of the CRF33_01B genomes in Southeast Asia.
  4. Fulltext The Global Burden of Cancer 2013
    Global Burden of Disease Cancer Collaboration, Fitzmaurice C, Dicker D, Pain A, Hamavid H, Moradi-Lakeh M, et al.
    JAMA Oncol, 2015 Jul;1(4):505-27.
    PMID: 26181261 DOI: 10.1001/jamaoncol.2015.0735
    IMPORTANCE: Cancer is among the leading causes of death worldwide. Current estimates of cancer burden in individual countries and regions are necessary to inform local cancer control strategies.

    OBJECTIVE: To estimate mortality, incidence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 28 cancers in 188 countries by sex from 1990 to 2013.

    EVIDENCE REVIEW: The general methodology of the Global Burden of Disease (GBD) 2013 study was used. Cancer registries were the source for cancer incidence data as well as mortality incidence (MI) ratios. Sources for cause of death data include vital registration system data, verbal autopsy studies, and other sources. The MI ratios were used to transform incidence data to mortality estimates and cause of death estimates to incidence estimates. Cancer prevalence was estimated using MI ratios as surrogates for survival data; YLDs were calculated by multiplying prevalence estimates with disability weights, which were derived from population-based surveys; YLLs were computed by multiplying the number of estimated cancer deaths at each age with a reference life expectancy; and DALYs were calculated as the sum of YLDs and YLLs.

    FINDINGS: In 2013 there were 14.9 million incident cancer cases, 8.2 million deaths, and 196.3 million DALYs. Prostate cancer was the leading cause for cancer incidence (1.4 million) for men and breast cancer for women (1.8 million). Tracheal, bronchus, and lung (TBL) cancer was the leading cause for cancer death in men and women, with 1.6 million deaths. For men, TBL cancer was the leading cause of DALYs (24.9 million). For women, breast cancer was the leading cause of DALYs (13.1 million). Age-standardized incidence rates (ASIRs) per 100 000 and age-standardized death rates (ASDRs) per 100 000 for both sexes in 2013 were higher in developing vs developed countries for stomach cancer (ASIR, 17 vs 14; ASDR, 15 vs 11), liver cancer (ASIR, 15 vs 7; ASDR, 16 vs 7), esophageal cancer (ASIR, 9 vs 4; ASDR, 9 vs 4), cervical cancer (ASIR, 8 vs 5; ASDR, 4 vs 2), lip and oral cavity cancer (ASIR, 7 vs 6; ASDR, 2 vs 2), and nasopharyngeal cancer (ASIR, 1.5 vs 0.4; ASDR, 1.2 vs 0.3). Between 1990 and 2013, ASIRs for all cancers combined (except nonmelanoma skin cancer and Kaposi sarcoma) increased by more than 10% in 113 countries and decreased by more than 10% in 12 of 188 countries.

    CONCLUSIONS AND RELEVANCE: Cancer poses a major threat to public health worldwide, and incidence rates have increased in most countries since 1990. The trend is a particular threat to developing nations with health systems that are ill-equipped to deal with complex and expensive cancer treatments. The annual update on the Global Burden of Cancer will provide all stakeholders with timely estimates to guide policy efforts in cancer prevention, screening, treatment, and palliation.

  5. Fulltext Membrane-associated glucose-methanol-choline oxidoreductase family enzymes PhcC and PhcD are essential for enantioselective catabolism of dehydrodiconiferyl alcohol
    Takahashi K, Hirose Y, Kamimura N, Hishiyama S, Hara H, Araki T, et al.
    Appl Environ Microbiol, 2015 Dec;81(23):8022-36.
    PMID: 26362985 DOI: 10.1128/AEM.02391-15
    Sphingobium sp. strain SYK-6 is able to degrade various lignin-derived biaryls, including a phenylcoumaran-type compound, dehydrodiconiferyl alcohol (DCA). In SYK-6 cells, the alcohol group of the B-ring side chain of DCA is initially oxidized to the carboxyl group to generate 3-(2-(4-hydroxy-3-methoxyphenyl)-3-(hydroxymethyl)-7-methoxy-2,3-dihydrobenzofuran-5-yl) acrylic acid (DCA-C). Next, the alcohol group of the A-ring side chain of DCA-C is oxidized to the carboxyl group, and then the resulting metabolite is catabolized through vanillin and 5-formylferulate. In this study, the genes involved in the conversion of DCA-C were identified and characterized. The DCA-C oxidation activities in SYK-6 were enhanced in the presence of flavin adenine dinucleotide and an artificial electron acceptor and were induced ca. 1.6-fold when the cells were grown with DCA. Based on these observations, SLG_09480 (phcC) and SLG_09500 (phcD), encoding glucose-methanol-choline oxidoreductase family proteins, were presumed to encode DCA-C oxidases. Analyses of phcC and phcD mutants indicated that PhcC and PhcD are essential for the conversion of (+)-DCA-C and (-)-DCA-C, respectively. When phcC and phcD were expressed in SYK-6 and Escherichia coli, the gene products were mainly observed in their membrane fractions. The membrane fractions of E. coli that expressed phcC and phcD catalyzed the specific conversion of DCA-C into the corresponding carboxyl derivatives. In the oxidation of DCA-C, PhcC and PhcD effectively utilized ubiquinone derivatives as electron acceptors. Furthermore, the transcription of a putative cytochrome c gene was significantly induced in SYK-6 grown with DCA. The DCA-C oxidation catalyzed by membrane-associated PhcC and PhcD appears to be coupled to the respiratory chain.
  6. Fulltext Transfer free graphene growth on SiO2 substrate at 250 °C
    Vishwakarma R, Rosmi MS, Takahashi K, Wakamatsu Y, Yaakob Y, Araby MI, et al.
    Sci Rep, 2017 03 02;7:43756.
    PMID: 28251997 DOI: 10.1038/srep43756
    Low-temperature growth, as well as the transfer free growth on substrates, is the major concern of graphene research for its practical applications. Here we propose a simple method to achieve the transfer free graphene growth on SiO2 covered Si (SiO2/Si) substrate at 250 °C based on a solid-liquid-solid reaction. The key to this approach is the catalyst metal, which is not popular for graphene growth by chemical vapor deposition. A catalyst metal film of 500 nm thick was deposited onto an amorphous C (50 nm thick) coated SiO2/Si substrate. The sample was then annealed at 250 °C under vacuum condition. Raman spectra measured after the removal of the catalyst by chemical etching showed intense G and 2D peaks together with a small D and intense SiO2 related peaks, confirming the transfer free growth of multilayer graphene on SiO2/Si. The domain size of the graphene confirmed by optical microscope and atomic force microscope was about 5 μm in an average. Thus, this approach will open up a new route for transfer free graphene growth at low temperatures.
  7. Surface reaction-diffusion kinetics on lattice at the microscopic scale
    Chew WX, Kaizu K, Watabe M, Muniandy SV, Takahashi K, Arjunan SNV
    Phys Rev E, 2019 Apr;99(4-1):042411.
    PMID: 31108654 DOI: 10.1103/PhysRevE.99.042411
    Microscopic models of reaction-diffusion processes on the cell membrane can link local spatiotemporal effects to macroscopic self-organized patterns often observed on the membrane. Simulation schemes based on the microscopic lattice method (MLM) can model these processes at the microscopic scale by tracking individual molecules, represented as hard spheres, on fine lattice voxels. Although MLM is simple to implement and is generally less computationally demanding than off-lattice approaches, its accuracy and consistency in modeling surface reactions have not been fully verified. Using the Spatiocyte scheme, we study the accuracy of MLM in diffusion-influenced surface reactions. We derive the lattice-based bimolecular association rates for two-dimensional (2D) surface-surface reaction and one-dimensional (1D) volume-surface adsorption according to the Smoluchowski-Collins-Kimball model and random walk theory. We match the time-dependent rates on lattice with off-lattice counterparts to obtain the correct expressions for MLM parameters in terms of physical constants. The expressions indicate that the voxel size needs to be at least 0.6% larger than the molecule to accurately simulate surface reactions on triangular lattice. On square lattice, the minimum voxel size should be even larger, at 5%. We also demonstrate the ability of MLM-based schemes such as Spatiocyte to simulate a reaction-diffusion model that involves all dimensions: three-dimensional (3D) diffusion in the cytoplasm, 2D diffusion on the cell membrane, and 1D cytoplasm-membrane adsorption. With the model, we examine the contribution of the 2D reaction pathway to the overall reaction rate at different reactant diffusivity, reactivity, and concentrations.
  8. Simulation of live-cell imaging system reveals hidden uncertainties in cooperative binding measurements
    Watabe M, Arjunan SNV, Chew WX, Kaizu K, Takahashi K
    Phys Rev E, 2019 Jul;100(1-1):010402.
    PMID: 31499827 DOI: 10.1103/PhysRevE.100.010402
    We propose a computational method to quantitatively evaluate the systematic uncertainties that arise from undetectable sources in biological measurements using live-cell imaging techniques. We then demonstrate this method in measuring the biological cooperativity of molecular binding networks, in particular, ligand molecules binding to cell-surface receptor proteins. Our results show how the nonstatistical uncertainties lead to invalid identifications of the measured cooperativity. Through this computational scheme, the biological interpretation can be more objectively evaluated and understood under a specific experimental configuration of interest.
  9. Fulltext High possibility of hepatocarcinogenesis in HBV genotype C1 infected Cambodians is indicated by 340 HBV C1 full-genomes analysis from GenBank
    Chuon C, Takahashi K, Matsuo J, Katayama K, Yamamoto C, Ko K, et al.
    Sci Rep, 2019 08 21;9(1):12186.
    PMID: 31434918 DOI: 10.1038/s41598-019-48304-z
    Approximately 75% of hepatocellular carcinomas (HCC) occur in Asia; core promoter mutations are associated with HCC in HBV genotype C, the dominant genotype in Cambodia. We analyzed these mutations in Cambodian residents and compared them with HBV full genomes registered in GenBank. We investigated the characteristics of 26 full-length HBV genomes among 35 residents positive for hepatitis B surface antigen in Siem Reap province, Cambodia. Genotype C1 was dominant (92.3%, 24/26), with one case of B2 and B4 each. Multiple mutations were confirmed in 24 Cambodian C1 isolates, especially double mutation at A1762T/G1764A in 18 isolates (75.0%), and combination mutation at C1653T and/or T1753V and A1762T/G1764A in 14 isolates (58.3%). In phylogenetic analysis, 16 of 24 isolates were located in the cluster with Laos, Thailand, and Malaysia. In 340 GenBank-registered C1 strains, 113 (33.2%) had combination mutation amongst which 16.5%, 34.2%, and 95.2% were found in ASC, chronic hepatitis, and liver cirrhosis (LC)/HCC respectively (P 
  10. High performance photoanodic catalyst prepared from an active organic photovoltaic cell - high potential gain from visible light
    Nagai K, Kuwabara T, Ahmad MF, Nakano M, Karakawa M, Taima T, et al.
    Chem Commun (Camb), 2019 Oct 15;55(83):12491-12494.
    PMID: 31573004 DOI: 10.1039/c9cc04759j
    Photoelectrochemical oxidation of thiols was enhanced with a threshold potential of -0.35 V vs. Ag/AgCl by the use of a ZnPc/PCBM:P3HT/ZnO electode, which was prepared by removing the PEDOT:PSS/Au electrode of an inverted OPV device and coating it with ZnPc. A co-photocatalysis property of ZnPc was observed in the photoelectrochemistry and scanning Kelvin probe microscopy.
  11. Cooperativity transitions driven by higher-order oligomer formations in ligand-induced receptor dimerization
    Watabe M, Arjunan SNV, Chew WX, Kaizu K, Takahashi K
    Phys Rev E, 2019 Dec;100(6-1):062407.
    PMID: 31962468 DOI: 10.1103/PhysRevE.100.062407
    While cooperativity in ligand-induced receptor dimerization has been linked with receptor-receptor couplings via minimal representations of physical observables, effects arising from higher-order oligomer, e.g., trimer and tetramer, formations of unobserved receptors have received less attention. Here we propose a dimerization model of ligand-induced receptors in multivalent form representing physical observables under basis vectors of various aggregated receptor states. Our simulations of multivalent models not only reject Wofsy-Goldstein parameter conditions for cooperativity, but show that higher-order oligomer formations can shift cooperativity from positive to negative.
  12. Fulltext Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2017: A Systematic Analysis for the Global Burden of Disease Study
    Global Burden of Disease Cancer Collaboration, Fitzmaurice C, Abate D, Abbasi N, Abbastabar H, Abd-Allah F, et al.
    JAMA Oncol, 2019 Dec 01;5(12):1749-1768.
    PMID: 31560378 DOI: 10.1001/jamaoncol.2019.2996
    IMPORTANCE: Cancer and other noncommunicable diseases (NCDs) are now widely recognized as a threat to global development. The latest United Nations high-level meeting on NCDs reaffirmed this observation and also highlighted the slow progress in meeting the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases and the third Sustainable Development Goal. Lack of situational analyses, priority setting, and budgeting have been identified as major obstacles in achieving these goals. All of these have in common that they require information on the local cancer epidemiology. The Global Burden of Disease (GBD) study is uniquely poised to provide these crucial data.

    OBJECTIVE: To describe cancer burden for 29 cancer groups in 195 countries from 1990 through 2017 to provide data needed for cancer control planning.

    EVIDENCE REVIEW: We used the GBD study estimation methods to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs). Results are presented at the national level as well as by Socio-demographic Index (SDI), a composite indicator of income, educational attainment, and total fertility rate. We also analyzed the influence of the epidemiological vs the demographic transition on cancer incidence.

    FINDINGS: In 2017, there were 24.5 million incident cancer cases worldwide (16.8 million without nonmelanoma skin cancer [NMSC]) and 9.6 million cancer deaths. The majority of cancer DALYs came from years of life lost (97%), and only 3% came from years lived with disability. The odds of developing cancer were the lowest in the low SDI quintile (1 in 7) and the highest in the high SDI quintile (1 in 2) for both sexes. In 2017, the most common incident cancers in men were NMSC (4.3 million incident cases); tracheal, bronchus, and lung (TBL) cancer (1.5 million incident cases); and prostate cancer (1.3 million incident cases). The most common causes of cancer deaths and DALYs for men were TBL cancer (1.3 million deaths and 28.4 million DALYs), liver cancer (572 000 deaths and 15.2 million DALYs), and stomach cancer (542 000 deaths and 12.2 million DALYs). For women in 2017, the most common incident cancers were NMSC (3.3 million incident cases), breast cancer (1.9 million incident cases), and colorectal cancer (819 000 incident cases). The leading causes of cancer deaths and DALYs for women were breast cancer (601 000 deaths and 17.4 million DALYs), TBL cancer (596 000 deaths and 12.6 million DALYs), and colorectal cancer (414 000 deaths and 8.3 million DALYs).

    CONCLUSIONS AND RELEVANCE: The national epidemiological profiles of cancer burden in the GBD study show large heterogeneities, which are a reflection of different exposures to risk factors, economic settings, lifestyles, and access to care and screening. The GBD study can be used by policy makers and other stakeholders to develop and improve national and local cancer control in order to achieve the global targets and improve equity in cancer care.

  13. Fulltext Resting Cyst Distribution and Molecular Identification of the Harmful Dinoflagellate Margalefidinium polykrikoides (Gymnodiniales, Dinophyceae) in Lampung Bay, Sumatra, Indonesia
    Thoha H, Muawanah, Bayu Intan MD, Rachman A, Sianturi OR, Sidabutar T, et al.
    Front Microbiol, 2019;10:306.
    PMID: 30846977 DOI: 10.3389/fmicb.2019.00306
    Margalefidinium polykrikoides, an unarmored dinoflagellate, was suspected to be the causative agent of the harmful algal blooms - associated with massive fish mortalities - that have occurred continually in Lampung Bay, Indonesia, since the first bloom event in October 2012. In this study, after examination of the morphology of putative M. polykrikoides-like cysts sampled in bottom sediments, cyst bed distribution of this harmful species was explored in the inner bay. Sediment samples showed that resting cysts, including several morphotypes previously reported as M. polykrikoides, were most abundant on the northern coast of Lampung Bay, ranging from 20.6 to 645.6 cysts g-1 dry sediment. Molecular phylogeny inferred from LSU rDNA revealed that the so-called Mediterranean ribotype was detected in the sediment while M. polykrikoides motile cells, four-cell chain forming in bloom conditions, belonged to the American-Malaysian ribotype. Moreover, hyaline cysts, exclusively in the form of four-cell chains, were also recorded. Overall, these results unequivocally show that the species M. polykrikoides is abundantly present, in the form of vegetative cells, hyaline and resting cysts in an Indonesian area.
  14. Fulltext Genomic analysis of Hepatitis B virus and its association with disease manifestations in Bangladesh
    Raihan R, Akbar SMF, Al Mahtab M, Takahashi K, Masumoto J, Tabassum S, et al.
    PLoS One, 2019;14(6):e0218744.
    PMID: 31251754 DOI: 10.1371/journal.pone.0218744
    The direct cytopathic effects of the hepatitis B virus (HBV) on subsequent liver damage are not fully understood in HBV-infected patients. However, associations between the prevalence of various HBV genotypes and the extent of liver damage have been reported from different parts of the world. The purpose of this study was to determine the distribution of HBV genotypes in patients with chronic HBV infection in Bangladesh, a country of 160 million people, of which approximately 3-6 million are chronically infected HBV patients. In addition, whole and partial genome sequencing of HBV was performed to evaluate the relationship between HBV mutations and genotypes. We found that 42% of the patients with low HBV DNA and normal levels of alanine aminotransferase (ALT) had HBV genotype D. In contrast, the HBV genotype C was dominant among patients with high HBV DNA levels (>2000 IU/ml) and elevated ALT and in patients with liver cirrhosis (LC) and hepatocellular carcinomas (HCC). Whole and partial genome sequences of HBV revealed that most patients with LC and HCC had HBV genotype C with mutations at the T1762/A1764 positions. It seems that Bangladesh represents a borderline country, situated within East Asia, which mainly consists of individuals with HBV genotypes B and C, whereas in the western parts of Asia, HBV genotypes A and D are prevalent. Bangladesh is, therefore, an excellent model for the comparison of the pathophysiology of three major HBV genotypes in a single population. The findings of this study suggest a possible association between HBV viral factors and the extent of liver damage in chronic HBV-infected patients.
  15. Fulltext Metal Oxide Compact Electron Transport Layer Modification for Efficient and Stable Perovskite Solar Cells
    Shahiduzzaman M, Fukaya S, Muslih EY, Wang L, Nakano M, Akhtaruzzaman M, et al.
    Materials (Basel), 2020 May 11;13(9).
    PMID: 32403454 DOI: 10.3390/ma13092207
    Perovskite solar cells (PSCs) have appeared as a promising design for next-generation thin-film photovoltaics because of their cost-efficient fabrication processes and excellent optoelectronic properties. However, PSCs containing a metal oxide compact layer (CL) suffer from poor long-term stability and performance. The quality of the underlying substrate strongly influences the growth of the perovskite layer. In turn, the perovskite film quality directly affects the efficiency and stability of the resultant PSCs. Thus, substrate modification with metal oxide CLs to produce highly efficient and stable PSCs has drawn attention. In this review, metal oxide-based electron transport layers (ETLs) used in PSCs and their systemic modification are reviewed. The roles of ETLs in the design and fabrication of efficient and stable PSCs are also discussed. This review will guide the further development of perovskite films with larger grains, higher crystallinity, and more homogeneous morphology, which correlate to higher stable PSC performance. The challenges and future research directions for PSCs containing compact ETLs are also described with the goal of improving their sustainability to reach new heights of clean energy production.
  16. Fulltext Comparison of Ranibizumab With or Without Verteporfin Photodynamic Therapy for Polypoidal Choroidal Vasculopathy: The EVEREST II Randomized Clinical Trial
    Lim TH, Lai TYY, Takahashi K, Wong TY, Chen LJ, Ruamviboonsuk P, et al.
    JAMA Ophthalmol, 2020 09 01;138(9):935-942.
    PMID: 32672800 DOI: 10.1001/jamaophthalmol.2020.2443
    Importance: The 2-year efficacy and safety of combination therapy of ranibizumab administered together with verteporfin photodynamic therapy (vPDT) compared with ranibizumab monotherapy in participants with polypoidal choroidal vasculopathy (PCV) are unclear.

    Objective: To compare treatment outcomes of ranibizumab, 0.5 mg, plus prompt vPDT combination therapy with ranibizumab, 0.5 mg, monotherapy in participants with PCV for 24 months.

    Design, Setting, and Participants: This 24-month, phase IV, double-masked, multicenter, randomized clinical trial (EVEREST II) was conducted among Asian participants from August 7, 2013, to March 2, 2017, with symptomatic macular PCV confirmed using indocyanine green angiography.

    Interventions: Participants (N = 322) were randomized 1:1 to ranibizumab, 0.5 mg, plus vPDT (combination therapy group; n = 168) or ranibizumab, 0.5 mg, plus sham PDT (monotherapy group; n = 154). All participants received 3 consecutive monthly ranibizumab injections, followed by a pro re nata regimen. Participants also received vPDT (combination group) or sham PDT (monotherapy group) on day 1, followed by a pro re nata regimen based on the presence of active polypoidal lesions.

    Main Outcomes and Measures: Evaluation of combination therapy vs monotherapy at 24 months in key clinical outcomes, treatment exposure, and safety. Polypoidal lesion regression was defined as the absence of indocyanine green hyperfluorescence of polypoidal lesions.

    Results: Among 322 participants (mean [SD] age, 68.1 [8.8] years; 225 [69.9%] male), the adjusted mean best-corrected visual acuity (BCVA) gains at month 24 were 9.6 letters in the combination therapy group and 5.5 letters in the monotherapy group (mean difference, 4.1 letters; 95% CI, 1.0-7.2 letters; P = .005), demonstrating that combination therapy was superior to monotherapy by the BCVA change from baseline to month 24. Combination therapy was superior to monotherapy in terms of complete polypoidal lesion regression at month 24 (81 of 143 [56.6%] vs 23 of 86 [26.7%] participants; P 

  17. Bioprospecting of indigenous marine microalgae with ammonium tolerance from aquaculture ponds for microalgae cultivation with ammonium-rich wastewaters
    Katayama T, Nagao N, Kasan NA, Khatoon H, Rahman NA, Takahashi K, et al.
    J Biotechnol, 2020 Nov 10;323:113-120.
    PMID: 32768414 DOI: 10.1016/j.jbiotec.2020.08.001
    We isolated fifty-two strains from the marine aquaculture ponds in Malaysia that were evaluated for their lipid production and ammonium tolerance and four isolates were selected as new ammonium tolerant microalgae with high-lipid production: TRG10-p102 Oocystis heteromucosa (Chlorophyceae); TRG10-p103 and TRG10-p105 Thalassiosira weissflogii (Bacillariophyceae); and TRG10-p201 Amphora coffeiformis (Bacillariophyceae). Eicosapentenoic acid (EPA) in three diatom strain was between 2.6 and 18.6 % of total fatty acids, which were higher than in O. heteromucosa. Only A. coffeiformi possessed arachidonic acid. Oocystis heteromucosa naturally grew at high ammonium concentrations (1.4-10 mM), whereas the growth of the other strains, T. weissflogii and A. coffeiformi, were visibly inhibited at high ammonium concentrations (>1.4 mM-NH4). However, two strains of T. weissflogii were able to grow at up to 10 mM-NH4 by gradually acclimating to higher ammonium concentrations. The ammonium tolerant strains, especially T. weissflogii which have high EPA contents, were identified as a valuable candidate for biomass production utilizing NH4-N media, such as ammonium-rich wastewater.
  18. Fulltext Taxon- and Growth Phase-Specific Antioxidant Production by Chlorophyte, Bacillariophyte, and Haptophyte Strains Isolated From Tropical Waters
    Rahman NA, Katayama T, Wahid MEA, Kasan NA, Khatoon H, Yamada Y, et al.
    Front Bioeng Biotechnol, 2020;8:581628.
    PMID: 33330417 DOI: 10.3389/fbioe.2020.581628
    Antioxidants found in microalgae play an essential role in both animals and humans, against various diseases and aging processes by protecting cells from oxidative damage. In this study, 26 indigenous tropical marine microalgae were screened. Out of the 26 screened strains, 10 were selected and were further investigated for their natural antioxidant compounds which include carotenoids, phenolics, and fatty acids collected in their exponential and stationary phases. The antioxidant capacity was also evaluated by a total of four assays, which include ABTS, DPPH, superoxide radical (O2•-) scavenging capacity, and nitric oxide (•NO-) scavenging capacity. This study revealed that the antioxidant capacity of the microalgae varied between divisions, strains, and growth phase and was also related to the content of antioxidant compounds present in the cells. Carotenoids and phenolics were found to be the major contributors to the antioxidant capacity, followed by polyunsaturated fatty acids linoleic acid (LA), eicosapentaenoic acid (EPA), arachidonic acid (ARA), and docosahexaenoic acid (DHA) compared to other fatty acids. The antioxidant capacity of the selected bacillariophytes and haptophytes was found to be positively correlated to phenolic (R2-value = 0.623, 0.714, and 0.786 with ABTS, DPPH, and •NO-) under exponential phase, and to carotenoid fucoxanthin and β-carotene (R2 value = 0.530, 0.581 with ABTS, and 0.710, 0.795 with O2•-) under stationary phase. Meanwhile, antioxidant capacity of chlorophyte strains was positively correlated with lutein, β-carotene and zeaxanthin under the exponential phase (R2 value = 0.615, 0.615, 0.507 with ABTS, and R2 value = 0.794, 0.659, and 0.509 with •NO-). In the stationary phase, chlorophyte strains were positively correlated with violaxanthin (0.755 with •NO-), neoxanthin (0.623 with DPPH, 0.610 with •NO-), and lutein (0.582 with •NO-). This study showed that antioxidant capacity and related antioxidant compound production of tropical microalgae strains are growth phase-dependent. The results can be used to improve the microalgal antioxidant compound production for application in pharmaceutical, nutraceutical, food, and feed industry.
  19. Fulltext Lipid accumulation patterns and role of different fatty acid types towards mitigating salinity fluctuations in Chlorella vulgaris
    Teh KY, Loh SH, Aziz A, Takahashi K, Effendy AWM, Cha TS
    Sci Rep, 2021 01 11;11(1):438.
    PMID: 33432049 DOI: 10.1038/s41598-020-79950-3
    Mangrove-dwelling microalgae are well adapted to frequent encounters of salinity fluctuations across their various growth phases but are lesser studied. The current study explored the adaptive changes (in terms of biomass, oil content and fatty acid composition) of mangrove-isolated C. vulgaris UMT-M1 cultured under different salinity levels (5, 10, 15, 20, 30 ppt). The highest total oil content was recorded in cultures at 15 ppt salinity (63.5% of dry weight) with uncompromised biomass productivity, thus highlighting the 'trigger-threshold' for oil accumulation in C. vulgaris UMT-M1. Subsequently, C. vulgaris UMT-M1 was further assessed across different growth phases under 15 ppt. The various short, medium and long-chain fatty acids (particularly C20:0), coupled with a high level of C18:3n3 PUFA reported at early exponential phase represents their physiological importance during rapid cell growth. Accumulation of C18:1 and C18:2 at stationary growth phase across all salinities was seen as cells accumulating substrate for C18:3n3 should the cells anticipate a move from stationary phase into new growth phase. This study sheds some light on the possibility of 'triggered' oil accumulation with uninterrupted growth and the participation of various fatty acid types upon salinity mitigation in a mangrove-dwelling microalgae.
  20. Fulltext Double-high in palmitic and oleic acids accumulation in a non-model green microalga, Messastrum gracile SE-MC4 under nitrate-repletion and -starvation cultivations
    Wan Afifudeen CL, Loh SH, Aziz A, Takahashi K, Effendy AWM, Cha TS
    Sci Rep, 2021 01 11;11(1):381.
    PMID: 33431982 DOI: 10.1038/s41598-020-79711-2
    Bioprospecting for biodiesel potential in microalgae primarily involves a few model species of microalgae and rarely on non-model microalgae species. Therefore, the present study determined changes in physiology, oil accumulation, fatty acid composition and biodiesel properties of a non-model microalga Messastrum gracile SE-MC4 in response to 12 continuous days of nitrate-starve (NS) and nitrate-replete (NR) conditions respectively. Under NS, the highest oil content (57.9%) was achieved despite reductions in chlorophyll content, biomass productivity and lipid productivity. However, under both NS and NR, palmitic acid and oleic acid remained as dominant fatty acids thus suggesting high potential of M. gracile for biodiesel feedstock consideration. Biodiesel properties analysis returned high values of cetane number (CN 61.9-64.4) and degree of unsaturation (DU 45.3-57.4) in both treatments. The current findings show the possibility of a non-model microalga to inherit superior ability over model species in oil accumulation for biodiesel development.
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