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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.
Fulltext Implementation of the ABCDEF Bundle for Critically Ill ICU Patients During the COVID-19 Pandemic: A Multi-National 1-Day Point Prevalence Study

Liu K, Nakamura K, Katsukawa H, Nydahl P, Ely EW, Kudchadkar SR, et al.

Front Med (Lausanne), 2021;8:735860.
PMID: 34778298 DOI: 10.3389/fmed.2021.735860

Background: Data regarding delivery of evidence-based care to critically ill patients in Intensive Care Units (ICU) during the COVID-19 pandemic is crucial but lacking. This study aimed to evaluate the implementation rate of the ABCDEF bundle, which is a collection of six evidence-based ICU care initiatives which are strongly recommended to be incorporated into clinical practice, and ICU diaries for patients with and without COVID-19 infections in ICUs, and to analyze the impact of COVID-19 on implementation of each element of the bundle and independent associated factors. Methods: A world-wide 1-day point prevalence study investigated the delivery of the ABCDEF bundle and ICU diary to patients without or with COVID-19 infections on 27 January 2021 via an online questionnaire. Multivariable logistic regression analysis with adjustment for patient demographics evaluated the impact of COVID-19 and identified factors in ICU administrative structures and policies independently associated with delivery. Results: From 54 countries and 135 ICUs, 1,229 patients were eligible, and 607 (49%) had COVID-19 infections. Implementation rates were: entire bundle (without COVID-19: 0% and with COVID-19: 1%), Element A (regular pain assessment: 64 and 55%), Element B (both spontaneous awakening and breathing trials: 17 and 10%), Element C (regular sedation assessment: 45 and 61%), Element D (regular delirium assessment: 39 and 35%), Element E (exercise: 22 and 25%), Element F (family engagement/empowerment: 16 and 30%), and ICU diary (17 and 21%). The presence of COVID-19 was not associated with failure to implement individual elements. Independently associated factors for each element in common between the two groups included presence of a specific written protocol, application of a target/goal, and tele-ICU management. A lower income status country and a 3:1 nurse-patient ratio were significantly associated with non-implementation of elements A, C, and D, while a lower income status country was also associated with implementation of element F. Conclusions: Regardless of COVID-19 infection status, implementation rates for the ABCDEF bundle, for each element individually and an ICU diary were extremely low for patients without and with COVID-19 infections during the pandemic. Strategies to facilitate implementation of and adherence to the complete ABCDEF bundle should be optimized and addressed based on unit-specific barriers and facilitators.
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
Normative Data and Associations of OCT Angiography Measurements of the Macula: The Singapore Malay Eye Study

Teo ZL, Sun CZ, Chong CCY, Tham YC, Takahashi K, Majithia S, et al.

Ophthalmol Retina, 2022 Nov;6(11):1080-1088.
PMID: 35580772 DOI: 10.1016/j.oret.2022.05.010

OBJECTIVE: To describe the normative quantitative parameters of the macular retinal vasculature, as well as their systemic and ocular associations using OCT angiography (OCTA).
DESIGN: Population-based, cross-sectional study.
SUBJECTS: Adults aged > 50 years were recruited from the third examination of the population-based Singapore Malay Eye Study.
METHODS: All participants underwent a standardized comprehensive examination and spectral-domain OCTA (Optovue) of the macula. OCT angiography scans that revealed pre-existing retinal disease, revealed macular pathology, and had poor quality were excluded.
MAIN OUTCOME MEASURES: The normative quantitative vessel densities of the superficial layer, deep layer, and foveal avascular zone (FAZ) were evaluated. Ocular and systemic associations with macular retinal vasculature parameters were also evaluated in a multivariable analysis using linear regression models with generalized estimating equation models.
RESULTS: We included 1184 scans (1184 eyes) of 749 participants. The mean macular superficial vessel density (SVD) and deep vessel density (DVD) were 45.1 ± 4.2% (95% confidence interval [CI], 37.8%-51.4%) and 44.4 ± 5.2% (95% CI, 36.9%-53.2%), respectively. The mean SVD and DVD were highest in the superior quadrant (48.7 ± 5.9%) and nasal quadrant (52.7 ± 4.6%), respectively. The mean FAZ area and perimeter were 0.32 ± 0.11 mm2 (95% CI, 0.17-0.51 mm) and 2.14 ± 0.38 mm (95% CI, 1.54-2.75 mm), respectively. In the multivariable regression analysis, female sex was associated with higher SVD (β = 1.25, P ≤ 0.001) and DVD (β = 0.75, P = 0.021). Older age (β = -0.67, P < 0.001) was associated with lower SVD, whereas longer axial length (β = -0.42, P = 0.003) was associated with lower DVD. Female sex, shorter axial length, and worse best-corrected distance visual acuity were associated with a larger FAZ area. No association of a range of systemic parameters with vessel density was found.
CONCLUSIONS: This study provided normative macular vasculature parameters in an adult Asian population, which may serve as reference values for quantitative interpretation of OCTA data in normal and disease states.
The harmful raphidophyte Chattonella (Raphidophyceae) in Western Pacific: Its red tides and associated fisheries damage over the past 50 years (1969-2019)

Lum WM, Benico G, Doan-Nhu H, Furio E, Leaw CP, Leong SCY, et al.

Harmful Algae, 2021 07;107:102070.
PMID: 34456025 DOI: 10.1016/j.hal.2021.102070

Red tides and associated fisheries damage caused by the harmful raphidophyte Chattonella were reassessed based on the documented local records for 50 years to understand the distribution and economic impacts of the harmful species in the Western Pacific. Blooms of Chattonella with fisheries damage have been recorded in East Asia since 1969, whereas they have been only recorded in Southeast Asia since the 1980s. Occurrences of Chattonella have been documented from six Southeast Asian countries, Indonesia, Malaysia, Philippines, Singapore, Thailand and Viet Nam, with mass mortalities mainly of farmed shrimp in 1980-1990s, and farmed fish in 2000-2010s. These occurrences have been reported with the names of C. antiqua, C. marina, C. ovata, C. subsalsa and Chattonella sp., owing to the difficulty of microscopic species identification, and many were not supported with molecular data. To determine the distribution of C. marina complex and C. subsalsa in Southeast Asia, molecular phylogeny and microscopic observation were also carried out for cultures obtained from Indonesia, Malaysia, Japan, Philippines, Russia, Singapore and Thailand. The results revealed that only the genotype of C. marina complex has been detected from East Asia (China, Japan, Korea and Russia), whereas both C. marina complex (Indonesia and Malaysia) and C. subsalsa (Philippines, Singapore and Thailand) were found in Southeast Asia. Ejection of mucocysts has been recognized as a diagnostic character of C. subsalsa, but it was also observed in our cultures of C. marina isolated from Indonesia, Malaysia, Japan, and Russia. Meanwhile, the co-occurrences of the two harmful Chattonella species in Southeast Asia, which are difficult to distinguish solely based on their morphology, suggest the importance of molecular identification of Chattonella genotypes for further understanding of their distribution and negative impacts.
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.
Fulltext Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life Years for 29 Cancer Groups From 2010 to 2019: A Systematic Analysis for the Global Burden of Disease Study 2019

Global Burden of Disease 2019 Cancer Collaboration, Kocarnik JM, Compton K, Dean FE, Fu W, Gaw BL, et al.

JAMA Oncol, 2022 Mar 01;8(3):420-444.
PMID: 34967848 DOI: 10.1001/jamaoncol.2021.6987

IMPORTANCE: The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) provided systematic estimates of incidence, morbidity, and mortality to inform local and international efforts toward reducing cancer burden.
OBJECTIVE: To estimate cancer burden and trends globally for 204 countries and territories and by Sociodemographic Index (SDI) quintiles from 2010 to 2019.
EVIDENCE REVIEW: The GBD 2019 estimation methods were used to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life years (DALYs) in 2019 and over the past decade. Estimates are also provided by quintiles of the SDI, a composite measure of educational attainment, income per capita, and total fertility rate for those younger than 25 years. Estimates include 95% uncertainty intervals (UIs).
FINDINGS: In 2019, there were an estimated 23.6 million (95% UI, 22.2-24.9 million) new cancer cases (17.2 million when excluding nonmelanoma skin cancer) and 10.0 million (95% UI, 9.36-10.6 million) cancer deaths globally, with an estimated 250 million (235-264 million) DALYs due to cancer. Since 2010, these represented a 26.3% (95% UI, 20.3%-32.3%) increase in new cases, a 20.9% (95% UI, 14.2%-27.6%) increase in deaths, and a 16.0% (95% UI, 9.3%-22.8%) increase in DALYs. Among 22 groups of diseases and injuries in the GBD 2019 study, cancer was second only to cardiovascular diseases for the number of deaths, years of life lost, and DALYs globally in 2019. Cancer burden differed across SDI quintiles. The proportion of years lived with disability that contributed to DALYs increased with SDI, ranging from 1.4% (1.1%-1.8%) in the low SDI quintile to 5.7% (4.2%-7.1%) in the high SDI quintile. While the high SDI quintile had the highest number of new cases in 2019, the middle SDI quintile had the highest number of cancer deaths and DALYs. From 2010 to 2019, the largest percentage increase in the numbers of cases and deaths occurred in the low and low-middle SDI quintiles.
CONCLUSIONS AND RELEVANCE: The results of this systematic analysis suggest that the global burden of cancer is substantial and growing, with burden differing by SDI. These results provide comprehensive and comparable estimates that can potentially inform efforts toward equitable cancer control around the world.
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.