Multimodal endoscopic system based on multispectral and photometric stereo imaging and analysis

We propose a multimodal endoscopic system based on white light (WL), multispectral (MS), and photometric stereo (PS) imaging for the examination of colorectal cancer (CRC). Recently, the enhancement of the diagnostic accuracy of CRC colonoscopy has been reported; however, tumor diagnosis for a variety of lesion types remains challenging using current endoscopy. In this study, we demonstrate that our developed system can simultaneously discriminate tumor distributions and provide three-dimensional (3D) morphological information about the colon surface using the WL, MS, and PS imaging modalities. The results demonstrate that the proposed system has considerable potential for CRC diagnosis. © 2019, OSA - The Optical Society. All rights reserved.1

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Five insights from the Global Burden of Disease Study 2019

The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a rules-based synthesis of the available evidence on levels and trends in health outcomes, a diverse set of risk factors, and health system responses. GBD 2019 covered 204 countries and territories, as well as first administrative level disaggregations for 22 countries, from 1990 to 2019. Because GBD is highly standardised and comprehensive, spanning both fatal and non-fatal outcomes, and uses a mutually exclusive and collectively exhaustive list of hierarchical disease and injury causes, the study provides a powerful basis for detailed and broad insights on global health trends and emerging challenges. GBD 2019 incorporates data from 281 586 sources and provides more than 3.5 billion estimates of health outcome and health system measures of interest for global, national, and subnational policy dialogue. All GBD estimates are publicly available and adhere to the Guidelines on Accurate and Transparent Health Estimate Reporting. From this vast amount of information, five key insights that are important for health, social, and economic development strategies have been distilled. These insights are subject to the many limitations outlined in each of the component GBD capstone papers.Peer reviewe

Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950-2019 : a comprehensive demographic analysis for the Global Burden of Disease Study 2019

Background: Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019. Methods: 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10–14 and 50–54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed age-specific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a Bayesian hierarchical cohort component model that analysed estimated age-specific fertility and mortality rates along with 1250 censuses and 747 population registry years. We classified location-years into seven categories on the basis of the natural rate of increase in population (calculated by subtracting the crude death rate from the crude birth rate) and the net migration rate. We computed healthy life expectancy (HALE) using years lived with disability (YLDs) per capita, life tables, and standard demographic methods. Uncertainty was propagated throughout the demographic estimation process, including fertility, mortality, and population, with 1000 draw-level estimates produced for each metric. Findings: The global TFR decreased from 2·72 (95% uncertainty interval [UI] 2·66–2·79) in 2000 to 2·31 (2·17–2·46) in 2019. Global annual livebirths increased from 134·5 million (131·5–137·8) in 2000 to a peak of 139·6 million (133·0–146·9) in 2016. Global livebirths then declined to 135·3 million (127·2–144·1) in 2019. Of the 204 countries and territories included in this study, in 2019, 102 had a TFR lower than 2·1, which is considered a good approximation of replacement-level fertility. All countries in sub-Saharan Africa had TFRs above replacement level in 2019 and accounted for 27·1% (95% UI 26·4–27·8) of global livebirths. Global life expectancy at birth increased from 67·2 years (95% UI 66·8–67·6) in 2000 to 73·5 years (72·8–74·3) in 2019. The total number of deaths increased from 50·7 million (49·5–51·9) in 2000 to 56·5 million (53·7–59·2) in 2019. Under-5 deaths declined from 9·6 million (9·1–10·3) in 2000 to 5·0 million (4·3–6·0) in 2019. Global population increased by 25·7%, from 6·2 billion (6·0–6·3) in 2000 to 7·7 billion (7·5–8·0) in 2019. In 2019, 34 countries had negative natural rates of increase; in 17 of these, the population declined because immigration was not sufficient to counteract the negative rate of decline. Globally, HALE increased from 58·6 years (56·1–60·8) in 2000 to 63·5 years (60·8–66·1) in 2019. HALE increased in 202 of 204 countries and territories between 2000 and 2019

Widespread Use of Antibiotics, Pesticides, and Other Aqua-Chemicals in Finfish Aquaculture in Rajshahi District of Bangladesh

Aquaculture is the fastest-growing, most dynamic, and vital food-producing sector compared to other food-producing industries. However, aquaculture production is hampered by a variety of bacterial, viral, fungal, and parasitic diseases. Fish farmers routinely apply various types of aqua-chemicals, particularly antibiotics and pesticides, to reduce the disease burden. Antibiotics and pesticides are widely used to increase fish production around the world, including Bangladesh. Between March 2020 and February 2021, a survey was conducted via face-to-face interviews with fish farmers in the Rajshahi district, Bangladesh, to determine the current status of the use of antibiotics, pesticides, and other aqua-chemicals in the rearing of freshwater finfishes. Nine active antibiotics ingredients belonging to 11 trade names of antibiotics, various pesticides, numerous disinfectants, and aqua-chemicals were found to be used in finfish rearing. The renamycin (active ingredient: oxytetracycline) was most commonly used antibiotics by freshwater finfish farmers in the study areas. In case of pesticides, sumithion and timsen were found to be used mostly by fish farmers. In addition, four distinct probiotics were found to be used in aquaculture in the study areas. The present study revealed several issues related to the use of aqua-drugs in the study areas. For instance, the majority of fish farmers (88%) lacked knowledge in the use of aqua-chemicals and antibiotics, and 81% of fish farmers were unaware about the effective dosages of chemicals in fish farming. Thirty seven percent of fish farmers in the study areas reported the indiscriminate use of chemicals. Furthermore, a considerable proportion of fish farmers (72%) reported ignorance about the residual effects of the aqua-chemicals on the aquatic environment and human health. As a result, this preliminary study suggests that the use of antibiotics, pesticides, and other aqua-chemicals in aquaculture should be strictly monitored and controlled by the responsible authorities of Bangladesh. Moreover, further research needs to be expanded on the detection of residues from aqua-drugs and antibiotics in the aquaculture system, and their consequences on the ecosystem and human health

Direct removal of circulating leukemia cells by magnetic hyperthermia

Statement of Purpose: Removal of cancer cells in the blood system is an important therapeutics for leukemia patients. Chemotherapy has been widely used to remove cancer cells in the bloodstream, however, side effects have been a serious problem in the process. In this study, leukemia cell-specific removal directly in the bloodstream was performed in a leukemia animal model, AKR mouse, by using target-specific magnetic hyperthermia. Magnetic hyperthermia has been widely reported in an animal xenograft model, and most of them were performed to reduce tumor cell masses artificially prepared in mouse body. This study proposes a possible method to treat genetically modified animal model of leukemia by treatment of iron oxide magnetic particles modified with a specific antibody targeted to leukemia cells, anti-EpCAM antibody, and subsequent irradiation of magnetic field to the whole body of animals. Heat induction by iron oxide nanoparticles under magnetic field induced the removal of attached leukemia cells on the iron oxide nanoparticles. Methods: EpCAM antibody-immobilized iron oxide nanoparticles (E-MNPs, Myltenyi Biotec Inc.) were injected to AKR mice, as a leukemia animal model. A home-made magnetic set-up was used to irradiate the magnetic field on the whole body of mice. The number of leukemia cells was counted using a single cell analysis system (CelSee Inc.) and histological analysis. Thymus, the origin of T-cell type leukemia, was also analyzed for the removal of cancer cells, by Tunnel assay. Results: When MOLT-3 cells (leukemia T-cells) were treated E-MNPs and subsequent magnetic irradiation, the cell proliferation was decreased to 87% of control cells which were not irradiated to the magnetic field. In AKR mice, the number of leukemia cells in the bloodstream following intravenous injection of E-MNPs and subsequent hyperthermic treatment was reduced to 25% of control mice (Figure 1). The removal efficiency of leukemia cells by magnetic hyperthermia directly in the bloodstream was nearly 75%. Tunnel assay analysis also supported that hyperthermic treatment with E-MNPs could induce the apoptosis of leukemia cells in the thymus (Figure 2). The histological analysis showed that there were no side-effects by treatment of E-MNPs and irradiation of the magnetic field to the whole body of mice. Conclusions: Until now, most of the studies on magnetic hyperthermia have reported the effect of magnetic particles to reduce the tumor mass in solid tumor xenograft. In this study, magnetic particles could be targeted to circulating leukemia cells specifically. The target-specific magnetic hyperthermia caused a decrease of cancer cells by induction of heat to the microenvironment of magnetic particles. This study proposes a new approach of leukemia therapy using a new nanomedicine optimized for magnetic hyperthermia directly in the circulating system in vivo.

Direct removal of circulating leukemia cells by magnetic hyperthermia

Statement of Purpose: Removal of cancer cells in the blood system is an important therapeutics for leukemia patients. Chemotherapy has been widely used to remove cancer cells in the bloodstream, however, side effects have been a serious problem in the process. In this study, leukemia cell-specific removal directly in the bloodstream was performed in a leukemia animal model, AKR mouse, by using target-specific magnetic hyperthermia. Magnetic hyperthermia has been widely reported in an animal xenograft model, and most of them were performed to reduce tumor cell masses artificially prepared in mouse body. This study proposes a possible method to treat genetically modified animal model of leukemia by treatment of iron oxide magnetic particles modified with a specific antibody targeted to leukemia cells, anti-EpCAM antibody, and subsequent irradiation of magnetic field to the whole body of animals. Heat induction by iron oxide nanoparticles under magnetic field induced the removal of attached leukemia cells on the iron oxide nanoparticles. Methods: EpCAM antibody-immobilized iron oxide nanoparticles (E-MNPs, Myltenyi Biotec Inc.) were injected to AKR mice, as a leukemia animal model. A home-made magnetic set-up was used to irradiate the magnetic field on the whole body of mice. The number of leukemia cells was counted using a single cell analysis system (CelSee Inc.) and histological analysis. Thymus, the origin of T-cell type leukemia, was also analyzed for the removal of cancer cells, by Tunnel assay. Results: When MOLT-3 cells (leukemia T-cells) were treated E-MNPs and subsequent magnetic irradiation, the cell proliferation was decreased to 87% of control cells which were not irradiated to the magnetic field. In AKR mice, the number of leukemia cells in the bloodstream following intravenous injection of E-MNPs and subsequent hyperthermic treatment was reduced to 25% of control mice (Figure 1). The removal efficiency of leukemia cells by magnetic hyperthermia directly in the bloodstream was nearly 75%. Tunnel assay analysis also supported that hyperthermic treatment with E-MNPs could induce the apoptosis of leukemia cells in the thymus (Figure 2). The histological analysis showed that there were no side-effects by treatment of E-MNPs and irradiation of the magnetic field to the whole body of mice. Conclusions: Until now, most of the studies on magnetic hyperthermia have reported the effect of magnetic particles to reduce the tumor mass in solid tumor xenograft. In this study, magnetic particles could be targeted to circulating leukemia cells specifically. The target-specific magnetic hyperthermia caused a decrease of cancer cells by induction of heat to the microenvironment of magnetic particles. This study proposes a new approach of leukemia therapy using a new nanomedicine optimized for magnetic hyperthermia directly in the circulating system in vivo

In vivo removal of radioactive cesium compound using Prussian blue-deposited iron oxide nanoparticles

Aim: To mitigate the side effects of medical treatment by Prussian blue (PB), a well-known adsorbent for radioactive cesium (Cs), PB-deposited magnetic nanoparticles (MNPs), were prepared and analyzed on the adsorbent capacity for Cs removal. Materials & methods: The PB-deposited MNPs were prepared by photo-deposition method and investigated for their Cs adsorption properties in vitro and in vivo. The distribution of the adsorbents was also evaluated in C57BL/6 mice. Results: PB-deposited MNPs provided an improved adsorbent capacity for Cs removal and reduced toxicity to blood cells compared with those of bulk PB. Conclusion: PB-deposited MNPs could be considered as an alternative of PB-based medicine to reduce the possible hazards caused by high dose of PB intake. © 2019 Future Medicine Ltd.1

Targeted removal of leukemia cells from the circulating system by whole-body magnetic hyperthermia in mice

Until now, magnetic hyperthermia was used to remove solid tumors by targeting magnetic nanoparticles (MNPs) to tumor sites. In this study, leukemia cells in the bloodstream were directly removed by whole-body hyperthermia, using leukemia cell-specific MNPs. An epithelial cellular adhesion molecule (EpCAM) antibody was immobilized on the surface of MNPs (EpCAM-MNPs) to introduce the specificity of MNPs to leukemia cells. The viability of THP1 cells (human monocytic leukemia cells) was decreased to 40.8% of that in control samples by hyperthermia using EpCAM-MNPs. In AKR mice, an animal model of lymphoblastic leukemia, the number of leukemia cells was measured following the intravenous injection of EpCAM-MNPs and subsequent whole-body hyperthermia treatment. The result showed that the leukemia cell number was also decreased to 43.8% of that without the treatment of hyperthermia, determined by Leishman staining of leukemia cells. To support the results, simulation analysis of heat transfer from MNPs to leukemia cells was performed using COMSOL Multiphysics simulation software. The surface temperature of leukemia cells adhered to EpCAM-MNPs was predicted to be increased to 82 °C, whereas the temperature of free cells without adhered MNPs was predicted to be 38 °C. Taken together, leukemia cells were selectively removed by magnetic hyperthermia from the bloodstream, because EpCAM-modified magnetic particles were specifically attached to leukemia cell surfaces. This approach has the potential to remove metastatic cancer cells, and pathogenic bacteria and viruses floating in the bloodstream. © 2020 The Royal Society of Chemistry.1