Global Burden of Disease Cancer Collaboration 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 equ...

Background The burden of inflammatory bowel disease (IBD) is rising globally, with substantial variation in levels and trends of disease in different countries and regions. Understanding these geographical differences is crucial for formulating effective strategies for preventing and treating IBD. We report the prevalence, mortality, and overall burden of IBD in 195 countries and territories between 1990 and 2017, based on data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017.Methods We modelled mortality due to IBD using a standard Cause of Death Ensemble model including data mainly from vital registrations. To estimate the non-fatal burden, we used data presented in primary studies, hospital discharges, and claims data, and used DisMod-MR 2.1, a Bayesian meta-regression tool, to ensure consistency between measures. Mortality, prevalence, years of life lost (YLLs) due to premature death, years lived with disability (YLDs), and disability-adjusted life-years (DALYs) were estimated. All of the estimates were reported as numbers and rates per 100 000 population, with 95% uncertainty intervals (UI). Findings In 2017, there were 6•8 million (95% UI 6•4-7•3) cases of IBD globally. The age-standardised prevalence rate increased from 79•5 (75•9-83•5) per 100 000 population in 1990 to 84•3 (79•2-89•9) per 100 000 population in 2017. The age-standardised death rate decreased from 0•61 (0•55-0•69) per 100 000 population in 1990 to 0•51 (0•42-0•54) per 100 000 population in 2017. At the GBD regional level, the highest age-standardised prevalence rate in 2017 occurred in high-income North America (422•0 [398•7-446•1] per 100 000) and the lowest agestandardised prevalence rates were observed in the Caribbean (6•7 [6•3-7•2] per 100 000 population). High Sociodemographic Index (SDI) locations had the highest age-standardised prevalence rate, while low SDI regions had the lowest age-standardised prevalence rate. At the national level, the USA had the highest age-standardised prevalence rate (464•5 [438•6-490•9] per 100 000 population), followed by the UK (449•6 [420•6-481•6] per 100 000). Vanuatu had the highest age-standardised death rate in 2017 (1•8 [0•8-3•2] per 100 000 population) and Singapore had the lowest (0•08 [0•06-0•14] per 100 000 population). The total YLDs attributed to IBD almost doubled over the study period, from 0•56 million (0•39-0•77) in 1990 to 1•02 million (0•71-1•38) in 2017. The agestandardised rate of DALYs decreased from 26•5 (21•0-33•0) per 100 000 population in 1990 to 23•2 (19•1-27•8) per 100 000 population in 2017.Interpretation The prevalence of IBD increased substantially in many regions from 1990 to 2017, which might pose a substantial social and economic burden on governments and health systems in the coming years. Our findings can be useful for policy makers developing strategies to tackle IBD, including the education of specialised personnel to address the burden of this complex disease.Funding Bill & Melinda Gates Foundation.

Summary Background Comprehensive and comparable estimates of health spending in each country are a key input for health policy and planning, and are necessary to support the achievement of national and international health goals. Previous studies have tracked past and projected future health spending until 2040 and shown that, with economic development, countries tend to spend more on health per capita, with a decreasing share of spending from development assistance and out-of-pocket sources. We aimed to characterise the past, present, and predicted future of global health spending, with an emphasis on equity in spending across countries. Methods We estimated domestic health spending for 195 countries and territories from 1995 to 2016, split into three categories—government, out-of-pocket, and prepaid private health spending—and estimated development assistance for health (DAH) from 1990 to 2018. We estimated future scenarios of health spending using an ensemble of linear mixed-effects models with time series specifications to project domestic health spending from 2017 through 2050 and DAH from 2019 through 2050. Data were extracted from a broad set of sources tracking health spending and revenue, and were standardised and converted to inflation-adjusted 2018 US dollars. Incomplete or low-quality data were modelled and uncertainty was estimated, leading to a complete data series of total, government, prepaid private, and out-of-pocket health spending, and DAH. Estimates are reported in 2018 US dollars, 2018 purchasing-power parity-adjusted dollars, and as a percentage of gross domestic product. We used demographic decomposition methods to assess a set of factors associated with changes in government health spending between 1995 and 2016 and to examine evidence to support the theory of the health financing transition. We projected two alternative future scenarios based on higher government health spending to assess the potential ability of governments to generate more resources for health. Findings Between 1995 and 2016, health spending grew at a rate of 4·00% (95% uncertainty interval 3·89–4·12) annually, although it grew slower in per capita terms (2·72% [2·61–2·84]) and increased by less than $1 per capita over this period in 22 of 195 countries. The highest annual growth rates in per capita health spending were observed in upper-middle-income countries (5·55% [5·18–5·95]), mainly due to growth in government health spending, and in lower-middle-income countries (3·71% [3·10–4·34]), mainly from DAH. Health spending globally reached $8·0 trillion (7·8–8·1) in 2016 (comprising 8·6% [8·4–8·7] of the global economy and $10·3 trillion [10·1–10·6] in purchasing-power parity-adjusted dollars), with a per capita spending of US$5252 (5184–5319) in high-income countries, $491 (461–524) in upper-middle-income countries, $81 (74–89) in lower-middle-income countries, and $40 (38–43) in low-income countries. In 2016, 0·4% (0·3–0·4) of heal...

Background: Ulcerative colitis (UC) is a form of inflammatory bowel disease (IBD). There are several chemical and herbal drug regimens for treatment of UC. Objectives: The aims of this study were to investigate the effects of Hypericum perforatum on histopathological and tissue malondialdehyde (MDA) level of colonic tissue in rat with induced UC. Materials and Methods: Two milliliters of 3% acetic acid was administered into the colon to induce UC. Seventy rats were divided into seven equal groups. Groups I and II received 1 mL of 600 and 300 mg/kg H. perforatum extract orally per day respectively; groups III and IV received 1 mL of 20% and 10% intra-colonic gel form of H. perforatum extract daily respectively; group V as positive control received 2 mL of intra-colonic asacol; group VI was a negative control receiving 0.5 mL/kg of normal saline after induction of UC; group VII received just intra-colonic gel base. All the animals were evaluated for histological changes and tissue MDA level seven days after the treatment. Results: H. perforatum extract in the two forms of trans-rectal and oral administration on the seventh day after the therapy could result in a more healing effect on acetic acid-induced damaged colonic tissue with a reduction in the MDA activity. In trans-rectal administration, the 20% gel form had a better healing response than the 10% gel form and was prominently more effect on the seventh day of the therapy. In oral administration of strawberry extract, the 600 mg/kg dosage had a better healing response than the 300 mg/kg and was significantly more effective on the seventh day of therapy. Conclusions: So H. perforatum may be considered as a treatment of choice for UC especially in gel form to broaden the current therapy options of the disease.

This work analyzes the effects of radiofrequency-electromagnetic field (RF-EMF) exposure on the reproductive system of male rats, assessed by measuring circulating levels of FSH, LH, inhibin B, activin B, prolactin, and testosterone. Twenty adult male Sprague-Dawley rats (180 ± 10 g) were exposed to 900 MHz RF-EMF in four equal separated groups. The duration of exposure was 1, 2, and 4 h/day over a period of 30 days and sham-exposed animals were kept under the same environmental conditions as the exposed group except with no RF-EMF exposure. Before the exposure, at 15 and 30 days of exposure, determination of the abovementioned hormone levels was performed using ELISA. At the end of the experiment, FSH and LH values of the long time exposure (LTE) group were significantly higher than the sham-exposed group (p < 0.05). Serum activin B and prolactin in the LTE group showed significant increase and inhibin B showed significant decrease than sham and short time exposed (STE) groups after 30 days RF-EMF exposure (p < 0.05). Also, a significant decrease in serum testosterone levels in the LTE group was found compared to short and moderate time exposed (MTE) groups after 30 days RF-EMF exposure (p < 0.05). Results suggest that reproductive hormone levels are disturbed as a result of RF-EMF exposure and it may possibly affect reproductive functions. However, testosterone and inhibin B concentrations as a fertility marker and spermatogenesis were decreased significantly.

BACKGROUND Some evidence, not in large study populations, suggests that nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) share common interactions. We aimed to determine the prevalence of NAFLD and MetS in a large population registered to Kavar Cohort Study center. We also assessed the role of each component of MetS in NAFLD existence. METHODS Data were obtained from 3415 volunteers who called and refereed to our center. Complete anthropometric and laboratory measurement and abdominal ultrasonography was done for these individuals to screen NAFLD and its grade. A questionnaire was also used to obtain information on demographical and medical history and alcohol consumption. MetS was defined in all participants based on the National Cholesterol Education Program Adult Treatment Panel III (2001) (NCEP/ATP-III) and criteria for clinical diagnosis of metabolic syndrome in Iranian adults (CCDMIA). RESULTS Among the refereed individuals, 2980 peoples were aged ≥18 years with male to women ratio of 1:2.45. NAFLD was diagnosed by ultrasound in 32.9% and 27.4% of men and women, respectively. MetS was detected in 65.9 and 64.6 of the patients with NAFLD (based on NCEP/ATP-III) and in 30.1% and 73.7% (based on CCDMIA) of men and women, respectively. There were no significant differences between two gender in none of the components (p>0.05). Although, OR for hyperglycemia and abdominal obesity were approximately high in CCDMIA criteria (0.9613 and 1.2082, respectively), the differences were not statistically significant. CONCLUSION NAFLD was associated with MetS. However, it was not possible to determine whether NAFLD predating the development of MetS

Generation of neurons from human induced pluripotent stem cells (hiPSCs) overcomes the limited access to human brain samples and greatly facilitates the progress of research in neurological diseases. However, it is still a challenge to generate a particular neuronal subtype with high purity and yield for determining the pathogenesis of diseased neurons using biochemical approaches. Motor neurons (MNs) are a specialized neuronal subtype responsible for governing both autonomic and volitional movement. Dysfunctions in MNs are implicated in a variety of movement diseases, such as amyotrophic lateral sclerosis (ALS). In this study, we generated functional MNs from human iPSCs via lentiviral delivery of transcription factors. Moreover, we optimized induction conditions by using different combinations of transcription factors and found that a single lentiviral vector expressing three factors (NGN2, ISL1, and LHX3) is necessary and sufficient to induce iPSC-MNs. These MNs robustly expressed general neuron markers (MAP2, SMI-32, and TUBB3), MN-specific markers (HB9 and ChAT), and showed electrical maturation and firing of action potentials within 3 weeks. This approach significantly improved the neuronal survival, yield, and purity, making it feasible to obtain abundant materials for biochemical studies in modeling movement diseases.

Nucleocytoplasmic transport (NCT) across the nuclear envelope is precisely regulated in eukaryotic cells, and it plays critical roles in maintenance of cellular homeostasis. Accumulating evidence has demonstrated that dysregulations of NCT are implicated in aging and age-related neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer’s disease (AD), and Huntington disease (HD). This is an emerging research field. The molecular mechanisms underlying impaired NCT and the pathogenesis leading to neurodegeneration are not clear. In this review, we comprehensively described the components of NCT machinery, including nuclear envelope (NE), nuclear pore complex (NPC), importins and exportins, RanGTPase and its regulators, and the regulatory mechanisms of nuclear transport of both protein and transcript cargos. Additionally, we discussed the possible molecular mechanisms of impaired NCT underlying aging and neurodegenerative diseases, such as ALS/FTD, HD, and AD.