Background: Recent evidence suggests that stroke is increasing as a cause of morbidity and mortality in younger adults, where it carries particular significance for working individuals. Accurate and up-to-date estimates of stroke burden are important for planning stroke prevention and management in younger adults. Objectives: This study aims to estimate prevalence, mortality and disability-adjusted life years (DALYs) and their trends for total, ischemic stroke (IS) and hemorrhagic stroke (HS) in the world for 1990-2013 in adults aged 20-64 years. Methodology: Stroke prevalence, mortality and DALYs were estimated using the Global Burden of Disease (GBD) 2013 methods. All available data on rates of stroke incidence, excess mortality, prevalence and death were collected. Statistical models were used along with country-level covariates to estimate country-specific stroke burden. Stroke-specific disability weights were used to compute years lived with disability and DALYs. Means and 95% uncertainty intervals (UIs) were calculated for prevalence, mortality and DALYs. The median of the percent change and 95% UI were determined for the period from 1990 to 2013. Results: In 2013, in younger adults aged 20-64 years, the global prevalence of HS was 3,725,085 cases (95% UI 3,548,098-3,871,018) and IS was 7,258,216 cases (95% UI 6,996,272-7,569,403). Globally, between 1990 and 2013, there were significant increases in absolute numbers and prevalence rates of both HS and IS for younger adults. There were 1,483,707 (95% UI 1,340,579-1,658,929) stroke deaths globally among younger adults but the number of deaths from HS (1,047,735 (95% UI 945,087-1,184,192)) was significantly higher than the number of deaths from IS (435,972 (95% UI 354,018-504,656)). There was a 20.1% (95% UI -23.6 to -10.3) decline in the number of total stroke deaths among younger adults in developed countries but a 36.7% (95% UI 26.3-48.5) increase in developing countries. Death rates for all strokes among younger adults declined significantly in developing countries from 47 (95% UI 42.6-51.7) in 1990 to 39 (95% UI 35.0-43.8) in 2013. Death rates for all strokes among younger adults also declined significantly in developed countries from 33.3 (95% UI 29.8-37.0) in 1990 to 23.5 (95% UI 21.1-26.9) in 2013. A significant decrease in HS death rates for younger adults was seen only in developed countries between 1990 and 2013 (19.8 (95% UI 16.9-22.6) and 13.7 (95% UI 12.1-15.9)) per 100,000). No significant change was detected in IS death rates among younger adults. The total DALYs from all strokes in those aged 20-64 years was 51,429,440 (95% UI 46,561,382-57,320,085). Globally, there was a 24.4% (95% UI 16.6-33.8) increase in total DALY numbers for this age group, with a 20% (95% UI 11.7-31.1) and 37.3% (95% UI 23.4-52.2) increase in HS and IS numbers, respectively. Conclusions: Between 1990 and 2013, there were significant increases in prevalent cases, total deaths and DALYs due to HS and IS in younger adults aged 20-64 years. Death and DALY rates declined in both developed and developing countries but a significant increase in absolute numbers of stroke deaths among younger adults was detected in developing countries. Most of the burden of stroke was in developing countries. In 2013, the greatest burden of stroke among younger adults was due to HS. While the trends in declining death and DALY rates in developing countries are encouraging, these regions still fall far behind those of developed regions of the world. A more aggressive approach toward primary prevention and increased access to adequate healthcare services for stroke is required to substantially narrow these disparities.
Background: There is increasing recognition of stroke as an important contributor to childhood morbidity and mortality. Current estimates of global childhood stroke burden and its temporal trends are sparse. Accurate and up-to-date estimates of childhood stroke burden are important for planning research and the resulting evidence-based strategies for stroke prevention and management. Objectives: To estimate the prevalence, mortality and disability-adjusted life years (DALYs) for ischemic stroke (IS), hemorrhagic stroke (HS) and all stroke types combined globally from 1990 to 2013. Methodology: Stroke prevalence, mortality and DALYs were estimated using the Global Burden of Disease 2013 methods. All available data on stroke-related incidence, prevalence, excess mortality and deaths were collected. Statistical models and country-level covariates were employed to produce comprehensive and consistent estimates of prevalence and mortality. Stroke-specific disability weights were used to estimate years lived with disability and DALYs. Means and 95% uncertainty intervals (UIs) were calculated for prevalence, mortality and DALYs. The median of the percent change and 95% UI were determined for the period from 1990 to 2013. Results: In 2013, there were 97,792 (95% UI 90,564-106,016) prevalent cases of childhood IS and 67,621 (95% UI 62,899-72,214) prevalent cases of childhood HS, reflecting an increase of approximately 35% in the absolute numbers of prevalent childhood strokes since 1990. There were 33,069 (95% UI 28,627-38,998) deaths and 2,615,118 (95% UI 2,265,801-3,090,822) DALYs due to childhood stroke in 2013 globally, reflecting an approximately 200% decrease in the absolute numbers of death and DALYs in childhood stroke since 1990. Between 1990 and 2013, there were significant increases in the global prevalence rates of childhood IS, as well as significant decreases in the global death rate and DALYs rate of all strokes in those of age 0-19 years. While prevalence rates for childhood IS and HS decreased significantly in developed countries, a decline was seen only in HS, with no change in prevalence rates of IS, in developing countries. The childhood stroke DALY rates in 2013 were 13.3 (95% UI 10.6-17.1) for IS and 92.7 (95% UI 80.5-109.7) for HS per 100,000. While the prevalence of childhood IS compared to childhood HS was similar globally, the death rate and DALY rate of HS was 6- to 7-fold higher than that of IS. In 2013, the prevalence rate of both childhood IS and HS was significantly higher in developed countries than in developing countries. Conversely, both death and DALY rates for all stroke types were significantly lower in developed countries than in developing countries in 2013. Men showed a trend toward higher childhood stroke death rates (1.5 (1.3-1.8) per 100,000) than women (1.1 (0.9-1.5) per 100,000) and higher childhood stroke DALY rates (120.1 (100.8-143.4) per 100,000) than women (90.9 (74.6-122.4) per 100,000) globally in 2013. Conclusions: Globally, between 1990 and 2013, there was a significant increase in the absolute number of prevalent childhood strokes, while absolute numbers and rates of both deaths and DALYs declined significantly. The gap in childhood stroke burden between developed and developing countries is closing; however, in 2013, childhood stroke burden in terms of absolute numbers of prevalent strokes, deaths and DALYs remained much higher in developing countries. There is an urgent need to address these disparities with both global and country-level initiatives targeting prevention as well as improved access to acute and chronic stroke care.
Immunization is one of the most significant achievements of public health over the last 100 years. Recently, however, people have been increasingly refusing to vaccinate. There are a large number of separate studies on how pervasive this behavior is and what factors influence it, but no systematic review has been undertaken so far that looked at these studies as a whole. To conduct an analysis of studies that examine vaccine refusal and negative attitudes towards vaccination, focusing on the methodological approaches to the study of these problems and evaluation of their quality. A systematic review of English-language studies published between 1980 and 2015, using the Web of Science™ Core Collection database. The final review dealt with 31 papers. The studies in question were mainly conducted in North America and Western Europe. They were published three years after conclusion, on average. We have identified five different approaches to the study of these problems: 1) studies of parents’ attitudes and behavior; 2) analysis of vaccination records; 3) studies of attitudes and behavior among the general population; 4) studies of medical professionals’ attitudes, behavior, and experience; and 5) others. We found that theoretical models were not commonly used at the planning stage, while the studies also lacked a common approach to the operationalization of vaccine refusal, as well as of negative attitudes towards vaccination. Several promising directions have been identified for future studies on vaccine refusal and negative attitudes towards vaccination.
A positive-deviance control–case life history study of injection drug users (IDUs) in New York City who had injected drugs for 8–15 years compared 21 IDUs who were antibody negative for both HIV and hepatitis C with 3 infected with both viruses and 11 infected with hepatitis C virus but not HIV. Eligible subjects were referred from other research studies and from community organizations that conduct testing for HIV and hepatitis C virus. Data were collected during 2005–2008 and were analyzed using life history and grounded theory approaches. They support grounded hypotheses that IDUs who are able to attain symbiotic goals like avoiding withdrawal and maintaining social support are assisted thereby in remaining uninfected with HIV or hepatitis C. These hypotheses should be tested using cohort studies and prevention trials to see if helping IDUs attain symbiotic goals reduces infection risk. The study’s limitations are noted.
Novel derivatives of tris(indol-3-yl)methane and tris(indol-3-yl)methylium salts with the alkyl substituents at the N-atoms of the indole rings were synthesized. An easy substitution of indole rings in trisindolylmethanes for other indoles under the action of acids is demonstrated, and the mechanism of substitution is discussed. To obtain trisindolylmethylium salts, the environmentally safe method of oxidation of trisindolylmethanes with air oxygen in acidic conditions was developed. Tris(1-alkylindol-3-yl)methanes and tris(1-alkylindol-3-yl)methylium salts represent three-bladed molecular propellers whose physico-chemical and biological properties strongly depend on the N-alkyl substituent. The cytotoxicity of novel compounds increased with the number of C atoms in the alkyl chains, with optimal number n = 3-5 whereas the derivatives with longer side chains were less cytotoxic. The most potent novel compounds killed human tumor cells at nanomolar-to-submicromolar concentrations, being one order of magnitude more potent than the prototype antibiotic turbomycin A [tris(indol-3-yl)methylium salt]. Apoptosis in HCT116 colon carcinoma cell line induced by tris(1-pentyl-1H-indol-3-yl)methylium methanesulfonate was detectable at concentrations tolerable by normal blood lymphocytes. Thus, N-alkyl substituted tris(1-alkylindol-3-yl)methylium salts emerge as perspective anticancer drug candidates.
We developed the synthesis of a series of thiophene-fused tetracyclic analogues of the antitumor drug ametantrone. The reactions included nucleophilic substitution of methoxy groups in 4,11-dimethoxyanthra[2,3-b]thiophene-5,10-diones with ethylenediamines, producing the derivatives of 4,11-diaminoanthra[2,3-b]thiophene-5,10-dione in good yields. Several compounds showed marked antiproliferative potency against doxorubicin-selected, P-glycoprotein-expressing tumor cells and p53-/- cells. The cytotoxicity of some novel compounds for P-glycoprotein-positive cells is highly dependent on N-substituent at the terminal amino group of ethylenediamine moiety. The cytotoxic potency of selected compounds correlated with their ability to attenuate the functions of topoisomerase I and telomerase, strongly suggesting that these enzymes are the major targets of antitumor activity of anthra[2,3-b]thiophene-5,10-dione derivatives.
A series of new 3-aminomethyl-411-dihydroxynaphtho[2,3-f]indole-5,10-diones 6-13 bearing the cyclic diamine in the position 3 of the indole ring was synthesized. The majority of new compounds demonstrated a superior cytotoxicity than doxorubicin against a panel of mammalian tumor cells with determinants of altered drug response, that is, Pgp expression or p53 inactivation. For naphtho[2,3-f]indole-5,10-diones 6-9 bearing 3-aminopyrrolidine in the side chains, the ability to bind double-stranded DNA and inhibit topoisomerases 1 and 2 mediated relaxation of supercoiled DNA were demonstrated. Only one isomer, (R)-4,11-dihydroxy-3-((pyrrolidin-3-ylamino)methyl)-1H-naphtho[2,3-f]indole-5,10-dione (7) induced the formation of specific DNA cleavage products similar to the known topoisomerase 1 inhibitors camptothecin and indenoisoquinoline MJ-III-65, suggesting a role of the structure of the side chain of 3-aminomethylnaphtho[2,3-f]indole-5,10-diones in interaction with the target. Compound 7 demonstrated an antitumor activity in mice with P388 leukemia transplants whereas its enantiomer 6 was inactive. Thus, 3-aminomethyl derivatives of 4,11-dihydroxynaphtho[2,3-f]indole-5,10-dione emerge as a new prospective chemotype for the search of antitumor agents. © 2014 Elsevier Masson SAS.
We describe the synthesis of derivatives of 4,11-diaminonaphtho[2,3-f]indole-5,10-dione and their cytotoxicity for human tumor cells that express major determinants of altered anticancer drug response, the efflux pump P-glycoprotein, and non-functional p53. Nucleophilic substitution of methoxy groups in 4,11-dimethoxynaphtho[2,3-f]indole-5,10-dione with various ethylenediamines yielded the derivatives of 4,11-diaminonaphtho[2,3-f]indole-5,10-dione, the indole containing analogues of the antitumor agent ametantrone. The cytotoxicity of novel compounds for multidrug resistant, P-glycoprotein-expressing tumor cells is highly dependent on the N-substituent at the terminal amino group of the ethylenediamine moiety. Whereas p53 null colon carcinoma cells were less sensitive to the reference drug doxorubicin than their counterparts with wild type p53, the majority of novel naphthoindole derivatives were equally potent for both cell lines, regardless of the p53 status.
Background: Robotic surgery undergoes its wide acceptance achieved due to minimizing trauma to patients. However, currently robotic surgery lacks a tactile feedback, and it is an essential limiting factor for its further expansion. The problem can be solved by utilization of Medical Tactile Endosurgical complex (MTEC). This complex measures and displays tactile properties of tissues during endoscopic surgeries in real time. It was developed in Lomonosov Moscow State University and officially admitted for clinical use in 2012. Materials and method: MTEC palpation device performs tactile examinations via pressure sensors located in the operating head of the device under a soft membrane. Sensors wirelessly transmit measurement results to a computer in real time. Computer performs processing and output of tactile data to a standard monitor and to specialized tactile display from which data can be read simply via a finger. Processing includes automated analysis of registered tactile data aimed at the identification of heterogeneities which simplifies the identification of lesion boundaries. The utilization of MTEC in endoscopic surgery was tested from January 2015 to December 2015 in hospital No. 31 (Moscow). Nine elective surgeries were performed with da Vinci robotic system (Intuitive Surgical, USA): 2 gastrectomies, 2 stomach resections, 2 resections of pancreas, 2 prostatectomies and 1 right hemicolectomy. Patients’ ages were from 30 to 76. During the surgeries an assistant performed tactile examination under the guidance of surgeon. Operating surgeon identified boundaries of pathological process using a tactile display, and assistant inspected the visualization of tactile data. Results: MTEC was first tested on visually identifiable lesions in stomach and intestine (5 cases). In all cases it correctly localized boundaries of pathological processes. Then the method was applied to pancreas and prostate pathologies and also led to correct decisions in all cases, including a case in which the whole pancreas was involved in process and hence no boundaries were detectable. Conclusion: Utilization of MTEC provides a tactile feedback in robotic surgery thus increasing its capabilities by correct identification of boundaries of a pathological process in the absence of sufficient visual data.
Testing Treatments is a book written to help everyone understand why testing treatments is so important, why treatment tests have to be fair, and how everyone can help to promote better research for better health care. The book proved to be very popular and its second edition has already been translated into a dozen languages, with more translations in the pipeline. The texts of the original English and all the translations are feely downloadable from Testing Treatments interactive at www.testingtreatments.org. The editors of all the different language websites have established an TTi Editorial Alliance, to share experiences and provide each other with mutual support. The TTi Editorial Alliance seeks to promote a world in which health professionals, patients and the public use reliable research to inform their health decisions. Its missions are (i) To promote a global network, involving members of the public in partnership with professionals, to communicate and discuss basic principles and general knowledge about testing treatments; (ii) to help the public increase critical thinking and skills in accessing, apprehending, appraising and using research evidence; and (iii) to help patients and the public to participate more actively in health research.
In the last decade, many studies have used automated processes to analyze magnetic resonance imaging (MRI) data such as cortical thickness, which is one indicator of neuronal health. Due to the convenience of image processing software (e.g., FreeSurfer), standard practice is to rely on automated results without performing visual inspection of intermediate processing. In this work, structural MRIs of 40 healthy controls who were scanned twice were used to determine the test–retest reliability of FreeSurfer-derived cortical measures in four groups of subjects—those 25 that passed visual inspection (approved), those 15 that failed visual inspection (disapproved), a combined group, and a subset of 10 subjects (Travel) whose test and retest scans occurred at different sites. Test–retest correlation (TRC), intraclass correlation coefficient (ICC), and percent difference (PD) were used to measure the reliability in the Destrieux and Desikan–Killiany (DK) atlases. In the approved subjects, reliability of cortical thickness/surface area/volume (DK atlas only) were: TRC (0.82/0.88/0.88), ICC (0.81/0.87/0.88), PD (0.86/1.19/1.39), which represent a significant improvement over these measures when disapproved subjects are included. Travel subjects’ results show that cortical thickness reliability is more sensitive to site differences than the cortical surface area and volume. To determine the effect of visual inspection on sample size required for studies of MRI-derived cortical thickness, the number of subjects required to show group differences was calculated. Significant differences observed across imaging sites, between visually approved/disapproved subjects, and across regions with different sizes suggest that these measures should be used with caution.
Importance: Cardiovascular disease is the leading cause of death in the United States but regional variation within the United States is large. Comparable and consistent state-level measures of total CVD burden and risk factors have not been produced previously. Objective: To quantify and describe levels and trends of lost health due to CVD within the United States from 1990 to 2016 including risk factors driving these changes. Design: CVD mortality, nonfatal health outcomes and associated risk factors were analyzed by age group, sex, and year from 1990 to 2016 using standardized approaches for data processing and statistical modeling. Burden of disease was estimated by for 10 groupings of CVD and comparative risk analysis was performed. Setting: United States of America Exposures: US states and the District of Columbia Main Outcome: CVD Disability-adjusted Life Years Results: Between 1990 and 2016, age-standardized CVD DALYs for all states decreased. Several states had large rises in their relative rank ordering for total CVD DALYs among states, including Arkansas, Oklahoma, Alabama, Kentucky, Missouri, Indiana, Kansas, Alaska, and Iowa. The rate of decline varied widely across states, and CVD burden increased for a small number of states in the most recent years. CVD DALYs remained twice as large among men as women. 3 Ischemic heart disease was the leading cause of CVD DALYs in all states but the second most common varied by state. Trends were driven by 12 groups of risk factors, with the largest attributable CVD burden due to dietary risk exposures followed by high systolic blood pressure, high body mass index, high total cholesterol, high fasting plasma glucose, tobacco smoking and low levels of physical activity. Increases in risk-deleted CVD DALY rates between 2006 and 2016 in 16 states suggests additional unmeasured risk beyond these traditional factors. Conclusions and Relevance: Large disparities in total burden of CVD persist between US states despite marked improvements in cardiovascular disease burden. Differences in CVD burden is largely attributable to modifiable risk exposures.
Question What is the burden of liver cancer globally, what are the major risk factors for liver cancer across countries, regions, and at the global level and how did these change between 1990 and 2015?
Findings There were 854 000 incident liver cancer cases and 810 000 deaths globally in 2015, contributing to 20 578 000 disability-adjusted life-years. Hepatitis B virus infection accounted for 265 000 liver cancer deaths (33%), alcohol for 245 000 (30%), hepatitis C virus infection for 167 000 (21%), and other causes for 133 000 (16%) deaths.
Meaning Most cases of liver cancer can be prevented through vaccination, antiviral treatment, safe blood transfusion and injection practices, as well as interventions to reduce excessive alcohol use.
Importance Liver cancer is among the leading causes of cancer deaths globally. The most common causes for liver cancer include hepatitis B virus (HBV) and hepatitis C virus (HCV) infection and alcohol use.
Objective To report results of the Global Burden of Disease (GBD) 2015 study on primary liver cancer incidence, mortality, and disability-adjusted life-years (DALYs) for 195 countries or territories from 1990 to 2015, and present global, regional, and national estimates on the burden of liver cancer attributable to HBV, HCV, alcohol, and an “other” group that encompasses residual causes.
Design, Settings, and Participants Mortality was estimated using vital registration and cancer registry data in an ensemble modeling approach. Single-cause mortality estimates were adjusted for all-cause mortality. Incidence was derived from mortality estimates and the mortality-to-incidence ratio. Through a systematic literature review, data on the proportions of liver cancer due to HBV, HCV, alcohol, and other causes were identified. Years of life lost were calculated by multiplying each death by a standard life expectancy. Prevalence was estimated using mortality-to-incidence ratio as surrogate for survival. Total prevalence was divided into 4 sequelae that were multiplied by disability weights to derive years lived with disability (YLDs). DALYs were the sum of years of life lost and YLDs.
Main Outcomes and Measures Liver cancer mortality, incidence, YLDs, years of life lost, DALYs by etiology, age, sex, country, and year.
Results There were 854 000 incident cases of liver cancer and 810 000 deaths globally in 2015, contributing to 20 578 000 DALYs. Cases of incident liver cancer increased by 75% between 1990 and 2015, of which 47% can be explained by changing population age structures, 35% by population growth, and −8% to changing age-specific incidence rates. The male-to-female ratio for age-standardized liver cancer mortality was 2.8. Globally, HBV accounted for 265 000 liver cancer deaths (33%), alcohol for 245 000 (30%), HCV for 167 000 (21%), and other causes for 133 000 (16%) deaths, with substantial variation between countries in the underlying etiologies.
Conclusions and Relevance Liver cancer is among the leading causes of cancer deaths in many countries. Causes of liver cancer differ widely among populations. Our results show that most cases of liver cancer can be prevented through vaccination, antiviral treatment, safe blood transfusion and injection practices, as well as interventions to reduce excessive alcohol use. In line with the Sustainable Development Goals, the identification and elimination of risk factors for liver cancer will be required to achieve a sustained reduction in liver cancer burden. The GBD study can be used to guide these prevention efforts.
Studying how the healthy human brain develops is important to understand early pathological mechanisms and to assess the influence of fetal or perinatal events on later life. Brain development relies on complex and intermingled mechanisms especially during gestation and first post-natal months, with intense interactions between genetic, epigenetic and environmental factors. Although the baby's brain is organized early on, it is not a miniature adult brain: regional brain changes are asynchronous and protracted, i.e. sensory-motor regions develop early and quickly, whereas associative regions develop later and slowly over decades. Concurrently, the infant/child gradually achieves new performances, but how brain maturation relates to changes in behavior is poorly understood, requiring non-invasive in vivo imaging studies such as magnetic resonance imaging (MRI). Two main processes of early white matter development are reviewed: (1) establishment of connections between brain regions within functional networks, leading to adult-like organization during the last trimester of gestation, (2) maturation (myelination) of these connections during infancy to provide efficient transfers of information. Current knowledge from post-mortem descriptions and in vivo MRI studies is summed up, focusing on T1- and T2-weighted imaging, diffusion tensor imaging, and quantitative mapping of T1/T2 relaxation times, myelin water fraction and magnetization transfer ratio.
Significant positive effects on subjective well-being can already be observed after a period as short as 4 weeks. Policy makers should support the provision of such time-efficient programs which are appealing to overweight population groups. Copyright Swiss School of Public Health 2015
Is in utero exposure to testosterone correlated with earnings? The question matters for understanding determinants of wage differences that have attracted so much attention among economists in the past decade. Evidence indicates that markers for early testosterone exposure are correlated with traits like risk-taking and aggressiveness. But it is not at all clear how such findings might map into labor market success. We combine unique data from the Russian Longitudinal Monitoring Survey with measured markers (2D:4D ratios) for testosterone exposure and find that lower digit ratios (higher T) correlate with higher wages for women and for men, when controlling for age, education and occupation. There is also some evidence of a potential non-linear, inverse U-effect of digit ratios on wages but this is sensitive to choice of specification. These findings are consistent with earlier work on prenatal T and success in careers (Coates et al., 2009) but inconsistent with the work of Gielen et al. (2016) who find differing effects for men and women.
Wave-shaped changes in the life span of Russian citizes remains mainly unexplained, but the last ten years provide some reasons to think that increase in the funding of the health care is accompanied by increase in the lenght of life
The paper deals with conceptual guidelines, basic aspects and spatial frameworks of the development of agritourism. The holistic approach, in this regard, includes the integrated and the comprehensive aspects of tourist stays in the countryside. The authors define the impact of agritourism on rural surroundings and analyze the influence of spending leisure time outside urban areas and consuming agritourism activities. Understanding the many components of agritourism is essential for future planning, management, business decisions and strategies. For success in agritourism, knowledge is necessary in many economic fields, including organization, management and marketing, among others. In addition, this article emphasizes products and services in agritourism and provides insight into the facilities and opportunities that are offered to tourists in rural areas. The research findings represent a useful tool for obtaining information about many elements of agritourism development and can serve as a relevant instrument in travel industry research or in academic investigation.
We developed the synthesis of a series of furan-fused tetracyclic analogues of the antitumor agent ametantrone. The reactions included nucleophilic substitution of propoxy groups in 4,11-dipropoxyanthra[2,3-b]furan-5,10-diones with ethylenediamines, producing the derivatives of 4,11-diaminoanthra[2,3-b] furan-5,10-dione in good yields. Studies of anti-proliferative activity on a panel of mammalian tumor cell lines demonstrated that anthra[2,3-b]furan-5,10- diones were the most potent derivatives among heteroarene-fused ametantrone analogues with one heteroatom. We identified several compounds that evoked a growth inhibitory effect at submicromolar concentrations. The anthra[2,3-b]furan-5,10-dione 9 with distal methylamino groups was markedly potent against drug-resistant cell lines with P-glycoprotein overexpression or p53 gene deletion. Furthermore, this derivative attenuated in vitro topoisomerase I-mediated DNA uncoiling at low micromolar concentrations. These results demonstrate that anthrafurandiones are a new class of heterocyclic anthraquinone derivatives with the properties potentially valuable for anticancer therapy.
This paper re-examines the gender wage gap in Russia between 1994 and 1998 taking into account the pervasiveness of Russia’s non-payment institutions. Using censored regression techniques we investigate wage discrimination at different sections of the income distribution and for various important sub-groups. We find that the wage gap is distributed unevenly. Most notably, women at the lower end of the income distribution suffer the highest degree of discrimination. However, we find that wage arrears and payment in-kind attenuated wage discrimination, particularly amongst the lowest paid workers, suggesting that Russian enterprise managers assigned importance to equity considerations when allocating these forms of non-payment.