Furanoflavones pongapin and lanceolatin B blocks the cell cycle and induce senescence in CYP1A1-overexpressing breast cancer cells

© 2018 Elsevier Ltd Expression of cytochrome P450-1A1 (CYP1A1) is suppressed under physiologic conditions but is induced (a) by polycyclic aromatic hydrocarbons (PAHs) which can be metabolized by CYP1A1 to carcinogens, and (b) in majority of breast cancers. Hence, phytochemicals or dietary flavonoids, if identified as CYP1A1 inhibitors, may help in preventing PAH-mediated carcinogenesis and breast cancer. Herein, we have investigated the cancer chemopreventive potential of a flavonoid-rich Indian medicinal plant, Pongamia pinnata (L.) Pierre. Methanolic extract of its seeds inhibits CYP1A1 in CYP1A1-overexpressing normal human HEK293 cells, with IC50 of 0.6 µg/mL. Its secondary metabolites, the furanoflavonoids pongapin/lanceolatin B, inhibit CYP1A1 with IC50 of 20 nM. Although the furanochalcone pongamol inhibits CYP1A1 with IC50 of only 4.4 µM, a semisynthetic pyrazole-derivative P5b, has ∼10-fold improved potency (IC50, 0.49 μM). Pongapin/lanceolatin B and the methanolic extract of P. pinnata seeds protect CYP1A1-overexpressing HEK293 cells from B[a]P-mediated toxicity. Remarkably, they also block the cell cycle of CYP1A1-overexpressing MCF-7 breast cancer cells, at the G0-G1 phase, repress cyclin D1 levels and induce cellular-senescence. Molecular modeling studies demonstrate the interaction pattern of pongapin/lanceolatin B with CYP1A1. The results strongly indicate the potential of methanolic seed-extract and pongapin/lanceolatin B for further development as cancer chemopreventive agents

Dermoscopy of Infectious Dermatoses (Infectiouscopy) in Skin of Color—A Systematic Review by the International Dermoscopy Society “Imaging in Skin of Color” Task Force

Dermoscopy has been showed to facilitate the non-invasive recognition of several infectious disorders (infectiouscopy) thanks to the detection of peculiar clues. Although most of the knowledge on this topic comes from studies involving light-skinned patients, there is growing evidence about its use also in dark phototypes. This systematic literature review summarizes published data on dermoscopy of parasitic, bacterial, viral and fungal dermatoses (dermoscopic findings, used setting, pathological correlation, and level of evidence of studies) and provides a homogeneous terminology of reported dermoscopic features according to a standardized methodology. A total of 66 papers addressing 41 different dermatoses (14 bacterial, 5 viral, 11 fungal infections, and 11 parasitoses/bites and stings) and involving a total of 1096 instances were included in the analysis. The majority of them displayed a level of evidence of V (44 single case reports and 21 case series), with only 1 study showing a level of evidence of IV (case-control analysis). Moreover, our analysis also highlighted a high variability in the terminology used in the retrieved studies. Thus, although promising, further studies designed according to a systematic and standardized approach are needed for better characterization of dermoscopy of infectious skin infections

Dermoscopy of Hair and Scalp Disorders (Trichoscopy) in Skin of Color—A Systematic Review by the International Dermoscopy Society “Imaging in Skin of Color” Task Force

Hair and scalp disorders are of significant interest for physicians dealing with dark phototypes due to their prevalence and potential aesthetic impact resulting from a higher tendency for scarring. In order to facilitate their non-invasive diagnosis, several dermoscopic studies have been published, yet data are sparse and no systematic analysis of the literature has been performed so far. This systematic literature review summarizes published data on trichoscopy of hair and scalp diseases (trichoscopic findings, used setting, pathological correlation, and level of evidence of studies). A total of 60 papers addressing 19 different disorders (eight non-cicatricial alopecias, nine cicatricial alopecias, and two hair shaft disorders) were assessed, for a total of 2636 instances. They included one cross-sectional analysis, 20 case-control studies, 25 case-series, and 14 single case-reports, so the level of evidence was V and IV in 65% and 33% of cases, respectively, with only one study showing a level of evidence of III. Notably, although there is a considerable body of literature on trichoscopy of hair/scalp diseases, our review underlined that potentially significant variables (e.g., disease stage or hair texture) are often not taken into account in published analyses, with possible biases on trichoscopic patterns, especially when it comes to hair shaft changes. Further analyses considering all such issues are therefore needed

Dermoscopy of Cutaneous Neoplasms in Skin of Color – A Systematic Review by the International Dermoscopy Society “Imaging in Skin of Color” Task Force

Over the last few decades, dermoscopy has been showed to facilitate the non-invasive diagnosis of both benign and malignant skin tumors, yet literature data mainly comes from studies on light phototypes. However, there is growing evidence that skin neoplasms may benefit from dermoscopic assessment even for skin of color. This systematic literature review evaluated published data in dark-skinned patients (dermoscopic features, used setting, pathological correlation, and level of evidence of studies), also providing a standardized and homogeneous terminology for reported dermoscopic findings. A total of 20 articles describing 46 different tumors (four melanocytic neoplasms, eight keratinocytic tumors, 15 adnexal cutaneous neoplasms, seven vascular tumors, four connective tissue tumors, and eight cystic neoplasms/others) for a total of 1724 instances were included in the analysis. Most of them showed a level of evidence of V (12 single case reports and six case series), with only two studies featuring a level of evidence of IV (case-control analysis). Additionally, this review also underlined that some neoplasms and phototypes are underrepresented in published analyses as they included only small samples and mainly certain tones of “dark skin” spectrum (especially phototype IV). Therefore, further studies considering such limitations are required for a better characterization

Dermoscopy of Inflammatory Dermatoses (Inflammoscopy) in Skin of Color—A Systematic Review by the International Dermoscopy Society “Imaging in Skin of Color” Task Force

Dermoscopic patterns of inflammatory dermatoses (inflammoscopy) have been extensively studied in the recent years, though data on patients with darker phototypes (IV-VI) are sparse. The aims of this systematic review were to summarize the current state of knowledge on inflammoscopy applied to skin of color and provide a standardized nomenclature of reported findings. Besides dermoscopic features, type of setting and magnification, number of cases, and histopathological correlation were analyzed. Eighty-five papers addressing 76 different dermatoses (25 papulosquamous dermatoses, 19 hyperpigmented dermatoses, seven hypopigmented dermatoses, four granulomatous dermatoses, two sclerotic dermatoses, five facial inflammatory dermatoses, and 14 miscellaneous conditions) for a total of 2073 instances were retrieved. Only one study showed a level of evidence of III (cross-sectional study), whereas 10 and 74 displayed a level of evidence of IV (case-control studies) and V (case-series and case-reports), respectively. Moreover, our analysis also highlighted that most of papers focalized on a limited number of dermatoses, with several conditions having only single dermoscopic descriptions. Additionally, few studies compared findings among phototypes belonging to the “skin of color” spectrum. Further studies designed according to a systematic approach and considering the above-mentioned issues are therefore needed

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

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

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries