Putterlickia neglecta (Celastraceae), a new species from southern Africa

Putterlickia neglecta, a new species here described and illustrated, is known from South Africa (Mpumalanga and northeastern KwaZulu-Natal), Swaziland and southern Mozambique. It is considered a near-endemic to the Maputaland Centre of Endemism. Plants grow as a shrub or small tree in savanna and thicket, or in the understory of inland, coastal and dune forests. Vegetatively it superficially resembles P. verrucosa, the species with which it has hitherto most often been confused. Both species have stems with prominently raised lenticels, but P. neglecta differs from P. verrucosa in having sessile to subsessile leaves with mostly entire, revolute leaf margins, flowers borne on pedicels 8–15 mm long, with petals up to 6 mm long and spreading or slightly recurved. Putterlickia verrucosa has leaves with distinct petioles, spinulose-denticulate margins, much smaller flowers borne on pedicels up to 4 mm long, with petals up to 2 mm long and erect or slightly spreading. The relatively large flowers of P. neglecta resemble those of P. pyracantha, but the latter differs in having stems with obscure or sunken lenticels, leaf margins entire or spinulose-denticulate and inflorescence axes as well as pedicels usually reddish. A comparative table to distinguish among the five currently recognized species of Putterlickia is provided.http://www.mapress.com/phytotaxahb201

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. Interpretation: Over the past 20 years, fertility rates have been dropping steadily and life expectancy has been increasing, with few exceptions. Much of this change follows historical patterns linking social and economic determinants, such as those captured by the GBD Socio-demographic Index, with demographic outcomes. More recently, several countries have experienced a combination of low fertility and stagnating improvement in mortality rates, pushing more populations into the late stages of the demographic transition. Tracking demographic change and the emergence of new patterns will be essential for global health monitoring. 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 burden of 87 risk factors in 204 countries and territories, 1990�2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: Rigorous analysis of levels and trends in exposure to leading risk factors and quantification of their effect on human health are important to identify where public health is making progress and in which cases current efforts are inadequate. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a standardised and comprehensive assessment of the magnitude of risk factor exposure, relative risk, and attributable burden of disease. Methods: GBD 2019 estimated attributable mortality, years of life lost (YLLs), years of life lived with disability (YLDs), and disability-adjusted life-years (DALYs) for 87 risk factors and combinations of risk factors, at the global level, regionally, and for 204 countries and territories. GBD uses a hierarchical list of risk factors so that specific risk factors (eg, sodium intake), and related aggregates (eg, diet quality), are both evaluated. This method has six analytical steps. (1) We included 560 risk�outcome pairs that met criteria for convincing or probable evidence on the basis of research studies. 12 risk�outcome pairs included in GBD 2017 no longer met inclusion criteria and 47 risk�outcome pairs for risks already included in GBD 2017 were added based on new evidence. (2) Relative risks were estimated as a function of exposure based on published systematic reviews, 81 systematic reviews done for GBD 2019, and meta-regression. (3) Levels of exposure in each age-sex-location-year included in the study were estimated based on all available data sources using spatiotemporal Gaussian process regression, DisMod-MR 2.1, a Bayesian meta-regression method, or alternative methods. (4) We determined, from published trials or cohort studies, the level of exposure associated with minimum risk, called the theoretical minimum risk exposure level. (5) Attributable deaths, YLLs, YLDs, and DALYs were computed by multiplying population attributable fractions (PAFs) by the relevant outcome quantity for each age-sex-location-year. (6) PAFs and attributable burden for combinations of risk factors were estimated taking into account mediation of different risk factors through other risk factors. Across all six analytical steps, 30 652 distinct data sources were used in the analysis. Uncertainty in each step of the analysis was propagated into the final estimates of attributable burden. Exposure levels for dichotomous, polytomous, and continuous risk factors were summarised with use of the summary exposure value to facilitate comparisons over time, across location, and across risks. Because the entire time series from 1990 to 2019 has been re-estimated with use of consistent data and methods, these results supersede previously published GBD estimates of attributable burden. Findings: The largest declines in risk exposure from 2010 to 2019 were among a set of risks that are strongly linked to social and economic development, including household air pollution; unsafe water, sanitation, and handwashing; and child growth failure. Global declines also occurred for tobacco smoking and lead exposure. The largest increases in risk exposure were for ambient particulate matter pollution, drug use, high fasting plasma glucose, and high body-mass index. In 2019, the leading Level 2 risk factor globally for attributable deaths was high systolic blood pressure, which accounted for 10·8 million (95 uncertainty interval UI 9·51�12·1) deaths (19·2% 16·9�21·3 of all deaths in 2019), followed by tobacco (smoked, second-hand, and chewing), which accounted for 8·71 million (8·12�9·31) deaths (15·4% 14·6�16·2 of all deaths in 2019). The leading Level 2 risk factor for attributable DALYs globally in 2019 was child and maternal malnutrition, which largely affects health in the youngest age groups and accounted for 295 million (253�350) DALYs (11·6% 10·3�13·1 of all global DALYs that year). The risk factor burden varied considerably in 2019 between age groups and locations. Among children aged 0�9 years, the three leading detailed risk factors for attributable DALYs were all related to malnutrition. Iron deficiency was the leading risk factor for those aged 10�24 years, alcohol use for those aged 25�49 years, and high systolic blood pressure for those aged 50�74 years and 75 years and older. Interpretation: Overall, the record for reducing exposure to harmful risks over the past three decades is poor. Success with reducing smoking and lead exposure through regulatory policy might point the way for a stronger role for public policy on other risks in addition to continued efforts to provide information on risk factor harm to the general public. 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

Putterlickia neglecta (Celastraceae), a new species from southern Africa

Putterlickia neglecta, a new species here described and illustrated, is known from South Africa (Mpumalanga and northeastern KwaZulu-Natal), Swaziland and southern Mozambique. It is considered a near-endemic to the Maputaland Centre of Endemism. Plants grow as a shrub or small tree in savanna and thicket, or in the understory of inland, coastal and dune forests. Vegetatively it superficially resembles P. verrucosa, the species with which it has hitherto most often been confused. Both species have stems with prominently raised lenticels, but P. neglecta differs from P. verrucosa in having sessile to subsessile leaves with mostly entire, revolute leaf margins, flowers borne on pedicels 8–15 mm long, with petals up to 6 mm long and spreading or slightly recurved. Putterlickia verrucosa has leaves with distinct petioles, spinulose-denticulate margins, much smaller flowers borne on pedicels up to 4 mm long, with petals up to 2 mm long and erect or slightly spreading. The relatively large flowers of P. neglecta resemble those of P. pyracantha, but the latter differs in having stems with obscure or sunken lenticels, leaf margins entire or spinulose-denticulate and inflorescence axes as well as pedicels usually reddish. A comparative table to distinguish among the five currently recognized species of Putterlickia is provided.http://www.mapress.com/phytotaxahb201

Impact of Metformin and compound C on NIS expression and iodine uptake in vitro and in vivo: a role for CRE in AMPK modulation of thyroid function

Item does not contain fulltextBACKGROUND: Although adenosine monophosphate activated protein kinase (AMPK) plays a crucial role in energy metabolism, a direct effect of AMPK modulation on thyroid function has only recently been reported, and much of its function in the thyroid is currently unknown. The aim of this study was to investigate the mechanism of AMPK modulation in iodide uptake. Furthermore, we wanted to investigate the potential of the AMPK inhibitor compound C as an enhancer of iodide uptake by thyrocytes. METHODS: The in vitro and in vivo effects of AMPK modulation on sodium-iodide symporter (NIS) protein levels and iodide uptake were examined in follicular rat thyroid cell-line cells and C57Bl6/J mice. Activation of AMPK by metformin resulted in a strong reduction of iodide uptake (up to sixfold with 5 mM metformin after 96 h) and NIS protein levels in vitro, whereas AMPK inhibition by compound C not only stimulated iodide uptake but also enhanced NIS protein levels both in vitro (up to sevenfold with 1 muM compound C after 96 h) and in vivo (1.5-fold after daily injections with 20 mg/kg for 4 days). We investigated the regulation of NIS expression by AMPK using a range of promoter constructs consisting of either the NIS promoter or isolated CRE (cAMP response element) and NF-kappaB elements, which are present within the NIS promoter. RESULTS: Metformin reduced NIS promoter activity (0.6-fold of control), whereas compound C stimulated its activity (3.4-fold) after 4 days. This largely coincides with CRE activation (0.6- and 3.0-fold). These experiments show that AMPK exerts its effects on iodide uptake, at least partly, through the CRE element in the NIS promoter. Furthermore, we have used AMPK-alpha1 knockout mice to determine the long-term effects of AMPK inhibition without chemical compounds. These mice have a less active thyroid, as shown by reduced colloid volume and reduced responsiveness to thyrotropin. CONCLUSION: NIS expression and iodine uptake in thyrocytes can be modulated by metformin and compound C. These compounds exert their effect by modulation of AMPK, which, in turn, regulates the activation of the CRE element in the NIS promoter. Overall, this suggests that the use of AMPK modulating compounds may be useful for the enhancement of iodide uptake by thyrocytes, which could be useful for the treatment of thyroid cancer patients with radioactive iodine

Trial by Dutch laboratories for evaluation of non-invasive prenatal testing. Part I-clinical impact

Contains fulltext : 171862.pdf (publisher's version ) (Open Access)OBJECTIVE: To evaluate the clinical impact of nationwide implementation of genome-wide non-invasive prenatal testing (NIPT) in pregnancies at increased risk for fetal trisomies 21, 18 and 13 (TRIDENT study). METHOD: Women with elevated risk based on first trimester combined testing (FCT >/= 1:200) or medical history, not advanced maternal age alone, were offered NIPT as contingent screening test, performed by Dutch University Medical laboratories. We analyzed uptake, test performance, redraw/failure rate, turn-around time and pregnancy outcome. RESULTS: Between 1 April and 1 September 2014, 1413/23 232 (6%) women received a high-risk FCT result. Of these, 1211 (85.7%) chose NIPT. One hundred seventy-nine women had NIPT based on medical history. In total, 1386/1390 (99.7%) women received a result, 6 (0.4%) after redraw. Mean turn-around time was 14 days. Follow-up was available in 1376 (99.0%) pregnancies. NIPT correctly predicted 37/38 (97.4%) trisomies 21, 18 or 13 (29/30, 4/4 and 4/4 respectively); 5/1376 (0.4%) cases proved to be false positives: trisomies 21 (n = 2), 18 (n = 1) and 13 (n = 2). Estimated reduction in invasive testing was 62%. CONCLUSION: Introduction of NIPT in the Dutch National healthcare-funded Prenatal Screening Program resulted in high uptake and a vast reduction of invasive testing. Our study supports offering NIPT to pregnant women at increased risk for fetal trisomy. (c) 2016 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd. (c) 2016 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd

Metformin lowers plasma triglycerides by promoting vldl-triglyceride clearance by brown adipose tissue in mice

Metformin is the first-line drug for the treatment of type 2 diabetes. Besides its well-characterized antihyperglycemic properties, metformin also lowers plasma VLDL triglyceride (TG). In this study, we investigated the underlying mechanisms in APOE*3-Leiden.CETP mice, a well-established model for human-like lipoprotein metabolism. We found that metformin markedly lowered plasma total cholesterol and TG levels, an effect mostly due to a decrease in VLDL-TG, whereas HDL was slightly increased. Strikingly, metformin did not affect hepatic VLDL-TG production, VLDL particle composition, and hepatic lipid composition but selectively enhanced clearance of glycerol tri[3H]oleate-labeled VLDL-like emulsion particles into brown adipose tissue (BAT). BAT mass and lipid droplet content were reduced in metformin-treated mice, pointing to increased BAT activation. In addition, both AMP-activated protein kinase a1 (AMPKa1) expression and activity and HSL and mitochondrial content were increased in BAT. Furthermore, therapeutic concentrations of metformin increased AMPK and HSL activities and promoted lipolysis in T37i differentiated brown adipocytes. Collectively, our results identify BAT as an important player in the TG-lowering effect of metformin by enhancing VLDL-TG uptake, intracellular TG lipolysis, and subsequent mitochondrial fatty acid oxidation. Targeting BAT might therefore be considered as a future therapeutic strategy for the treatment of dyslipidemia. © 2014 by the American Diabetes Association.