Influence of weight reduction on blood pressure: a meta-analysis of randomized controlled trials

Increased body weight is a strong risk factor for hypertension. A meta-analysis of randomized controlled trials was performed to estimate the effect of weight reduction on blood pressure overall and in population subgroups. Twenty-five randomized, controlled trials (comprising 34 strata) published between 1966 and 2002 with a total of 4874 participants were included. A random-effects model was used to account for heterogeneity among trials. A net weight reduction of -5.1 kg (95% confidence interval [CI], -6.03 to -4.25) by means of energy restriction, increased physical activity, or both reduced systolic blood pressure by -4.44 mm Hg (95% CI, -5.93 to -2.95) and diastolic blood pressure by -3.57 mm Hg (95% CI, -4.88 to -2.25). Blood pressure reductions were -1.05 mm Hg (95% CI, -1.43 to -0.66) systolic and -0.92 mm Hg (95% CI, -1.28 to -0.55) diastolic when expressed per kilogram of weight loss. As expected, significantly larger blood pressure reductions were observed in populations with an average weight loss >5 kg than in populations with less weight loss, both for systolic (-6.63 mm Hg [95% CI, -8.43 to -4.82] vs -2.70 mm Hg [95% CI, -4.59 to -0.81]) and diastolic (-5.12 mm Hg [95% CI, -6.48 to -3.75] vs -2.01 mm Hg [95% CI, -3.47 to -0.54]) blood pressure. The effect on diastolic blood pressure was significantly larger in populations taking antihypertensive drugs than in untreated populations (-5.31 mm Hg [95% CI, -6.64 to -3.99] vs -2.91 mm Hg [95% CI, -3.66 to -2.16]). This meta-analysis clearly shows that weight loss is important for the prevention and treatment of hypertension.     

Trends in health expectancy indicators in the older adult population in Belgium between 1997 and 2004

The objective is to assess if longer life in Belgium is associated with more healthy years through the evaluation of trends (1997–2004) in health expectancy indicators at ages 65 and 80 covering different health domains: self-perceived health, chronic morbidity, disease clusters, and disability. Information was obtained from Belgian Health Interview Surveys. Health expectancies were calculated using the Sullivan method. Among males at age 65, the increase in years expected to live without chronic morbidity, without a disease cluster or without disability exceeded the increase of the life expectancy (LE). The rise in LE in good self-perceived health was equal to the gain in LE. Among women at age 65 and among men and women at age 80, none of the changes in the expected years of life in good health in any health domain were statistically significant. At age 65 among women, the increase in LE was smaller than the increase in years without chronic disease or without disability. The increase in years without disease clusters was less that the LE increase. At age 80 among men, the years without disability increased as the LE, with a shift toward years with moderate limitations. In any other health domains for men (except co-morbidity) and in all domains for women the years in good health either decreased or increased less than the LE. The recent rise in life expectancy in Belgium is, among the youngest old and especially among males, accompanied by an improved health status. At age 80 and particularly among women expansion of unhealthy years prevails.

Thrombopoietin cooperates with FLT3-ligand in the generation of plasmacytoid dendritic cell precursors from human hematopoietic progenitors

Type 1 interferon-producing cells (IPCs), also known as plasmacytoid dendritic cell (DC) precursors, represent the key effectors in antiviral innate immunity and triggers for adaptive immune responses. IPCs play important roles in the pathogenesis of systemic lupus erythematosus (SLE) and in modulating immune responses after hematopoietic stem cell transplantation. Understanding IPC development from hematopoietic progenitor cells (HPCs) may provide critical information in controlling viral infection, autoimmune SLE, and graft-versus-host disease. FLT3-ligand (FLT3-L) represents a key IPC differentiation factor from HPCs. Although hematopoietic cytokines such as interleukin-3 (IL-3), IL-7, stem cell factor (SCF), macrophage-colony-stimulating factor (M-CSF), and granulocyte M-CSF (GM-CSF) promote the expansion of CD34+ HPCs in FLT3-L culture, they strongly inhibit HPC differentiation into IPCs. Here we show that thrombopoietin (TPO) cooperates with FLT3-L, inducing CD34+ HPCs to undergo a 400-fold expansion in cell numbers and to generate more than 6 x 10(6) IPCs per 10(6) CD34+ HPCs within 30 days in culture. IPCs derived from HPCs in FLT3-L/TPO cultures display blood IPC phenotype and have the capacity to produce large amounts of interferon-alpha (IFN-alpha) and to differentiate into mature DCs. This culture system, combined with the use of adult peripheral blood CD34+ HPCs purified from G-CSF-mobilized donors, permits the generation of more than 10(9) IPCs from a single blood donor.     

Ancient plant DNA reveals High Arctic greening during the Last Interglacial

Summer warming is driving a greening trend across the Arctic, with the potential for large-scale amplification of climate change due to vegetation-related feedbacks [Pearson et al., Nat. Clim. Chang. (3), 673–677 (2013)]. Because observational records are sparse and temporally limited, past episodes of Arctic warming can help elucidate the magnitude of vegetation response to temperature change. The Last Interglacial ([LIG], 129,000 to 116,000 y ago) was the most recent episode of Arctic warming on par with predicted 21st century temperature change [Otto-Bliesner et al., Philos. Trans. A Math. Phys. Eng. Sci. (371), 20130097 (2013) and Post et al., Sci. Adv. (5), eaaw9883 (2019)]. However, high-latitude terrestrial records from this period are rare, so LIG vegetation distributions are incompletely known. Pollen-based vegetation reconstructions can be biased by long-distance pollen transport, further obscuring the paleoenvironmental record. Here, we present a LIG vegetation record based on ancient DNA in lake sediment and compare it with fossil pollen. Comprehensive plant community reconstructions through the last and current interglacial (the Holocene) on Baffin Island, Arctic Canada, reveal coherent climate-driven community shifts across both interglacials. Peak LIG warmth featured a ∼400-km northward range shift of dwarf birch, a key woody shrub that is again expanding northward. Greening of the High Arctic—documented here by multiple proxies—likely represented a strong positive feedback on high-latitude LIG warming. Authenticated ancient DNA from this lake sediment also extends the useful preservation window for the technique and highlights the utility of combining traditional and molecular approaches for gleaning paleoenvironmental insights to better anticipate a warmer future.

The Arctic is greening as shrub biomass increases and vegetation ranges shift north in response to summer warming (1, 2). This process—one of the clearest terrestrial manifestations of climate change thus far—has major implications both for local ecosystems and for global energy balance and biogeochemical systems (3–5). In particular, taller shrubs darken otherwise snow-covered surfaces, contributing to the albedo feedback (6, 7), and enhanced evapotranspiration is expected to result in a positive greenhouse feedback (8). Shrub cover also impacts soil thermal regime, which may impact permafrost vulnerability (9–11). Because feedbacks related to Arctic greening are complex and potentially large in magnitude, estimating the extent and rate of northward shrub migration is a vital component of predicting future warming.Past warm periods serve as valuable analogs for understanding the extent of Arctic greening under well-constrained climate conditions. The Last Interglacial (LIG; Marine Isotope Stage [MIS] 5e, 129 to 116 ka [thousands of years before present]) was ∼1 °C warmer than the preindustrial period globally, but the Arctic experienced amplified warming due to higher summer insolation anomalies and positive feedbacks at high latitudes (12, 13). The Eastern Canadian Arctic and Greenland, in particular, were likely ∼4 to 8 °C warmer in summer than present (Fig. 1) (14–18). LIG sediment records from this region thus provide an archive of the vegetation response to Arctic warming at levels comparable to predicted 21^st-century climate change (19).Open in a separate windowFig. 1.Map of Baffin Island and Lake CF8 study area. The symbols represent maximum LIG temperature anomalies based on terrestrial proxy records (shape indicates proxy type) from Baffin Island and Greenland (see SI Appendix, Table S1 for metadata). The shaded regions indicate Arctic bioclimate subzones delineations (29), including modern Betula range in subzones D and E. We note that a small outlier population of Betula occurs east of the D/E boundary on Baffin Island (not captured by vegetation map resolution) (38).While most High Arctic lake basins were scraped clean by ice sheet erosion during the last glaciation and thus only contain postglacial sediments, lakes with small, low-relief catchments within regions of cold-based, slow-flowing ice were protected from erosion. Several such sites have been discovered on eastern Baffin Island, Arctic Canada and contain stratified records of multiple interglacials (20–22). Previous work from Lake CF8 on northeastern Baffin Island (Fig. 1 and SI Appendix, Fig. S1) demonstrates that its sediment record spans at least three interglacials (∼200 ka), including a substantially warmer-than-present LIG as indicated by chironomids, diatoms, and geochemical proxies (15, 23).We targeted the multi-interglacial record from Lake CF8 to assess the vegetation response to pronounced warmth during the LIG and moderate warmth during the Holocene. Pollen produced by some key shrubs and trees, including Betula (birch), is efficiently wind-transported and thus present in lake sediments far north of their ranges (24, 25). We therefore analyzed both sedimentary ancient DNA (sedaDNA), which is sourced locally from within the lake catchment and does not include pollen-derived DNA (26), and fossil pollen to generate a robust vegetation record spanning the last ∼130 ka. Taken together, DNA-inferred plant communities and pollen-inferred July air temperatures provide insight into Arctic plant range shifts under strong summer warming.     

Bilirubin protects astrocytes from its own toxicity by inducing up-regulation and translocation of multidrug resistance-associated protein 1 (Mrp1)

Unconjugated bilirubin (UCB) causes encephalopathy in severely jaundiced neonates by damaging astrocytes and neurons. Astrocytes, which help defend the brain against cytotoxic insults, express the ATP-dependent transporter, multidrug resistance-associated protein 1 (Mrp1), which mediates export of organic anions, probably including UCB. We therefore studied whether exposure to UCB affects the expression and intracellular localization of Mrp1 in cultured mouse astroglial cells (>95% astrocytes). Mrp1 was localized and quantitated by confocal laser scanning microscopy and double immunofluorescence labeling by using specific antibodies against Mrp1 and the astrocyte marker glial fibrillary acidic protein, plus the Golgi marker wheat germ agglutinin (WGA). In unexposed astrocytes, Mrp1 colocalized with WGA in the Golgi apparatus. Exposure to UCB at a low unbound concentration (Bf) of 40 nM caused rapid redistribution of Mrp1 from the Golgi throughout the cytoplasm to the plasma membrane, with a peak 5-fold increase in Mrp1 immunofluorescence intensity from 30 to 120 min. Bf above aqueous saturation produced a similar but aborted response. Exposure to this higher Bf for 16 h markedly decreased Trypan blue exclusion and methylthiazoletetrazoilum activity and increased apoptosis 5-fold by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling assay. These toxic effects were modestly increased by inhibition of Mrp1 activity with 3-([3-(2-[7-chloro-2-quinolinyl]ethenyl)phenyl-(3-dimethylamino-3-oxopropyl)-thio-methyl]thio)propanoic acid (MK571). By contrast, Bf=40 nM caused injury only if Mrp1 activity was inhibited by MK571, which also blocked translocation of Mrp1. Our conclusion is that in astrocytes, UCB up-regulates expression of Mrp1 and promotes its trafficking from the Golgi to the plasma membrane, thus moderating cytotoxicity from UCB, presumably by limiting its intracellular accumulation.