Physical activity at work may not be health enhancing. A systematic review with meta-analysis on the association between occupational physical activity and cardiovascular disease mortality covering 23 studies with 655 892 participants

ObjectivesEmerging evidence suggests contrasting health effects for leisure-time and occupational physical activity. In this systematic review, we synthesized and described the epidemiological evidence regarding the association between occupational physical activity and cardiovascular disease (CVD) mortality.MethodsA literature search was performed in PubMed, Embase, CINAHL, PsycINFO and Evidence-Based Medicine Reviews, from database inception to 17 April 2020. Articles were included if they described original observational prospective research, assessing the association between occupational physical activity and CVD mortality among adult workers. Reviews were included if they controlled for age and gender and at least one other relevant variable. We performed meta-analyses on the associations between occupational physical activity and CVD mortality.ResultsWe screened 3345 unique articles, and 31 articles (from 23 studies) were described in this review. In the meta-analysis, occupational physical activity showed no significant association with overall CVD mortality for both males [hazard ratio (HR) 1.00, 95% confidence interval (CI) 0.87–1.15] and females (HR 0.95, 95% CI 0.82–1.09). Additional analysis showed that higher levels of occupational physical activity were non-significantly associated with a 15% increase in studies reporting on the outcome ischemic heart disease mortality (HR 1.15, 95% CI 0.88–1.49).ConclusionsWhile the beneficial association between leisure-time physical activity and CVD mortality has been widely documented, occupational physical activity was not found to have a beneficial association with CVD mortality. This observation may have implications for our appreciation of the association between physical activity and health for workers in physically demanding jobs, as occupational physical activity may not be health enhancing.     

Incidence of urinary tract infection among patients with type 2 diabetes in the UK General Practice Research Database (GPRD)

The objective of this observational study was to quantify the incidence of urinary tract infections (UTI) among diabetes patients and compare this risk to patients without diabetes. Type 2 diabetes patients and a matched sample of patients without diabetes were identified from GPRD. Patients were followed for 1-year from their study index date until the first record of a UTI or a censored event. The incidence of UTI was 46.9 per 1000 person-years (95% confidence interval (CI) 45.8–48.1) among diabetes patients and 29.9 (95% CI 28.9–30.8) for patients without diabetes. Compared to the non-diabetes patients, the risk of UTI was 1.53 (95% CI 1.46–1.59) for all diabetes patients; and 2.08 (95% CI 1.93–2.24) for patients with previously diagnosed diabetes. In general practice, across gender and age, the risk of developing a UTI is higher for patients with type 2 diabetes compared to patients without diabetes.     

Vorausverfügungen im klinischen Alltag

Die Anaesthesiologie - Im klinischen Alltag entstehen immer wieder Situationen, in denen das Behandlungsteam und die Angehörigen mit der Frage der Therapieausweitung bzw. -begrenzung bei...     

Critical slowing down suggests that the western Greenland Ice Sheet is close to a tipping point

The Greenland Ice Sheet (GrIS) is a potentially unstable component of the Earth system and may exhibit a critical transition under ongoing global warming. Mass reductions of the GrIS have substantial impacts on global sea level and the speed of the Atlantic Meridional Overturning Circulation, due to the additional freshwater caused by increased meltwater runoff into the northern Atlantic. The stability of the GrIS depends crucially on the positive melt-elevation feedback (MEF), by which melt rates increase as the overall ice sheet height decreases under rising temperatures. Melting rates across Greenland have accelerated nonlinearly in recent decades, and models predict a critical temperature threshold beyond which the current ice sheet state is not maintainable. Here, we investigate long-term melt rate and ice sheet height reconstructions from the central-western GrIS in combination with model simulations to quantify the stability of this part of the GrIS. We reveal significant early-warning signals (EWS) indicating that the central-western GrIS is close to a critical transition. By relating the statistical EWS to underlying physical processes, our results suggest that the MEF plays a dominant role in the observed, ongoing destabilization of the central-western GrIS. Our results suggest substantial further GrIS mass loss in the near future and call for urgent, observation-constrained stability assessments of other parts of the GrIS.

During the last century, the Greenland Ice Sheet (GrIS) has lost mass at an accelerating rate (1, 2). The mass loss is caused by solid ice discharge into the North Atlantic and surface melting due to increasing temperatures. The relative contribution of the latter has increased from 42% before 2005 to 68% between 2009 and 2012, and surface runoff caused 84% of the increase in mass reduction since 2009 (3). The complete melting of the GrIS would cause a global sea level rise of more than 7 m (4, 5). Continued melting of the GrIS has been suggested to potentially lead to a collapse of the Atlantic Meridional Overturning Circulation via increased freshwater flux into the North Atlantic (6, 7), which may, in turn, trigger a cascade of transitions in additional tipping elements such as the Amazon rainforest and the tropical monsoon systems (6, 8–10).In addition to the centennial-scale variability associated with the increasing trend in mean temperatures related to anthropogenic climate change, the pace of mass loss has decadal-scale fluctuations caused by natural variations in external oceanic and atmospheric forcing. The imprints of these natural, decadal-scale fluctuations are spatially heterogeneous across the GrIS. Since the early 2000s, periods of persistently negative phases of the North Atlantic Oscillation (NAO) and a positive phase of the East Atlantic Pattern (11) have led to a weakening and southward shift of the jet stream, and more persistent blocking (12) over Greenland during summer, resulting in overall increased mass reduction rates (2, 13). On the other hand, a slowing down of mass loss since 2013—which inverted again in 2019—was caused by more periods with a persistent positive NAO (14). Moreover, recent observations show that the Jakobshavn glacier has been advancing again since 2016 due to anomalous wintertime heat loss in the boundary current around southern Greenland (15). However, these natural fluctuations do not have a sustained impact on melt rates comparable to the longer-term trend toward overall increasing melt rates caused by anthropogenic global warming (Fig. 1A).Open in a separate windowFig. 1.(A) Summer sea level temperatures from the Ilulissat station in CWG (25) (blue curves) and Arctic temperature anomalies (26) (red curves). The linear trend of the station data (dashed blue curve) corresponds to 1.3 °C warming per century. Arctic temperature anomalies are shown only for comparison; only the station data (blue curves) are used for our analysis. (B) Melt rates from the CWG ice core stack (blue curve) and the NU peninsula core (red curve), given as z scores with respect to a normal distribution (18). (C) Detrended logarithmic CWG (blue curve) and NU (red curve) melt rates. A Gaussian filter with bandwidth σ=30 y was used for detrending. The runoff and melt time series are preprocessed in this way before computing the EWS indicators to exclude potential biases by underlying trends; in particular, we take the logarithm of the melt rates in order to account for skewed data distributions. (D) The variance of the CWG (blue curves) and NU (red curves) melt rates. (E) The AC1 of the CWG (blue curves) and NU (red curves) melt rates. Note that the AC1, despite a significantly positive trend, appears to have at least temporarily stabilized in the last few decades. It should be noted, however, that the AC1 is generally influenced by (multi)decadal variability (27). The window size for computing the variance and the AC1 is w=70 y, and values are plotted at the windows’ endpoints. Data for the first w=70 y are omitted to ensure that all windows contain the same number of data points. The dashed lines in D and E indicate linear trends of the variance and AC1, and P values for positive slopes as determined from a phase surrogate test are indicated in the legend (see Materials and Methods). The statistical significance of the positive trends is robust across wide ranges of the bandwidth σ and the sliding window size (SI Appendix, Fig. S1).Early model simulations suggest that melting of the GrIS is inevitable beyond a critical global mean temperature threshold of 0.8 °C to 3.2 °C above preindustrial levels, with a best estimate of 1.6 °C (16). More recent comprehensive modeling results show that, for the representative concentration pathway 8.5 (RCP8.5), the GrIS melts entirely until AD 3000 (5). Arctic temperatures have increased more than the global average (17) (Fig. 1A), and the nonlinear increase in GrIS melt rates and runoff that have recently been detected (18) (Fig. 1B) suggests that the critical temperature threshold may be closer than previously thought. We emphasize that the surface mass balance turning negative is not a necessary condition for stability loss, and the temperature may reach a critical threshold years before a turning point in the mass balance (16).Idealized models of critical transitions in natural systems suggest that the loss of stability of an equilibrium (fixed point) is observable before the abrupt transition (19). In dynamical systems with random forcing, one can show that, if a system approaches a bifurcation where an equilibrium point loses its stability, the variance of the fluctuations around the equilibrium will increase, as will the characteristic decay time of the autocorrelation function of these fluctuations. The change in dynamics that occurs as stability is lost is often called critical slowing down, and the associated statistical precursor signs in terms of rising variance and lag-one autocorrelation (AC1) are called early-warning signals (EWS) (19). Such statistical EWS associated with critical slowing down are, for example, detectable in the temperature proxy from the North Greenland Ice Core Project before several of the Dansgaard–Oeschger events of the last glacial interval (20, 21), as well as before other abrupt transitions in past climates (22). In the context of anthropogenic global warming, EWS are expected to precede potential abrupt transitions in the Earth system’s major tipping elements, such as the polar ice sheets, the Atlantic Meridional Overturning Circulation, or the tropical monsoon systems (23). We investigate here a possible tipping point for the GrIS based on the theory of critical slowing down.In the following, we will first show that central-western Greenland (CWG) melt rates exhibit robust and significant EWS. We then reconstruct the corresponding CWG ice sheet height changes and show that they can be captured well by a simple model focusing on the melt elevation feedback (MEF). We then demonstrate that pronounced EWS can also be found in the fluctuations of the reconstructed ice sheet height around the equilibrium of the model and show that these EWS are consistent with the theoretical expectations provided by the MEF model.     

Inhibition of coagulation,fibrinolysis, and endothelial cell activation by a p38 mitogen-activated protein kinase inhibitor during human endotoxemia

P38 mitogen-activated protein kinase (MAPK) is an important component of intracellular signaling cascades that initiate various inflammatory cellular responses. To determine the role of p38 MAPK in the procoagulant response to lipopolysaccharide (LPS), 24 healthy subjects were exposed to an intravenous dose of LPS (4 ng/kg), preceded 3 hours earlier by orally administered 600 or 50 mg BIRB 796 BS (a specific p38 MAPK inhibitor), or placebo. The 600-mg dose of BIRB 796 BS strongly inhibited LPS-induced coagulation activation, as measured by plasma concentrations of the prothrombin fragment F1 + 2. BIRB 796 BS also dose dependently attenuated the activation and subsequent inhibition of the fibrinolytic system (plasma tissue-type plasminogen activator, plasmin-alpha2-antiplasmin complexes, and plasminogen activator inhibitor type 1) and endothelial cell activation (plasma soluble E-selectin and von Willebrand factor). Activation of p38 MAPK plays an important role in the procoagulant and endothelial cell response after in vivo exposure to LPS.     

Granulocyte colony-stimulating factor administration to healthy volunteers: analysis of the immediate activating effects on circulating neutrophils

In four healthy volunteers, we analyzed in detail the immediate in vivo effects on circulating neutrophils of subcutaneous administration of 300 micrograms of granulocyte colony-stimulating factor (G-CSF). Neutrophil activation was assessed by measurement of degranulation. Mobilization of secretory vesicles was shown by a decrease in leukocyte alkaline phosphatase content of the circulating neutrophils. Furthermore, shortly postinjection, Fc gamma RIII was found to be upregulated from an intracellular pool that we identified by immunoelectron microscopy as secretory vesicles. Intravascular release of specific granules was shown by increased plasma levels of lactoferrin and by upregulation of the expression of CD66b and CD11b on circulating neutrophils. Moreover, measurement of fourfold elevated plasma levels of elastase, bound to its physiologic inhibitor alpha 1- antitrypsin, indicated mobilization of azurophil granules. However, no expression of CD63, a marker of azurophil granules, was observed on circulating neutrophils. G-CSF--induced mobilization of secretory vesicles and specific granules could be mimicked in whole blood cultures in vitro, in contrast to release of azurophil granules. Therefore, we postulate that the most activated neutrophils leave the circulation, as observed shortly postinjection, and undergo subsequent stimulation in the endothelial microenvironment, resulting in mobilization of azurophil granules. Our data demonstrate that G-CSF should be regarded as a potent immediate activator of neutrophils in vivo.