27 research outputs found
Alcohol use and burden for 195 countries and territories, 1990-2016 : a systematic analysis for the Global Burden of Disease Study 2016
Background Alcohol use is a leading risk factor for death and disability, but its overall association with health remains complex given the possible protective effects of moderate alcohol consumption on some conditions. With our comprehensive approach to health accounting within the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we generated improved estimates of alcohol use and alcohol-attributable deaths and disability-adjusted life-years (DALYs) for 195 locations from 1990 to 2016, for both sexes and for 5-year age groups between the ages of 15 years and 95 years and older. Methods Using 694 data sources of individual and population-level alcohol consumption, along with 592 prospective and retrospective studies on the risk of alcohol use, we produced estimates of the prevalence of current drinking, abstention, the distribution of alcohol consumption among current drinkers in standard drinks daily (defined as 10 g of pure ethyl alcohol), and alcohol-attributable deaths and DALYs. We made several methodological improvements compared with previous estimates: first, we adjusted alcohol sales estimates to take into account tourist and unrecorded consumption; second, we did a new meta-analysis of relative risks for 23 health outcomes associated with alcohol use; and third, we developed a new method to quantify the level of alcohol consumption that minimises the overall risk to individual health. Findings Globally, alcohol use was the seventh leading risk factor for both deaths and DALYs in 2016, accounting for 2.2% (95% uncertainty interval [UI] 1.5-3.0) of age-standardised female deaths and 6.8% (5.8-8.0) of age-standardised male deaths. Among the population aged 15-49 years, alcohol use was the leading risk factor globally in 2016, with 3.8% (95% UI 3.2-4-3) of female deaths and 12.2% (10.8-13-6) of male deaths attributable to alcohol use. For the population aged 15-49 years, female attributable DALYs were 2.3% (95% UI 2.0-2.6) and male attributable DALYs were 8.9% (7.8-9.9). The three leading causes of attributable deaths in this age group were tuberculosis (1.4% [95% UI 1. 0-1. 7] of total deaths), road injuries (1.2% [0.7-1.9]), and self-harm (1.1% [0.6-1.5]). For populations aged 50 years and older, cancers accounted for a large proportion of total alcohol-attributable deaths in 2016, constituting 27.1% (95% UI 21.2-33.3) of total alcohol-attributable female deaths and 18.9% (15.3-22.6) of male deaths. The level of alcohol consumption that minimised harm across health outcomes was zero (95% UI 0.0-0.8) standard drinks per week. Interpretation Alcohol use is a leading risk factor for global disease burden and causes substantial health loss. We found that the risk of all-cause mortality, and of cancers specifically, rises with increasing levels of consumption, and the level of consumption that minimises health loss is zero. These results suggest that alcohol control policies might need to be revised worldwide, refocusing on efforts to lower overall population-level consumption.Peer reviewe
Conformational Dynamics Accompanying the Proteolytic Degradation of Trimeric Collagen I by Collagenases
Collagenases are the principal enzymes responsible for
the degradation
of collagens during embryonic development, wound healing, and cancer
metastasis. However, the mechanism by which these enzymes disrupt
the highly chemically and structurally stable collagen triple helix
remains incompletely understood. We used a single-molecule magnetic
tweezers assay to characterize the cleavage of heterotrimeric collagen
I by both the human collagenase matrix metalloproteinase-1 (MMP-1)
and collagenase from <i>Clostridium histolyticum</i>. We
observe that the application of 16 pN of force causes an 8-fold increase
in collagen proteolysis rates by MMP-1 but does not affect cleavage
rates by <i>Clostridium</i> collagenase. Quantitative analysis
of these data allows us to infer the structural changes in collagen
associated with proteolytic cleavage by both enzymes. Our data support
a model in which MMP-1 cuts a transient, stretched conformation of
its recognition site. In contrast, our findings suggest that <i>Clostridium</i> collagenase is able to cleave the fully wound
collagen triple helix, accounting for its lack of force sensitivity
and low sequence specificity. We observe that the cleavage of heterotrimeric
collagen is less force sensitive than the proteolysis of a homotrimeric
collagen model peptide, consistent with studies suggesting that the
MMP-1 recognition site in heterotrimeric collagen I is partially unwound
at equilibrium
Strain Tunes Proteolytic Degradation and Diffusive Transport in Fibrin Networks
Proteolytic degradation of fibrin, the major structural
component
in blood clots, is critical both during normal wound healing and in
the treatment of ischemic stroke and myocardial infarction. Fibrin-containing
clots experience substantial strain due to platelet contraction, fluid
shear, and mechanical stress at the wound site. However, little is
understood about how mechanical forces may influence fibrin dissolution.
We used video microscopy to image strained fibrin clots as they were
degraded by plasmin, a major fibrinolytic enzyme. Applied strain causes
up to 10-fold reduction in the rate of fibrin degradation. Analysis
of our data supports a quantitative model in which the decrease in
fibrin proteolysis rates with strain stems from slower transport of
plasmin into the clot. We performed fluorescence recovery after photobleaching
(FRAP) measurements to further probe the effect of strain on diffusive
transport. We find that diffusivity perpendicular to the strain axis
decreases with increasing strain, while diffusivity along the strain
axis remains unchanged. Our results suggest that the properties of
the fibrin network have evolved to protect mechanically loaded fibrin
from degradation, consistent with its function in wound healing. The
pronounced effect of strain upon diffusivity and proteolytic susceptibility
within fibrin networks offers a potentially useful means of guiding
cell growth and morphology in fibrin-based biomaterials
Himalaya to Hengduan: dynamics of alpine treelines under climate change
Alpine treelines serve as vital indicators of the impacts of climate change on tree growth and forest distribution. They offer valuable insights into how shifting temperature and precipitation patterns affect ecosystems in treeline ecotones. Analyzing the age structure of tree stands at treelines provides a glimpse into how different generations of trees have responded to changing environmental conditions and aids in predicting future changes. Moreover, studying the spatiotemporal distribution of tree species at treelines helps us gain a comprehensive understanding of how forests adapt to climate variations. Tree rings at treelines can elucidate the climatic factors that limit tree growth and establishment patterns. Mountain environments, characterized by low temperatures at higher elevations, create constraints on tree growth. However, the intricate interplay between temperature and water availability, driven by precipitation gradients, means that predicting treeline shifts based solely on temperature changes is overly simplistic and may not fully reflect the complex reality. To assess the potential for such interactions, we contrasted the dendroecological performance of different tree species (Abies spectabilis, Betula utilis, Abies georgei and Larix potaninii) in the trans-Himalayan zone, Nepal and Hengduan Mountains, China. We reconstructed the stand age structure by using dendrochronology. Statistical determination of climate-growth responses demonstrated that treeline is moisture sensitive in Himalaya, and temperature as well as moisture sensitive in Hengduan region. There was abundant seedling recruitment with consistent range shift of A. spectabilis and B. utilis treelines in Nepal, and lower seedling recruitment with lower shifting rates of treelines of A. georgei and L. potaninii in Hengduan Mountains. We identify both moisture and temperature as critical environmental factors in determining tree radial growth and treeline response to climate. However, modifying factors such as microhabitat conditions and biotic interactions are also highly important to improve accuracy of treeline dynamics