Hearing impairment negatively affects well-being and is a major contributor to years lived with disability. The World Health Organization (WHO) estimates that 466 million people were living with ...disabling hearing impairment in 2018 and this estimate is projected to rise to 630 million by 2030 and to over 900 million by 2050. However, these projections are based on a hearing impairment classification that does not fully reflect the provisions of the International classification of functioning, disability and health for assessing all forms of functional impairments. Here we make the case for a review of the concept of disabling hearing loss adopted by WHO after the recommendation of the Global Burden of Disease (GBD) Expert Group on Hearing Impairment in 2008. The need for an independent classification system for all impairments and disabilities as a complement to the well-established International statistical classification of diseases and related health problems, was first suggested in 1976 by the World Health Assembly. As a result, in 1980 WHO developed the International classification of impairments, disabilities and handicaps. One of the key features of this system was the use of qualifiers such as mild, moderate, severe and profound to distinguish various levels of observed or measured deviations outside of the range considered for normal functioning for any health condition. This categorization has been reinforced in the subsequent revisions to the system, such as the International Classification of Functioning, Disability and Health, and accompanied with descriptions of typical problems encountered in daily activities at various levels of severity. The classification, notably, does not use the term disabling, as it recognizes the needs of all persons with functional impairments for appropriate intervention.
Epidemiologic and clinical research has provided a large body of evidence supporting the developmental origins of health and disease (DOHaD), but there has been a relative dearth of mechanistic ...studies in humans due to the complexity of working with large, longitudinal cohorts. Nonetheless, animal models of undernutrition have provided substantial evidence for the potential epigenetic, metabolic, and endocrine mechanisms behind DOHaD. Furthermore, recent research has explored the interaction between the environment and the gastrointestinal system by investigating how the gut microbial ecology may impact the capacity for nutrient processing and absorption in a manner that may limit growth. This review presents a summary of current research that supports the concept of DOHaD, as well as potential mechanisms and interactions that explain how nutrition in utero and during early childhood influences lifelong health.
Developmental origins of metabolic diseases Hoffman, Daniel J.; Powell, Theresa L.; Barrett, Emily S. ...
Physiological reviews,
07/2021, Letnik:
101, Številka:
3
Journal Article
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Almost 2 billion adults in the world are overweight, and more than half of them are classified as obese, while nearly one-third of children globally experience poor growth and development. Given the ...vast amount of knowledge that has been gleaned from decades of research on growth and development, a number of questions remain as to why the world is now in the midst of a global epidemic of obesity accompanied by the “double burden of malnutrition,” where overweight coexists with underweight and micronutrient deficiencies. This challenge to the human condition can be attributed to nutritional and environmental exposures during pregnancy that may program a fetus to have a higher risk of chronic diseases in adulthood. To explore this concept, frequently called the developmental origins of health and disease (DOHaD), this review considers a host of factors and physiological mechanisms that drive a fetus or child toward a higher risk of obesity, fatty liver disease, hypertension, and/or type 2 diabetes (T2D). To that end, this review explores the epidemiology of DOHaD with discussions focused on adaptations to human energetics, placental development, dysmetabolism, and key environmental exposures that act to promote chronic diseases in adulthood. These areas are complementary and additive in understanding how providing the best conditions for optimal growth can create the best possible conditions for lifelong health. Moreover, understanding both physiological as well as epigenetic and molecular mechanisms for DOHaD is vital to most fully address the global issues of obesity and other chronic diseases.
Exercise is essential in regulating energy metabolism and whole-body insulin sensitivity. To explore the exercise signaling network, we undertook a global analysis of protein phosphorylation in human ...skeletal muscle biopsies from untrained healthy males before and after a single high-intensity exercise bout, revealing 1,004 unique exercise-regulated phosphosites on 562 proteins. These included substrates of known exercise-regulated kinases (AMPK, PKA, CaMK, MAPK, mTOR), yet the majority of kinases and substrate phosphosites have not previously been implicated in exercise signaling. Given the importance of AMPK in exercise-regulated metabolism, we performed a targeted in vitro AMPK screen and employed machine learning to predict exercise-regulated AMPK substrates. We validated eight predicted AMPK substrates, including AKAP1, using targeted phosphoproteomics. Functional characterization revealed an undescribed role for AMPK-dependent phosphorylation of AKAP1 in mitochondrial respiration. These data expose the unexplored complexity of acute exercise signaling and provide insights into the role of AMPK in mitochondrial biochemistry.
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•Identification of the human muscle acute exercise signaling repertoire•Integrated AMPK substrate prediction in human muscle and cells•Targeted validation of exercise-regulated AMPK substrates•AKAP1 phosphorylation by AMPK that regulates mitochondrial respiration
Combining phosphoproteomics, biochemical, and bioinformatics approaches, Hoffman et al. perform a global analysis of exercise signaling in human skeletal muscle and reveal an interconnected network of kinases and AMPK substrates in response to exercise. Among these, AKAP1 is shown to regulate mitochondrial respiration via AMPK-dependent phosphorylation.
Government interventions are critical to addressing the global tobacco epidemic, a major public health problem that continues to deepen. We systematically synthesize research evidence on the ...effectiveness of government tobacco control policies promoted by the Framework Convention on Tobacco Control (FCTC), supporting the implementation of this international treaty on the tenth anniversary of it entering into force.
An overview of systematic reviews was prepared through systematic searches of five electronic databases, published up to March 2014. Additional reviews were retrieved from monthly updates until August 2014, consultations with tobacco control experts and a targeted search for reviews on mass media interventions. Reviews were assessed according to predefined inclusion criteria, and ratings of methodological quality were either extracted from source databases or independently scored.
Of 612 reviews retrieved, 45 reviews met the inclusion criteria and 14 more were identified from monthly updates, expert consultations and a targeted search, resulting in 59 included reviews summarizing over 1150 primary studies. The 38 strong and moderate quality reviews published since 2000 were prioritized in the qualitative synthesis. Protecting people from tobacco smoke was the most strongly supported government intervention, with smoke-free policies associated with decreased smoking behaviour, secondhand smoke exposure and adverse health outcomes. Raising taxes on tobacco products also consistently demonstrated reductions in smoking behaviour. Tobacco product packaging interventions and anti-tobacco mass media campaigns may decrease smoking behaviour, with the latter likely an important part of larger multicomponent programs. Financial interventions for smoking cessation are most effective when targeted at smokers to reduce the cost of cessation products, but incentivizing quitting may be effective as well. Although the findings for bans on tobacco advertising were inconclusive, other evidence suggests they remain an important intervention.
When designing and implementing tobacco control programs, governments should prioritize smoking bans and price increases of tobacco products followed by other interventions. Additional studies are needed on the various factors that can influence a policy's effectiveness and feasibility such as cost, local context, political barriers and implementation strategies.
This article analyzes the extent to which two institutional logics around climate change—the climate change “convinced” and the climate change “skeptical” logics—are truly competing or talking past ...each other in a way that can be described as a logic schism. Drawing on the concept of framing from social movement theory, it uses qualitative field observations from the largest climate deniers conference in the United States and a data set of almost 800 op-eds from major news outlets over a 2-year period to examine how convinced and skeptical arguments of opposing logics employ frames and issue categories to make arguments about climate change. This article finds that the two logics are engaging in different debates on similar issues with the former focusing on solutions while the latter debates the definition of the problem. It concludes that the debate appears to be reaching a level of polarization where one might begin to question whether meaningful dialogue and problem solving has become unavailable to participants. The implications of such a logic schism is a shift from an integrative debate focused on addressing interests, to a distributive battle over concessionary agreements with each side pursuing its goals by demonizing the other. Avoiding such an outcome requires the activation of, as yet, dormant “broker” categories (technology, religion, and national security), the redefinition of existing ones (science, economics, risk, ideology), and the engagement of effective “climate brokers” to deliver them.
Abstract
Global coastlines potentially contain significant amounts of plastic debris, with harmful implications for marine and coastal ecosystems, fisheries and tourism. However, the global amount, ...distribution and origin of plastic debris on beaches and in coastal waters is currently unknown. Here we analyze beaching and resuspension scenarios using a Lagrangian particle transport model. Throughout the first 5 years after entering the ocean, the model indicates that at least 77% of positively buoyant marine plastic debris (PBMPD) released from land-based sources is either beached or floating in coastal waters, assuming no further plastic removal from beaches or the ocean surface. The highest concentrations of beached PBMPD are found in Southeast Asia, caused by high plastic inputs from land and limited offshore transport, although the absolute concentrations are generally overestimates compared to field measurements. The modeled distribution on a global scale is only weakly influenced by local variations in resuspension rates due to coastal geomorphology. Furthermore, there are striking differences regarding the origin of the beached plastic debris. In some exclusive economic zones (EEZ), such as the Indonesian Archipelago, plastic originates almost entirely from within the EEZ while in other EEZs, particularly remote islands, almost all beached plastic debris arrives from remote sources. Our results highlight coastlines and coastal waters as important reservoirs of marine plastic debris and limited transport of PBMPD between the coastal zone and the open ocean.
•High cigarette exposure associated with low taste perception on the tongue-tip.•Former, light, or menthol smokers reported greater whole mouth taste perception.•Patterns of smoking and taste ...associations were most evident in younger smokers.•Both history and dependency measures are needed to clarify associations with taste.
We identified associations between cigarette-smoking and taste function in the U.S. NHANES 2013–2014. Adults ≥ 40 years (n = 2849, nearly half former or current smokers) rated whole-mouth and tongue-tip bitter (1 mM quinine) and salt (1 M NaCl, 0.32 M NaCl) intensities and reported smoking history (pack years, PY), dependence (time to first cigarette, TTFC) and menthol/non-menthol use. Perceived intensity on the tongue-tip averaged just below moderate for quinine and moderate to strong for 1 M NaCl. Current chronic smokers (≥ 20 PY) reported lower bitter and salty intensities on the tongue-tip (β: -2.0, 95% CI: -3.7 to -0.4 and β: -3.6, 95% CI: -6.9 to -0.3, respectively) than never smokers. Similarly, compared to never smokers, dependent current smokers (TTFC ≤ 30 min) and dependent chronic smokers (≥ 20 PY, TTFC ≤ 30 min) rated less bitter (β: -2.0, 95% CI: -4.0 to 0.1 and β: -2.9, 95% CI: -4.5 to -1.3, respectively) and salty (β: -5.3, 95% CI: -9.3 to -1.4 and β: -4.7, 95% CI: -8.6 to -0.7, respectively) intensities on the tongue-tip. Depressed tongue-tip intensity in dependent smokers (with/without chronicity) versus never smokers was significant in younger (40–65 years), but not older (> 65 years) adults. Former smokers, non-chronic/less dependent smokers, and menthol smokers were more likely to report elevated whole-mouth quinine and 1 M NaCl intensities. Tongue-tip and whole-mouth taste intensity concordance varied between smokers and never smokers—current dependent smokers were more likely to rate tongue-tip quinine and NaCl lower than their respective whole-mouth tastants (OR: 1.8, 95% CI: 1.0 to 3.1 and OR: 1.8, 95% CI: 1.1 to 2.8, respectively). In summary, these U.S. nationally-representative data show that current smoking with chronicity and/or dependence associates with lower tongue-tip intensity for bitter and salty stimuli. Smokers with greater exposure to nicotine and/or dependence showed greater risk of taste alterations, with implications for diet- and smoking-related health outcomes.
Zebrafish are increasingly being utilized as a model system to investigate the function of the growing list of risk genes associated with neurodevelopmental disorders. This is due in large part to ...the unique features of zebrafish that make them an optimal system for this purpose, including rapid, external development of transparent embryos, which enable the direct visualization of the developing nervous system during early stages, large progenies, which provide considerable tractability for performing high-throughput pharmacological screens to identify small molecule suppressors of simple behavioral phenotypes, and ease of genetic manipulation, which has been greatly facilitated by the advent of CRISPR/Cas9 gene editing technologies. This review article focuses on studies that have harnessed these advantages of the zebrafish system for the functional analysis of genes that are strongly associated with the following neurodevelopmental disorders: autism spectrum disorders (ASD), epilepsy, intellectual disability (ID) and schizophrenia. We focus primarily on studies describing early morphological and behavioral phenotypes during embryonic and larval stages resulting from loss of risk gene function. We highlight insights into basic mechanisms of risk gene function gained from these studies as well as limitations of studies to date. Finally, we discuss advances in
neural circuit imaging in zebrafish, which promise to transform research using the zebrafish model by illuminating novel circuit-level mechanisms with relevance to neurodevelopmental disorders.
Microsatellite genotyping errors will be present in all but the smallest data sets and have the potential to undermine the conclusions of most downstream analyses. Despite this, little rigorous ...effort has been made to quantify the size of the problem and to identify the commonest sources of error. Here, we use a large data set comprising almost 2000 Antarctic fur seals Arctocephalus gazella genotyped at nine hypervariable microsatellite loci to explore error detection methods, common sources of error and the consequences of errors on paternal exclusion. We found good concordance among a range of contrasting approaches to error‐rate estimation, our range being 0.0013 to 0.0074 per single locus PCR (polymerase chain reaction). The best approach probably involves blind repeat‐genotyping, but this is also the most labour‐intensive. We show that several other approaches are also effective at detecting errors, although the most convenient alternative, namely mother–offspring comparisons, yielded the lowest estimate of the error rate. In total, we found 75 errors, emphasizing their ubiquitous presence. The most common errors involved the misinterpretation of allele banding patterns (n = 60, 80%) and of these, over a third (n = 22, 36.7%) were due to confusion between homozygote and adjacent allele heterozygote genotypes. A specific test for whether a data set contains the expected number of adjacent allele heterozygotes could provide a useful tool with which workers can assess the likely size of the problem. Error rates are also positively correlated with both locus polymorphism and product size, again indicating aspects where extra effort at error reduction should be directed. Finally, we conducted simulations to explore the potential impact of genotyping errors on paternity exclusion. Error rates as low as 0.01 per allele resulted in a rate of false paternity exclusion exceeding 20%. Errors also led to reduced estimates of male reproductive skew and increases in the numbers of pups that matched more than one candidate male. Because even modest error rates can be strongly influential, we recommend that error rates should be routinely published and that researchers make an attempt to calculate how robust their analyses are to errors.
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