Could routine vaccinations prevent dementia? Poynton‐Smith, Emma; Orrell, Martin; Morley, John E. ...
International journal of geriatric psychiatry,
July 2023, 2023-07-00, 20230701, Letnik:
38, Številka:
7
Journal Article
The global environment annually receives thousands of tons of engineered nanomaterials (ENMs, particles less than 100 nm diameter). These particles have high active surface area, unique chemical ...properties, and can enter cells. Humanity uses many ENMs for their biological reactivity (e.g. microbicides), but their environmental effects are complex. We cataloged 2102 experimental results on whole organisms for 22 particle classes (mainly on Ag, Zn, Ti, and Cu) to assess biological responses, effective and lethal concentrations, and bioaccumulation of ENMs. Most responses were negative and varied significantly by particle type, functional group of organism, and type of response. Smaller particles tended to be more toxic. Aquatic organisms responded more negatively than did terrestrial organisms. Animals generally were most sensitive and plants least. Silver ENMs generally had the strongest negative effects. Effective and lethal concentrations generally exceeded modeled environmentally relevant concentrations and organisms usually did not accumulate or biomagnify to concentrations above those in their environment. However, most experiments lasted less than a week and were not field studies. Research to date is probably insufficient to understand chronic effects and long-term biomagnification. Numerous unique and untested ENMs continue to enter environments at accelerating rates, and our analysis indicates potential for negative effects. Our data suggest substantial research is still required to understand the ultimate influence of ENMs as they continue to accumulate in the environment. Around 40% of the papers with experimental data for ENMs failed with respect to reporting means, sample sizes, or experimental error, or they did not have proper experimental design (e.g. lack of true controls). We need more high-quality experiments that are more realistic (field or mesocosm), longer duration, contain a wider range of organisms, and account for complex food web structure.
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•Engineered nanomaterials can harm plants, heterotrophic and autotrophic microbes, and animals.•Animals were most harmed, plants least.•50% lethal concentrations exceeded most environmentally relevant concentrations.•Biodilution was more common than biomagnification.•Most experiments were too short or too unrealistic to assess chronic environmental effects.
To estimate the global burden of hip and knee osteoarthritis (OA) as part of the Global Burden of Disease 2010 study and to explore how the burden of hip and knee OA compares with other conditions.
...Systematic reviews were conducted to source age-specific and sex-specific epidemiological data for hip and knee OA prevalence, incidence and mortality risk. The prevalence and incidence of symptomatic, radiographic and self-reported hip or knee OA were included. Three levels of severity were defined to derive disability weights (DWs) and severity distribution (proportion with mild, moderate and severe OA). The prevalence by country and region was multiplied by the severity distribution and the appropriate disability weight to calculate years of life lived with disability (YLDs). As there are no deaths directly attributed to OA, YLDs equate disability-adjusted life years (DALYs).
Globally, of the 291 conditions, hip and knee OA was ranked as the 11th highest contributor to global disability and 38th highest in DALYs. The global age-standardised prevalence of knee OA was 3.8% (95% uncertainty interval (UI) 3.6% to 4.1%) and hip OA was 0.85% (95% UI 0.74% to 1.02%), with no discernible change from 1990 to 2010. Prevalence was higher in females than males. YLDs for hip and knee OA increased from 10.5 million in 1990 (0.42% of total DALYs) to 17.1 million in 2010 (0.69% of total DALYs).
Hip and knee OA is one of the leading causes of global disability. Methodological issues within this study make it highly likely that the real burden of OA has been underestimated. With the aging and increasing obesity of the world's population, health professions need to prepare for a large increase in the demand for health services to treat hip and knee OA.
A GGGGCC hexanucleotide repeat expansion in the C9orf72 gene is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia (C9ALS/FTD). C9orf72 encodes two C9orf72 ...protein isoforms of unclear function. Reduced levels of C9orf72 expression have been reported in C9ALS/FTD patients, and although C9orf72 haploinsufficiency has been proposed to contribute to C9ALS/FTD, its significance is not yet clear. Here, we report that C9orf72 interacts with Rab1a and the Unc‐51‐like kinase 1 (ULK1) autophagy initiation complex. As a Rab1a effector, C9orf72 controls initiation of autophagy by regulating the Rab1a‐dependent trafficking of the ULK1 autophagy initiation complex to the phagophore. Accordingly, reduction of C9orf72 expression in cell lines and primary neurons attenuated autophagy and caused accumulation of p62‐positive puncta reminiscent of the p62 pathology observed in C9ALS/FTD patients. Finally, basal levels of autophagy were markedly reduced in C9ALS/FTD patient‐derived iNeurons. Thus, our data identify C9orf72 as a novel Rab1a effector in the regulation of autophagy and indicate that C9orf72 haploinsufficiency and associated reductions in autophagy might be the underlying cause of C9ALS/FTD‐associated p62 pathology.
Synopsis
C9ALS/FTD‐associated C9orf72 is a Rab1a effector that controls initiation of autophagy by regulating ULK1 complex trafficking. Disruption of C9orf72 function inhibits autophagy and mimics the p62 pathology found in C9ALS/FTD patients. C9ALS/FTD iNeurons display reduced autophagy.
C9orf72 regulates ULK1 complex‐dependent initiation of autophagy.
C9orf72 is a Rab1a effector that controls trafficking of the ULK1 complex.
C9orf72 deficiency inhibits autophagy and mimics C9ALS/FTD p62 pathology.
C9ALS/FTD patient‐derived iNeurons display reduced autophagy.
ALS/FTD‐associated C9orf72 is a Rab1a effector that controls initiation of autophagy by regulating ULK1 complex trafficking.
Intraspecific variation in behavior and diet can have important consequences for population and ecosystem dynamics. Here, we examine how differences in reproductive investment and spatial ecology ...influence individual diet specialization in male and female southern sea otters (Enhydra lutris nereis). We hypothesize that greater reproductive constraints and smaller home ranges of females lead to more pronounced intraspecific competition and increased specialization. We integrate stable carbon (δ¹³C) and nitrogen (δ¹³N) isotope analysis of sea otter vibrissae with long-term observational studies of five subpopulations in California. We define individual diet specialization as low ratios of within-individual variation (WIC) to total population niche width (TNW). We compare isotopie and observational based metrics of WIC/TNW for males and females to data on population densities, and movement patterns using both general linear and linear mixed-effects models. Consistent with our hypothesis, increasing population density is associated with increased individual diet specialization by females but not by males. Additionally, we find the amount of coastline in a sea otter's home range positively related with individual dietary variability, with increased range span resulting in weaker specialization for both males and females. We attribute our results to sex-based differences in movement, with females needing to specialize in their small ranges to maximize energy gain, and posit that the paradigm of individual prey specialization in sea otters with increased intraspecific competition may be a pattern driven largely by females. Our work highlights a potentially broader role of sex in the mechanistic pressures promoting and maintaining diet specialization.
Objective To examine changes in representation of women among first authors of original research published in high impact general medical journals from 1994 to 2014 and investigate differences ...between journals.Design Observational study.Study sample All original research articles published in Annals of Internal Medicine, Archives of Internal Medicine, The BMJ, JAMA, The Lancet, and the New England Journal of Medicine (NEJM) for one issue every alternate month from February 1994 to June 2014.Main exposures Time and journal of publication.Main outcome measures Prevalence of female first authorship and its adjusted association with time of publication and journal, assessed using a multivariable logistic regression model that accounted for number of authors, study type and specialty/topic, continent where the study was conducted, and the interactions between journal and time of publication, study type, and continent. Estimates from this model were used to calculate adjusted odds ratios against the mean across the six journals, with 95% confidence intervals and P values to describe the associations of interest.Results The gender of the first author was determined for 3758 of the 3860 articles considered; 1273 (34%) were women. After adjustment, female first authorship increased significantly from 27% in 1994 to 37% in 2014 (P<0.001). The NEJM seemed to follow a different pattern, with female first authorship decreasing; it also seemed to decline in recent years in The BMJ but started substantially higher (approximately 40%), and The BMJ had the highest total proportion of female first authors. Compared with the mean across all six journals, first authors were significantly less likely to be female in the NEJM (adjusted odds ratio 0.68, 95% confidence interval 0.53 to 0.89) and significantly more likely to be female in The BMJ (1.30, 1.01 to 1.66) over the study period.Conclusions The representation of women among first authors of original research in high impact general medical journals was significantly higher in 2014 than 20 years ago, but it has plateaued in recent years and has declined in some journals. These results, along with the significant differences seen between journals, suggest that underrepresentation of research by women in high impact journals is still an important concern. The underlying causes need to be investigated to help to identify practices and strategies to increase women’s influence on and contributions to the evidence that will determine future healthcare policies and standards of clinical practice.
Increased awareness, interest and use of assistive technology (AT) presents substantial opportunities for many citizens to become, or continue being, meaningful participants in society. However, ...there is a significant shortfall between the need for and provision of AT, and this is patterned by a range of social, demographic and structural factors. To seize the opportunity that assistive technology offers, regional, national and sub-national assistive technology policies are urgently required. This paper was developed for and through discussion at the Global Research, Innovation and Education on Assistive Technology (GREAT) Summit; organized under the auspices of the World Health Organization's Global Collaboration on Assistive Technology (GATE) program. It outlines some of the key principles that AT polices should address and recognizes that AT policy should be tailored to the realities of the contexts and resources available. AT policy should be developed as a part of the evolution of related policy across a number of different sectors and should have clear and direct links to AT as mediators and moderators for achieving the Sustainable Development Goals. The consultation process, development and implementation of policy should be fully inclusive of AT users, and their representative organizations, be across the lifespan, and imbued with a strong systems-thinking ethos. Six barriers are identified which funnel and diminish access to AT and are addressed systematically within this paper. We illustrate an example of good practice through a case study of AT services in Norway, and we note the challenges experienced in less well-resourced settings. A number of economic factors relating to AT and economic arguments for promoting AT use are also discussed. To address policy-development the importance of active citizenship and advocacy, the need to find mechanisms to scale up good community practices to a higher level, and the importance of political engagement for the policy process, are highlighted. Policy should be evidence-informed and allowed for evidence-making; however, it is important to account for other factors within the given context in order for policy to be practical, authentic and actionable.
Implications for Rehabilitation
The development of policy in the area of asssitive technology is important to provide an overarching vision and outline resourcing priorities.
This paper identifies some of the key themes that should be addressed when developing or revising assistive technology policy.
Each country should establish a National Assistive Technology policy and develop a theory of change for its implementation.
The coronavirus disease 2019 (COVID-19) pandemic is unlike anything seen before by modern science-based medicine. Health systems across the world are struggling to manage it. Added to this struggle ...are the effects of social confinement and isolation. This brings into question whether the latest guidelines are relevant in this crisis. We aim to support urologists in this difficult situation by providing tools that can facilitate decision making, and to minimise the impact and risks for both patients and health professionals delivering urological care, whenever possible. We hope that the revised recommendations will assist urologist surgeons across the globe to guide the management of urological conditions during the current COVID-19 pandemic.
The coronavirus disease 2019 (COVID-19) pandemic is unlike anything seen before by modern science-based medicine. As a scientific society, the European Association of Urology, via the guidelines, section offices, and the European Urology family of journals, we believe that it is important that we try to support urologists in this difficult situation. We aim to do this by providing tools that can facilitate decision making with the goal to minimise the impact and risks for both patients and health professionals delivering urological care, whenever possible, although it is clear that it is not always possible to mitigate them entirely. We hope that these revised recommendations will fill an important urological practice void and assist urologist surgeons across the globe as they do their very best to deal with the crisis of our generation.
This article reports on a study which evaluated five dimensions of first-year university students' engagement in Welsh universities during the COVID-19 pandemic. The study utilises a student ...engagement scale which was previously used with undergraduate students in Australian universities. Our findings provide insights on five dimensions of student engagement including academic, intellectual, peer, student-staff and online engagement which were explored during the COVID-19 pandemic. Findings indicate that the Student-Staff Engagement scale obtained the highest mean value, and the Academic Engagement Scale acquired the lowest score. The highest and lowest engagement-scale items in this study illustrates the shifting profile of first-year students who demonstrated contrasting study habits, forms of communication with peers and interactions with university staff to pre-pandemic students. The results also indicate that engagement is a complex concept and further work is required to better understand student engagement within contemporary universities which have embraced a hybrid mode of teaching and learning. The paper calls for a more robust theorising of the engagement concept and the authors of this article argue that the online dimension of student engagement requires expanding to mirror the experiences of undergraduates studying in the hybrid university.
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