Abstract
Background
Hospitalized COVID-19 patients tend to be older and frequently have hypertension, diabetes, or coronary heart disease, but whether these comorbidities are true risk factors (ie, ...more common than in the general older population) is unclear. We estimated associations between preexisting diagnoses and hospitalized COVID-19 alone or with mortality, in a large community cohort.
Methods
UK Biobank (England) participants with baseline assessment 2006–2010, followed in hospital discharge records to 2017 and death records to 2020. Demographic and preexisting common diagnoses association tested with hospitalized laboratory-confirmed COVID-19 (March 16 to April 26, 2020), alone or with mortality, in logistic models.
Results
Of 269 070 participants aged older than 65, 507 (0.2%) became COVID-19 hospital inpatients, of which 141 (27.8%) died. Common comorbidities in hospitalized inpatients were hypertension (59.6%), history of fall or fragility fractures (29.4%), coronary heart disease (21.5%), type 2 diabetes (type 2, 19. 9%), and asthma (17.6%). However, in models adjusted for comorbidities, age group, sex, ethnicity, and education, preexisting diagnoses of dementia, type 2 diabetes, chronic obstructive pulmonary disease, pneumonia, depression, atrial fibrillation, and hypertension emerged as independent risk factors for COVID-19 hospitalization, the first 5 remaining statistically significant for related mortality. Chronic kidney disease and asthma were risk factors for COVID-19 hospitalization in women but not men.
Conclusions
There are specific high-risk preexisting comorbidities for COVID-19 hospitalization and related deaths in community-based older men and women. These results do not support simple age-based targeting of the older population to prevent severe COVID-19 infections.
Inherited genetic variation influencing leukocyte telomere length provides a natural experiment for testing associations with health outcomes, more robust to confounding and reverse causation than ...observational studies. We tested associations between genetically determined telomere length and aging‐related health outcomes in a large European ancestry older cohort. Data were from n = 379,758 UK Biobank participants aged 40–70, followed up for mean of 7.5 years (n = 261,837 participants aged 60 and older by end of follow‐up). Thirteen variants strongly associated with longer telomere length in peripheral white blood cells were analyzed using Mendelian randomization methods with Egger plots to assess pleiotropy. Variants in TERC, TERT, NAF1, OBFC1, and RTEL1 were included, and estimates were per 250 base pairs increase in telomere length, approximately equivalent to the average change over a decade in the general white population. We highlighted associations with false discovery rate‐adjusted p‐values smaller than .05. Genetically determined longer telomere length was associated with lowered risk of coronary heart disease (CHD; OR = 0.95, 95% CI: 0.92–0.98) but raised risk of cancer (OR = 1.11, 95% CI: 1.06–1.16). Little evidence for associations were found with parental lifespan, centenarian status of parents, cognitive function, grip strength, sarcopenia, or falls. The results for those aged 60 and older were similar in younger or all participants. Genetically determined telomere length was associated with increased risk of cancer and reduced risk of CHD but little change in other age‐related health outcomes. Telomere lengthening may offer little gain in later‐life health status and face increasing cancer risks.
We estimated associations between measured telomere length (TL) and several aging outcomes by using TL‐associated inherited genetic variants, which are robust to later environmental exposures (confounders)(top X). Genetically determined TL was associated with increased risks of cancers and reduced risks of cardiovascular disease, but little change in other studied age‐related health outcomes. There was genetic evidence consistent with these findings being caused through telomere length itself, rather than through another (unknown) pathway (bottom X).
To investigate the effectiveness of a school-based program promoting outdoor activities in Taiwan for myopia prevention and to identify protective light intensities.
Multi-area, cluster-randomized ...intervention controlled trial.
A total 693 grade 1 schoolchildren in 16 schools participated. Two hundred sixty-seven schoolchildren were in the intervention group and 426 were in the control group.
Initially, 24 schools were randomized into the intervention and control groups, but 5 and 3 schools in the intervention and control groups, respectively, withdrew before enrollment. A school-based Recess Outside Classroom Trial was implemented in the intervention group, in which schoolchildren were encouraged to go outdoors for up to 11 hours weekly. Data collection included eye examinations, cycloplegic refraction, noncontact axial length measurements, light meter recorders, diary logs, and questionnaires.
Change in spherical equivalent and axial length after 1 year and the intensity and duration of outdoor light exposures.
The intervention group showed significantly less myopic shift and axial elongation compared with the control group (0.35 diopter D vs. 0.47 D; 0.28 vs. 0.33 mm; P = 0.002 and P = 0.003) and a 54% lower risk of rapid myopia progression (odds ratio, 0.46; 95% confidence interval CI, 0.28-0.77; P = 0.003). The myopic protective effects were significant in both nonmyopic and myopic children compared with controls. Regarding spending outdoor time of at least 11 hours weekly with exposure to 1000 lux or more of light, the intervention group had significantly more participants compared with the control group (49.79% vs. 22.73%; P < 0.001). Schoolchildren with longer outdoor time in school (≥200 minutes) showed significantly less myopic shift (measured by light meters; ≥1000 lux: 0.14 D; 95% CI, 0.02-0.27; P = 0.02; ≥3000 lux: 0.16 D; 95% CI, 0.002-0.32; P = 0.048).
The school-based outdoor promotion program effectively reduced the myopia change in both nonmyopic and myopic children. Outdoor activities with strong sunlight exposure may not be necessary for myopia prevention. Relatively lower outdoor light intensity activity with longer time outdoors, such as in hallways or under trees, also can be considered.
The aim of this study was to investigate the effect of outdoor activity during class recess on myopia changes among elementary school students in a suburban area of Taiwan.
Prospective, comparative, ...consecutive, interventional study.
Elementary school students 7 to 11 years of age recruited from 2 nearby schools located in a suburban area of southern Taiwan.
The children of one school participated in the interventions, whereas those from the other school served as the control group. The interventions consisted of performing a recess outside the classroom (ROC) program that encouraged children to go outside for outdoor activities during recess. The control school did not have any special programs during recess.
Data were obtained by means of a parent questionnaire and ocular evaluations that included axial length and cycloplegic autorefraction at the beginning and after 1 year.
Five hundred seventy-one students were recruited for this study, of whom 333 students participated in the interventional program, and 238 students were in the control school. At the beginning of the study, there were no significant differences between these 2 schools with regard to age, gender, baseline refraction, and myopia prevalence (47.75% vs. 49.16%). After 1 year, new onset of myopia was significantly lower in the ROC group than in the control group (8.41% vs. 17.65%; P<0.001). There was also significantly lower myopic shift in the ROC group compared with the control group (-0.25 diopter D/year vs. -0.38 D/year; P = 0.029). The multivariate analysis demonstrated that the variables of intervention of the ROC program and higher school year proved to be a protective factor against myopia shift in nonmyopic subjects (P = 0.020 and P = 0.017, respectively). For myopic subjects, school year was the only variable significantly associated with myopia progression (P = 0.006).
Outdoor activities during class recess in school have a significant effect on myopia onset and myopic shift. Such activities have a prominent effect on the control of myopia shift, especially in nonmyopic children.
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Biological age measures outperform chronological age in predicting various aging outcomes, yet little is known regarding genetic predisposition. We performed genome‐wide association scans of two ...age‐adjusted biological age measures (PhenoAgeAcceleration and BioAgeAcceleration), estimated from clinical biochemistry markers (Levine et al., 2018; Levine, 2013) in European‐descent participants from UK Biobank. The strongest signals were found in the APOE gene, tagged by the two major protein‐coding SNPs, PhenoAgeAccel—rs429358 (APOE e4 determinant) (p = 1.50 × 10−72); BioAgeAccel—rs7412 (APOE e2 determinant) (p = 3.16 × 10−60). Interestingly, we observed inverse APOE e2 and e4 associations and unique pathway enrichments when comparing the two biological age measures. Genes associated with BioAgeAccel were enriched in lipid related pathways, while genes associated with PhenoAgeAccel showed enrichment for immune system, cell function, and carbohydrate homeostasis pathways, suggesting the two measures capture different aging domains. Our study reaffirms that aging patterns are heterogeneous across individuals, and the manner in which a person ages may be partly attributed to genetic predisposition.
A genome‐wide association study for differences in aging rates was performed in the UK Biobank sample using two previously established aging measures. Results suggest that one was associated with genes involved in lipid metabolism and blood pressure, while the other was associated with genes involved in immune functioning. APOE e4 was associated with faster aging in the measure reflecting lipid age, yet paradoxically, was associated with reduced aging in the measure reflecting immune functioning and inflammation.
The novel respiratory disease COVID-19 produces varying symptoms, with fever, cough, and shortness of breath being common. In older adults, it has been found that preexisting dementia is a major risk ...factor for COVID-19 severity in the UK Biobank (UKB). In another UK study of 16,749 patients hospitalized for COVID-19, dementia was among the common comorbidities and was associated with higher mortality. Additionally, impaired consciousness, including delirium, is common in severe cases. The ApoE e4 genotype is associated with both dementia and delirium, with the e4e4 (homozygous) genotype associated with a 14-fold increase in risk of Alzheimer's disease compared to the common e3e3 genotype, in populations with European ancestries. The need to test associations between ApoE e4 alleles and COVID-19 severity, using the UKB data, is also emphasized.
In this paper we review the methodological underpinnings of the general pharmacogenetic approach for uncovering genetically-driven treatment effect heterogeneity. This typically utilises only ...individuals who are treated and relies on fairly strong baseline assumptions to estimate what we term the 'genetically moderated treatment effect' (GMTE). When these assumptions are seriously violated, we show that a robust but less efficient estimate of the GMTE that incorporates information on the population of untreated individuals can instead be used. In cases of partial violation, we clarify when Mendelian randomization and a modified confounder adjustment method can also yield consistent estimates for the GMTE. A decision framework is then described to decide when a particular estimation strategy is most appropriate and how specific estimators can be combined to further improve efficiency. Triangulation of evidence from different data sources, each with their inherent biases and limitations, is becoming a well established principle for strengthening causal analysis. We call our framework 'Triangulation WIthin a STudy' (TWIST)' in order to emphasise that an analysis in this spirit is also possible within a single data set, using causal estimates that are approximately uncorrelated, but reliant on different sets of assumptions. We illustrate these approaches by re-analysing primary-care-linked UK Biobank data relating to CYP2C19 genetic variants, Clopidogrel use and stroke risk, and data relating to APOE genetic variants, statin use and Coronary Artery Disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The complex relationship between life course traumas and cardiovascular disease (CVD) and the underpinning pathways are poorly understood. We aimed to (1) examine the associations of three separate ...assessments including childhood, adulthood (after 16 years of age), and lifetime traumas (childhood or adulthood) with CVD; (2) examine the associations between diverse life course traumatic profiles and CVD; and (3) examine the extent to which PhenoAge, a well‐developed phenotypic aging measure, mediated these associations. Using data from 104,939 participants from the UK Biobank, we demonstrate that subgroups of childhood, adulthood, and lifetime traumas were associated with CVD. Furthermore, life course traumatic profiles were significantly associated with CVD. For instance, compared with the subgroup experiencing nonsevere traumas across life course, those who experienced nonsevere childhood and severe adulthood traumas, severe childhood and nonsevere adulthood traumas, or severe traumas across life course had significantly higher odds of CVD (odds ratios: 1.07–1.33). Formal mediation analyses suggested that phenotypic aging partially mediated the above associations. These findings suggest a potential pathway from life course traumas to CVD through phenotypic aging, and underscore the importance of policy programs targeting traumas over the life course in ameliorating inequalities in cardiovascular health.
Using data from 104,939 participants from the UK Biobank, we demonstrate that subgroups of childhood, adulthood, and lifetime traumas, as well as life course traumatic profiles, are associated with cardiovascular disease (CVD). Our findings suggest a potential pathway from life course traumas to CVD through phenotypic aging, and underscore the importance of policy programs targeting traumas over the life course in ameliorating inequalities in cardiovascular health.
Biodegradable Piezoelectric Force Sensor Curry, Eli J.; Ke, Kai; Chorsi, Meysam T. ...
Proceedings of the National Academy of Sciences,
01/2018, Letnik:
115, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Measuring vital physiological pressures is important for monitoring health status, preventing the buildup of dangerous internal forces in impaired organs, and enabling novel approaches of using ...mechanical stimulation for tissue regeneration. Pressure sensors are often required to be implanted and directly integrated with native soft biological systems. Therefore, the devices should be flexible and at the same time biodegradable to avoid invasive removal surgery that can damage directly interfaced tissues. Despite recent achievements in degradable electronic devices, there is still a tremendous need to develop a force sensor which only relies on safe medical materials and requires no complex fabrication process to provide accurate information on important biophysiological forces. Here, we present a strategy for material processing, electromechanical analysis, device fabrication, and assessment of a piezoelectric Poly-L-lactide (PLLA) polymer to create a biodegradable, biocompatible piezoelectric force sensor, which only employs medical materials used commonly in Food and Drug Administration-approved implants, for the monitoring of biological forces. We show the sensor can precisely measure pressures in a wide range of 0–18 kPa and sustain a reliable performance for a period of 4 d in an aqueous environment. We also demonstrate this PLLA piezoelectric sensor can be implanted inside the abdominal cavity of a mouse to monitor the pressure of diaphragmatic contraction. This piezoelectric sensor offers an appealing alternative to present biodegradable electronic devices for the monitoring of intraorgan pressures. The sensor can be integrated with tissues and organs, forming self-sensing bionic systems to enable many exciting applications in regenerative medicine, drug delivery, and medical devices.
Xylem, the most abundant tissue on Earth, is responsible for lateral growth in plants. Typical xylem has a radial system composed of ray parenchyma cells and an axial system of fusiform cells. In ...most angiosperms, fusiform cells comprise vessel elements for water transportation and libriform fibers for mechanical support, while both functions are performed by tracheids in other vascular plants such as gymnosperms. Little is known about the developmental programs and evolutionary relationships of these xylem cell types.
Through both single-cell and laser capture microdissection transcriptomic profiling, we determine the developmental lineages of ray and fusiform cells in stem-differentiating xylem across four divergent woody angiosperms. Based on cross-species analyses of single-cell clusters and overlapping trajectories, we reveal highly conserved ray, yet variable fusiform, lineages across angiosperms. Core eudicots Populus trichocarpa and Eucalyptus grandis share nearly identical fusiform lineages, whereas the more basal angiosperm Liriodendron chinense has a fusiform lineage distinct from that in core eudicots. The tracheids in the basal eudicot Trochodendron aralioides, an evolutionarily reversed trait, exhibit strong transcriptomic similarity to vessel elements rather than libriform fibers.
This evo-devo framework provides a comprehensive understanding of the formation of xylem cell lineages across multiple plant species spanning over a hundred million years of evolutionary history.
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