scholarly journals Genealogy of the neurodegenerative diseases based on a meta-analysis of age-stratified incidence data

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Daniela Gerovska ◽  
Haritz Irizar ◽  
David Otaegi ◽  
Isidre Ferrer ◽  
Adolfo López de Munain ◽  
...  

Abstract While the central common feature of the neurodegenerative diseases (NDs) is the accumulation of misfolded proteins, they share other pathogenic mechanisms. However, we miss an explanation for the onset of the NDs. The mechanisms through which genetic mutations, present from conception are expressed only after several decades of life are unknown. We aim to find clues on the complexity of the disease onset trigger of the different NDs expressed in the number of steps of factors related to a disease. We collected brain autopsies on diseased patients with NDs, and found a dynamic increase of the ND multimorbidity with the advance of age. Together with the observation that the NDs accumulate multiple misfolded proteins, and the same misfolded proteins are involved in more than one ND, motivated us to propose a model for a genealogical tree of the NDs. To collect the dynamic data needed to build the tree, we used a Big-data approach that searched automatically epidemiological datasets for age-stratified incidence of NDs. Based on meta-analysis of over 400 datasets, we developed an algorithm that checks whether a ND follows a multistep model, finds the number of steps necessary for the onset of each ND, finds the number of common steps with other NDs and the number of specific steps of each ND, and builds with these findings a parsimony tree of the genealogy of the NDs. The tree discloses three types of NDs: the stem NDs with less than 3 steps; the trunk NDs with 5 to 6 steps; and the crown NDs with more than 7 steps. The tree provides a comprehensive understanding of the relationship across the different NDs, as well as a mathematical framework for dynamic adjustment of the genealogical tree of the NDs with the appearance of new epidemiological studies and the addition of new NDs to the model, thus setting the basis for the search for the identity and order of these steps. Understanding the complexity, or number of steps, of factors related to disease onset trigger is important prior deciding to study single factors for a multiple steps disease.

Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Elizabeth Mostofsky ◽  
Elizabeth A Penner ◽  
Murray A Mittleman

Introduction: Short-term psychological stress is associated with an immediate physiologic response. We assessed the hypothesis that brief episodes of anger may trigger the onset of acute myocardial infarction (MI) and other acute coronary syndromes (ACS). Methods: We performed a literature search of the CINAHL, Embase, PubMed and PsycInfo databases from January 1966 through June 2012 using the key words “anger”, “hostility”, “myocardial infarction” and “acute coronary syndrome” without restrictions. We also reviewed the reference lists of retrieved articles and spoke with authors of relevant work to identify unpublished data. We used an inverse-variance-weighted random effects model to perform a meta-analysis of all epidemiological studies that reported relative risks and 95% confidence intervals (CI) for the association between outbursts of anger and nonfatal MI or ACS. Results: The meta-analysis included four independent case-crossover studies of anger and risk of MI or ACS published between 1995 and 2007 and one unpublished report. Combined, there were 4546 MI cases (two studies) and 462 ACS cases (two studies), including 180 that experienced an episode of anger in the two hours prior to disease onset; two studies were restricted to first MI or ACS and two included first and recurrent events. All studies used the Onset Anger Scale to assess anger episodes, but the studies differed in the cutoff used to define exposure. The association between outbursts of anger and disease risk in the following two hours was 3.46 (95%CI 2.08-5.76; p<0.001). The results were similar for studies of first and recurrent events and were similar for studies of MI and ACS. Conclusions: There is a higher risk of MI and ACS shortly after outbursts of anger. Some of the between-study heterogeneity may be due to regional differences in the type of anger expression and the interpretation of the questions. Further research is necessary to evaluate whether the risk is lower among people who are regularly active.


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Maryam Zare Jeddi ◽  
Rozita Soltanmohammadi ◽  
Giulia Barbieri ◽  
Aline S. C. Fabricio ◽  
Gisella Pitter ◽  
...  

Abstract Exposure to per- and polyfluoroalkyl substances (PFAS), ubiquitous persistent environmental contaminants, has led to substantial global concern due to their potential environmental and human health effects. Several epidemiological studies have assessed the possible association between PFAS exposure and risk of metabolic syndrome (MetS), however, the results are ambiguous. The aim of this study was to assess the current human epidemiologic evidence on the association between exposure to PFAS and MetS. We performed a systematic search strategy using three electronic databases (PubMed, Scopus, and Web of Science) for relevant studies concerning the associations of PFAS with MetS and its clinical relevance from inception until January 2021. We undertook meta-analyses where there were five or more studies with exposure and outcomes assessments that were reasonably comparable. The pooled odd ratios (ORs) were calculated using random effects models and heterogeneity among studies was assessed by I2 index and Q test. A total of 12 cross-sectional studies (10 studies on the general population and two studies in the occupational settings) investigated the association between PFAS exposure and MetS. We pooled data from seven studies on the general population for perfluorooctanoic acid (PFOA) and perfluorooctanesulfonate (PFOS) and five studies for perfluorohexanesulfonate (PFHxS) and perfluorononanoic acid (PFNA). Predominately, most studies reported no statistically significant association between concentrations of PFAS and MetS. In the meta-analysis, the overall measure of effect was not statistically significant, showing no evidence of an association between concentrations of PFOA, PFOS, PFNA, and PFHxS and the risk of MetS. Based on the results of the meta-analysis, current small body of evidence does not support association between PFAS and MetS. However, due to limited number of studies and substantial heterogeneity, results should be interpreted with caution. Further scrutinizing cohort studies are needed to evaluate the association between various and less well-known PFAS substances and their mixture with MetS and its components in both adults and children in different settings.


2020 ◽  
Author(s):  
Adam Runacres ◽  
Kelly A. Mackintosh ◽  
Melitta A. McNarry

Abstract Introduction Exercise is widely accepted to improve health, reducing the risk of premature mortality, cardiovascular disease (CVD) and cancer. However, several epidemiological studies suggest that the exercise-longevity relationship may be ‘J’ shaped; with elite athlete’s likely training above these intensity and volume thresholds. Therefore, the aim of this meta-analysis was to examine this relationship in former elite athletes. Methods 38,047 English language articles were retrieved from Web of Science, PubMed and SportDiscus databases published after 1970, of which 44 and 24 were included in the systematic review and meta-analysis, respectively. Athletes were split into three groups depending on primary sport: Endurance (END), Mixed/Team, or power (POW). Standard mortality ratio’s (SMR) and standard proportionate mortality ratio (SPMR) were obtained, or calculated, and combined for the meta-analysis. Results Athletes lived significantly longer than the general population (male SMR 0.69 [95% CI 0.61–0.78]; female SMR 0.51 [95% CI 0.40–0.65]; both p < 0.01). There was no survival benefit for male POW athletes compared to the general population (SMR 1.04 [95% CI 0.91–1.12]). Although male athlete’s CVD (SMR 0.73 [95% CI 0.62–0.85]) and cancer mortality (SMR 0.75 [95% CI 0.63–0.89]), were significantly reduced compared to the general population, there was no risk-reduction for POW athletes CVD mortality (SMR 1.10 [0.86–1.40]) or END athletes cancer mortality (SMR 0.73 [0.50–1.07]). There was insufficient data to calculate female sport-specific SMR’s. Discussion Overall, athletes live longer and have a reduced incidence of both CVD and cancer mortality compared to the general population, refuting the ‘J’ shape hypothesis. However, different health risks may be apparent according to sports classification, and between sexes, warranting further investigation. Trial registration PROSPERO (registration number: CRD42019130688).


2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Abdou Fatawou Modiyinji ◽  
Jean Joel Bigna ◽  
Sebastien Kenmoe ◽  
Fredy Brice N. Simo ◽  
Marie A. Amougou ◽  
...  

Abstract Background Hepatitis E virus (HEV) is a major cause of acute hepatitis in humans worldwide and have high burden in the resource-limited countries. Better knowledge of the epidemiology of hepatitis in animals in Africa can help to understand the epidemiology among humans. The objective of this study was to summarize the prevalence of HEV infection and distribution of HEV genotypes among animals in Africa. Methods In this systematic review and meta-analysis, we comprehensively searched PubMed, EMBASE, African Journals Online, and Africa Index Medicus from January 1st, 2000 to March 22th, 2020 without any language restriction. We considered cross-sectional studies of HEV infection in animals in Africa. Study selection, data extraction, and methodological quality of included studies were done independently by two investigators. Prevalence data were pooled using the random-effects meta-analysis. This review was registered in PROSPERO, CRD42018087684. Results Twenty-five studies (13 species and 6983 animals) were included. The prevalence (antibodies or ribonucleic acid [RNA]) of HEV infection in animals varied widely depending on biological markers of HEV infection measured: 23.4% (95% confidence interval; 12.0–37.2) for anti-HEV immunoglobulins G, 13.1% (3.1–28.3) for anti-HEV immunoglobulins M, and 1.8% (0.2–4.3) for RNA; with substantial heterogeneity. In subgroup analysis, the immunoglobulins G seroprevalence was higher among pigs 37.8% (13.9–65.4). The following HEV genotypes were reported in animals: Rat-HEV genotype 1 (rats and horses), HEV-3 (pigs), HEV-7 (dromedaries), and Bat hepeviruses (bats). Conclusions We found a high prevalence of HEV infection in animals in Africa and HEV genotypes close to that of humans. Some animals in Africa could be the reservoir of HEV, highlighting the need of molecular epidemiological studies for investigating zoonotic transmission.


2021 ◽  
pp. 1-12
Author(s):  
Mingyue Qu ◽  
Hanxu Shi ◽  
Kai Wang ◽  
Xinggang Wang ◽  
Nan Yu ◽  
...  

Background: Multiple lines of evidence indicate protective effects of carotenoids in Alzheimer’s disease (AD). However, previous epidemiological studies reported inconsistent results regarding the associations between carotenoids levels and the risk of AD. Objective: Our study aims to evaluate the associations of six major members of carotenoids with the occurrence of AD by conducting a systematic review and meta-analysis. Methods: Following PRISMA guidelines, a comprehensive literature search of PubMed, Web of Science, Ebsco, and PsycINFO databases was conducted, and the quality of each included studies was evaluated by a validated scoring systems. Standardized mean differences (SMD) with 95%confidence intervals (CI) were determined by using a random effects model. Heterogeneity was evaluated by I2 statistics. Publication bias was detected using funnel plots and Egger’s test. Results: Sixteen studies, with 10,633 participants were included. Pooled analysis showed significantly lower plasma/serum levels of lutein (SMD = –0.86, 95%CI: –1.67 to –0.05, p = 0.04) and zeaxanthin (SMD = –0.59; 95%CI: –1.12 to –0.06, p = 0.03) in patients with AD versus cognitively intact controls, while α-carotene (SMD = 0.21, 95%CI: –0.68 to 0.26, p = 0.39), β-carotene (SMD = 0.04, 95%CI: –0.57 to 0.65, p = 0.9), lycopene (SMD = –0.12, 95%CI: –0.96 to 0.72, p = 0.78), and β-cryptoxanthin (SMD = –0.09, 95%CI: –0.83 to 0.65, p = 0.81) did not achieve significant differences. Conclusion: Of six major members of carotenoids, only lutein and zeaxanthin concentrations in plasma/serum were inversely related to the risk of AD. More high-quality longitudinal studies are needed to verify these findings.


Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 207
Author(s):  
Diane L. Ritchie ◽  
Marcelo A. Barria

The accumulation and propagation in the brain of misfolded proteins is a pathological hallmark shared by many neurodegenerative diseases such as Alzheimer’s disease (Aβ and tau), Parkinson’s disease (α-synuclein), and prion disease (prion protein). Currently, there is no epidemiological evidence to suggest that neurodegenerative disorders are infectious, apart from prion diseases. However, there is an increasing body of evidence from experimental models to suggest that other pathogenic proteins such as Aβ and tau can propagate in vivo and in vitro in a prion-like mechanism, inducing the formation of misfolded protein aggregates such as amyloid plaques and neurofibrillary tangles. Such similarities have raised concerns that misfolded proteins, other than the prion protein, could potentially transmit from person-to-person as rare events after lengthy incubation periods. Such concerns have been heightened following a number of recent reports of the possible inadvertent transmission of Aβ pathology via medical and surgical procedures. This review will provide a historical perspective on the unique transmissible nature of prion diseases, examining their impact on public health and the ongoing concerns raised by this rare group of disorders. Additionally, this review will provide an insight into current evidence supporting the potential transmissibility of other pathogenic proteins associated with more common neurodegenerative disorders and the potential implications for public health.


Author(s):  
Ying Pin Chua ◽  
Ying Xie ◽  
Poay Sian Sabrina Lee ◽  
Eng Sing Lee

Background: Multimorbidity presents a key challenge to healthcare systems globally. However, heterogeneity in the definition of multimorbidity and design of epidemiological studies results in difficulty in comparing multimorbidity studies. This scoping review aimed to describe multimorbidity prevalence in studies using large datasets and report the differences in multimorbidity definition and study design. Methods: We conducted a systematic search of MEDLINE, EMBASE, and CINAHL databases to identify large epidemiological studies on multimorbidity. We used the Preferred Reporting Items for Systematic Reviews and Meta-analysis Extension for Scoping Reviews (PRISMA-ScR) protocol for reporting the results. Results: Twenty articles were identified. We found two key definitions of multimorbidity: at least two (MM2+) or at least three (MM3+) chronic conditions. The prevalence of multimorbidity MM2+ ranged from 15.3% to 93.1%, and 11.8% to 89.7% in MM3+. The number of chronic conditions used by the articles ranged from 15 to 147, which were organized into 21 body system categories. There were seventeen cross-sectional studies and three retrospective cohort studies, and four diagnosis coding systems were used. Conclusions: We found a wide range in reported prevalence, definition, and conduct of multimorbidity studies. Obtaining consensus in these areas will facilitate better understanding of the magnitude and epidemiology of multimorbidity.


2020 ◽  
pp. 1901815
Author(s):  
Thomas A. Wills ◽  
Samir S. Soneji ◽  
Kelvin Choi ◽  
Ilona Jaspers ◽  
Elizabeth K. Tam

BackgroundUse of electronic cigarettes (e-cigarettes) is prevalent among adolescents and young adults but there has been limited knowledge about health consequences in human populations. We conduct a systematic review and meta-analysis of results on respiratory disorder from studies of general-population samples and consider the mapping of these results to findings about biological processes linked to e-cigarettes in controlled laboratory studies.MethodWe conduct a literature search and meta-analysis of epidemiological studies on the association of e-cigarette use with asthma and with chronic obstructive pulmonary disease (COPD). We then discuss findings from laboratory studies about effects of e-cigarettes on four biological processes: cytotoxicity, oxidative stress/inflammation, susceptibility to infection, and genetic expression.ResultsEpidemiological studies, both cross-sectional and longitudinal, show a significant association of e-cigarette use with asthma and COPD, controlling for cigarette smoking and other covariates. For asthma (n=15 studies), the pooled adjusted odds ratio (AOR) was 1.39 (CI 1.28–1.51); for COPD (n=9 studies) the AOR was 1.49 (CI 1.36–1.65). Laboratory studies consistently show an effect of e-cigarettes on biological processes related to respiratory harm and susceptibility to illness, with e-cigarette conditions differing significantly from clean-air controls though sometimes less than for cigarettes.ConclusionsThe evidence from epidemiological studies meets established criteria for consistency, strength of effect, temporality, and in some cases a dose-response gradient. Biological plausibility is indicated by evidence from multiple laboratory studies. We conclude that e-cigarette use has consequences for asthma and COPD, which is of significant concern for respirology and public health.


2003 ◽  
Vol 228 (5) ◽  
pp. 568-571 ◽  
Author(s):  
Ladislav Novotný ◽  
Libor Vítek

Bilirubin, a major intravascular product of heme catabolism, is a potent antioxidant compound. Numerous studies have been published showing the relationship between serum bilirubin levels and atherosclerosis. In the present investigation all the epidemiological studies available on the effect of serum bilirubin levels and atherosclerotic disease were analyzed. Studies on the epidemiology of atherosclerotic diseases in relation to serum bilirubin levels were searched in the MEDLINE database. Selected studies were subdivided according to serum bilirubin levels and severity of atherosclerotic disease. Because of the limited number of females involved in the studies, only males were included into meta-analysis. Associations for ordered categorical variables (bilirubin and natural history of graded atherosclerosis) were assessed to find correlation and linear trend between analyzed variables. A stratified analysis was conducted to compare risks of clinical outcomes. Eleven relevant studies were used for analysis. A close negative relationship was found between serum bilirubin levels and severity of atherosclerosis (Spearman rank coefficient r = −0.31, P < 0.0001). The linear trend was confirmed in analysis of proportions with x2 values for both disease conditions to be very significant ( P < 0.0001). Unambiguous inverse relationship between serum bilirubin levels and atherosclerosis was demonstrated in this preliminary meta-analytic study. These results indicate the importance of hem oxygenase-related products in the prevention of oxidative stress-mediated diseases.


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